Biol 3500 Final

Two procedures are currently used to solve the structures of complex proteins: *require human interaction & are too slow for determining structures of thousands of proteins in a cell.

(1) X-ray crystallography, in which crystals of the protein are bombarded with X-rays, and the diffraction patterns of the X-rays are used to determine the structure (2) nuclear magnetic resonance (NMR), which provides information on the positions of specific atoms within a molecule by using the magnetic properties of their nuclei.

Gene Cloning require a cloning vector: a stable, replicating DNA molecule to which a foreign DNA fragment can be attached for introduction into a cell. An effective cloning vector has three important characteristics:

(1) an origin of replication, which ensures that the vector is replicated within the cell (2) selectable markers, which enable any cells containing the vector to be selected or identified (3) one or more unique restriction sites into which a DNA fragment can be inserted.

three different processes affect gene regulation by altering chromatin structure:

(1) chromatin remodeling, (2) the modification of histone proteins (3) DNA methylation.

RNA sequencing - five steps:

(1) isolation of the RNA molecules of interest; (lysed and chemically extracted to get total RNA of the cell-rRNA is 90%) (2) conversion of the RNA to complementary DNA (cDNA) sequences by transcriptase enzyme. (3) fragmentation and preparation of the cDNAs for sequencing; broken into overlapping fragments ~200 bp; Adaptors added to the ends. (4) sequencing of the cDNA-amplified using PCR and sequenced using sequencing platform like Illumina. (5) assembly of the sequence reads into RNA transcripts- comparing overlap in the sequenced fragments.

The Process of Transposition

(1) staggered breaks are made in the target DNA (2) the transposable element is joined to single-stranded ends of the target DNA (3) DNA is replicated at the single-strand gaps. A transposase enzyme, often encoded by the transposable element, is used to make the staggered breaks in DNA and to integrate the transposable element into a new site.

variance -A statistic that provides key information about a distribution; indicates the variability of a group of measurements, or how spread out the distribution is. Distributions can have the same mean but different variances

(1) subtract the mean from each measurement and square the value obtained, (2) add all of these squared deviations together, and (3) divide that sum by the number of original measurements minus 1.

The translation of an mRNA molecule takes place on a ribosome.

(1) tRNA charging, in which tRNAs bind to amino acids; (2) initiation, in which the components necessary for translation are assembled at the ribosome; (3) elongation, in which amino acids are joined, one at a time, to the growing polypeptide chain; (4) termination

Receptors in signal-transduction pathways usually have three parts: (1) an extracellular domain that protrudes from the cell and binds the signaling molecule; (2) a transmembrane domain that passes across the membrane and conducts the signal to the interior of the cell; and

(3) an intracellular domain that extends into the cytoplasm and, upon the binding of the signaling molecule, undergoes a chemical or conformational change that is transmitted to molecules of the signal-transduction pathway in the cytoplasm.

Key Innovations in Molecular Genetics (1) the development of recombinant DNA technology, which allowed DNA from different sources to be combined; (2) the invention of the polymerase chain reaction, which allowed very small quantities of specific DNA fragments to be quickly amplified;

(3) the development of quick and accurate methods of determining DNA sequences; and (4) the engineering of CRISPR-Cas systems for accurate and efficient editing of genome sequences.

DNA sequencing determines the sequence of bases in a DNA molecule. Allows genetic information in DNA to be read, providing an enormous amount of info about gene structure and function.

- Dideoxy (Sanger) sequencing -Illumina Sequencing -single-molecule real-time (SMRT) sequencing -PacBio -DNA fingerprinting

EFFECTS OF DELETIONS

- If the deletion includes the centromere, then the chromosome will not segregate in meiosis or mitosis and will usually be lost. - Many deletions are lethal In Heterozygous individuals May Have Defects for 3 reasons: 1. may produce imbalances in the amounts of gene products (like an extra gene copy) 2. normally recessive mutations may be expressed when the wild-type allele has been deleted (pseudodominance) 3. some genes must be present in two copies for normal function. When a single copy of a gene is not sufficient to produce a wild-type phenotype the gene is haploinsufficient.

Limits to the Response to Selection

- all individuals in the population may have become homozygous for the alleles that encode the selected trait. - leveling off takes place because natural selection opposes further change in the characteristic.

Many of the viruses that cause cancer in animals are retroviruses. HTLV-1: T-cell leukemia in humans. DNA viruses, unlike Rv's do not use reverse transcription. Rv's can contribute to cancer by:

- mutating or rearranging host genes, converting proto-oncogenes into oncogenes - altering the expression of host genes. If the provirus inserts near a proto-oncogene, viral promoters can stimulate high levels of expression of the proto-oncogene, leading to cell proliferation.

LIMITATIONS OF PCR

- requires prior knowledge of at least part of the sequence of the target DNA -the capacity of PCR to amplify extremely small amounts of DNA makes contamination a significant problem. -accuracy. Taq polymerase can't proofread. -fragments amplified by Taq pol is less than 2000 bp

Determination of Cellular Proteins The basic procedure for characterizing the proteome is to first separate the proteins found in a cell and then to identify and quantify the individual proteins.

- two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), in which the proteins are separated in one dimension by charge, separated in a second dimension by mass, and then stained. Separates proteins into spots. -liquid chromatography also separates. -mass spectrometry: determine molecular mass by ionizing molecule and its migration rate in an electrical field.

Which of the following statements are TRUE? Select all:

-- Some cancers are caused by hereditary mutations -- some cancers are causes by environmental factors -- some cancers are caused by viruses -- some cancers are caused by errors during DNA replication

Which of these statements is FALSE? Select all that apply. - cervical cancer is associated with a viral infection - tumors often show clonal evolution

-- most tumors arise from germ-line mutations that we accumulate as we age -- somatic mutations don't contribute to cancer

What are ways that viruses can cause cancer? Choose all that are correct.

-- viruses can copy and mutate proto-oncogenes into oncogenes -- viruses can insert near a proto-oncogene, trigging its overexpression

Autopolyploidy caused by accidents of mitosis or meiosis that produce extra sets of chromosomes, all derived from a single species

--Nondisjunction of all chromosomes in mitosis in an early 2n embryo produces an autotetraploid (4n). --An autotriploid (3n) may arise when nondisjunction in meiosis produces a diploid gamete that then fuses with a normal haploid gamete to produce a triploid zygote --triploids may arise from a cross between an autotetraploid that produces 2n gametes and a diploid that produces 1n gametes.

termination of transcription in eukaryotes

--RNA polymerase I requires a termination factor similar to the rho factor --RNA polymerase III ends transcription after transcribing a terminator sequence that produces a string of uracil nucleotides in the RNA molecule. --RNA polymerase II often continues to synthesize RNA hundreds or more nucleotides. pre-mRNA is cleaved at a specific site. Cleavage cuts the pre-mRNA into two pieces: the mRNA that will eventually encode the protein and another piece of RNA that has its 5′ end trailing out of the RNA polymerase. An enzyme (called Rat1 in yeast) attaches to the 5′ end of this RNA and moves toward the 3′ end, where the RNA polymerase continues the transcription of RNA. Rat1 is a 5′→3′ exonuclease—an enzyme capable of degrading RNA in the 5′→3′ direction. Like a guided torpedo, Rat1 homes in on the polymerase, chewing up the RNA as it moves. When Rat1 reaches the transcription machinery, transcription terminates.

uniparental disomy Inheritance of both chromosomes of a homologous pair from a single parent.

--a trisomic embryo can survive if one of the three chromosomes is lost early in development. If, just by chance, the two remaining chromosomes are both from the same parent, uniparental disomy results. --ex: Some ppl with CF inherit 2 copies of chrom 7 that carries defective allele from the heterozygous parent and no copy of normal allele from other parent.

Morgan additional crosses

--crossed a white-eyed female and a red-eyed male & produced all red-eyed females and all white-eyed males. --crossed the F1 heterozygous females with their white-eyed father, the red-eyed F2 females with white-eyed males, and white-eyed females with white-eyed males. In all these crosses, the results were consistent with Morgan's conclusion that the white-eye trait is an X-linked characteristic.

TRANSLOCATIONS IN MEIOSIS (cont. pt 3)

--each of the gametes produced by alternate segregation possesses one complete set of the chromosome segments (viable progeny) --In contrast, gametes produced by adjacent-1 and adjacent-2 segregation are not viable because some chromosome segments are present in two copies, whereas others are missing.

INVERSIONS IN MEIOSIS

--homozygous for an inversion: no issues separating. --hetero: gene order of the two homologs differs, and the homologous sequences can align and pair only if the two chromosomes form an inversion loop. Also have reduced recombination among genes located in inverted region. Crossing over does not prod. viable offspring=no recomb. progeny.

EFFECTS OF INVERSIONS

--may break a gene into two parts, with one part moving to a new location and destroying the function of that gene. --if gene positions are altered by an inversion, their expression may be altered, an outcome referred to as a position effect.

Translocation (movement of genetic material between nonhomologous chromosomes or within the same chromosome.)

--nonreciprocal translocation, genetic material moves from one chromosome to another without any reciprocal exchange. (AB•CDG and MN•OPEFQRS) --reciprocal translocation: two-way exchange btwn chroms (AB•CDQRS and MN•OPEFG.)

Effects of Aneuploidy

--usually alters the phenotype drastically. --lethal in most plants/animals --most likely due to abnormal gene dosage

GENOME EDITING WITH CRISPR-Cas -requires crRNA and tracrRNA that pair and then combine with Cas9 to form an effector complex. -required presence of a sequence in the target DNA (the DNA to be cleaved): protospacer-adjacent motif (PAM)

-A 20-nucleotide region of the sgRNA pairs with DNA -By altering the sequence of the sgRNA, it is possible to direct the action of the effector complex to any specific DNA sequence desired. This relatively long recognition sequence makes CRISPR-Cas9 much more specific than restriction enzymes

tag-SNPs The few SNPs used to identify a haplotype

-Because the SNPs in a haplotype are inherited together, a haplotype consisting of thousands of SNPs can be identified with the use of only a few SNPs.

conducting a mutagenesis screen Mutations can be induced by exposing the organisms to radiation, chemical mutagens, or transposable elements (DNA sequences that insert randomly into the DNA)

-CRISPR Cas

targeted mutagenesis mutations are induced at specific locations to study their effects. -oligonucleotide-directed mutagenesis: uses an oligonucleotide to introduce a mutant sequence into a DNA molecule.

-CRISPR-Cas9 can be used -site-directed mutagenesis, is to cut out a short sequence of nucleotides with restriction enzymes and replace it with a synthetic oligonucleotide—a short DNA fragment that contains the desired mutated sequence.

3. DNA Methylation Most common on cytosine bases adjacent to guanine nucleotides 5′−mC G−3′ 3′−G Cm−5′ *the first m is above C and 2nd is under C.

-CpG islands: DNA regions with many CpG sequences often found near transcription start sites; methylated when genes are inactive but are demethylated before the initiation of transcription. -Gene repression (x inactivation in female mammals)

p53 stabilizes genome affects apoptosis (cell death). If TP53 is mutated, cells cont. to divide and do undergo programmed death.

-DNA-binding protein that functions as a transcription factor, regulating transcription, and most of the mutations in TP53 that are associated with cancer occur in the DNA-binding domain of p53. -critical for proper functioning of the G1/S checkpoint in the cell cycle. If DNA damage is present, p53 is activated and prevents the cell from moving into S phase, where DNA replication would normally take place. This pause allows for DNA-repair. -If damaged, DNA damaged and leads to mutations that can add to cancer process.

Cancer-causing chromosome rearrangements: deletions, inversions, and translocations

-Deletions can result in the loss of one or more tumor-suppressor genes. - Inversions: the chromosome breaks can lie within tumor-suppressor genes, disrupting their function and cause cell division. -Translocations and inversions can bring together sequences from two different genes, generating a fusion protein that stimulates some aspect of the cancer process. -Rearrangements: transfer of a potential cancer-causing gene to a new location, where it is activated by different regulatory sequences.

Transcription Factors (TF's) -most have helix-turn-helix, zinc finger, or leucine zipper (to help bind) -Recruit cofactors (proteins) which stimulate or repress transcription

-General TF's bind to the core promoter and are part of the basal transcription apparatus—the complex of RNA polymerase, TF's, and other proteins needed to initiate. -apparatus binds to a core promoter located immediately upstream -Other TF's bind to a regulatory promoter, which is located upstream of the core promoter, and to enhancers. -Some TF's are activators, stimulating transcription; others are repressors, inhibiting transcription. -

Many eukaryotic genomes, especially those of multicellular organisms, are filled with segmental duplications (duplicated regions greater than 1000 bp that are almost identical in sequence.) -*importance: give rise to new genes.

-In most segmental duplications, the two copies are found on the same chromosome (intrachromosomal duplications), but in others, the two copies are found on different chromosomes (interchromosomal duplications). -can arise from anything causing duplications like crossing over. -the original copy of the segment can continue its function while the new copy undergoes mutation.

MicroRNAs (miRNAs) are a class of small RNA molecules that pair with complementary sequences on mRNA and degrade the mRNA or inhibit its translation.

-Many tumor cells exhibit reduction in the expression of many miRNAs. -Lower levels contribute to cancer by allowing oncogenes to be expressed @ high levels. -High levels also cancerous.

unequal crossing over can cause insertions and deletions

-Normally 2 DNA molec. produce no change in # of nucleotides in either molecule. Misaligned pairing, however, can cause unequal crossing over, which results in one DNA molecule with an insertion and the other with a deletion

CONTROL OF TRANSPOSITION

-Organisms methylate DNA in regions where transposons are common (usually suppresses transcription preventing the production of the transposase enzyme necessary for transposition) -Alterations of chromatin structure - some animals use Piwi-interacting RNAs to silence transposons.

THIRD-GEN SEQUENCING TECHNOLOGIES -single-molecule real-time (SMRT) sequencing: easier to seq. whole genome bcuz of longer fragments used to find seq. of single DNA/RNA molecules. - nanopore seq: strand of DNA is passed through a tiny hole—a nanopore—in a membrane. Each of the 4 bases causes a characteristic disruption, so the sequence of DNA can be read by analyzing the membrane current as the strand passes, one nucleotide at a time, through the nanopore; simultaneous, longer reads, high error rate

-PacBio: analyzes DNA synthesis of single molecules of DNA; adaptors are added to the end of each DNA fragment to produce a closed circle of DNA for sequencing. --when the DNA polymerase reaches the end of the fragment, it proceeds around the adaptor and sequences the other strand. --costs more, high error rate

Why Does Attenuation Take Place in the trp Operon?

-Repression is never complete and attenuation can further reduce transcription. -attenuation and repression respond to different signals: repression responds to cellular levels of tryptophan, whereas attenuation responds to the availability of tRNAs charged with tryptophan.

If the lac operon is repressed and no permease is being produced, how does lactose get into the cell to inactivate the repressor and turn on transcription? The inducer is actually allolactose, which must be produced from lactose by β-galactosidase. If β-galactosidase production is repressed, how can lactose metabolism be induced?

-Repression never completely shuts down. -There is still a low level of transcription, and a few molecules of β-galactosidase, permease, and transacetylase are synthesized. -When lactose appears in the medium, the permease that is present transports a small amount of lactose into the cell. There, the few molecules of β-galactosidase that are present convert some of the lactose into allolactose, which then induces transcription.

haplotype The specific set of SNPs and other genetic variants observed on a single chromosome or part of a chromosome

-SNPs w/in a haplotype are physically linked & tend to be inherited together. -New haplotypes can arise through mutation or crossing over, which breaks up the particular set of SNPs -SNPs and other genetic variants that are located close together on a chromosome will be strongly associated as haplotypes. -The nonrandom association between genetic variants within a haplotype is called linkage disequilibrium

DNA Fingerprinting -uses microsatellites, or short tandem repeats (STRs), which are very short DNA sequences repeated in tandem. --primers used in PCR are tagged with fluorescent labels

-STRs detected with PCR, using primers flanking the microsatellite repeats so that a DNA fragment containing the repeated sequences is amplified. DNA from a person with more repeats will produce a longer amplified segment than will DNA from a person with fewer repeats. 1. fragments are separated on a gel or by a capillary electrophoresis machine (fragments pass through laser) 2. computer calculates & fragments show as peaks on a graph. Homozygotes for an STR allele have a single tall peak; heterozygotes have two shorter peaks.

chromosome mutations both cause cancer and result from it.

-Some types of tumors are consistently associated with specific chromosome mutations -Yet many cancers are not associated with specific types of chromosome abnormalities, and individual gene mutations are now known to contribute to many types of cancer.

MUTATION AND NATURAL SELECTION Eventually, these two forces reach an equilibrium in which the number of alleles added by mutation is balanced by the number of alleles removed by selection.

-The frequency of a deleterious recessive allele at equilibrium (ˆq) is equal to the square root of the mutation rate divided by the selection coefficient: -The frequency of a deleterious dominant allele at equilibrium can be shown to be:

a phenotypic correlation may result from a genetic correlation (the genes affecting two characteristics are associated)

-The primary genetic cause of phenotypic correlations is pleiotropy, the effect of one gene on 2 or more characteristics --ex: Height and hand size are therefore phenotypically correlated in humans, and this correlation is due to a genetic correlation.

An intragenic suppressor mutation takes place in the same gene that contains the mutation being suppressed.

-The suppressor may change a second nucleotide in the same codon altered by the original mutation, producing a codon that specifies the same amino acid that was specified by the original, nonmutated codon -may also work by suppressing a frameshift mutation -can make compensatory changes in the protein

transcriptomics study of examining the expression of the genome.

-The transcriptome includes mRNAs that code for proteins, as well as other types of RNAs. -Use of microarrays, which rely on nucleic acid hybridization.

Elongation process (RNA)

-Transcription bubble. RNA pol w/ sigma factor -pausing caused by backtracking -If a mistake made, RNA pol backtracks and cleaves last two nucleotides from RNA chain.

-Ionizing radiation such as X-rays and gamma rays damages DNA by dislodging electrons from atoms; these electrons then break phosphodiester bonds and alter the structure of bases.

-Ultraviolet light causes mutations primarily by producing pyrimidine dimers that disrupt replication and transcription. -The SOS system enables bacteria to overcome replication blocks but introduces mistakes in replication.

single-nucleotide polymorphism (SNP) A site in the genome where individual members of a species differ in a single base pair. -Can be found every ~1000 bp

-a variant must reach a frequency of at least 1% in a population; thus, very rare variations are not usually considered SNPs. -Arising through mutation, SNPs are inherited as allelic variants in the same way as alleles that produce phenotypic differences (such as blood types), although SNPs often do not produce phenotypic differences.

Transposable elements—DNA sequences that can move about in the genome—are often a cause of mutations.

-can insert themselves at different locations in the genome and disrupt it or cause chrom. rearrangements (deletions, duplication, inversions)

knockout mice: mutations that disable a gene are added or induced. are particularly helpful in determining the function of a gene: the phenotype of the knockout mouse often gives a good indication of the function of the missing gene. [[Mice that carry inserted sequences at specific locations are called knock-in mice.]]

-created by using CRISPR-Cas technology -The insertion of neo both disrupts the target gene and provides a convenient marker for finding disabled gene copies -viral thymidine kinase (tk) gene also inserted & makes the cells sensitive to the antimicrobial gancyclovir.

mutations also result from spontaneous chemical changes in DNA. Depurination is a common cause.

-depurination, the loss of a purine base from a nucleotide. An apurinic site cannot act as a template for a complementary base in replication. -an incorrect nucleotide (most often adenine) is incorporated into the newly synthesized DNA strand opposite the apurinic site, frequently leading to an incorporated error. The incorporated error is then transformed into a replicated error at the next round of replication.

Dideoxy Sequencing -based on replication. fragment to be sequenced is used as a template. 1. fragment to be sequenced needs to be amplified by PCR or by cloning in bacteria.

-dideoxyribonucleoside triphosphates (ddNTPs) used as substrates & added to DNA and terminate DNA synthesis. Unlike, dNTPs they lack a 3'-OH group. 2. Copies of the target DNA isolated and split into 4 samples 3. Each sample is placed in a different tube and the following added: Many copies of a primer that is complementary to one end of the target DNA strand, All four types of ddNTPs, 1/4 of ddNTPs (ddATP, ddCTP, ddGTP, or ddTTP), which will terminate DNA synthesis as soon as it is added to growing chain. Each tube gets different one; DNA polymerase

contig A set of two or more overlapping DNA fragments that form a contiguous stretch of DNA.

-each clone can be cut with a series of restriction enzymes and the resulting fragments then separated by gel electrophoresis. A computer program is then used to examine the restriction patterns of all the clones and look for areas of overlap. The overlap is then used to arrange the clones in order -the whole genome is assembled by putting together the sequences of all overlapping contigs

Another molecular tool for precisely cutting DNA is the CRISPR-Cas system. --occur naturally in bacteria and archaea and are used to protect these organisms against bacteriophages, plasmids, and other invading DNA elements

-encoded by DNA sequences -array consists of a series of palindromic sequences -When bacteriophage or plasmid DNA enters a prokaryotic cell, proteins cut up the foreign DNA and insert bits of it into a CRISPR array, which then serves as a memory of the invader. -array is transcribed into a long precursor CRISPR RNA (pre-crRNA), which is cleaved into short crRNAs. -The crRNAs combine with proteins called CRISPR-associated (Cas) proteins to form effector complexes. The Cas proteins have nuclease activity—the ability to cut DNA. *If the same foreign DNA (the protospacer) enters the cell in the future, a CRISPR-Cas complex recognizes and attaches to it and destroys it.*

GENOME SIZE AND NUMBER OF GENES The genomes of eukaryotic organisms are larger than those of prokaryotes.

-eukaryotic genomes also contain more protein-encoding genes than do prokaryotic genomes and the genomes of multicellular eukaryotes have more genes than do the genomes of single-celled eukaryotes. -Most of the DNA in multicellular eukaryotes is noncoding, and many genes are interrupted by introns. In more complex eukaryotes, both the number and the length of the introns are greater. -In contrast to prokaryotes, there is no correlation between genome size and number of genes in eukaryotes.

The rate of clonal evolution depends on

-frequency in which new mutations arise - Mutated DNA repairing genes - Mutations in genes that affect chromosome segregation and duplicating or deleting genes on chroms.

forward genetics study of gene function that begins with a mutant phenotype and proceeds to a gene that encodes the phenotype.

-identification and isolation of random mutations that affect a phenotype of interest. -radiation, chemical mutagens, and transposable elements are all used to create mutations for genetic analysis.

APPLICATIONS OF PCR -detect the presence of a particular DNA sequence in a sample. -locate rare and secretive animals through the collection and analysis of environmental DNA (eDNA)

-identify genetic variation in natural populations. -isolation of DNA from ancient sources, such as DNA from Neanderthals/crime scenes. -introduce new sequences into a fragment of DNA -real-time PCR (qPCR), is used to measure the starting amount of nucleic acid. The amount of DNA amplified is measured as the reaction proceeds.

Genetic maps (also called linkage maps) provide a rough approximation of the locations of genes relative to the locations of other known genes. -refined by techniques like: analysis of restriction sites, the polymerase chain reaction, and DNA sequencing.

-individual organisms of known genotype are crossed, and the frequency of recombination between loci is determined by examining the progeny. -For linked genes, the rate of recombination is proportional to the physical distance between the loci. -measured in cM

ADVANTAGES OF CRISPR-Cas9 -precise edits can be made almost anywhere in the genome. -Cas9 protein and specific sgRNAs can be introduced into many types of cells to edit them. -detect viruses -precise changes to nucleotide sequences. -

-introduce new DNA sequences into whole animals and humans (or induce mutations to study diseases) -correcting genetic defects (gene therapy) -treating infectious diseases by eliminating viral DNA from human cells.

Z-Linked Characteristics

-males are the homogametic sex (ZZ) and carry two sex-linked alleles; thus, males may be homozygous or heterozygous. -the male inherits Z chromosomes, along with any Z-linked alleles, from both his mother and his father. -Females are the heterogametic sex (ZW) and possess only a single Z-linked allele. The inheritance of Z-linked characteristics is the same as that of X-linked characteristics, except that the pattern of inheritance in males and females is reversed. -the female always inherits her W chromosome from her mother, and she inherits her Z chromosome, along with any Z-linked alleles, from her father.

phenotypic correlation the association is between two phenotypes of the same individual

-may be due to environmental or genetic correlations.

regression -> y= a +bx -Analysis of how one variable changes in response to another variable. -The variable b is the slope of the regression line, regression coefficient and can be calculated (b=cov *xy*/s^2*x*) *means it's a subscript

-plot x and y values. 1. The overall relation between these two variables is depicted by the regression line, which is the line that best fits all the points on the graph. 2. After the regression coefficient has been calculated, the y intercept can be calculated by substituting the regression coefficient and the mean values of x and y into the following equation: a=¯y−b¯x

restriction enzymes recognize specific nucleotide sequences in DNA and make double-stranded cuts at those sequences (called restriction sites).

-produced naturally by bacteria and are used in defense against viruses. A bacterium protects its own DNA from a restriction enzyme by modifying the recognition sequence, usually by adding methyl groups to its DNA. -most of these enzymes recognize a sequence of 4 or 6 bp (or 8 bp at most) -cohesive ends spontaneously pair to connect the fragments; joined by DNA Ligase.

TRANSPOSABLE ELEMENTS A substantial part of the genomes of most multicellular organisms consists of moderately and highly repetitive sequences and the percentage of repetitive sequences is usually higher in those species with larger genomes.

-repetitive seq. arose through transposable elements.

two basic approaches to amplifying a specific DNA fragment:

-replicating the DNA within cells: (in vivo) -replicating the DNA enzymatically outside of cells (in vitro).

Metastasis is a complex process, requiring that cancer cells escape from the primary tumor site, evade the immune system, travel to a distant site, adhere to existing cells at the new site, and receive nutrients and growth factors necessary for sustained growth.

-requires numerous cellular changes induced by somatic mutation at a number of genes. -often encode components of the extracellular matrix and the cytoskeleton. Others encode adhesion proteins, which help hold cells together. -metastases sometimes composed of cells from more than one subclone found within the primary tumor.

mass spectrometry method

-researchers first digest protein with the enzyme trypsin, which cleaves the protein into smaller peptide fragments. -Mass spectrometry is then used to separate the peptides on the basis of their mass-to-charge ratio -A computer program then searches through a database of proteins to find a match between the profile generated and the profile of a known protein, allowing the protein in the sample to be identified.

Termination process (RNA)

-rho dependent terminators stop in presence of rho factors. -rho dependent terminators: Causes RNA pol to pause and allows rho to catch up.

An intergenic suppressor mutation occurs in a gene other than the one bearing the original mutation that it suppresses.

-sometimes work by changing the way the mRNA is translated. -(a) A wild-type sequence produces a full-length, functional protein. (b) A base substitution at a site in that gene produces a premature stop codon, resulting in a truncated, nonfunctional protein. (c) A base substitution at a site in another gene, which in this case encodes tRNA, alters the anticodon of tRNATyr; tRNATyr can then pair with the stop codon produced by the original mutation, allowing tyrosine to be incorporated into the protein and translation to continue.

Complex proteins often contain regions, called protein domains, that have specific shapes or functions.

-stable over time -protein domains found in humans are also found in other multicellular eukaryotes. -The sequence from a newly identified gene can be scanned against a database of known domains. If the gene sequence encodes one or more domains whose functions have been previously determined, the functions of those domains can provide important information about possible functions of the new gene.

Characteristics of Transposable Elements Short flanking direct repeats—3 to 12 bp long present on both sides of most transposable elements. [ex: 5′−ACAGTTCAG...CTGAACTGT−3′ 3′−TGTCAAGTC...GACTTGACA−5′ ] ^^ both inverted & complementary

-staggered cuts are made in the target DNA that leave short single-stranded pieces of DNA on either side of the transposable element. -many have terminal inverted repeats—9 to 40 bp that are inverted complements of each other. *[from left to right in the top strand is the same as the sequence from right to left in the bottom strand.]

Gene Regulation 1. Alteration of DNA or chromatin structure

-takes place primarily in eukaryotes. -can help determine which sequences are available for transcription or the rate at which sequences are transcribed. -DNA methylation and changes in chromatin structure are two processes that play a pivotal role in gene regulation.

in vitro amplify DNA enzymatically in a test tube outside cells. This amplification is done with the polymerase chain reaction (PCR)-DNA replication catalyzed by a DNA polymerase.

-the amount of DNA doubles w/ each replication. -PCR allows DNA fragments to be amplified a billionfold within just a few hours, and it can be used with extremely small amounts of original DNA, even a single molecule.

A testcross for two independently assorting genes is expected to produce a

1 : 1 : 1 : 1 phenotypic ratio in the progeny. If they don't they are not assorting independently.

Another process that brings change to allelic frequencies is migration or gene flow. A H-W law assumption is that it does not take place but many populations do experience it.

1) it prevents populations from becoming genetically different from one another (2) it increases genetic variation within populations.

transcription requires three major components:

1. A DNA template 2. The raw materials (ribonucleotide triphosphates) needed to build a new RNA molecule 3. The transcription apparatus, consisting of the proteins necessary for catalyzing the synthesis of RNA

Levels of Gene Regulation

1. Alteration of DNA or chromatin structure 2. Level of transcription 3. mRNA processing 4. regulation of mRNA stability 5. level of Translation 6. Post-translation modification

causes of aneuploidy

1. Deletion of centromere during mitosis or meiosis (Mt's can't attach) 2. the small chromosome generated by a Robertsonian translocation may be lost in mitosis or meiosis. 3. Aneuploidy may arise through nondisjunction, the failure of homologous chromosomes or sister chromatids to separate in meiosis or mitosis

Types of Aneuploidy More than one aneuploid mutation may occur in the same individual.

1. Nullisomy is the loss of both members of a homologous pair of chromosomes. It is represented as 2n − 2, where n refers to the haploid number of chromosomes. Thus, among humans, who normally possess 2n = 46 chromosomes, a nullisomic zygote has 44 chromosomes. 2. Monosomy is the loss of a single chromosome, represented as 2n − 1. A human monosomic zygote has 45 chromosomes. 3. Trisomy is the gain of a single chromosome, represented as 2n + 1. A human trisomic zygote has 47 chromosomes. The gain of a chromosome means that there are three homologous copies of one chromosome. (Down syndrome) 4. Tetrasomy is the gain of two homologous chromosomes, represented as 2n + 2. A human tetrasomic zygote has 48 chromosomes. Tetrasomy is not the gain of any two extra chromosomes but rather the gain of two homologous chromosomes, so that there are four homologous copies of a particular chromosome.

Characteristics of cytoplasmically inherited traits

1. Present in males and females. 2. Usually inherited from one parent, typically the maternal parent. 3. Reciprocal crosses give different results. 4. Exhibit extensive phenotypic variation, even within a single family.

Elongation process (DNA)

1. Primase makes primers that provide 3'-OH group to which DNA Pol can attach. 2. Primer is requires only at 5' end of newly synthesized strand. New primer generated @ the beginning of each okazaki fragment (lagging strand) 3. DNA ligase--catalyzes the formation of a phosphodiester bond between adjacent 3′-OH and 5′-phosphate groups in a DNA molecule without adding another nucleotide to the strand.

Initiation process (RNA)

1. Promoter recognition -10 consensus TATA box

initiation of transcription in eukaryotes

1. RNA polymerase II & general transcription factors assemble @ core promoter. TFIID bins to TATA box. 2. conformational change

LIMITATIONS OF GENETIC MAPS

1. Resolution 2. The distances on a genetic map are approximations of real physical distances along a chromosome

role of sex chromosomes in human sex determination:

1. The X chromosome contains genetic information essential for both sexes; at least one copy of an X chromosome is required for human development. 2. The male-determining gene is located on the Y chromosome. A single copy of this chromosome, even in the presence of several X chromosomes, usually produces a male phenotype. 3. The absence of the Y chromosome usually results in a female phenotype. 4. Genes affecting fertility are located on the X and Y chromosomes. A female usually needs at least two copies of the X chromosome to be fertile. 5. Additional copies of the X chromosome may upset normal development in both males and females, producing physical problems and intellectual disabilities that increase as the number of extra X chromosomes increases.

Random inactivation of X chromosomes requires 2 steps:

1. The cell somehow assesses, or counts, how many X chromosomes are present. 2. One X chromosome is selected to become the active X chromosome, and all others are inactivated

another way to calculate narrow-sense heritability: h^2= R/S -h2 can be calculated by conducting a response-to-selection experiment:

1. The selection differential is obtained by subtracting the population mean from the mean of the selected parents. 2. The selected parents are then interbred, and the mean phenotype of their offspring is measured. 3. The difference between the mean of the offspring and that of the original population is the response to selection, which can be used with the selection differential to estimate heritability.

Gene Regulation 3. mRNA processing

1. a 5′ cap is added 2. the 3′ end is cleaved and polyadenylated 3. introns are removed -determine the movement of the mRNA into the cytoplasm, whether the mRNA can be translated, the rate of translation, and the amino acid sequence of the protein produced, as well as mRNA stability.

COMPONENTS OF GENETIC VARIANCE VG=VA+VD+VI

1. additive genetic variance (VA) comprises the additive effects of genes on the phenotype that can be summed. 2. dominance genetic variance (VD); ex: TT and Tt have same phenotype. 3. gene interaction variance (VI)

TRANSLOCATIONS IN MEIOSIS (cont.) Normally, homologous centromeres separate and move toward opposite poles in anaphase I of meiosis. With a reciprocal translocation, the chromosomes may segregate in three different ways.

1. alternate segregation- N1 and N2 move toward one pole, and T1 and T2 move toward the opposite pole. 2. adjacent-1 segregation, N1 and T2 move toward one pole, and T1 and N2 move toward the other pole. In both alternate and adjacent-1 segregation, homologous centromeres segregate to opposite poles. 3. Adjacent-2 segregation, in which N1 and T1 move toward one pole and T2 and N2 move toward the other, is rare because the two homologous chromosomes usually separate in meiosis.

To determine whether a population's genotypes are in Hardy-Weinberg equilibrium, compare the expected genotypic frequencies with the observed genotypic frequencies.

1. calculate allelic frequency 2. find the expected genotypic frequencies by using the square of the allelic frequencies 3. compare the observed and expected genotypic frequencies by using a chi-square goodness-of-fit test.

Calculating allelic frequencies for genes at X-linked loci -Remember: females have two X-linked alleles, whereas a male only have one X-linked allele. -Suppose there are two alleles at an X-linked locus, X^A and X^a. Females may be either homozygous (XAXA or XaXa) or heterozygous (XAXa). All males are hemizygous (XAY or XaY).

1. count the number of copies of XA: we multiply the number of XAXA females by two and add the number of XAXa females and the number of XAY males. We then divide the sum by the total number of alleles at the locus, which is twice the total number of females plus the number of males: (see first equation) - Similarly, the frequency of the Xa allele is: (2nd equation) 2. The frequencies of X-linked alleles can also be calculated from genotypic frequencies by adding the frequency of the females that are homozygous for the allele, half the frequency of the females that are heterozygous for the allele, and the frequency of males that are hemizygous for the allele: (third equation)

map-based sequencing short sequenced fragments are assembled into a whole-genome sequence

1. creating detailed genetic and physical maps of the genome, which provide known locations of genetic markers (restriction sites, genes, or known DNA sequences) at regularly spaced intervals along each chromosome. These markers are later used to help align the short, sequenced fragments in their correct order. 2. Next, these large-insert clones are put together in their correct order on the chromosome using a high-density map of genetic markers

Thomas Hunt Morgan experiment

1. crossed pure-breeding red-eyed females with his white-eyed male, producing F1 progeny that had red eye 2. crossed the F1 flies. all the female F2 flies possessed red eyes, but half the male F2 flies had red eyes and the other half had white eyes.

Locating DNA Fragments with Probes (a DNA or RNA molecule with a base sequence complementary to a sequence in the gene of interest.)

1. cut the DNA into fragments by using one or more restriction enzymes and then separate the fragments with gel electrophoresis. 2. Next, the separated fragments must be denatured and transferred to a permanent solid medium [ex: southern blotting] 3. membrane is placed in a hybridization solution containing a labeled probe; probe binds to DNA fragments w/ complimentary sequence. 4. membrane washed and reveals bound probe

In RNA interference, or RNAi, the RISC pairs with complementary sequences on mRNA and either cleaves the mRNA or prevents it from being translated. Turns off the expression of specific genes. The effect of silencing a gene with siRNAs can be a source of insight into the gene's function.

1. design siRNAs that will be recognized and cleaved by Dicer 2. sequence synthesized 3. E.coli are then transformed with the plasmid. Transcription will proceed in both directions, producing two complementary RNA molecules that will pair to form a double-stranded RNA molecule recognized by Dicer. 4. Deliver the double stranded siRNA to the target cells.

Epigenetic changes—alterations to chromatin structure that affect gene expression—are seen in many cancer cells.

1. genes encoding proteins that are important regulators of epigenetic changes are often mutated in some types of cancer. 2. cancer cells have significant alterations to their DNA methylation patterns and histone structure. One type of epigenetic alteration often observed in cancer cells is an overall lower level of DNA methylation (hypomethylation). 3. some specific CpG islands have extra methylation = may inhibit transcription of tumor-suppressor genes 4. histone proteins in nucleosomes are often abnormally modified in cancer cells. Modifications like methylation and acetylation alters chromatin structure and affects whether transcription occurs.

phenotypic variance (Vp) VP=VG+VE+VGE

1. genetic variance (Vg) 2. environmental variance, VE. 3. genetic-environmental interaction variances (Vge)

positional cloning Method that allows for the isolation of genes on the basis of their position on a gene map; examines inheritance of a phenotype in association with the inheritance of previously mapped genetic markers.

1. geneticists use mapping studies to establish linkage between molecular markers and a phenotype of interest 2. narrow down the location of the gene by using additional molecular markers clustered in the chromosomal region where the gene resides. CHROMOSOME WALKING 3. all genes located within the region are identified

A population may eventually stop responding to artificial selection because ________ (select all that apply).

1. individuals in the population have become homozygous for the alleles responsible for the trait. 2. natural selection opposes any further change in the characteristic.

initiation process (DNA)

1. initiator proteins 2. helicase unwinds 3. SSBP stabilize unwound DNA 4. DNA Gyrase relieves strain ahead of replication fork

Whole‑genome shotgun sequencing is a method used to sequence genomic DNA. Arrange the steps of whole‑genome shotgun sequencing in order from first to last.

1. isolate genomic DNA. 2. break DNA into large fragments that are approximately 150,000 bp in length 3. insert DNA into BACs 4. Break DNA into fragments that are approximately 1000 bp in length. 5. Insert DNA into plasmids. 6. Sequence DNA 7. Computationally assemble sequences from each BAC. 8. Computationally assemble the genome from overlapping BACs

EFFECTS OF TRANSLOCATIONS

1. link genes that were on different chroms=affect gene expression 2. Breaks may disrupt gene function within the gene

To use bacteria to produce large quantities of a human protein:

1. locate and isolate the desired gene 2. insert it into a bacterial cell (stably) since Linear fragments of DNA are quickly degraded by bacteria. Also must replicate successfully so it can pass on when cell divides. 3. ensure that the gene is properly transcribed and translated. 4. search through many cells to find the one containing the recombinant DNA. Needle in haystack.

Initiation of Translation

1. mRNA binds to the small subunit of the ribosome. 2. initiator tRNA binds to the mRNA through base pairing between the initiation codon and the anticodon. 3.the large ribosomal subunit joins the initiation complex.

When a translocation carrier produces gametes, the translocation chromosome segregates in one of three different ways.

1. may separate from the normal chromosomes 14 and 21 in anaphase I of meiosis. half of the gametes produced will have the translocation chromosome and no other copies of chromosomes 21 and 14; The other half of the gametes produced by this first type of segregation will be normal, each with a single copy of chromosomes 21 and 14 2. translocation chromosome may separate from chromosome 14 and pass into the same cell with the normal chromosome 21. produces abnormal gametes only; half will have two functional copies of chromosome 21 (one normal and one attached to chromosome 14) and the other half will lack chromosome 21. If a gamete with the two functional copies of chromosome 21 fuses with a normal gamete carrying a single copy of chromosome 21, the resulting zygote will have familial Down syndrome. If a gamete lacking chromosome 21 fuses with a normal gamete, the resulting zygote will have monosomy 21 and will be spontaneously aborted. 3. the translocation chromosome and the normal copy of chromosome 14 segregate together. Abnormal progeny=half result in monosomy 14 and the other half result in trisomy 14. All are spontaneously aborted.

sexual reproduction consists of two processes that lead to an alternation of haploid and diploid cells:

1. meiosis produces haploid gametes (spores in plants) 2. fertilization produces diploid zygotes

FACTORS INFLUENCING RESPONSE TO SELECTION

1. narrow-sense heritability-largely determines the degree of resemblance between parents and offspring. When high, offspring will tend to resemble their parents; when low, there will be little resemblance between parents and offspring. 2. how much selection there is- measured by selection differential, (the difference between the mean phenotype of the selected parents and the mean phenotype of the original population).

microarrays limitations

1. need prior knowledge of gene sequences in order to construct the array, and sometimes this information does not exist. 2. similar sequences will sometimes hybridize to the same probe on a microarray, creating cross-hybridization artifacts. 3. microarrays provide a limited ability to quantify the degree of gene expression.

Suppose a scientist identified two E. coli mutants, called huh1 and huh2. The mutants have constitutive expression of the nop operon, which includes the genes nop1 and nop2. One of the mutants is a point mutation in a DNA‑binding site, and the other mutant is a deletion of the gene that encodes the DNA‑binding protein. 1.Which term describes the regulatory function of the DNA-binding protein?

1. negative regulator

Transposable Elements in Eukaryotes (2 groups) [ex: Ty elements in yeast, the copia elements in Drosophila, and the Alu sequences in humans.]

1. structurally similar to transposable elements in bacteria, typically ending in short inverted repeats and transposing as DNA 2. comprises retrotransposons: these elements use RNA intermediates, and many are similar in structure and movement to retroviruses; retrotransposons also generate flanking direct repeats at the point of insertion

Calculations of mutation rates are affected by three factors.

1. they depend on the frequency with which changes in DNA take place 2. the probability that when an alteration in DNA takes place, it will be repaired. Most cells possess a number of mechanisms for repairing altered DNA, so most alterations are corrected before they are replicated 3. the probability that a mutation will be detected; mutations are usually detected by their phenotypic effects.

Transcription in Eukaryotes

1. transcription factors bind to DNA. General transcription factors combine w/ RNA Pol to form basal transc. apparatus 2. t. factors bind to enhancers.

Transposable Elements in Bacteria

1.insertion sequence: simplest transposable element in bacteria; carries only the genetic information necessary for its movement; can be passed by one cell to the next; 2. composite transposon: The two insertion sequences each have terminal inverted repeats, so the composite transposon also ends in inverted repeats; generate flanking direct repeats at their sites of insertion 3. Noncomposite transposons: lack insertion sequences but have terminal inverted repeats and carry information not related to transposition.

Heat can disrupt hydrogen bonding between DNA strands. Which of the following DNA strands would denature at the HIGHEST temperature?

10% AT and 90% GC

Males with Li-Fraumeni syndrome have a 75% lifetime risk of cancer, and females have a lifetime risk of almost

100%. There is no cure.

How many genotypes are possible at a locus with five alleles?

15

Calculating Allelic Frequencies 1. 1. To calculate the allelic frequency from the numbers of the genotypes, we count the # of copies of an allele present at a locus in a sample and divide by the total # of all alleles in the sample: frequency of an allele= # of copies of the allele / # of copies of all alleles at the locus

2. For a locus with only two alleles (A and a), the frequencies of the alleles are usually represented by the symbols p and q. The frequencies can be calculated as follows: (PICTURE ATTACHED) where nAA, nAa, and naa represent the #'S of AA, Aa, and aa individuals, and N represents the total number of individuals in the sample. To obtain the # of copies of the allele in the numerator of the equation, we add twice the number of homozygotes (because each has two copies of the allele for which the frequency is being calculated) to the # of heterozygotes (because each has a single copy of the allele). We divide by 2N because each diploid individual has two alleles at a locus. The sum of the allelic frequencies always equals 1 (p + q = 1); after p has been obtained, q can be determined by subtraction: q = 1 − p.

reaction in one of the four tubes: the one that received ddATP: 1. primer pairs with its complementary sequence at one end of each template strand, providing a 3′-OH group for the initiation of DNA synthesis.

2. Wherever DNA polymerase encounters a T on the template strand, it uses, at random, either a dATP or a ddATP to introduce an A into the newly synthesized strand. Because there is more dATP than ddATP in the reaction mixture, dATP is incorporated most often, allowing DNA synthesis to continue. --Occasionally, ddATP is incorporated into the strand, and synthesis terminates.

THE EFFECTS OF GENETIC DRIFT 1. produces change in allelic frequencies within a population that are just as likely to increase or decrease.

2. reduction of genetic variation. When an allele has reached a frequency of 1, we say that it has reached fixation. (all homozygous for 1 allele). Which is fixed depends on initial frequencies of the alleles. If both alleles are 0.5, then they are equally probable to be fixed. If one is more common, that one is most likely to be fixed. 3. different populations diverge genetically from one another over time. All eventually reach fixation for one allele or another.

Attenuation results when which regions of the 5' UTR pair?

3 and 4

CAUSES OF GENETIC DRIFT-SAMPLING ERROR 1. reduction in population size (limited food, space, etc) 2. founder effect, which results from the establishment of a population by a small number of individuals [ex: Isle Royal wolves]

3. genetic bottleneck, which develops when a population undergoes a drastic reduction in size.

ILLUMINA SEQUENCING (widely used) Special (dNTPs) that have a fluorescent tag attached are used, with a different colored tag for each type of dNTP. 1. target DNA cleaved into millions of short overlapping fragments. 2. Fragments attached to a flow cell & are amplified, creating clusters of up to 1000 copies of each fragment on the surface. 3. Fragments denatured; a solution of primers, DNA polymerase, and the special nucleotides is added.

4. Primer attaches to each DNA template, & the first nucleotide is incorporated into the new strand. 5. The solution is washed away, & the tag on the added nucleotide is excited with a laser, which causes it to fluoresce. (A, T, G, or C) produce different colors, so that reveals the type of nucleotide just added. 6. Terminator and the fluorescent tag are chemically removed, and the process is repeated. 7. As the nucleotides are added one at a time, the sequence is read as a series of flashes of colored light from each cluster of DNA.

What unusual feature of the y-chrom allows some recombination among the genes found on it?

8 large palindromes allow crossing over within the y-chrom.

The Ames test is based on the principle that both cancer and mutations result from damage to DNA, and the results of experiments have demonstrated that..

90% of known carcinogens are also mutagens. Ames proposed that mutagenesis in bacteria could serve as an indicator of carcinogenesis in humans.

In humans, blood types A and B are codominant to each other and each is dominant to O. What blood types are possible among the offspring of a couple of blood types A and B? Choose all correct answers.

A B AB 0

missense mutation

A base substitution that results in a different amino acid in the protein.

frequency distribution

A concise graphical method of summarizing values. In genetics, the phenotypes found in a group of individuals are usually displayed as a frequency distribution. Typically, the phenotypic classes are plotted on the horizontal (x) axis, and the numbers (or proportions) of individuals in each class are plotted on the vertical (y) axis.

anticipation

A genetic trait becomes more strongly expressed, or is expressed at an earlier age, as it is passed from generation to generation. [ex: The mutation that causes myotonic dystrophy consists of an unstable region of DNA that can increase in size as the gene is passed from generation to generation.]

Mendelian population

A group of interbreeding, sexually reproducing individuals that have a common set of genes--the gene pool.

linkage group

A group of linked genes.

tips for recognizing sex-linked X inheritance

A male always inherits his X chromosome from his mother, not from his father. Thus, an X-linked characteristic is not passed directly from father to son; if a male clearly inherits a trait from his father—and his mother is not heterozygous—it cannot be X linked.

dosage compensation

A mechanism to equalize the amount of protein produced by X-linked genes and autosomal genes. In placental mammals, dosage compensation is accomplished by the random inactivation of one X chromosome in the cells of females.

reverse genetics Begin with a genotype—a DNA sequence—and proceed to the phenotype by altering the sequence or inhibiting its expression.

A molecular approach to the study of gene function that begins with a genotype (a DNA sequence) and proceeds to the phenotype by altering the sequence or by inhibiting its expression.

forward mutation

A mutation that alters the wild-type phenotype.

homologous chromosomes

A pair of chromosomes that are alike in structure and size and that carry genetic information for the same set of hereditary characteristics. One chromosome of a homologous pair is inherited from the male parent, and the other is inherited from the female parent.

gene deserts Note: Most eukaryotic organisms contain vast amounts of DNA that does not encode proteins.

A region of a genome that is gene poor—that is, a long stretch of DNA, possibly consisting of hundreds of thousands to millions of base pairs, that is completely devoid of any known genes or other functional sequences.

single-nucleotide polymorphisms (SNPs)

A site in the genome where individual members of a species differ in a single base pair.

haplotype

A specific set of linked genetic variants or alleles on a single chromosome or on part of a chromosome.

An organism that has been permanently altered by the addition of a DNA sequence to its genome is said to be transgenic, and the foreign DNA that it carries is called a transgene

A transgenic mouse is produced by injecting cloned DNA into the pronucleus of a fertilized egg and then implanting the egg in a female mouse.

Inbreeding is usually measured by the inbreeding coefficient,F, which is a measure of the probability that two alleles are identical by descent.

A value of 0 indicates that mating is occurring randomly in a large population; a value of 1 indicates that all alleles are identical by descent.

3. Inversions (a chromosome segment is inverted—turned 180 degrees)

AB•CDEFG --> AB•CFEDG --the chromosome must break in two places. --paracentric inversions: do not include centromere --pericentric inversions: include centromere "peri i=include"

Crossing over, which takes place in prophase I of meiosis, is the exchange of genetic material between nonsister chromatids.

After a single crossover has taken place, the two chromatids that did not participate in crossing over are unchanged; gametes that receive these chromatids are nonrecombinants. The other two chromatids, which did participate in crossing over, now contain new combinations of alleles; gametes that receive these chromatids are recombinants.

THE EFFECT OF MIGRATION ON ALLELIC FREQUENCIES Ex: migration between 2 populations that differ in the frequency of an allele a. Suppose that the frequency of this allele in population I is qI and in population II is qII. In each generation, a representative sample of the individuals in population I migrates to population II and reproduces, adding its alleles to population II's gene pool. Migration is only from population I to population II (unidirectional), and all the assumptions of the Hardy-Weinberg law (large population size, random mating, etc.) apply except the absence of migration.

After migration, population II consists of two types of individuals. Some are migrants; they make up proportion m of population II, and they carry alleles from population I, so the frequency of allele a in the migrants is qI. The other individuals in population II are the original residents. If the migrants make up proportion m of population II, then the residents make up proportion 1 - m; because the residents originated in population II, the frequency of allele a in this group is qII. After migration, the frequency of allele a in the merged population II (q′II) is: q'II= qI(m)+qII(1-m). qI(m) is the contribution to q made by the copies of allele a in the migrants and qII(1 - m) is the contribution to q made by the copies of allele a in the residents. The change in the allelic frequency due to migration (Δq) will be: Δq=m(qI - qII)

microarrays Ordered array of known DNA fragments, fixed to a solid support in an orderly pattern, which serve as probes to detect the presence of complementary sequences; often used to assess the expression of genes in various tissues and under different conditions.

After the microarray has been constructed, mRNA, DNA, or cDNA isolated from experimental cells is labeled with fluorescent nucleotides and applied to the array; complimentary molecules will emit. -Scan often converted to a heat map (visual representation of a continuous variable). The color Is indicator of the value of the variable.

Which of the following statements describes an example of genetic drift?

Allele m Is lost when a virus kills all but a few individuals, and just by chance, none of the survivors possess allele m.

The study of the proteome is termed proteomics. Goal is to determine the proteome: the complete set of proteins found in a given cell.

Although proteins are encoded by DNA sequences, many proteins undergo modifications after translation, and in more complex eukaryotes, there are many more proteins than genes; make up 50% of cell mass.

translocation carriers -->do not have Down syndrome

Although they possess only 45 chromosomes, their phenotypes are normal because they have two copies of the long arms of chromosomes 14 and 21, and the short arms (which are lost) carry no essential genetic information.

TRANSLOCATIONS IN MEIOSIS a reciprocal translocation takes place, producing chromosomes AB•CDQRST and M•NOPEFG.

An individual heterozygous for this translocation would possess one normal copy and one translocated copy of each chromosome. Each of these chromosomes contains segments that are homologous to segments of two other chromosomes. When the homologous segments pair in prophase I of meiosis, crosslike configurations consisting of all four chromosomes form

compound heterozygote

An individual who carries two different alleles at a locus that result in a recessive phenotype.

Order the steps required to analyze gene expression from a particular cell type using a DNA microarray.

Answer: -extract mRNA from cells -reverse transcribe mRNA to cDNA -label cDNA with a fluorescent molecule -add cDNA to microarray and incubate -wash away unbound cDNA -visualize microarray and analyze resulting data Explanation:-In order to analyze gene expression from a particular cell type, a pool of mRNA must first be isolated from a sample. Is mRNA typically added directly to a microarray? Consider what other steps must occur first.

mutagen

Any environmental agent that significantly increases the rate of mutation above the spontaneous rate.

Calculating the probability of various gametes pairing. USE MULTIPLICATION RULE. the probability of a sperm containing allele A is p and the probability of an egg containing allele A is p.

Applying the multiplication rule, we find that the probability that these two gametes will combine to produce an AA homozygote is p × p = p2. Same for sperm. An Aa heterozygote can be produced in one of two ways: (1) a sperm containing allele A may combine with an egg containing allele a (p × q) or (2) an egg containing allele A may combine with a sperm containing allele a (p × q). Thus, the probability of alleles A and a combining to produce an Aa heterozygote is 2pq.

coupling, or cis, configuration.

Arrangement of linked genes in which wild-type alleles of two or more genes are found on one chromosome, and mutant alleles are on the homologous chromosome. [ex: the most numerous progeny types are those with a green thorax and brown puparium and those with a purple thorax and black puparium]

repulsion, or trans, configuration

Arrangement of two linked genes in which each of a homologous pair of chromosomes contains one wild-type (dominant) allele and one mutant (recessive) allele. [ex: the most numerous progeny types are those with a green thorax and black puparium and those with a purple thorax and brown puparium]

[NEGATIVE CONTROL] When a molecule called a corepressor is present, it binds to the repressor and makes it capable of binding to the operator.

As long as the level of product U is high, it is available to bind to the repressor and activate it, preventing transcription; when all of product U is used up, the repressor is no longer activated by product U and cannot bind to the operator. The inactivation of the repressor allows the transcription of the structural genes and the synthesis of enzymes G, H, and I, resulting in the conversion of precursor T into product U.

In attenuation, transcription begins at the transcription start site, but termination takes place prematurely, before the RNA polymerase even reaches the structural genes.

Attenuation takes place in a number of operons that encode enzymes participating in the biosynthesis of amino acids.

In meioses in which there is a single crossover, half the gametes are recombinants and half are nonrecombinants (because a single crossover affects only two of the four chromatids).

Because each crossover leads to half recombinant gametes and half nonrecombinant gametes, the total percentage of recombinant gametes is always half the percentage of meioses in which crossing over takes place. Even if crossing over between two genes takes place in every meiosis, only 50% of the resulting gametes are recombinants. Thus, the frequency of recombinant gametes is always half the frequency of crossing over, and the maximum proportion of recombinant gametes is 50%.

dioecious

Belonging to a species in which an individual organism has either male or female reproductive structures.

Given the following figure, what would be the effect of a mutation that occurred in the insulator that prevented the binding of the insulator-binding protein?

Both Enhancer 1 and Enhancer II would be able to stimulate the transcription of Genes A and B.

How do amino acids in DNA binding proteins interact with DNA?

By forming hydrogen bonds with DNA bases.

lac Mutations (Jacob and Monod)

By using different combinations of mutations on the bacterial and plasmid DNA, they determined that some parts of the lac operon are cis acting (able to control the expression of genes only on the same piece of DNA), whereas other parts are trans acting (able to control the expression of genes on other DNA molecules).

heterokaryon

Cell possessing two nuclei derived from different cells through cell fusion. --The two nuclei of a heterokaryon eventually also fuse, generating a hybrid cell that contains chromosomes from both cell lines.

If the tumor cells remain localized, the tumor is said to be benign; if the cells invade other tissues, the tumor is said to be malignant.

Cells that travel to other sites in the body, where they establish secondary tumors, have undergone metastasis.

multifactorial characteristics

Characteristic determined by multiple genes and environmental factors. [ex: human height]

sex-limited characteristic

Characteristic encoded by autosomal genes and expressed in only one sex. Both males and females carry genes for sex-limited characteristics, but the characteristics appear in only one of the sexes. -precocious puberty

Sex-influenced characteristics

Characteristic encoded by autosomal genes that are more readily expressed in one sex. For example, an autosomal dominant gene may have higher penetrance in males than in females, or an autosomal gene may be dominant in males but recessive in females.

polygenic characteristics

Characteristic encoded by genes at many loci.

continuous characteristics or quantitative characteristics

Characteristic that displays a large number of possible phenotypes that are not easily distinguished, such as human height.

discontinuous characteristics.

Characteristic that exhibits only a few, easily distinguished phenotypes. An example is seed shape, in which seeds are either round or wrinkled.

threshold characteristic [ex: Diseases-both genetic and environmental, contribute; If enough of the susceptibility factors are present, the disease develops; otherwise, it is absent.]

Characteristic that has only two phenotypes (presence and absence) but whose expression depends on an underlying susceptibility that varies continuously.

Meristic characteristics [ex: litter size: a female mouse can have 4, 5, or 6 pups, but not 4.13 pups.]

Characteristic whose phenotype varies in whole numbers, such as number of vertebrae, but may be caused by continuous genetic variation.

tandem duplication

Chromosome rearrangement in which a duplicated chromosome segment is adjacent to the original segment.

displaced duplication

Chromosome rearrangement in which the duplicated segment is some distance from the original segment, either on the same chromosome or on a different one. [ex: AB•CDEFGEF--> AB•CDEFFEG] When the duplication is inverted, it is called a reverse duplication.

Chromosome mutations can be grouped into three basic categories: chromosome rearrangements, aneuploidy, and polyploidy

Chromosome rearrangements alter the structure of chromosomes (duplicated, translocation, deleted, or inverted.) aneuploidy, the number of chromosomes is altered Polyploidy-one or more complete sets of chromosomes are added. A polyploid is any organism that has more than two sets of chromosomes (3n, 4n, 5n, or more).

structural variants

Collective term for chromosome rearrangements and copy-number variations.

normal distribution

Common type of frequency distribution that exhibits a symmetrical, bell-shaped curve; usually arises when a large number of independent factors contribute to a measured value.

hermaphroditism

Condition in which an individual organism possesses both male and female reproductive structures. True hermaphrodites produce both male and female gametes.

genetic mosaicism

Condition in which regions of tissue within a single individual have different chromosome constitutions. [Turner syndrome and XO/XX fruit flies]

DNA structure

DNA consists of two long chains of nucleotides twisted into a double helix and joined by hydrogen bonds between the complementary bases A-T or G-C. Sugar, phosphate, and a base. -Nucleotides connected by covalent bonds.

regulatory genes

DNA sequence that encodes a protein or RNA molecule that interacts with other DNA sequences and affects transcription or translation of those sequences. (usually prod. DNA-binding proteins or RNA molecules that affect gene expression.)

Another spontaneously occurring chemical change that takes place in DNA is deamination, the loss of an amino group (NH2) from a base.

Deamination may be spontaneous or may be induced by mutagenic chemicals. Deamination can alter the pairing properties of a base; this chemical change is a transition mutation.

SPINDLE-ASSEMBLY CHECKPOINT (Metaphase)

Delays anaphase until all chroms are aligned on metaphase plate and sister kinetochores are attached to spindle microtubules from opposite poles. If all chroms are not properly aligned, the checkpoint blocks the destruction of cyclin B.

copy-number variations

Difference among individual organisms in the number of copies of any large DNA sequence (larger than 1000 bp).

genomic imprinting

Differential expression of a gene depending on whether it is inherited from the male or female parent.

Oncogenes

Dominant-acting gene that stimulates cell division, leading to the formation of tumors and contributing to cancer; arises from a mutated copy of a normal cellular gene (proto-oncogene).

A two-strand double crossover between two linked genes produces only nonrecombinant gametes.

Double crossovers between two genes go undetected, so map distances between distant genes tend to underestimate genetic distances.

segmental duplications

Duplicated chromosome segments larger than 1000 bp. Most segmental duplications are intrachromosomal duplications (i.e., the two copies are found on the same chromosome), but others are interchromosomal duplications (the two copies are found on different chromosomes).

cyclin B combines with a CDK to form an inactive complex called mitosis-promoting factor (MPF), which needs to be activated by removal of phosphate group.

During G1, cyclin B levels are low, so the amount of MPF is also low. High levels of active MPF stimulate mitosis, and low levels of MPF bring a return to interphase conditions. The G2/M checkpoint is at the end of G2, before the cell enters mitosis.

TAUTOMERIC SHIFTS--in which the positions of protons (hydrogen atoms) in the DNA bases change)

Each of the four DNA bases exists in different chemical forms, called tautomers. -A-T and G-C pairing common, but if the bases are in their rare tautomeric forms, other base pairings are possible.

How does transposition cause mutations and chromosome rearrangements?

Element inserts itself into a gene, destroying its function. Chromosome rearrangements arise because transposition includes the breaking and exchange of DNA sequences. Multiple copies of a transposable element may undergo homologous recombination, producing chrom. rearrangements.

X-Linked Color Blindness in Humans

Females: X+X+ and X+Xc, which produce normal color vision, and XcXc, which produces color blindness. Males: X+Y, which produces normal color vision, and XcY, which produces color blindness.

DETERMINING THE FREQUENCIES LOCI WITH MULTIPLE ALLELES -count up the number of copies of an allele by adding twice the number of homozygotes to the number of heterozygotes that possess the allele, then dividing this sum by twice the number of individuals in the sample.

For a locus with three alleles (A1, A2, and A3) and six genotypes (A1A1, A1A2, A2A2, A1A3, A2A3, and A3A3), the frequencies (p, q, and r) of the alleles are as follows:

To calculate a genotypic frequency, we simply add up the number of individuals possessing a genotype and divide by the total number of individuals in the sample (N).

For a locus with three genotypes—, AA, Aa, and aa— the frequency (f) of each genotype is as follows: f(AA)=# of AA individuals/N f(Aa)=# of Aa individuals/N f(aa)=# of aa individuals/ N *The sum of all the genotypic frequencies always equals 1.*

With multiple alleles, the genotypic frequencies expected at equilibrium are the square of the allelic frequencies. For an autosomal locus with three alleles, the equilibrium genotypic frequencies are (p + q + r)^2 = p^2 + 2pq + q^2 + 2pr + 2qr + r^2. --These proportions are those of the genotypes among males and among females, rather than the proportions among the entire population. Thus, p2 is the expected proportion of females with the genotype X1X1; if females make up 50% of the population, then the expected proportion of this genotype in the entire population is 0.5 × p^2.

For an X-linked locus with two alleles, X^1 and X^2, the equilibrium frequencies of the female genotypes are (p + q)^2 = p^2 + 2pq + q^2, where p^2 is the frequency of X^1X^1, 2pq is the frequency of X^1X^2, and q^2 is the frequency of X^2X^2. Males have only a single X-linked allele, so the frequencies of the male genotypes are p (frequency of X^1Y) and q (frequency of X^2Y).

With inbreeding -- the proportion of heterozygotes decreases by 2Fpq, and half of this value (Fpq) is added to the proportion of each homozygote each generation.

Frequencies would be: f(AA)=p^2+Fpq f(Aa)=2pq−2Fpq f(aa)=q^2+Fpq

somatic-cell hybridization

Fusion of somatic cells of different types. Used for positioning genes on chromosomes.

special preparation and staining of chromosomes with a dye called Giemsa reveals

G bands, which distinguish areas of DNA that are rich in adenine-thymine (A-T) base pairs.

unbalanced gametes difference in # creates unbalanced gene dosage in the zygote, which is often lethal.-->triploids offspring not usually viable.

Gamete that has a variable number of chromosomes; some chromosomes may be missing and others may be present in more than one copy.

recombinant gametes

Gamete with new combinations of alleles.

nonrecombinant gametes or parental gametes

Gametes that contain only original combinations of alleles that were present in the parents

linkage analysis

Gene mapping based on the detection of physical linkage between genes, as measured by the rate of recombination in the progeny of a cross.

linked genes

Genes located close together on the same chromosome. --Linked genes travel together in meiosis, eventually arriving at the same destination (the same gamete), and are not expected to assort independently.

homologous genes

Genes that are evolutionarily related

cell line

Genetically identical cells that divide indefinitely and can be cultured in the laboratory.

When genotypes are in the expected proportions of p^2, 2pq, and q^2, the population is said to be in...

Hardy-Weinberg equilibrium.

A regulator gene helps control the expression of the structural genes of the operon by increasing or decreasing their transcription.

Has its own promoter, not part of operon, and is transcribed into a short mRNA, which is translated into a small protein.

Base analogs are mutagenic because of which characteristic?

Have structures similar to those of any of the four standard nitrogenous bases of DNA. DNA polymerases cannot distinguish these analogs from the standard bases, so if base analogs are present during replication, they may be incorporated into newly synthesized DNA molecules.

realized heritability

Heritability determined by a response-to-selection experiment. If certain assumptions are met, realized heritability is identical with narrow-sense heritability.

2. Histone Modification called "histone code" bcuz they encode info that affects how genes are expressed. Can also provide recognition sites for proteins that bind to DNA and regulate transcription.

Histone code: -Histone tails modified by the addition or removal of phosphate groups, methyl groups, or acetyl groups. -ubiquitin is added to or removed from the histones. - have a globular domain and positively charged tails that interact with negative charged phosphate groups on DNA.

Klinefelter syndrome

Human condition in which cells contain one or more Y chromosomes and multiple X chromosomes (most commonly XXY but may also be XXXY, XXXXY, or XXYY). People with Klinefelter syndrome are male in appearance but frequently have small testes and reduced facial and pubic hair; they are often taller than normal and sterile, and most have normal intelligence.

triple-X syndrome

Human condition in which cells contain three X chromosomes. A person with triple-X syndrome has a female phenotype with no distinctive features other than a tendency to be tall and thin; a few such females are sterile, but many menstruate regularly and are fertile.

sister chromatids

Identical copies of a chromosome; full sets of these are created during the S subphase of interphase.

CHANGE IN THE FREQUENCY OF A RECESSIVE ALLELE DUE TO NATURAL SELECTION selection against a rare recessive allele is very inefficient, and its removal from the population is slow.

If allele A2 is lethal and recessive, W11 = W12 = 1, whereas W22 = 0. The frequency of the A2 allele decreases over time (because A2A2 homozygotes produce no offspring), and the rate of decrease is proportional to the frequency of the allele.

Let's assume that there are two different alleles, designated G1 and G2, with frequencies p and q, respectively. If there are 45 copies of G1 and 5 copies of G2 in the population, p = 0.90 and q = 0.10. Suppose that a mutation changes a G1 allele into a G2 allele. After this mutation, there are 44 copies of G1 and 6 copies of G2, and the frequency of G2 has increased from 0.10 to 0.12. Mutation has changed the allelic frequencies.

If copies of G1 continue to mutate to G2, the frequency of G2 will increase and the frequency of G1 will decrease. The amount by which G2 will change (Δq) as a result of mutation depends on (1) the rate of G1-to-G2 mutation (μ) and (2) p, the frequency of G1 in the population. When p is large, there are many copies of G1 available to mutate to G2, and the amount of change will be relatively large. As more mutations occur and p decreases, there will be fewer copies of G1 available to mutate to G2. The change in G2 as a result of mutation equals the mutation rate times the allelic frequency:

Allopolyploidy arises from hybridization between two species; the resulting polyploid carries chromosome sets derived from two or more species.

If gametes from species I and II fuse, a hybrid with six chromosomes (ABCGHI) is created. The hybrid has the same number of chromosomes as both diploid species, so the hybrid is considered diploid. However, because the hybrid chromosomes are not homologous, they will not usually pair and segregate properly in meiosis; thus, this hybrid is functionally haploid and sterile. --may also arise when nondisjunction during meiosis leads to a 2n gamete, which then fuses with a 1n or 2n gamete from a different species to produce a polyploid individual.

Mendel's principle of segregation says that each individual organism possesses two alleles at a locus and that each of those two alleles has an equal probability of passing into a gamete. Thus, the frequencies of alleles in gametes will be the same as the frequencies of alleles in the parents. These frequencies will also be those in the gametes.

If mating is random (one of the assumptions of the Hardy-Weinberg law), the gametes will come together in random combinations, which can be represented by a Punnett square. -Whenever the frequencies of alleles in a randomly mating population are p and q, the frequencies of the genotypes in the next generation will be p^2, 2pq, and q^2

Is the inheritance of alleles at one locus independent of the inheritance of alleles at a second locus?

If the answer to this question is yes, then the genes are assorting independently; if the answer is no, then the genes are probably linked.

Strand slippage can occur when one nucleotide strand forms a small loop.

If the looped-out nucleotides are on the newly synthesized strand, an insertion results. At the next round of replication, the insertion will be replicated, and both strands will contain the insertion. If the looped-out nucleotides are on the template strand, then the newly replicated strand will have a deletion, and this deletion will be perpetuated in subsequent rounds of replication.

CALCULATING HERITABILITY BY ELIMINATION OF VARIANCE COMPONENTS If we eliminate all environmental variance (VE = 0), then VGE = 0 (because if either VG or VE equals 0, no genetic-environmental interaction can take place), and VP = VG. we could make VG equal to 0 by raising genetically identical individuals, causing VP to be equal to VE.

In a typical experiment, we might raise cloned or highly inbred, identically homozygous individuals in a defined environment and measure their phenotypic variance to estimate VE. We might then raise a group of genetically variable individuals and measure their phenotypic variance (VP). Using the VE calculated for the genetically identical individuals, we could obtain the genetic variance of the variable individuals by subtraction: VG=VP-VE - CALCULATE broad-sense heritability: H^2=VG/VP

Both prokaryotic and eukaryotic DNA can be methylated.

In eukaryotes, cytosine bases are most often methylated to form 5-methylcytosine, and methylation is often related to gene expression.

EFFECTS OF CHROMOSOME DUPLICATIONS -Duplications may have major effects on the phenotype

In heterozygotes, problems in chromosome pairing arise at prophase I of meiosis because the 2 chromosomes are not homologous throughout their length. The pairing and synapsis of homologous regions require that one or both chromosomes loop and twist so that these regions are able to line up

2. Deletions --chromosome deletion: the loss of a chromosome segment

In individuals heterozygous for deletions, the normal chromosome must loop out during the pairing of homologs in prophase I of meiosis to allow the homologous regions of the two chromosomes to align and undergo synapsis.

In bacteria, gene regulation maintains internal flexibility, turning genes on and off in response to environmental changes.

In multicellular eukaryotic organisms, gene regulation also brings about cell differentiation.

Protein-protein interactions can also be analyzed with protein microarrays. With this technique, a large number of different proteins are applied to a solid support in an orderly array of spots, with each spot containing a different protein.

In one application, each spot contains an antibody for a different protein, labeled with a tag that fluoresces when bound. An extract of tissue is applied to the microarray. A spot of fluorescence appears when a protein in the extract binds to an antibody, indicating the presence of that particular protein in the tissue.

Barr bodies

Inactivated X chromosome that appears as a condensed, darkly staining body in the nuclei of most cells of female placental mammals.

Loss of heterozygosity

Inactivation of the remaining wild-type allele of a heterozygote. Common mechanism: -deletion on the chromosome that carried the normal copy of the tumor-suppressor gene

inbreeding - One form of nonrandom mating; Preferential mating between related individuals.

Inbreeding is positive assortative mating for relatedness, but it differs from other types of assortative mating bcuz it affects all genes. Inbreeding causes a departure from the Hardy-Weinberg equilibrium frequencies. -More homozygotes and less heterozygotes

gynandromorphs in XX/XO mosaics, any X-linked recessive genes present in the cells with a single X chromosome will be expressed.

Individual organism that is a genetic mosaic for the sex chromosomes, possessing tissues with different sex-chromosome constitutions.

effective population size (Ne) Effective number of breeding adults in a population

Influenced by the number of individuals contributing genes to the next generation, their sex ratio, variation between individuals in reproductive success, fluctuations in population size, age structure of the population, and whether mating is random.

cytoplasmic inheritance

Inheritance of characteristics encoded by genes located in the cytoplasm. Because the cytoplasm is usually contributed entirely by one parent, most cytoplasmically inherited characteristics are inherited from only one parent.

gene interaction

Interaction between genes at different loci that affect the same characteristic.

THE GENERAL SELECTION MODEL Used to predict the effect of natural selection on allelic frequencies; requires knowledge of both the initial allelic frequencies and the fitness values of the genotypes.

It assumes that mating is random and that the only force acting on a population is natural selection. The general selection model can be used to calculate the allelic frequencies after any type of selection. It is also possible to work out formulas for determining the change in allelic frequencies when selection is against recessive, dominant, or codominant traits, as well as traits in which the heterozygote has the highest fitness

E. coli can use glucose or other sugars; use AA to make proteins or produce enzymes to make an AA.

It is energetically expensive so it uses gene regulation. When the environment changes, new genes are expressed, and proteins appropriate for the new environment are synthesized. -gene regulation is the key to success for unicellular flexibility and multicellular specialization of cells.

Key events of the cell cycle are controlled by cyclin-dependent kinases (CDKs).

Kinases are enzymes that phosphorylate (add phosphate groups to) other proteins. -Functional only w/ cyclins. Cyclin levels rise and fall thru life cycle. -Cyclins specify which protein CDK will phosphorylate.

DNA Transposons (Class II)- possess terminal inverted repeats and transpose as DNA.

Like Class I, they generate flanking direct repeats at their points of insertion into DNA. Unlike Class I, all active forms of Class II encode transposase, which is required for their movement. Some encode resolvase, repressors, and other proteins. Their transposition may be replicative or nonreplicative, but they never use RNA intermediates.

genome-wide association studies

Looking for nonrandom associations between the presence of a trait and alleles at many different loci scattered across the genome. Unlike linkage analysis, this approach does not trace the inheritance of genetic markers and traits in a genetic cross or family. Rather, it looks for associations between traits and particular suites of alleles in a population.

Loss-of-function mutations cause the complete or partial absence of normal protein function. A loss-of-function mutation is one that so alters the structure of the protein that the protein no longer works correctly, or one that occurs in regulatory regions that affect the transcription, translation, or splicing of the protein.

Loss-of-function mutations are frequently recessive, in which case a diploid individual must be homozygous for the mutation before the effects of the loss of the functional protein can be exhibited. [ex: CF]

Complementation

Manifestation of two different mutations in the heterozygous condition as the wild-type phenotype; indicates that the mutations are at different loci. -There is a lack of complementation when two recessive mutations occur at the same locus, producing a mutant phenotype.

in situ hybridization -requires that the cells be fixed and the chromosomes be spread on a microscope slide and denatured. - also used to determine the distribution of specific mRNA molecules in tissues, serving as a source of insight into how gene expression differs among cell types.

Method used to determine the chromosomal location of a gene or another specific DNA fragment or the tissue distribution of an mRNA by using a labeled probe that is complementary to the sequence of interest.

DNA methylation and the deacetylation of histones both repress transcription.

Methylation attracts deacetylases, which remove acetyl groups from the histone tails, stabilizing the nucleosome structure and repressing transcription. Demethylation of DNA allows acetyltransferases to add acetyl groups, disrupting nucleosome structure and permitting transcription.

Small populations lose genetic variation over time through inbreeding and genetic drift, often with catastrophic consequences for survival and reproduction.

Migration, whether occurring naturally or through genetic rescue, introduces new genetic variation that counteracts the effects of genetic drift and inbreeding.

In affinity capture, an antibody to a specific protein is used to capture one protein from a complex mixture of proteins. The protein captured will "pull down" with it any proteins with which it physically interacts. The pulled-down mixture of proteins can then be analyzed by mass spectrometry to identify the proteins.

Modifications of affinity capture and other techniques can be used to determine the complete set of protein interactions in a cell, termed the interactome.

Aneuploidy in Humans

Most aneuploids in humans are due to missegregation of chromosomes in meiosis I during oogenesis, the formation of eggs in females. --each pair of homologous chromosomes must undergo at least one crossover for the two homologous chromosomes to segregate properly during meiosis. Crossovers connect the two chromosomes, creating tension when the homologs are pulled in opposite directions during metaphase I. This tension is necessary for the two homologs to separate properly in anaphase I.

Which is the correct order of steps in a mutagenesis screen?

Mutagenesis, identification of mutants, verification of genetic basis, positional cloning.

Inhibitory genes involved in cancer are termed tumor-suppressor genes

Mutated inhibitory genes generally act in a recessive manner because both copies of alleles must be mutated to remove all inhibition. -Defects in both copies of a tumor-suppressor gene are usually required to cause cancer.

expanding nucleotide repeats -nucleotide expansion occurs within the coding part of a gene, producing a toxic protein that has extra glutamine -In other diseases, the repeat is outside the coding region of a gene and affects its expression. -hairpins may interfere with normal replication by causing strand slippage, misalignment of the sequences, or stalling of replication.

Mutations in which the number of copies of a set of nucleotides increases; cause of familial ALS, fragile-x syndrome (intellectual disability). -anticipation: diseases caused by expanding nucleotide repeats become more severe in each generation.

which type of mutation in telomerase is associated with cancer cells?

Mutations that increase the expression of telomerase.

spontaneous mutations

Mutations that occur under normal conditions.

In a female human cell, what would be the effect on X inactivation if a mutation occurred in the Xist gene making it nonfunctional?

Neither X chromosome would be inactivated.

A neutral mutation is a missense mutation that alters the amino acid sequence of a protein but does not significantly change its function.

Neutral mutations occur when one amino acid is replaced by another that is chemically similar, or when the affected amino acid has little influence on protein function.

Recombination is also reduced within a pericentric inversion.

No dicentric bridges or acentric fragments are produced, but the recombinant chromosomes have too many copies of some genes and no copies of others, so gametes that receive the recombinant chromosomes cannot produce viable progeny.

linkage disequilibrium

Nonrandom association between alleles in a haplotype.

In nonreplicative transposition (cut-and-paste transposition), the transposable element is excised from the old site and inserted at a new site without any increase in the number of its copies.

Nonreplicative transposition requires the replication of only the few nucleotides that constitute the flanking direct repeats. Retrotransposons use replicative transposition only.

Proto-oncogenes

Normal cellular gene responsible for basic cellular function, but when mutated, it may become an oncogene and contribute to the development of cancer.

Orthologs & paralogs

Orthologs: Homologous genes found in different species that evolved from the same gene in a common ancestor. Paralog: Homologous genes in the same species (arising by duplication of a single gene in the evolutionary past-giving rise to the alpha- and beta-subunit genes)

Some operons are inducible: their transcription is normally off and must be turned on.

Other operons are repressible: their transcription is normally on and must be turned off.

Determine which of the genomic traits are associated with prokaryotes or eukaryotes. These traits include relative genome size, number of genes, gene density, and number of exons.

PROKARYOTE -relatively small genome -500 to 7000 genes -about one gene every 1000 bp-few, if any, introns EUKARYOTE -relatively large, variable size genome -6000 to 30000 genes -about one gene every 2000 to 100000 bp -multiple introns

Penetrance

Percentage of individual organisms having a particular genotype that express the expected phenotype.

sequential hermaphroditism

Phenomenon in which the sex of an individual organism changes in the course of its lifetime; the organism is male at one age or developmental stage and female at a different age or stage. [[slipper limpet]]

phenocopy

Phenotype produced by environmental factors alone that is the same as the phenotype produced by a genotype.

haploid

Possessing a single set of chromosomes (one genome).

diploid

Possessing two sets of chromosomes (two genomes).

hemizygous

Possession of a single allele at a locus. Males of organisms with XX-XY sex determination are hemizygous for X-linked loci because their cells possess a single X chromosome.

whole-genome shotgun sequencing small-insert clones are prepared directly from genomic DNA and sequenced.

Powerful computer programs then assemble the entire genome by examining overlap among the small-insert clones. The requirement for overlap means that most of the genome must be sequenced many times. The average number of times a nucleotide in the genome is sequenced is called the sequencing coverage.

Hardy-Weinberg law Assumptions If a population is large; randomly mating; and not affected by mutation, migration, or natural selection, then: ---when its assumptions are met, reproduction alone does not alter allelic or genotypic frequencies, and the allelic frequencies determine the frequencies of genotypes---

Prediction 1 the allelic frequencies of a population do not change, and Prediction 2 the genotypic frequencies stabilize (will not change) after one generation in the proportions p^2 (the frequency of AA), 2pq (the frequency of Aa), and q^2 (the frequency of aa), where p equals the frequency of allele A and q equals the frequency of allele a.

multiple alleles

Presence of more than two alleles within a group of organisms; however, each individual member of the group has only two of the possible alleles. -the genotype of each individual diploid organism still consists of only 2 alleles

Bioinformatics is an interdisciplinary field that combines molecular biology and computer science; it centers on the development of databases, computer-search algorithms, gene-prediction software, and other analytical tools that are used to make sense of DNA-, RNA-, and protein-sequence data.

Primary databases contain the sequence information, along with information that describes the source of the sequence and its determination. Secondary databases contain the results of analyses carried out on the primary sequence data, such as information about particular sequence patterns, variations, mutations, and evolutionary relationships.

Principle of Segregation

Principle of heredity discovered by Mendel that states that each individual diploid organism possesses two alleles at a locus and that these two alleles separate when gametes are formed, one allele going into each gamete.

Narrow-sense heritability (h2)

Proportion of phenotypic variance that results from the additive genetic variance.

Lyon hypothesis

Proposal by Mary Lyon in 1961 that one X chromosome in each female cell becomes inactivated (a Barr body), and that which of the X chromosomes is inactivated is random and varies from cell to cell.

rRNA

RNA molecule that is a structural component of the ribosome. Along w/ ribosomal proteins make up the ribosome where proteins are made.

mutagenesis screen Method for identifying genes that influence a specific phenotype or function.

Random mutations are induced in a population of organisms, and individual organisms with mutant phenotypes are identified. These individual organisms are crossed to determine the genetic basis of the phenotype and to map the location of mutations that cause the phenotype.

monoecious

Refers to an individual organism that has both male and female reproductive structures.

[NEGATIVE CONTROL] Transcription of a negative inducible operon is turned on when an inducer is present and binds to the repressor protein.

Regulatory proteins frequently have two binding sites: one that binds to DNA and another that binds to a small molecule such as an inducer. -The binding of the inducer alters the shape of the repressor, preventing it from binding to DNA. Proteins such as this repressor, which change shape upon binding to another molecule, are called allosteric proteins.

Theta replication

Replication of circular DNA that is initiated by the unwinding of the two nucleotide strands, producing a replication bubble. Unwinding continues at one or both ends of the bubble, making it progressively larger. DNA replication on both of the template strands is simultaneous with unwinding until the two replication forks meet.

overdominance

Selection in which the heterozygote has higher fitness than either homozygote; neither allele eliminated.

genic sex determination

Sex determination in which the sexual phenotype is specified by genotypes at one or more loci, but there are no obvious differences in the chromosomes of males and females. -[some plants, fungi, protozoans, and fishes.]

polycistronic mRNA

Single RNA molecule transcribed from a group of several genes; uncommon in eukaryotes. --produced when a single terminator is present at the end of a group of several genes that are transcribed together, instead of each gene having its own terminator

pseudoautosomal regions

Small region of the X and Y chromosomes that contains homologous gene sequences. --In humans, there are pseudoautosomal regions at both tips of the X and Y chromosomes.

Gel electrophoresis provides a way to separate and visualize DNA fragments.

Small wells are made at one end of the gel, solutions of DNA fragments are placed in the wells and an electrical current is passed through the gel. -The DNA fragments migrate toward the positive end of the gel, separating the DNA. -Small fragments migrate faster -gel stained with dye or labelled to visualize.

Most cases of colorectal cancer are sporadic (no family hx), but a few families display a clear genetic predisposition to it. Among the earliest steps is a mutation that inactivates the APC gene; this mutation increases the rate of cell division, leading to polyp formation..

Someone with family hx inherits 1 defective copy of APC gene. Devlop in ppl w/o fam hx too. -rare for polyps to develops mutations later in tumor progression. -inflammation is risk factor

Many of these chromosome rearrangements originate when double-stranded breaks occur in the DNA molecule found within a chromosome. Double-stranded breaks in DNA often cause cell death, so organisms have evolved elaborate mechanisms to repair breaks by reconnecting the broken ends of DNA.

Sometimes the wrong ends are connected, leading to a chromosome rearrangement. - can also arise through errors in crossing over or when crossing over occurs between repeated DNA sequences.

The principle of segregation in relation to chromosome theory of heredity.

States that a diploid organism possesses two alleles for a characteristic, each of which is located at the same position, or locus, on one of the two homologous chromosomes. These chromosomes segregate in meiosis, and each gamete receives one homolog.

Why is knowledge of a proteins structure important?

Structure often provides important information about how a protein functions and the types of proteins with which it is likely to interact.

chromsome types:

Submetacentric. The centromere is displaced toward one end, creating a long arm and a short arm. (On human chromosomes, the short arm is designated by the letter p and the long arm by the letter q.) Acrocentric. The centromere is near one end, producing a long arm and a knob, or satellite, at the other end. Telocentric. The centromere is at or very near the end of the chromosome

Physical maps are based on the direct analysis of DNA, and they place genes in relation to distances measured in number of base pairs, kilobases, or megabases. Physical maps generally have higher resolution and are more accurate than genetic maps.

Techniques used to create: -restriction mapping, which determines the positions of restriction sites in DNA. When a piece of DNA is cut (digested) with a restriction enzyme and the fragments are separated by gel electrophoresis, the number of restriction sites in the DNA and the distances between them can be determined by the number and positions of bands on the gel

complementation test

Test designed to determine whether two different mutations are at the same locus (are allelic) or at different loci (are nonallelic). Two individuals that are homozygous for two independently derived mutations are crossed, producing F1 progeny that are heterozygous for the mutations. If the mutations are at the same locus, the F1 will have a mutant phenotype. If the mutations are at different loci, the F1 will have a wild-type phenotype.

Attenuation in the trp Operon of E. coli

The 5′ UTR of the trp operon can fold into one of two secondary structures. When the tryptophan level is high, the 3 + 4 structure forms, transcription is terminated within the 5′ UTR, and no additional tryptophan is synthesized. When the tryptophan level is low, the 2 + 3 structure forms, transcription continues through the structural genes, and tryptophan is synthesized.

The RB protein helps control a cell's progression through the G1/S checkpoint by binding transcription factor E2F. -If mutated, cells pass through the G1/S checkpoint without the normal controls that prevent cell proliferation.

The E2F transcription factor stimulates the transcription of genes that produce enzymes necessary for the replication of DNA, and the cell moves into the S phase of the cell cycle.

Elongation of transcription in eukaryotes

The RNA polymerase maintains a transcription bubble during elongation. ---The two strands of the DNA are unwound, and nucleotides that are complementary to the template strand are added to the growing 3′ end of the RNA molecule. As it funnels through the polymerase, the DNA-RNA hybrid hits a wall of amino acids and bends at almost a right angle; this bend positions the end of the DNA-RNA hybrid at the active site of the polymerase, where new nucleotides are added to the 3′ end of the growing RNA molecule. The newly synthesized RNA is separated from the DNA and runs through another cleft in the enzyme before exiting from the polymerase.

The FLC gene encodes a regulatory protein (a transcription factor) that represses the activity of other genes that affect flowering. As long as FLC is transcriptionally active, flowering remains suppressed.

The activity of FLC is controlled by another locus called flowering locus D (FLD), which stimulates flowering by repressing the action of FLC; flowering is stimulated because FLD represses the repressor. -FLD stimulates flowering in Arabidopsis by deacetylating the chromatin that surrounds FLC, thereby removing its inhibitory effect on flowering

Gene Regulation 4. regulation of mRNA stability

The amount of protein produced depends not only on the amount of mRNA synthesized but also on the rate at which the mRNA is degraded.

Haploinsufficiency

The appearance of an abnormal trait in an individual cell or organism that is heterozygous for that trait.

in vivo a DNA fragment is inserted into a bacterial cell and the cell is allowed to replicate the DNA. Each time the cell divides, one or more copies of the DNA fragment are passed on to each daughter cell.

The cells are then lysed to release their DNA, and the desired fragment is isolated from the rest of the bacterial DNA. This procedure is termed gene cloning because identical copies (clones) of the original piece of DNA are replicated within bacterial cells.

interference

The degree to which one crossover interferes with additional crossovers in the same region.

HOW ARE CANDIDATE GENES THAT ARE IDENTIFIED BY POSITIONAL CLONING EVALUATE IT TO DETERMINE WHETHER THEY ENCODE THE PHENOTYPE OF INTEREST?

The expression pattern of the genes can be examined, and the coding region of copies of the genes from individuals with the mutant phenotype can be compared with the coding region of wild type individuals.

How is a gene inserted into a plasmid cloning vector?

The gene and plasmid are cut with the same restriction enzyme and mixed together. DNA ligase is used to seal necks in the sugar phosphate backbone.

incomplete penetrance

The genotype does not always produce the expected phenotype. [ex: human polydactyly-having extra fingers or toes caused by dominant allele]

Which of the following statements about chromosomal inversions is NOT true?

The inversion mutations will not likely have pronounced phenotypic effects since there is no loss of genetic material.

The amount of change in q is directly proportional to the amount of migration (m); as the amount of migration increases, the change in allelic frequency increases.

The magnitude of change is also affected by the difference in allelic frequencies between the two populations (​qI − qII); when the difference is large, the change in allelic frequency will be large. --eventually, the frequency of population II equals that of population I. When qI − qII = 0, there will be no further change in the allelic frequency of population II

sex-determining region Y (SRY) gene

The male-determining gene in mammals, located on the Y chromosome. -This gene is found in XX males and is missing from rare XY females; it is also found on the Y chromosome of other mammals. -SRY gene encodes a protein called a transcription factor that promotes differentiation of the testes.

The frequency with which a wild-type allele at a locus changes into a mutant allele is referred to as the mutation rate.

The mutation rate is generally expressed as the number of mutations per biological unit, which may be mutations per cell division, per gamete, or per round of replication.

template strand

The nucleotide strand used for transcription

This regulator protein can bind to a region of the operon called the operator and affect whether transcription can take place.

The operator usually overlaps the 3′ end of the promoter and sometimes the 5′ end of the first structural gene

IMPORTANCE OF DUPLICATIONS IN EVOLUTION

The original copy can provide the essential function, whereas an extra copy from the duplication is free to undergo mutation and change.

Whenever a reverse mutation occurs, the frequency of G2 decreases and the frequency of G1 increases. The rate of change due to reverse mutations equals the reverse mutation rate times the allelic frequency of G2(Δq = vq).

The overall change in allelic frequencies is a balance between the opposing forces of forward mutation and reverse mutation:

genetic maternal effect

The phenotype of the offspring is determined by the genotype of the mother. In cytoplasmic inheritance, the genes for a characteristic are inherited from only one parent, usually the mother. In genetic maternal effect, the genes are inherited from both parents, but the offspring's phenotype is determined not by its own genotype but by the genotype of its mother.

heritability

The proportion of the total phenotypic variation that is due to genetic differences

COLLINEARITY BETWEEN RELATED GENOMES many genes are present in the same order in related genomes, a phenomenon that is sometimes termed collinearity. -In spite of these large differences in chromosome number and genome size, the positions and order of many genes within the genomes are remarkably conserved. Over evolutionary time, regions of DNA between the genes (intergenic regions) have increased, decreased, and undergone rearrangements, whereas the genes themselves have stayed relatively constant in order and content.

The reason for collinearity among genomes is that they are descended from a common ancestral genome, and evolutionary forces have maintained the same gene order in the genomes of descendants. ex: [grasses—plants in the family Poaceae]

REGULATION OF THE lac OPERON (negative inducible operon) -LacI: regulator gene w/ its own promoter. Transcribed into short mRNA that is translated into a repressor.

The repressor consists of four identical polypeptides and has two types of binding sites; one type of site binds to allolactose and the other binds to DNA. -When there's no lactose, the repressor binds to the lac operator lacO (overlaps 3' of promoter and 5' end of lac z) -When the repressor is bound to the operator, the binding of RNA polymerase is blocked, and transcription is prevented. When lactose is present, some of it is converted into allolactose, which binds to the repressor and causes the repressor to be released (inactivated) from the operator. RNA polymerase then binds to the promoter and transcribes.

gain-of-function mutation causes the cell to produce a protein or gene product whose function is not normally present.

The result could be an entirely new gene product or one produced in an inappropriate tissue or at an inappropriate time in development. -Gain-of-function mutations are frequently dominant in their expression because a single copy of the mutation leads to the presence of a new gene product.

homogametic sex

The sex (male or female) that produces gametes that are all alike with respect to sex chromosomes. For example, in the XX-XY sex-determining system, the female produces only X-bearing gametes.

heterogametic sex

The sex (male or female) that produces two types of gametes with respect to sex chromosomes. For example, in the XX-XY sex-determining system, the male produces both X-bearing and Y-bearing gametes.

At one end of the operon is a set of structural genes (a,b,c) --> transcribed into a single mRNA, which is translated to produce enzymes A, B, and C. These enzymes carry out a series of biochemical reactions that convert precursor molecule X into product Y.

The transcription of structural genes a, b, and c is under the control of a single promoter, which lies upstream of the first structural gene. RNA polymerase binds to the promoter and then moves downstream, transcribing the structural genes.

the results of crossing over within a paracentric inversion. (AB•CDEFG) x (AB•EDCFG) NO RECOMBINANT GAMETES

The two outer chromatids, which did not participate in crossing over, contain original, nonrecombinant gene sequences. The two inner chromatids, which did participate in crossing over, are highly abnormal: each has 2 copies of some genes and no copies of others. One of the four chromatids now has 2 centromeres (dicentric chromatid); the other lacks a centromere (acentric chromatid) --Meiosis II: 4 gametes. Two of the gametes contain the OG nonrecombinant chromosomes. The other two gametes contain recombinant chromosomes that are missing some genes; these gametes will not produce viable offspring.

The first genomes to be sequenced were small virus genomes; Humans completed in 2003.

The ultimate goal of structural genomics is to determine the ordered nucleotide sequences of entire genomes of organisms, providing the sequence information that is used to answer other questions

With independent assortment, nonrecombinant and recombinant gametes are produced in equal proportions.

These four types of gametes join with the single type of gamete produced by the homozygous parent of the testcross to produce four kinds of progeny in equal proportions

VARIATION IN MUTATION RATES

These higher values in eukaryotes may be due to the fact that the rates are calculated per gamete, and that several cell divisions are required to produce a gamete, whereas mutation rates in prokaryotic cells are calculated per cell division

Which of the following statements CORRECTLY describes nonsense mutations? X- They cause a nonfunctional amino acid to replace a functional amino acid. X- They change the nucleotide sequence of a gene but do not change the sequence of the resulting protein. X- They result in the insertion or deletion of a small number of nucleotides to the DNA. X- They cannot revert to wild type.

They convert a codon for a particular amino acid within a gene into a stop codon.

Bacterial enhancers increase the rate of transcription at genes that are distant from the enhancer.

They do this by causing the DNA between the promoter and the enhancer to loop out, so that the transcription activator bound to the enhancer directly interacts with RNA polymerase at the promoter.

familial Down syndrome

They have 46 chromosomes, but an extra copy of part of chromosome 21 is attached to another chromosome through a translocation. --Familial Down syndrome arises in offspring whose parents are carriers of chromosomes that have undergone a Robertsonian translocation, most commonly between chromosome 21 and chromosome 14: the long arm of 21 and the short arm of 14 exchange places.---> one chrom w/ long arms of 14 & 21 and v. short arms of 14 & 21. Small one lost after few cell divisions.

Which of the following is characteristic of retrotransposons?

They transpose through an RNA intermediate.

DNase I hypersensitive sites Chromatin region that becomes sensitive to digestion by the enzyme DNase I.

This relaxation of the chromatin structure allows regulatory proteins access to binding sites on the DNA.

yeast artificial chromosome (YAC) is a DNA molecule that has a yeast origin of replication, a pair of telomeres, and a centromere

Ti plasmid, part of which is transferred to a plant cell when R. radiobacter infects a plant. Part of the Ti plasmid DNA integrates into one of the plant chromosomes, where it is transcribed and translated to produce several enzymes that help support the bacterium

Natural selection depends on Fitness: the relative reproductive success of a genotype (relative-its success compared to success of other genotypes in population). Values (W) range from 0 to 1.

To calculate fitness for each genotype, we take the mean number of offspring produced by a genotype and divide it by the mean number of offspring produced by the most prolific genotype. --A related variable is the selection coefficient (s), which is the relative intensity of selection against a genotype. The selection coefficient is equal to 1 − W

PLASMID VECTORS -multiple unique restriction sites and selectable markers, as well as an origin of replication -Inside the cells, the plasmids replicate and multiply as the cells themselves multiply.

To insert a DNA sequence into a plasmid vector: 1. cut the foreign DNA fragment and the plasmid w/ the same restriction enzyme. 2. If the restriction enzyme makes staggered cuts in the DNA, complementary sticky ends are produced on the foreign DNA and the plasmid. 3. When DNA and plasmids are then mixed together, some of the foreign DNA fragments will pair with the cut ends of the plasmids. 4. DNA ligase is used to seal the nicks in the sugar-phosphate backbone, creating a recombinant plasmid that contains the foreign DNA fragment

Gene Regulation 2. Level of transcription

Transcription is the first step in the process of info transfer from DNA to protein; limiting the production of a protein early in the process makes sense, and transcription is an important point of gene regulation in both bacterial and eukaryotic cells.

Consider the regulation of galactose metabolism through GAL4. GAL4 binds to a UAS sequence to activate gene expression, but this activation is repressed by GAL80. Normally, in the presence of galactose, GAL3 removes GAL80 from GAL4. Which of the following would result from a mutation that caused GAL80 to be absent?

Transcription of the target genes would always occur ??

retrotransposons (Class I)- transpose through an RNA intermediate. In this case, RNA is transcribed from the transposable element (DNA) and is then copied back into DNA by a special enzyme called reverse transcriptase.

Transposable elements found in bacteria are DNA transposons. Both DNA transposons and retrotransposons are found in eukaryotes, although retrotransposons are more common. -NOT found in prokaryotes.

base substitution, the alteration of a single nucleotide in the DNA Purines: Adenine/Guanine Pyrimidines: Cytosine, Thymine, Uracil

Two types: 1. transition, a purine is replaced by a different purine or, alternatively, a pyrimidine is replaced by a different pyrimidine 2. transversion, a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine. The number of possible transversions is twice the number of possible transitions, but transitions arise more frequently because transforming a purine into a different purine or a pyrimidine into a different pyrimidine is easier than transforming a purine into a pyrimidine, or vice versa.

REPAIR OF BREAKS PRODUCED BY CRISPR-Cas9 -once DNA cleaved, the cell immediately uses its DNA-repair mechanisms to try to repair the break. --> edits target sequence

Two ways by which double-strand breaks are repaired: 1. nonhomologous end joining 2. homology directed repair (not efficient)

Codominance

Type of allelic interaction in which the heterozygote simultaneously expresses the phenotypes of both homozygotes.

amphidiploid can undergo normal meiosis to produce balanced gametes with 6 chromosomes each.

Type of allopolyploid in which two different diploid genomes are combined such that every chromosome has one and only one homologous partner and the genome is functionally diploid.

incomplete dominance

Type of dominance in which the phenotype of the heterozygote falls in between the phenotypes of the two homozygotes.

Epistasis

Type of gene interaction in which a gene at one locus masks or suppresses the effects of a gene at a different locus. -the gene that does the masking is called an epistatic gene -the gene whose effect is masked is a hypostatic gene. -Epistatic genes may be recessive or dominant in their effects.

Biotechnology

Use of biological processes, particularly molecular genetics and recombinant DNA technology, to produce products of commercial value.

frameshift mutations: changes in the reading frame of the gene.

Usually alter all AA encoded by the nucleotides following the mutation, so they generally have drastic effects on the phenotype. Some frameshifts also introduce premature stop codons, terminating protein synthesis early and resulting in a shortened protein;

equation that represents all the potential contributions to the phenotypic variance:

VP=VA+VD+VI+VE+VGE

chromosome mutations

Variations in the number and structure of chromosomes; often affects many genes and has large phenotypic effects.

Northern blotting: RNA is transferred from a gel to a solid support, such as a nitrocellulose or nylon membrane.

Western blotting is the transfer of protein from a gel to a membrane; probe is usually an antibody, used to determine the size of a particular protein and the pattern of the protein's expression.

incorporated error

When a base substitution causes a mispaired base to be incorporated into a newly synthesized nucleotide chain. -The original incorporated error (the T-G mispairing) leads to a replicated error (the C • G base pair instead of the original T • A base pair), which creates a permanent mutation because all the base pairings are correct and there is no way for repair systems to detect the error.

coordinate induction- The simultaneous synthesis of several proteins stimulated by a specific molecule, the inducer.

When lactose is absent from the medium in which E. coli grows, few molecules of each protein are produced. If lactose is added to the medium and glucose is absent, the rate of synthesis of all three proteins simultaneously increases about a thousandfold within 2 to 3 minutes (7b) -allolactose is the inducer.

MISPAIRING BETWEEN DNA CAN ARISE THROUGH WOBBLE

When normal, protonated, and other forms of the bases are able to pair because of flexibility in the DNA helical structure. -have been detected in dNA molec. and responsible for some mispairings in replication.

THERE IS NO UNIVERSAL HERITABILITY FOR A CHARACTERISTIC

When the environmental factors that affect a characteristic differ between two groups, the heritabilities for the two groups often differ as well.

SUMMARY OF EFFECTS OF MUTATION -change due to mutation in a single generation is extremely small, and as the frequency of p drops as a result of mutation, the amount of change will become even smaller; if it's the only force acting on a population for a long time, mutation rates will determine allelic frequencies.

When the only evolutionary force acting on a population is mutation, allelic frequencies change over time because some alleles mutate into others. -Eventually, these allelic frequencies reach equilibrium and are determined only by the forward and reverse mutation rates; genotypic frequencies will also remain the same.

One way that HPVs cause cancer is by producing proteins that attach to and inactivate the protein products of RB and p53.

When these proteins are inactivated, cells are stimulated to progress through the cell cycle and divide without the normal controls that prevent cell proliferation. Human papillomaviruses can also stimulate cancer by causing high expression of growth-promoting proteins.

gene interaction variance (VI) -genes at different loci may interact in the same way that alleles at the same locus interact.

When this gene interaction takes place, the effects of the genes are not additive. Coat color in Labs exhibits gene interaction: BB ee and bb ee both produce yellow dogs because the effects of alleles at the B locus are masked when two e alleles are present at the E locus.

arrangement, in which each chromosome contains one wild-type and one mutant allele, is called the repulsion, or trans, configuration.

Whether the alleles in the heterozygous parent are in coupling or repulsion determines which phenotypes will be most common among the progeny of a testcross. [ex: the most numerous progeny types are those with a green thorax and black puparium and those with a purple thorax and brown puparium]

Explain how synthetic probes are created to screen a DN a library when the protein encoded by the gene is known.

With the use of the genetic code and the amino acid sequence of the protein, possible nucleotide sequences that cover a small region of the gene can be deduced. A mixture of all the possible nucleotide sequences that might encode the protein, taking into consideration synonymous codons, is used to probe the library. To minimize the number of sequences required, a region of the protein that has relatively little degeneracy in its codons is selected.

When a single locus with two alleles encodes a characteristic, there are three genotypes possible: AA, Aa, and aa. The number of genotypes encoding a characteristic is 3n, where n equals the number of loci, each with two alleles, that influence the characteristic.

With two loci, each with two alleles, there are 3^2 = 9 genotypes possible.

Much of gene regulation in bacteria and eukaryotes is accomplished by proteins that bind to DNA sequences and affect their expression. These regulatory proteins generally have discrete functional parts—called domains, typically consisting of 60-90 AA—that are responsible for binding to DNA.

Within a domain, only a few AA actually make contact w/ the DNA. These AA often form hydrogen bonds with the bases or interact with the sugar-phosphate backbone of the DNA; affect expression of gene; other molecules can compete with DNA-binding proteins for regulatory sites on the DNA since they are not bound permanently.

Which of the following statements is NOT true of DNA methylation? T-- Cytosines on both strands are usually methylated. T-- It is carried out by DNA methyltransferases. T-- It is associated with transcription repression. T-- It occurs on cytosines adjacent to guanines.

X-- Methylation is permanent and cannot be reversed.

Tip for recognizing sex-linked Y inheretence.

Y-linked traits can be inherited only from the father's side of the family. Thus, a Y-linked trait can be inherited only from the paternal grandfather (the father's father), never from the maternal grandfather (the mother's father).

Chargaff's Rule

[A]=[T] and [G]=[C], they pair up across from one another forming two strands also called base pairing.

Determining the number of genotypes possible will be

[n(n + 1)/2] where n equals the number of different alleles at a locus. Working crosses with multiple alleles is no different from working crosses with two alleles;

amino acid structure

a central carbon atom bonded to an amino group, a hydrogen atom, a carboxyl group, and an R (radical) group that differs for each amino acid. --Joined by peptide bonds

aneuploidy affects the number of gene copies but not their nucleotide sequences

a change in the number of individual chromosomes

constitutive genes (unregulated)

a few structural genes, particularly those that encode essential cellular functions (often called housekeeping genes), are expressed continually; not regulated.

multigene family

a group of evolutionarily related genes that arose through repeated duplication and evolution of an ancestral gene.

In replicative transposition (also called copy-and-paste transposition), a new copy of the transposable element is introduced at...

a new site while the old copy remains behind at the original site, so the number of transposable element copies increases as a result of transposition.

There are two types of transcriptional control: negative control

a regulatory protein is a repressor, binding to DNA and inhibiting transcription

There are two types of transcriptional control: positive control

a regulatory protein is an activator, stimulating transcription.

the ab initio approach find genes by looking for

a. Common sequences found in most genes.

Y chromosome shape

acrocentric

Metagenomics A field of genetics in which the genome sequences of an entire group of organisms that inhabit a common environment are sampled and determined.

addresses 2 important issues: (1) the identification and study of microbes that cannot be cultured in the laboratory (2) the study of the community structure of microorganisms.

Gene Regulation 6. Post-translation modification

affect protein stability and whether the proteins become active

regulatory elements [DNA sequences that are not transcribed at all but still play a role in regulating genes and other DNA sequences]

affect the expression of DNA sequences to which they are physically linked. -common in both bacterial and eukaryotic cells, and much of gene regulation in both types of organisms takes place through the action of proteins produced by regulatory genes that recognize and bind to regulatory elements

Recombinant DNA technology a set of molecular techniques for locating, isolating, altering, and studying DNA segments; goal is to combine DNA of two sources.

aka genetic engineering, encompasses many molecular techniques that can be used to analyze, alter, and recombine virtually any DNA sequences from any number of sources.

autopolyploidy

all chromosome sets are from a single species

At mutational equilibrium, the frequency of G2(ˆq) will be

allelic frequency at equilibrium is determined solely by the forward (μ) and reverse (v) mutation rates.

What type of organism results from the hybridization of a diploid gamete from one species with a diploid gamete from a different species?

allotetraploid

Epigenetics Study of:

alterations to DNA and chromatin structure that affect traits and are passed on to other cells or generations but are not caused by changes in the DNA base sequence.

silent mutation

altering the DNA sequence without changing the amino acid sequence of the protein. -some do have phenotypic effects: -if tRNA'S bind to different synonymous codons--> affect rate of protein synthesis--> influence phenotype by affecting amount of protein in the cell or folding the protein.

the increase in chromosome number in polyploidy is often associated with

an increase in cell size, and many polyploids are physically larger than diploids.

polyploidy

an increase in the number of chromosome sets.

suppressor mutation A suppressor mutation occurs at a site distinct from the site of the original mutation

an individual with a suppressor mutation is a double mutant, possessing both the original mutation and the suppressor mutation but exhibiting the phenotype of the nonmutated wild type. Geneticists distinguish between two classes of suppressor mutations: intragenic and intergenic.

mutation

an inherited change in the DNA sequence of genetic information; the descendants that inherit the change may be cells or organisms.

The average numbers of offspring produced by three genotypes are GG=6, Gg=3, and gg=2. What is the fitness of Gg?

b. 3/6 = 0.5

In Lubbock TX, rainfall and temperature exhibit a significant correlation of -0.7. Which conclusion is correct?

b. There is usually more rainfall when the temperature is low.

To ensure transcription and translation, a foreign gene is usually inserted into an expression vector, which—in addition to the usual origin of replication, restriction sites, and selectable markers—contains sequences required for transcription and translation in bacterial cells

bacteria do not have the capacity to carry out modifications; thus, a functional protein can be produced only in a eukaryotic cell.

Gender is a category assigned by the individual or others based on

behavior and cultural practices. One's gender need not coincide with one's biological sex.

c-MYC is often expressed at high levels in cancer cells. c-MYC helps to drive cell division and the development of cancer.

c-MYC binds to the promoters of miRNA genes and decreases their transcription, decreasing the amount of the miRNAs (some suppress tumor development).

When a population is in mutational equilibrium which of the following is true?

c. The number of forward mutations is equal to the number of reverse mutations.

In each generation, 10 random individuals migrate from population A to population B. What will Happen to allelic frequency q as a result of migration when q is equal in populations A and B?

c. q will not change in either A or B.

THE MAGNITUDE OF GENETIC DRIFT can be assessed either by examining the change in allelic frequencies within a single population or by examining the magnitude of genetic differences that accumulate among populations.

can be estimated from the variance in allelic frequency. Variance (s2) is a statistical measure that describes the variability of a trait. The the variance in allelic frequency is determined by two parameters: the allelic frequencies (p and q) and the population size (N). Genetic drift is maximal when p and q are equal (each 0.5).

engineered nucleases Protein consisting of the part of a restriction enzyme that cleaves DNA, combined with another protein that recognizes and binds to a specific DNA sequence;

capable of making unique double-stranded cuts in DNA at predetermined sequences. Engineered nucleases can be custom designed to bind to and cut any particular DNA sequence. -include zinc-finger nucleases (ZFNs), which use a DNA-binding domain called a zinc finger attached to a restriction enzyme & transcription activator-like effector nuclease (TALEN) - a protein of a type that normally binds to sequences in promoters is attached to a restriction enzyme.

mRNA

carries the coding instructions for a polypeptide chain from DNA to a ribosome.

When glucose is available, genes that participate in the metabolism of other sugars are turned off through a process known as catabolite repression (glucose is preferred and the metabolism of other sugars is repressed in the presence of glucose)

catabolite repression results from positive control (transcription is turned on) in response to low glucose. -catabolite activator protein (CAP) binds to a site that is about 22 nucleotides long and is located at or near upstream of the promoter of the lac genes. RNA polymerase does not bind efficiently to many promoters unless CAP is first bound to the DNA. Before CAP can bind, it must form a complex with a modified nucleotide called 3′, 5′-cyclic adenosine monophosphate (cyclic AMP, or cAMP), which is important in cellular signaling processes in both bacterial and eukaryotic cells. -High glucose= lower cAMP to bind DNA. and vise versa w/ RNA Pol too. -RNA Pol also will have low affinity for lac promoter and little transcription occurs.

reverse mutation

changes a mutant phenotype back into the wild type.

nonsense mutation

changes a sense codon (one that specifies an amino acid) into a nonsense codon (one that terminates translation) -If a nonsense mutation occurs early in the mRNA sequence, the protein will be truncated and usually nonfunctional.

1. Chromatin Remodeling [ex: SWI-SNF in yeast, humans, Drosophila,euk]

chromatin-remodeling complexes: proteins that bind directly to particular sites on DNA and reposition the nucleosomes, allowing other transcription factors and RNA polymerase to bind to promotors and initiate transcription... -Uses hydrolysis of ATP to reposition nucleosomes and exposing promoters to regulatory proteins and RNA Pol. -complexes may cause nucleosomes to slide along DNA or cause conformational change in DNA so that the DNA bound to the nucleosome is exposed.

allopolyploidy

chromosome sets are from two or more species.

To calculate the interference, we first determine the coefficient of coincidence, which is the ratio of observed double crossovers to expected double crossovers:

coefficient of coincidence= # of observed double crossovers/# of expected double crossovers

antisense RNA

control gene expression by binding to sequences on mRNA and inhibiting its translation.

What statistical measure is used to measure broad-sense heritability in twin studies?

correlation coefficient

Arrangement in which wild-type alleles are found on one chromosome and mutant alleles are found on the other chromosome, is referred to as

coupling, or cis, configuration. [ex: the most numerous progeny types are those with a green thorax and brown puparium and those with a purple thorax and black puparium]

phosphodiester linkage

covalent bonds that join adjacent nucleotides between the -OH group of the 3' carbon of one nucleotide and the phosphate on the 5' carbon of the next

Upon transposing to a new site, transposable elements:

create a duplication of a target sequence on each side of them.

Patients with schizophrenia have higher levels of DNA methylation at the promoter of the reelin gene. What is the likely impact that this has on reelin expression?

decreased transcription

standard deviation -The mean plus or minus one standard deviation (¯x±s) includes approximately 66% of the measurements in a normal distribution; the mean plus or minus two standard deviations (¯x±2s) includes approximately 95% of the measurements; and the mean plus or minus three standard deviations (¯x±3s) includes approximately 99% of the measurements. Thus, only 1% of a normally distributed population lies outside the range of (¯x±3s).

defined as the square root of the variance: s=√s2

deletion mapping

deletion mapping. Special staining methods have been developed that reveal characteristic banding patterns on chromosomes. The absence of one or more of the bands that are normally seen on a chromosome reveals the presence of a chromosomal deletion (loss of a chromosome segment). We can assign genes to regions of chromosomes by studying the association between a phenotype or product encoded by a gene and particular chromosomal deletions.

alleles

different versions of a gene

for single crossovers, the frequency of recombinant gametes is half the frequency of crossing over because...

each crossover takes place between only 2 of the 4 chromatids of a homologous pair.

the relation between genotype and phenotype is straightforward:

each genotype produces a single phenotype, and most phenotypes are encoded by a single genotype.

Structural genes

encode proteins that are used in metabolism or biosynthesis or that play a structural role in the cell.

A eukaryotic DNA sequence that promotes transcription at distant promoters is called a(n):

enhancer.

directional selection one allele or trait is favored over another

ex: In a population with three genotypes (A1A1, A1A2, and A2A2) with fitnesses W11, W12, and W22, we can identify six different types of natural selection. In type 1 selection, a dominant allele A1 confers a fitness advantage. In Type 2 selection, the A2 allele increases and the A1 allele decreases. Type 3 and type 4 selection are also directional selection, but in these cases, there is incomplete dominance, and the heterozygote has a fitness that is intermediate between the two homozygotes. Type 5 has overdominance and type 6, underdominance.

HERITABILITY DOES NOT INDICATE THE DEGREE TO WHICH A CHARACTERISTIC IS GENETICALLY DETERMINED

ex: None of the rabbits in this group carries a gene for polydactyly, but a few of the rabbits are polydactylous because of environmental factors. Broad-sense heritability for polydactyly in this group is zero because there is no genetic variation for polydactyly; all the variation is due to environmental factors.

The response to selection (R) depends on narrow-sense heritability (h2) and the selection differential (S): R=h^2×S

ex: estimated the narrow-sense heritability of abdominal bristle number in a population of fruit flies to be 0.52. The mean number of bristles in the population was 35.3. They selected individual flies with a mean bristle number of 40.6 and intercrossed them to produce the next generation. The selection differential was 40.6 − 35.3 = 5.3, so they predicted that the response to selection would be R=0.52×5.3=2.8 -They therefore expected the average number of abdominal bristles in the offspring of their selected flies to be 35.3 + 2.8 = 38.1.

correlation coefficient (r): measures the strength of the association of characteristics. --The correlation coefficient (r) is obtained by dividing the covariance of x and y by the product of the standard deviations of x and y: r=cov xy/sxsy -A correlation coefficient can theoretically range from −1 to +1. A positive value indicates that there is a direct association between the variables: as one variable increases, the other variable also tends to increase. 0= no association

ex: human height (x) and arm length (y) The covariance is computed by: (1) taking the x value for an individual and subtracting from it the mean of x (¯x); (2) taking the y value for the same individual and subtracting from it the mean of y (¯y); (3) multiplying the results of these two subtractions; (4) adding the results for all the xy pairs; and (5) dividing this sum by n − 1 (where n equals the number of xy pairs).

X-linked traits are passed from father to daughter but never from:

father to son, and Y-linked traits are passed from father to all sons

Insertion or removal of one or more nucleotide base pairs in DNA within a gene often results in a _____ mutation.

frameshift

The chromosome theory of heredity

genes are located on chromosomes, which serve as vehicles for the segregation of genes in meiosis.

Gene Expression and Reporter Sequences

genomic fragments are first cloned in BACs or other vectors that are capable of holding the coding region of a gene plus its regulatory sequences. The coding region of a gene whose expression is to be studied is then replaced with a reporter sequence, which encodes an easily observed product.

Functional genomics uses both bioinformatics and laboratory-based experimental approaches in its effort to define the functions of DNA sequences.

goals include include the identification of all the RNA molecules transcribed from a genome, called the transcriptome of that genome, and all the proteins encoded by the genome, called the proteome.

The narrow sense heritability for a trait is 0.4 and the selection differential is 0.5. What is the predicted response to selection?

h^2= R/S divide h^2/1 by reciprocal: h^2/1= R/S*h^2/1 --> 0.5*0.4=0.2 =R

Knowing the _____ of a trait has great practical importance because it allows statistical predictions regarding the phenotypes of offspring to be made on the basis of the parents' phenotypes.

heritability

Because all the chromosome sets in autopolyploids are from the same species, they are

homologous and attempt to align in prophase I of meiosis, which usually results in sterility.

quantitative trait loci (QTLs) chromosomal regions containing genes that control polygenic (quantitative) characteristics

if the inheritance of a genetic marker is associated consistently with the inheritance of a particular phenotype, such as increased height, then that marker must be linked to a QTL that affects height. The key is to have enough genetic markers so that QTLs can be detected throughout the genome.

In a diploid organism, a homozygous individual has two copies of the same allele. These two copies may be the same in state, which means that the two alleles are alike in structure and function but do not have a common origin.

in a homozygous individual may be the same because they are identical by descent; that is, the copies are descended from a single allele that was present in an ancestor.

Transposable elements are found

in practically all organisms.

Indels that do not affect the reading frame are called:

in-frame insertions: Insertion of some multiple of three nucleotides that do not alter the reading frame of the gene. in-frame deletions: Deletion of some multiple of three nucleotides that do not alter the reading frame of the gene.

How could a male phenotype exist without a Y chromosome?

indication that not the entire Y chromosome that determines maleness in humans; rather, it is a gene on the Y chromosome.

What is the molecular basis of the epigenetic effect of royal jelly on female honeybees?

inhibits Dnmt3, causes less DNA methylation

Which of the following pairs of sequences would you expect to be found in a DNA-based transposable element?

inverted repeats and a gene for transposase

How does chromosome duplication alter the phenotype?

likely due to imbalances in the amounts of gene products (abnormal gene dosage). The amount of a particular protein synthesized by a cell is often directly related to the number of copies of its corresponding gene

After a gene has been identified, it must be annotated, which means

linking its sequence information to other information about its function and expression, the protein it encodes, and similar genes in other species.

HORIZONTAL GENE TRANSFER a way of gaining new genetic information

may take place through the bacterial uptake of DNA from the environment (transformation), through the exchange of plasmids, and through viral vectors (transduction).

Deletions frequently accompany translocations. Robertsonian translocation the long arms of two acrocentric chromosomes become joined to a common centromere through a translocation, generating a ....

metacentric chromosome with 2 long arms and another chromosome with 2 very short arms. The smaller chromosome is often lost because very small chromosomes do not have enough mass to segregate properly during mitosis and meiosis. Result: an overall reduction in chromosome number. -- cause of some cases of Down syndrome.

What is it called when cancer cells migrate to other places in the body?

metastasis

In progeny that result from a double crossover, only the

middle allele should differ from the alleles present in the nonrecombinant progeny.

Duplications and deletions often arise from unequal crossing over, in which chromosomes

misalign during crossing over.

When linked genes undergo some crossing over, the result is

mostly nonrecombinant progeny and a few recombinant progeny.

Although new combinations of existing genes may arise through recombination in meiosis, all genetic variants ultimately arise through...

mutation !!

passengers

mutations that arise randomly in the process of tumor development and do not contribute to cancer progression. Many passengers are located in introns (regions between genes) and in other DNA that is not transcribed and translated, but they can also arise within protein-encoding genes.

induced mutations

mutations that result from changes caused by environmental chemicals or radiation.

When _____ is high for a particular trait, offspring tend to resemble their parents for that trait.

narrow-sense heritability

pleiotropy

one gene affects multiple characteristics. [ex: Phenylketonuria-recessive allele; propensity for developing tumors, obesity]

A testcross includes:

one parent who shows the dominant phenotype for one or more genes and a second parent who is homozygous recessive for these genes.

dominant epistasis

only a single copy of an allele is required to inhibit the expression of an allele at a different locus.

Allelic frequencies calculation 2 is used in the equation to denote a diploid organism with two copies of alleles at the a locus.

p=f(A)= 2nAA+nAa/ 2N q=f(a)=2naa+nAa/ 2N *When a population is in Hardy-Weinberg equilibrium, the distribution of genotypic frequencies depends solely on the allelic frequencies.*

DNA polymerase I

possesses 5′ → 3′ exonuclease activity, which is used to remove the primers laid down by primase and replace them with DNA nucleotides by synthesizing in a 5′ → 3′ direction. --removes the RNA nucleotides of the primer, replacing them with DNA nucleotides.

Outcrossing -MORE HETEROZYGOTES than predicted

preferential mating between unrelated individuals.

intercalating agents -Cause frameshift mutations= severe -Can reverse mutations

produce mutations by sandwiching themselves (intercalating) between adjacent bases in DNA, distorting the three-dimensional structure of the helix and causing single-nucleotide insertions and deletions in replication.

Autophagy has been shown to suppress tumor formation under some conditions and promote tumor growth under others.

proteins, cytoplasm, damaged organelles, and other cellular components are engulfed by vesicles within the cell and transported to lysosomes, where they are degraded and their components recycled. -mutations in p53 alter autophagy, leading to cancer.

What are normal genes that promote cell division under appropriate conditions called?

proto-oncogenes

RNA sequencing A method in which cDNA molecules are copied from the RNA molecules present in a cell and sequenced.

provides detailed information about gene expression, including the types and number of RNA molecules produced by transcription, the presence of alternatively processed RNA molecules, differential expression of the two alleles in a diploid individual, and different RNA molecules generated by bidirectional or overlapping transcription of DNA sequences.

Transposition can involve exchange of DNA sequences and recombination, which often leads to DNA:

rearrangements.

rate of recombination [calculation]

recombination frequency= # of recombinant progeny/total # of progeny x 100%

Selfing reproduce by self-fertilization (F = 1). With selfing, each homozygote produces only progeny of the same homozygous genotype (AA × AA produces all AA; aa × aa produces all aa), whereas only half the progeny of a heterozygote has the same genotype as the parent (Aa × Aa produces 1/4 AA, 1/2 Aa, and 1/4 aa).

reduces the proportion of heterozygotes in the population by half with each generation, until all genotypes in the population are homozygous. -higher probability of deleterious or lethal traits (inbreeding depression)

What statistical measure is used to measure narrow-sense heritability by comparing parents to their offspring?

regression coefficient

Some mRNA molecules contain regulatory sequences called riboswitches, where..

regulatory molecules can bind and affect gene expression by influencing the formation of secondary structures in the mRNA. -Common in bacteria; present in archaea, fungi and plants. -typically found in the 5′ UTR of the mRNA & can fold into compact RNA secondary structures with a base stem and several branching hairpins.

Broad-sense heritability (H2) -ranges from 0 to 1. 0= all result from environmental factors. Between 0 and 1= both genetic and environmental factors influence phenotypic variance. 1=all result from genotypic differences.

represents the proportion of phenotypic variance that is due to genetic variance.

Gene Regulation 5. level of Translation

requires a large number of enzymes, protein factors, and RNA molecules. All of these factors, as well as the availability of AA affect the rate at which proteins are produced and therefore provide points at which gene expression can be controlled. -Translation can also be affected by sequences in mRNA, such as those in the 5′ and 3′ untranslated regions.

Double crossovers in which both crossovers are on the same two strands (two-strand double crossovers)...

result in functional recombinant chromosomes.

Genetic Drift (change in allelic frequencies due to sampling error) The smaller the gametic sample, the greater the chance that its composition will deviate from that of the parental gene pool.

sampling error arises when gametes unite to produce progeny. Many organisms produce a large number of gametes, but when population size is small, a limited number of gametes unite to produce the individuals of the next generation, and chance influences which alleles are present in this limited sample

fragile sites

sites that develop constrictions or gaps when the cells are grown in culture and that are prone to breakage under certain conditions. --Fragile sites are often replicated late in S phase. At these sites, the enzymes that replicate DNA may stall while unwinding of the DNA continues leading to long stretches of DNA that are unwound and vulnerable to breakage.

Most environmental factors associated with cancer cause

somatic mutations that stimulate cell division or otherwise affect the process of cancer progression.

telomeres

specific DNA sequences and associated proteins located at the tips of whole linear chromosomes

The principle of independent assortment in relation to chromosome theory of heredity.

states that in meiosis, each pair of homologous chromosomes assorts independently of other homologous pairs. With this new perspective, it is easy to see that because the number of chromosomes in most organisms is limited, there are certain to be more genes than chromosomes, so some genes must be present on the same chromosome and should not assort independently [ex: Mendel's peas]

Polymerase Chain Reaction requires a DNA template from which a new DNA strand can be copied and a pair of single-stranded primers, each with a 3′-OH group to which new nucleotides can be added. The primers used in PCR are short fragments of DNA, typically 17-25 nucleotides long, that are complementary to known sequences on the template.

steps in figure -Taq polymerase: stable at high temp & adds nucleotides -reverse-transcription PCR: reverse transcriptase is used to convert RNA into complementary DNA, which can then be amplified by the usual polymerase chain reaction.

A final process that brings about changes in allelic frequencies is natural selection;

takes place when individuals with adaptive traits produce a greater number of offspring than do individuals not carrying such traits. Enables populations to become better adapted to their environments

Positive assortative mating

tendency for like individuals to mate

Negative assortative mating

tendency for unlike individuals to mate.

Many organisms, including some plants, insects, and reptiles, and all mammals (including humans), have

the XX-XY sex-determining system

insertions and deletions (collectively called indels): [most frequent type of mutation]

the addition or removal, respectively, of one or more nucleotide pairs Can lead to: -Frameshift mutations -In-frame insertions or deletions -insert. or delet. of any multiple of 3 nucleotides can leave reading frame intact.

the recombinant preogeny is the one present in

the fewest numbers. and the nonrecombinant progeny will be in the highest numbers.

Genomics is..

the field of genetics that attempts to understand the content, organization, function, and evolution of the genetic information contained in whole genomes.

Comparative genomics -Prokaryotes with the smallest genomes tend to occupy restricted habitats, whereas those with the largest genomes are usually found in complex environments.

the field of genomics that studies similarities and differences in gene content, function, and organization among genomes of different organisms.

underdominance

the heterozygote has lower fitness than either homozygote (W11 > W12 < W22).

The Ras signal-transduction pathway conducts signals from growth factors and hormones to the nucleus and stimulates the cell cycle.

the normal ras proto-oncogene is a key player in a signal-transduction pathway that relays a signal from growth factors to the nucleus, where the signal stimulates cell division. When ras is mutated, the protein it produces continually relays a stimulatory signal for cell division, even when growth factors are absent.

The influence of environment on a characteristic can also complicate the relation between genotype and phenotype. When environmental factors affect the phenotype, a single genotype can produce a range of phenotypes.

the phenotypic ranges of different genotypes can overlap, making it difficult to know whether individuals differ in phenotype because of genetic or environmental differences

Humans, like Drosophila, have XX-XY sex determination, but in humans, maleness is primarily determined by

the presence of a particular gene (SRY) on the Y chromosome.

nontemplate strand

the strand of DNA that is not used to transcribe mRNA; this strand is identical to the mRNA except that T nucleotides in the DNA are replaced by U nucleotides in the mRNA

Structural genomics [ex: genetic and physical maps of a genome's chromosomes]

the study of the organization and sequence of the genetic information contained within a genome, providing the basic DNA sequence information that is used in functional and evolutionary studies.

clonal evolution

the tumor cells accumulate somatic mutations that allow them to become increasingly more aggressive in their proliferative properties

The gene pool of a population can also be described in terms of allelic frequencies (Proportion of a particular allele within a population.)

the types and numbers of alleles, rather than genotypes, have real continuity from one generation to the next and make up the gene pool of a population.

continuous characteristic can

theoretically assume any value between two extremes; the number of phenotypes is limited only by our ability to precisely measure them.

The sequences recognized by a restriction enzyme are located randomly within the genome. --used whenever DNA fragments must be cut or joined. In a typical restriction reaction, a concentrated solution of purified DNA is placed in a small tube with a buffer solution and a small amount of restriction enzyme. The reaction mixture is then heated to the optimal temperature for the enzyme, usually 37°C. Often within an hour, the enzyme cuts the appropriate restriction sites in all the DNA molecules, producing a set of DNA fragments.

there is a relation between the length of the recognition sequence and the number of times it is present in a genome: there will be fewer longer recognition sequences than shorter ones, because the probability of the occurrence of longer ones (ex: 6 bp vs 4 bp) are more common.

As a result of X inactivation, female placental mammals are functionally hemizygous at the cellular level for X-linked genes. In females that are heterozygous at an X-linked locus, approximately 50% of the cells express one allele and 50% express the other allele;

thus, in heterozygous females, proteins encoded by both alleles are produced, but not within the same cell. This functional hemizygosity means that the cells in an individual female are not identical with respect to the expression of the genes on the X chromosome; females are mosaics for the expression of X-linked genes.

An operon is a group of genes that share a common promoter and are..

transcribed as a unit, producing a single mRNA molecule that encodes several proteins; control expression of genes by regulating transcription. -common in bacteria and archaea, not as much in Euk.

eukaryotic RNA pol I

transcribes large ribosomal RNA molecules.

euk RNA pol III

transcribes other small RNA molecules—specifically tRNAs, small rRNAs, some miRNAs, and some snRNAs. -- RNA polymerases I, II, and III are found in all eukaryotes.

euk RNA pol II

transcribes pre-mRNAs, snoRNAs, some miRNAs, and some snRNAs

Chronic myelogenous leukemia and Burkitt lympohoma are often caused by ____________.

translocations

Genome-wide association studies

use numerous SNPs scattered across the genome to find genes of interest.

primary Down syndrome

usually arises from spontaneous nondisjunction during egg formation: about 75% of the nondisjunction events that cause Down syndrome are maternal in origin, most arising in meiosis I. Most children with Down syndrome are born to unaffected parents

bacteriophages (phages)

viruses that exclusively infect bacteria

Nilsson-Ehle cross of white wheat kernels with purple kernels. the phenotypic ratio expected in the F2 is 1/16 purple, 4/16 dark red, 6/16 red, 4/16 light red, and 1/16 white.

when two heterozygotes are crossed, we expect progeny in the proportions 1/4A+A+, 1/2A+A−, and 1/4A−A−. At the second locus, two heterozygotes are also crossed, and again we expect progeny in the proportions 1/4B+B+, 1/2B+B−, and 1/4B−B−. --multiplication rule: A+A+(1/4) and the probability of obtaining genotype B+B+(1/4), or 1/4×1/4=1/16 ---> Thus, the overall probability of obtaining red kernels in the F2 progeny is 1/16+1/16+1/4=6/16.

ZZ-ZW sex-determining system

{{bearded dragons. birds, some reptiles, butterflies, some amphibians, and some fishes.}} -female is heterogametic and the male is homogametic -Females in this system are ZW; after meiosis, half of the eggs have a Z chromosome and the other half have a W chromosome. Males are ZZ;