Genetics Test 3
Chromosome loss
One of the sister chromatids does not migrate to a pole Leads to normal and monosomic daughter cells
Chromosome numbers can vary in two ways
*Euploidy* -> changes in the entire set of chromosomes. Occurs sometimes in animals and frequently in plants. *Anueploidy* -> changes in individual chromosomes rather than in the complete set. Regarded as abnormal conditions. Always abnormal. Ex: Trisomy 21
Nondisjunction in meiosis I
*Nondisjunction in meiosis I: All four gametes are abnormal.*During meiosis I, during fertilization, these gametes produce an individual that is trisomic for the missing chromosome.
Meiotic Nondisjunction
*Nondisjunction* is the failure of chromosomes to segregate properly during cell division. The result is one cell gets too many and one too few chromosomes. Nondisjunction can occur in both mitosis and meiosis. In rare cases, all the chromosomes can undergo nondisjunction and migrate to one daughter cell. -> *complete nondisjunction* -> gives you triploid zygote.
DNA __________ further compacts the bacterial chromosome
*Supercoiling* Because DNA is a long thin molecule -> twisting can dramatically change its conformation. Because the two strands within DNA already coil around each other, the formation of additional coils due to twisting forces is called *DNA supercoiling*. Both underwinding and overwinding of the DNA double helix can cause supercoiling of the helix.
Chromosomal variation
*Why study?* They can have major effects on the phenotype of the organism and they can have major effects on the phenotype of the offspring of an organism and they have been an important force in the evolution of species.
Cytogenetics
*the field that involves the microscopic examination of chromosomes* It typically examines the chromosomal composition of a specific cell or organism This allows the detection of individuals with abnormal chromosome number or structure This also provides a way to distinguish between species
In sexually-reproducing species...
- Even-numbered sets of chromosomes are usually maintained reliably generation to generation because they lead to balanced gametes. -Odd-numbered sets of chromosomes are usually NOT maintained reliably because they lead to unbalanced gametes. Sterility is generally a detrimental trait -> However, it can be agriculturally desirable because it may result in seedless fruits and flowers.
Deletion
-Deletions and duplications are changes in the total amount of genetic material within a single chromosome. When a *deletion* occurs, a segment of chromosomal material is missing. In other words, the affected chromosome is deficient in a significant amount of genetic material.
Deletions may produce a mutant phenotype because of...
1) *Breakpoint effects*: Break occurs within a gene 2) *Position effects*: The gene is compromised because it is in a new position. Shifted to a new location
Main similar features of chromosomes
1) Size 2) Location of the centromere 3) Banding patterns All seen in a *karyotype*
Key features of eukaryotic chromosomes
1) they are usually linear 2) occur in sets. Many species are diploid, meaning that somatic cells contain 2 sets of chromosomes. 3) a typical chromosome is tens of millions to hundreds of millions of base pairs in length. 4) Genes are interspersed throughout the chromosome. A typical chromosome contains between a few hundred and several thousand different genes. 5) Each chromosome contains many origins of replication that are interspersed about every 100,000 bp. 6) Each chromosome contains a centromere that forms a recognition site for the kinetochore proteins. 7) Telomeres contain specialized sequences located at both ends of the linear chromosome. 8) Repetitive sequences are commonly found near centromeric and telomeric regions, but they may also be interspersed throughout the chromosome.
Globin gene family
14 homologous genes on three different chromosomes. All are derived from a single ancestral gene. Accumulation of different mutations in the members of the gene family created: 1) Globin genes that are expressed during diff stages of human dev. 2) Globin proteins that are more specialized in their function
If four loci are unlinked, a tetrahydrid produces ___ types of gametes in ____ proportions. A. 4 ; equal B. 8 ; unequal C. 8 ; equal D. 16 ; unequal E. 16 ; equal
16; equal They have to be equal (numbers have to be really close)
Down Syndrome (Trisomy 21)
21 is the smallest chromosome. Karyotype = 47, XX or XY, +21 The most common chromosomal abnormality Only chromosomal abnormality compatible with long-term survival Non-disjunction event is more likely to occur in females. In addition, there is a pronounced maternal age effect. Why? Because the eggs are older -> more likely to have more problems with spindle formation. Predisposed to Alzheimers early because the gene for Alzheimers is located on chromosome 21.
If three loci are completely linked, a trihydrid produces ___ types of gametes in ____ proportions. A. 2 ; equal B. 2 ; unequal C. 4 ; equal D. 8 ; unequal E. 8 ; equal
2; equal No matter how many genes -> no crossing over -> 2 gametes and equal
A plant is 2n = 80, is crossed with a plant that is 6n = 60. The hybrid is A. likely sterile and has 70 chromosomes B. likely fertile and has 70 chromosomes C. likely sterile and has 140 chromosomes D. likely fertile and has 140 chromosomes
2n = 80 -> female (n=40) 6n = 60-> male (3n=30) You get 70 chromosomes They will not find each other during metaphase -> most likely sterile.
Extreme Klinefelter Syndrome
48, XXXY 48, XXYY 49, XXXY
In bean plants, 2n = 12. How many different chromosomes are there? Assume homozygosity at each locus. A. 2 B. 6 C. 12 D. 24
6
In bean plants, 2n = 12. How many different double trisomics are possible?
6 chromosomes 5+4+3+2+1 = 15
For polyploid organisms, x = number of chromosomes per set and n = number of chromosomes in a gamete. A hexaploid organism has 60 chromosomes. Which of the following is CORRECT? A. x = 10 ; n = 10 B. x = 10 ; n = 20 C. x = 10 ; n = 30 D. x = 20 ; n = 20 E. x = 20 ; n = 30
6x = 60 x = 10 2n = 60 n = 30
Dude and Dudette are chromosomally normal. Their daughter, Duda, has triple X syndrome. Which event could NOT have produced Duda? A. non-disjunction in meiosis I in Dude B. non-disjunction in meiosis II in Dude C. non-disjunction in meiosis I in Dudette D. non-disjunction in meiosis II in Dudette E. All of the above are possible explanations
A
How is a bacterium that contains two nucleoids similar to a diploid eukaryotic cell?
A bacterium with two nucleoids is similar to a diploid eukaryotic cell because it would have two copies of each gene. The bacterium is different, however, with regard to alleles. A eukaryotic cell can have two different alleles for the same gene. For example, a cell from a pea plant could be heterozygous, Tt, for the gene that affects height. By comparison, a bacterium with two nucleoids has two identical chromosomes. Therefore, a bacterium with two nucleoids is homozygous for its chromosomal genes.
Position effect
A change in phenotype that occurs when the position of a gene changes from one chromosomal site to a different location.
Translocations
A chromosomal translocation occurs when a segment of one chromosome becomes attached to each other. Alter the sizes of chromosomes, as well as the position of the centromere.
Interstitial deletion
A chromosome has broken in two places to produce three chromosomal fragments. The central fragment is lost, and the two outer pieces reattach to each other.
Chromosomal Inversions
A chromosome with an inversion contains a segment that has been flipped to the opposite direction. It is classified to the location of the centromere. When a chromosome contains an inversion, the total amount of genetic material remains the same as in a normal chromosome. *Many do not have phenotypic consequences*.
Histones
A class of five proteins (H1, H2A, H2B, H3, and H4) They are all small, basic, ubiquitous, and evolutionary-conserved. The "beads-on-a-string" model Core particle -> Two molecules each of H2A, H2B, H3 and H4. 146 bp of DNA wrapped ~1.65 times around the octamer. An h1 monomer on the outside. Linker DNA -> Links beads together Shortens the DNA length about seven-fold DNA double helix -> chromosome -> beads on a string
Cri-du-chat syndrome
A human disorder caused by a deletion. Lejeune Syndrome About half of the 5p arm is missing. Karyotype will still be 46. Karyotype = 46, XX or XY, 5p- Infants have high-pitched cry, similar to that of the meowing of a cat.
How can a triploid human be produced?
A normal egg is fertilized by two normal sperm. The resulting triploid invididual has two chromosomes from the egg plus four more chromosomes donated by the two sperm.
Origin of replication
A nucleotide sequence that functions as an initiation site for the assembly of several proteins required for DNA replication. Bacterial chromosomes have one origin of replication.
Cohesin
A protein complex that facilitates the alignment of sister chromatids.
Condensin
A protein complex that plays a role in the condensation of interphase chromosomes to become metaphase chromosomes.
Inversion
A rearrangement that reverses the order of genes in a chromosome Most inversions do not result in an abnormal phenotype. In the rare cases that they do, the mutant phenotype is due to breakpoint effect and position effect. About 2% of the human population carries inversions. Most are phenotypically normal. However, a few can produce offspring with genetic abnormalities.
Robertsonian translocation
A specific type of reciprocal translocation It involves two non-homologous acrocentric chromosomes, which fuse at the centromere and lose their short arms. Two p arms are lost -> q arms are fused.
Chromosomes are further compacted by anchoring the 30 nm fiber into radial loop domains along the nuclear matrix
A third level of compaction involves interactions between the 30 nm fibers and a filamentous network of proteins in the nucleus called the *nuclear matrix*. Consists of two parts -*nuclear lamina*: collection of filaments that line the inner nuclear membrane. *internal nuclear matrix*: connected to the nuclear lamina and fills the interior of the nucleus.
Interchromosomal
A. Non-reciprocal = Chromosomal segment moves from one chromosome to another B. Reciprocal = Two non-homologous chromosomes exchange chromosome segments
One bp of DNA is approximately 0.34 nm in length. A bacterial chromosome is about 4 million bp in length and is organized into about 100 loops that are about 40k bp in length. If it was stretched out linearly, how long would one loop be? If a bacterial chromosomal loop is circular, what would be its diameter?
A. One loop is 40,000 bp. One base pair is 0.34 nm, which equals 0.3410-3 µm. If we multiply the two together: (40,000)(0.3410-3) = 13.6 µm B. Circumference = πD 13.6 µm = πD D = 4.3
47, XYY Condition
Above average height and sub-average intelligence. The relationship between XYY and aggressive, psychopathic or criminal behavior has aroused great public interest.
Inversion heterozygote
An individual carrying one copy of a normal chromosome and one copy of an inverted chromosome.
Balanced translocation
Are at risk of having offspring with an *unbalanced translocation*, in which significant portions of genetic material are duplicated and/or deleted. Abnormality or lethality.
Type II Topoisomerase
Are usually multimeric proteins Induce transient double-strand breaks into the double helix. Changes supercoils two at a time
Reciprocal translocations
Arise from two different mechanisms: 1) Chromosomal breakage and DNA repair 2) Abnormal crossovers Are usually without phenotypic consequences
Paracentric
Arm ratio is unchanged. Crossing over results in two normal, one with no centromere, and a dicentric chromosome.
Metaphase chromosomes
As cells enter M phase, the level of compaction changes dramatically *MOST CONDENSED* In metaphase chromosomes the radial loops are highly compacted and stay anchored to a scaffold The scaffold is formed from the nuclear matrix Histones are needed for the compaction of radial loops Two multiprotein complexes help to form and organize metaphase chromosomes Condensin = Plays a critical role in chromosome condensation Cohesin = Plays a critical role in sister chromatid alignment Both contain a category of proteins called SMC proteins Acronym = Structural maintenance of chromosomes SMC proteins use energy from ATP and catalyze changes in chromosome structure
If you assume the average length of linker DNA is 50 bp, approximately how many nucleosomes are found in the haploid human genome, which contains 3 billion bp?
Assuming a size of 3 billion bp, and if we assume that 146 bp wrap around a histone octamer, with 50 bp in the intervening region: 3,000,000,000/196 = 15,306,122, or about 15.3 million
Types of polyploids
Autopolyploids: Allopolyploids: Chromosomes are from more than one species. Derived from closely related species.
In humans, faulty tooth enamel is an X-linked dominant trait. A couple with abnormal teeth have a son with Klinefelter syndrome and normal teeth. In which parent did nondisjunction occur? A. Dad B. Mom C. Both dad and mom D. Either dad or mom E. Neither parent
B. Mom The kid is normal. The dad must be X^FY. Mom must have been X^FX^FX^fX^f (starting with tetrad)
Highly repetitive sequences
Base sequences that are found tens of thousands or even millions of times throughout a genome.
Myoglobin
Better at binding and storing oxygen in muscle cells.
Hemoglobins
Better at binding and transporting oxygen via red blood cells.
Supercoils
Can be best explained in the following manner: One strand of a double-stranded circular covalently closed DNA molecule is cut One end is rotated a complete turn around its complementary strand its complementary strand, while the other end is fixed => a supercoil is introduced into the molecule
Double Anueploidies
Can have XYY with down-syndrome ex: XXY with down-syndrome
In bean plants, 2n= 12. Which is true?
Cant be a tetrasomic cell with 16 chromosomes because the cell: 2n + 2 = 14 Cant be a trisomic gamete with 13 chromosomes because it would be n + 2 = 8 Because the cell is haploid you would add two
Cri du chat
Caused by a deletion in a segment if the short arm of chromosome 5. Symptoms: mental deficiencies, unique facial anomalies, and an unusual catlike cry during infancy.
With colchicine
Cell subsequently reenters interphase as colchicine is removed after late prophase.
What is the function of a centromere? At what stage of the cell cycle would you expect the centromere to be the most important?
Centromeres are structures found in eukaryotic chromosomes that provide an attachment site for kinetochore proteins so that the chromosomes are sorted (i.e., segregated) during mitosis and meiosis. They are most important during M phase.
Which of the following karyotypes is written correctly? A. 46, X B. 48, XXY, +21 C. 49, XXXYY D. Choices A and B E. Choices B and C
Choices B and C
Intrachromosomal
Chromosomal segment moves from one part of the chromosome to another
Endoreduplication
Chromosome doubling due to an aborted cell division. It may occur naturally or artificially (treatment with *colchicine* - messes up with spindle fiber formation -> binds to tubulin)
Prokaryotes contain...
Circular DNA
Familial Down Syndrome
Classic Down syndrome- trisomy 21 About 5% of cases are due to a *Robertsonian translocation* (14/21) -This can recur in the family The families in question have a high risk of spontaneous abortion due to other chromosome abnormalities. Mother or father must be translocation carrier. When united with a normal gamete and a carrier, you will get one normal offspring, a translocation carrier, trisomy 21, and monosomy 21 (lethal)
Georgi Karpechenko
Conducted an interspeciess cross between raddish and cabbage. Both are diploid and contains 18 chromosomes. Therefore the interspecies hybrid contains 18 chromosomes. However, the radish and cabbage are not closely related. Their chromosomes are distinctly different from one another and cannot synapse -> *sterile hybrid*. But an allotetraploid would be *fertile*. Would contain 36 chromosomes which undergo proper synapsis.
Histone proteins
Consists of a globular domain and a flexible, charged amino terminus called an amino terminal tail. Are very basic proteins because they contain a large number of positively charged lysine and arginine amino acids. The arginines play a major role in binding to the DNA.
Autopolyploids
Contain multiple copies of the same genome. ex: potato and strawberry
A human somatic cell is dividing mitotically. If one chromosome undergoes nondisjunction, what chromosome complement will end up in the two daughter cells? A. 46, 45 B. 46, 44 C. 44, 48 D. 45, 47
D. Because 46+1=47 46-1=45
Topoisomers
DNA conformations that differ with regard to supercoiling.
Genetic material in viruses is...
DNA or RNA but not both Double-stranded or single-stranded Circular or linear
Repetitive sequences
DNA sequences that are present in many copies in the genome.
Wolf-Hirschhorn syndrome
Deletion in the four short arm. Karyotype = 46, XX or XY, 4p-
Pseudodominance
Deletions may lead to pseudodominance. Uncovering of the recessive allele Ex: Aa but big A is deleted. a becomes dominant because A is gone.
Phenotypic consequences from chromosomal deletions
Depends on the size of the deletion and whether it includes genes or portions of genes that are vital to the development of the organism. Larger deletions tend to be more harmful because more genes are missing.
Radial loop domains
During interphase, chromatin is organized into loops, and are anchored to the nuclear matrix. The chromosomal DNA of eukaryotic soecies contains sequences called *matrix-attachment regions, or scaffold-attachment regions*, which are interspersed at regular intervals throughout the genome. The MARs bind to specific proteins in the nuclear matrix -> forming chromosomal loops. Radial loop domains organize the chromosomes.
Consider two closely-related diploid species...
Each species produces haploid gametes, so the hybrid is termed an *allodiploid*. However, normal pairing during meiosis I may not be possible and thus the hybrid is sterile. -The chromosome sets are *homeologous*. If endoreduplication occurs, the duplicated chromosomes can now normally pair with each other and the hybrid is no longer sterile. If somehow the chromosomes that couldnt find each other and now have a partner -> can be fertile. Sterile hybrid ends up because a1 will not find b1 normally. There's no built in partner.
A color blind man mates with a woman with normal vision whose father was color-blind. They have a color-blind son with Klinefelter syndrome. In which parent did nondisjunction occur? In which meiotic division would the nondisjunction have occurred?
Either dad or mom. Meosis II in mom; meiosis I in dad.
Terminal deletion
End of the chromosome is lost. More likely because one step.
Unequal crossing over
Ends up with parentals. Will end up with ABD in one chromosome and a duplication of C on the other: ABCCD
Genome
Entire genetic complement of a cell or a virus In eukaryotes, it refers to one complete set of nuclear chromosomes. Eukaryotes possess a mitochondrial genome. Plants also have a chloroplast genome.
The compaction of eukaryotic chromosomes
Euchromatin: less condensed -> lighter Heterchromatin: highly condensed -> darker Eukaryotes contain an enormous amount of genetic material Humans, for example, have a genome consisting of ~ 3 x 10^9 bp This corresponds to about 1m of DNA The average adult human body contains about 10^13 cells -> 2 x 10^13 m of DNA A typical eukaryotic chromosome contains 1-20 cm of DNA. During metaphase, this is packaged into a length of only 1-20 micrometer.
Translocation
Ex: familial Down Syndrome Due to a translocation, a person may have one copy of chromosome 14, one copy of chromosome 21, and one copy of a chromosome that is a fusion between chromosome 14 and 21. The individual has a normal phenotype because the total amount of genetic material is present. During meiosis, these three types of chromosomes replicate and segregate from each other. However, because the three chromosomes cannot segregate evenly, six possible types of gametes may be produced.
Polyploidy
Fairly common in plants because of the absence of sex chromosomes. Polyploidy plants tend to be larger or more hardy than their diploid counterparts. Bananas are triploid. Cotton is hexaploid. Strawberries are octaploid. In humans, polyploidy is always lethal. Polyploidy is rare in animals.
Edwards Syndrome
First described by John Edwards in 1960 Karyotype = 47, XX or XY, + 18
Centromeres and the genetic stability of chromosomes
For a chromosome to be reliably transmitted during cell division, it has to be linear and possess only one chromosome In other words, it has to be a monocentric rod chromosome Acentric, dicentric and ring chromosomes are not reliably transmitted to daughter cells Chromosomal (or centric) fusion occurs when two non-homologous chromosomes are joined at their centromeres to form a large single metacentric chromosome Chromosomal (or centric) fission occurs when a chromosome splits at its centromere, thus generating two smaller chromosomes Ex: human chromosome 2 is metacentric, formed by fusion of two acrocentric chromosomes from chimpanzees.
Telomere structure
Found at the end of linear chromosomes. Provide three functions: Protective from degredation, ensure replication, prevent chromosomes from sticking to each other Contain no genes Instead it repeats short sequences and are extremely conserved throughout evolution -> 5'-TTAGGG-3'
Repetitive sequences
Found in many bacterial species May play a role in a variety of genetic processes, including DNA folding, DNA replication, gene regulation, and genetic recombination.
Homologous genes
Genes derived from a single ancestral genes.
Mitotic Abnormalities
Genetic abnormalities that occur after fertlization leads to mosaicism. Part of the organism contains cells that are genetically different from other parts. The size and location of the mosaic region depends on the timing and location of the original abnormality In the most extreme case, the error could take place during the first mitotic division ex: Drosophila egg that is XX. One of the X's is lost during the first mitotic division. This produces an XX cell and an XO cell. -> *bilateral gynandromorph*
Four different histone proteins
H2A, H2B, H3, and H4. *Core histones* another histone, H1, is called the linker histone. It binds to the DNA in the linker region between nucleosomes and may help to compact adjacent nucleosomes. Linker histones are less tightly bound to the DNA than are the core histones. Non-histone proteins bound to the linker region play a role in organization and compaction of chromosomes, and their presence may affect the expression of nearby genes.
Interstitial deletion
Happens in the middle. Two breaks and reattachment of outer pieces.
Inversion heterozygote
Has one copy of a normal chromosome and one copy of an inverted chromosome. They also may have a high probablity of producing gametes that are abnormal in their genetic content. The abnormality is due to *crossing-over* in the inverted segment.
Euploid
Have a chromosome number that is an exact multiple of a chromosome set. In Drosophila melanogaster, a single set is composed of four different chromosomes.
Point centromere
Having a centromere with a defined DNA sequence
Compare hetero and euchromatin. What are the differences?
Heterochromatin is more tightly packed than euchromatin. This is due to a greater compaction of the radial loop domains. Functionally, euchromatin can be transcribed into RNA, while heterochromatin is inactive. Heterochromatin is most abundant in the centromeric regions of the chromosomes and in the telomeric regions.
47, XXX Syndrome
Highly variable expression. Usually benign consequences. Under-development of genitalia, mental retardation, deficiencies in speech development. Might be perfectly fertile.
If observed DCO = expected DCO
I = 0 No interference
If observed DCO = 0
I = 1 Complete interference
If observed DCO > expected DCO
I would have to be negative. Negative interference -> not only did it interfere, but it increased the probability of the DCO occurring.
If observed DCO < expected DCO
I would have to be positive. Positive interference -> making it less likely to happen
Meiotic nondisjunction
If nondisjunction occurs during anaphase I of meiosis I, this means that at least one pair of homologous chromosomes did not separate. The end result is two cells that have an extra copy of one chromosome and two cells that are missing that chromosome. In humans, n + 1 designates a cell with 23 chromosomes plus an extra copy of one for a total of 24 chromosomes. n - 1 designates a cell missing a chromosome for a total of only 22 chromosomes in humans. If nondisjunction occurs during anaphase II of meiosis II, it means that at least one pair of sister chromatids did not separate. In this scenario, two cells will have the normal haploid number of chromosomes. Additionally, one cell will have an extra chromosome (n + 1) and one will be missing a chromosome (n - 1).
Paracentric inversion
If the centromere is found outside the inverted region One product is a piece of chromosome without any centromere--*an acentric fragment*--lost in cell divisions. The other product is a *dicentric* chromosome that contains two centromeres. The region of the chromosome connecting the two centromeres is a *dicentric bridge*. The net result: one normal chromosome, one with an inversion, and two chromosomes that contain deletions.
Pericentric inversion
If the centromere lies within the inverted region of the chromosome Only occurs between two. Results in chromosomes where one segment is deleted and a different segment is duplicated.
Three-factor cross
If the three loci are unlinked -> 8 different gametes and 8 different phenotypes If the three loci are linked -> 2 different gametes If the three loci are incompletely linked -> 8 different gametes and 8 different phenotypes *Make sure you study this slide*
Nucleosomes become closely associated to form a 30-nm fiber
In eukaryotic chromatin, nucleosomes associate with each other to form a more compact structure that is 30 nm in diameter. Chromatin samples were exposed to a solid resin that could bind to histone H1 and remove it from the DNA. However, the removal of H1 depended on the NaCl []. A moderate salt [] removed H1, but a solution with no added salt did not remove H1. -With salt -> beads on a string -No salt -> more compact conformation *These results suggest that the nucleosomes are packaged into a more compact unit and that H1 has a role in the packaging and compaction of nucleosomes*
Chromosome territory
In the cell nucleus, each chromosome occupies a nonoverlapping region called a chromosome territory. The binding of each chromosome to the nuclear matrix is thought to play a key role in forming these chromosome territories.
Genome size....roughly with evolutionary complexity
Increases
Nucleoid
Inside a bacterial cell, a chromosome is highly compacted and found within a region of the cell
In more complex eukaryotes such as mammals and plants, protein-encoding genes tend to be much longer due to the presence of _____________
Introns; noncoding intervening sequences. The size of introns ranges from less than 100 bp to more than 10,000 bp. Therefore, the presence of large introns can greatly increase the lengths of eukaryotic genes.
Inversion
Involves a change in the direction of the genetic material along a single chromosome.
Third mechanism of DNA compaction
Involves the formation of radial loop domains Play a role in compaction Serves to organize the chromosomes within the nucleus. Each chromosome in the nucleus is located in a discrete and nonoverlapping chromosome territory.
Klinefelter Syndrome
Karyotype = 47, XXY Only in males. Therapy may help -> testosterone and mastectomy
Tetra-X
Karyotypes = 48, XXXX Symptoms tend to be more severe than those of the 47, XXX syndrome.
Penta-X
Karyotypes = 49, XXXXX Symptoms tend to be more severe than those of the 47, XXX syndrome.
Euchromatin
Less condensed regions are capable of gene transcription.
When deletions are homozygous, it is often...
Lethal.
Anatomy of chromosome
Light bands -> less condensed DNA Dark bands -> highly condensed DNA Telomere -> Protects ends and ensures their proper replication. Centromere -> Essential for chromosome segregation
When deletions are heterozygous, it is often...
Maybe lethal. Deletions upset the genetic balance. Deletions unmask recessive lethal alleles. Recessive lethal will only kill when there are two copies. If big A is gone, a will act as a lethal allele because it is no longer masked by dominant allele.
When did the nondisjunction event occur? A. Meiosis I B. Meiosis II C. Both meiosis I and II D. Either meiosis I or II
Meiosis II
In individuals that are homozygous for a reciprocal translocation, all chromosome pairs can synapse properly.
Meiosis occurs normally.
Nonallelic homologous recombination
Misaligned crossover that occurs at homologous sites. The alleles of neighboring genes are not properly aligned. The result is that one chromatid has a duplication and another chromatid has a deletion.
Aneuploidy
Monosomy = One homologue is missing Trisomy = One extra homologue is present Tetrasomy = Two extra homologues are present Double monosomy = Two different homologues are missing Double trisomy = Two different extra homologues are present Nullisomy = A pair of chromosomes is missing Note: These definitions apply to a *Diploid* cell
Chrysanthemum chromosome
More chromosomes -> bigger chrysanthemums
Unbalanced gametes
More of some genes, less of others.
Eukaryotic Chromosomes
Most of the DNA does not code for proteins in higher organisms. In humans, the actual number of genes is 20-25,000, although the genome can theoretically contain about 1,000,000 In salamanders, closely-related species may have genomes that differ greatly in size, yet contain the same number of genes. A eukaryotic chromosome contains a long, linear DNA molecule. Three types of DNA sequences are needed for chromosome replication and segregation. -Origins of replication -Centromeres -Telomeres A single chromosome usually has a few hundred to several thousand genes. In lower eukaryotes like yeast -> genes are small -> contain very few introns Higher eukaryotes like mammals -> genes are long -> contain many introns
Euploidy
Most species of animals are diploid. Some euploidy variations are naturally occurring. -Bees Polyploids are organisms in which the number of chromosome sets exceeds two.
Gamete abnormality with inversions
Mostly occurs in the crossing over phase (Prophase I). During meiosis I, pairs of homologous sister chromatids synapse with each other. For the normal chromosome and inversion chromosome to synapse properly, an inversion loop must form to permit the homologous genes on both chromosomes. Individuals carrying large inversions are more likely to produce abnormal gametes.
Positive and negative supercoiling
Negative supercoiling: due to an underwinding force
Supercoils are eliminated by a...
Nick in the DNA
Higher order structures
Nucleosomes associate with each other to form a more compact structure termed the 30 nm fiber. Histone H1 plays a role in this compaction. At moderate salt concentrations, H1 is removed. The result is the classic beads-on-a-string morphology. At low salt concentrations, H1 remains bound. Beads associate together into a more compact morphology. The 30 nm fiber shortens the total length of DNA another seven-fold. Its structure has proven difficult to determine. Two models have been proposed -Solenoid: much more symmetrical, left-handed, more tightly wound. -Zigzag: much more of a Z shape Both will have a 30 nm diameter. A third level of compaction involves interaction between the 30 nm fiber and the *nuclear matrix* Nuclear lamina Fibers that line the inner nuclear membrane Internal matrix proteins Connected to nuclear lamina and fills interior of nucleus Structural and functional role remains controversial
Duplication
Occurs when a section of a chromosome is repeated compared with a normal chromosome.
Simple translocation
Occurs when a single piece of chromosome is attached to another chromosome.
Translocation
Occurs when one segment of a chromosome becomes attached to a different chromosome or to a different part of the same chromosome.
Interference
Once one cross over event has occurred, the likelihood of a second crossover in the same region can be altered. A crossover in region A can make the crossover in region B either impossible or more possible. ex: y = 1.56 map units from w. Therefore the probability of a CO between y and w is.... .0156% W is 4.06 map units from ec...Therefore, the probability of a CO between w and ec is... .0406% Thus the probability is = 0.000634 (multiply the two numbers) However, since we used 10,000 flies, multiply 10,000 by 0.000634 -> 6.34 If you count 10,000 flies, you expect 6.34 flies to undergo a double crossover. So we see a reduction in the double crossover from the expected, or *interference* Quantification of this intereference is I = 1-C C = observed DCO/ expected DCO. In our example, 6/6.34 = 0.946. Therefore, I 1-0.946 = 0.054.
Describe the two main mechanisms by which the bacterial DNA becomes compacted
One mechanism is the formation of loop domains. Loops of DNA are anchored to DNA-binding proteins. Secondly, the DNA double helix is supercoiled to make it more compact, much like twisting a rubber band
Turner Syndrome
Only one X chromosome. No Y chromosome. 45, X or 45, XO Only in females
Polyploid
Organisms with three or more sets of chromosomes.
Three regions required for chromosomal replication and segregation
Origins of replication Centromeres Telomeres-> prevent chromosomal rearrangements such as translocations. They protect chromosomes from digestion via enzymes and an unusual form
Leghemoglobin
Plants have a form of globin gene called *leghemoglobin* So the first globin gene must have been present in the common ancestor of both animals and plants. Moreover, invertebrates have myogoblin but *NOT* hemoglobin. Therefore, the globin duplication must have occurred after the divergence between verts and inverts.
Nondisjunction in meiosis II
Produces 2 n, and one n+1 and n-1 50% normal gametes. 50% abnormal gametes. n-1 would be nullisomy gamete n+1 would be disomy gamete
Trisomy
Produces more viable offspring than monosomy. 150% is better than 50%. In plants, trisomic individuals are viable but their phenotypes may be affected. In humans, trisomies for chromosomes 13, 18, 21, and X are compatible with survival.
SMC proteins
Proteins that use energy from ATP to catalyze changes in chromosome structure.
Facultative heterochromatin
Refers to chromatin that can occasionally interconvert between heterochromatin and euchromatin. ex: Barr body. The conversion of one X chromosome to heterochromatin occurs during embryonic development in the somatic cells of the body.
Constitutive heterochromatin
Refers to chromosomal regions that are always heterochromatic and permanently inactive with regard to transcription. Contains highly repetitive sequences rather than gene sequences.
Genomes
Refers to the entire complement of genetic material in an organism or species. For bacteria, the genome is a single circular chromosome. For eukaryotes, the nuclear genome refers to one haploid set of chromosomes that resides in the cell nucleus.
Exons
Regions of an RNA molecule that remain after splicing has removed the introns.
Topoisomerase I
Relaxes negative supercoils. This enzyme can bind to a negatively supercoiled region and introduce a break in one of the DNA strands. After one DNA strand has been broken, the DNA molecule rotates to relieve the tension that is caused by negative supercoiling. This relaxes negative supercoiling. The broken strand is then repaired.
Chromosome structure change
Results from chromosomal breaks and abnormal rejoining The cause may be spontaneous or induced (radiation). The loss of a portion of a chromosome
Mitotic nondisjunction
Results from meiotic nondisjunction -> When this occurs during embryonic stages of development, it may lead to a patch of tissue in the organism that has an altered chromosome number.
Amphidiploid
Same as allotetraploid. Contains two complete sets of chromosomes from two different species. Will form if endoreduplication occurs with two different species.
Roan antelope and sable antelope
Same chromosomes and homeologous. Will not have the same bands as the other homologue. The allodiploid is fertile because the homeologous chromosomes can properly synapse during meiosis.
DNA supercoiling
Second important way to compact the bacterial chromosome.
Moderately repetitive sequences
Sequences that are found in a few hundred to several thousand times in the genome.
30-nm fiber
Shortens the length of DNA another sevenfold. *Solenoid model*: Suggests a helical structure in which contact between nucleosomes produces a symmetrically compact structure within the 30-nm fiber. *Zigzag model*: linker regions within the 30-nm structure are variably bent and twisted. The structure with four nucleosomes revealed that the linker DNA zigzags back and forth between each nuclesome, a feature consistent with the zigzag model.
Mitotic disjunction
Sister chromatids separate improperly. Leads to trisomic and monsomic daughter cells.
About chromosomal duplications
Sometimes a crossover may occur at misaligned sites on the homologs. In some cases, a chromosome may carry two or more homologous segments of DNA that have identical or similar sequences.
Telomeres
Specialized repeated sequences of DNA found at the ends of normal chromosomes.
Nonhistone proteins
Stability, gene expression, but not associated with the octomer but the linker. Histone octamers have histone tails.
Heterochromatin
Stains deeply DNA is condensed Replicates later during the S phase Contains relatively few genes Found close to centromeres and telomeres In some species, could comprise almost an entire chromosome. Two types: - Constitutive heterochomatin: Regions that are always heterochromatic Permanently inactive with regard to transcription Usually contain highly repetitive sequences -Faculative heterochromatin: Regions that can interconvert between euchromatin and heterochromatin Example: Barr body formation during development in female
Euchromatin
Stains lightly by DNA-binding chemicals DNA is relatively extended and open Contains the vast majority of genes
Chromosomal variation can occur in two basic ways:
Structure and number
Aneuploidy
Such variation involves an alteration in the number of particular chromosomes, so the total number of chromosomes is not an exact multiple of a set. Often causes an abnormal phenotype. The level of gene expression is influenced by the number of genes per cell.
T/F In general changes in chromosome number have a more severe effect on survival than changes in chromosome structure.
T
T/F Interference is not equivalent in all parts of the chromosome
T
T/F A single chromosome usually has a few hundred to several thousand different genes.
T A typical eukaryotic gene is several thousand to tens of thousands of base pairs in length.
A plant has a diploid chromosome number of 40. Which of the following statements is TRUE? A. A tetrasomic CELL has 42 chromosomes B. A double nullisomic cell has 36 chromosomes C. A triploid CELL has 80 chromosomes D. Two of above are true E. All of the above are true F. None of above is true
Tetrasomy : 2n + 2 Double nullisomy: 2n - 2 - 2 Triploid cell would have 60 chromosomes
C-value paradox
The amount of DNA does not correlate with evolutionary complexity, nor is it directly proportional to number of genes. Differences in genome size among species of Arthropods -> 250-fold Fish -> 350-fold Angiosperms -> 1000-fold
Which of the following terms should not be used to describe a barr body? A chromatin B Euchromatin C Heterochromatin D Chromosome E Genome
The answer is B and E. A Barr body is composed of a type of highly compacted chromatin called heterochromatin. Euchromatin is not so compacted. A Barr body is not composed of euchromatin. A Barr body is one chromosome, the X chromosome. The term genome refers to all the types of chromosomes that make up the genetic composition of an individual.
Pericentric
The arm ratio is often changed. Crossing over results in one duplicated and one deleted.
Chromatin
The association between DNA and proteins that are found within chromosomes.
Bacterial Chromosomes
The bacterial chromosome is found in a region called the *nucleoid*. It is not membrane bound. E.Coli genome 4.7 x 10^6 bp -> linear duplex of about 1.5 mm Every 10 bp is 3.4 nm DNA is ~ 700 X the length of the cell Therefore the DNA must be in a highly condensed configuration The first way to promote compaction is the formation of domain loops. The number of loops varies according to the size of the bacterial chromosome. E.coli has 50-100 with 40k-80k bp of DNA in each loop. DNA is condensed with the help of various classes of binding proteins These are positively-charged Collectively referred to as histone-like
What is a bacterial nucleoid? With regard to cellular membranes, what is the difference between a bacterial nucleoid and a eukaroytic nucleus?
The bacterial nucleoid is a region in a bacterial cell that contains a compacted circular chromosome. Unlike the eukaryotic nucleus, a nucleoid is not surrounded by a membrane.
On rare occasions, a chromosome can suffer a small deletion that removes the centromere. When this occurs, the chromosome usually is not found within subsequent daughter cells. Explain why a chromosome without a centromere is not transmitted very efficiently from mother to daughter cells.
The centromere is the attachment site for the kinetochore, which attaches to the spindle. If a chromosome is not attached to the spindle, it is free to "float around" within the cell, and it may not be near a pole when the nuclear membrane re-forms during telophase. If a chromosome is left outside of the nucleus, it is degraded during interphase. That is why the chromosome without a centromere may not be found in daughter cells.
The supercoiling of DNA
The chromosomal DNA in both prokaryotes and eukaryotes is highly compacted. Supercoiling only occurs in DNA molecules with fixed ends. Supercoiling doesn't work in linear DNA.
Chromosome function is influenced by DNA supercoiling
The chromosomal DNA in living bacteria is negatively supercoiled. Negative supercoiling has consequences: affects DNA function by creating tension on the DNA strands that may be released by DNA strand separation. May promote DNA strand separation in small regions. This enhances genetic activities such as replication and transcription that require the DNA strands to be separated.
Topoisomerase
The enzyme that creates or alleviates supercoils
Salamander genomes
The genome of P larselli is greater than relatives because of the accumulation of repetitive DNA sequences. Such highly repetitive sequences do not encode proteins, and their function remains a matter of controversy and great interest.
What types of genetic activities occur during interphase? Explain why these activities cannot occur during M phase.
The main activities that can occur during interphase are transcription and DNA replication. For these activities to occur, the DNA must be in a relatively loose conformation. During M phase, there is relatively little genetic activity, although there is evidence that a few genes are transcribed. However, during M phase most genes are transcriptionally inactive.
Endopolyploidy
The phenomenon in which some somatic cells of an animal have more sets of chromosomes than other somatic cells. In humans some cells are polyploid. ex: muscle cells, liver cells, megakaryocytes (form platelets)
Duplications
The presence of an extra segment of a chromosome. Considered by position and order. As the number of duplicate copies of a segment increases, the likelihood of unequal crossing over would also increase Therefore, once the process has started there is a tendency for the number of copies to increase over evolutionary time The majority of small chromosomal duplications have no phenotypic effect However, they are vital because they provide raw material for additional genes This can ultimately lead to the formation of *gene families.* Two or more genes that are similar to each other
Mosaicism
The presence of two or more cell lines in an individual, one or more of which are abnormal.
Nucleosome
The repeating structural unit within eukaryotic chromatin is the nucleosome--a double-stranded segment of DNA wrapped around an octamer of histone proteins. Each octamer contains eight histone subunits: two copies each of four different histone proteins. The DNA is negatively supercoiled over the surface of this octamer. The chromatin of eukaryotic cells contains a repeating pattern in which the nucleosomes are connected by linker regions of DNA that vary in length from 20-100 bp, depending on the species and cell type. It has been suggested that the overall structure of connected nucleosomes resembles beads on a string. *Shortens the length of the DNA molecule about sevenfold*
In individuals that are heterozygous for a reciprocal translocation, the homologous chromosome parts pair as best as they can in Prophase I
The result is a cross-shaped structure.
When the parental nor the DCO classes can be identified...
Therefore, the genes are NOT incompletely linked. In addition, they are NOT independently assorting. 2^3 = 8 . 1/8 probability of each happening, but they are not. The genes are not completely linked either because the cross did not yield two classes only. Suppose two genes are linked and the third is unlinked. How do you know which is which? Thus, the four largest classes are the parentals and the four lowest are recombinants. Consider genes a and b -> linked. Consider genes b and c -> independently assorting and unlinked
Duplications tend to be *less* harmful than deletions
They generally allow for viable offspring. Abnormalities due to upsetting of the genetic balance.
Robertsonian translocation
This type of translocation arises from breaks near the centromeres of two nonhomologous acrocentric chromosomes.
Heterochromatin
Tightly compacted regions of chromosomes. These regions of the chromosome are transcriptionally inactive. Most abundant in centromeric and telomeric regions.
The formation of __________________ helps make the bacterial chromosome more compact
To fit within the bacterial cell -> DNA needs to be compacted about 1000 fold. Involves the formation of *loop domains*. Is a segment of chromosomal DNA folded into a structure that resembles a loop. DNA-binding proteins anchor the base of the loops in place. *The number of loops varies according to the size of the bacterial chromosome and species*. This looped structure compacts the circular chromosome about 10-fold.
Monosomy
Tolerated in some plants In drosophila -> Haplo-IV Lethal in humans except for the *X chromosome*
DNA gyrase
Topoisomerase II; an enzyme that introduces negative supercoils into DNA using energy from ATP. Gyrase can also relax positive supercoils. Can also untangle DNA molecules. Also cuts DNA strands
A plant has a diploid chromosome number of 40. A TRISOMIC GAMETE would have ___ chromosomes.
Trisomic cell: 2n + 1 = 41 Trisomic GAMETE: n + 2 = 22 n = 20 Trisomic gamete would have 22 chromosomes. Trisomy is three copies -> I have copies, so I would add two copies. Hence n + 2 = 22
Patau Syndrome
Trisomy 13 Karyotype = 47, XX or XY, + 13
T/F Aneuploidy commonly causes an abnormal phenotype -> It leads to an imbalance in the amount of gene products
True
T/F It is only Klinefelter's syndrome if the organism is diploid and you inherited an extra X
True
T/F Aneuploidy of sex chromosome has less severe phenotypic effects than that of autosomes. Why?
True Because we have Barr Bodies on the X chromosome. The Y chromosome is too small and doesn't contain a lot of genes.
Chronic myelogenous leukemia
Tumor of certain white blood cells. Typically occurs in adults. 90% of patients have a reciprocal translocation. *t(9q, 22q)* t stands for translocation, 9q and 22q are the chromosomes involved. Results in larger 9 and smaller 22 chromosome. *Small chromosome is called a Philadelphia chromosome*.
Nondisjunction results in an uneven distribution of chromosomes during cell replication. If nondisjunction occurs during meiosis I, the homologous chromosomes do not separate. If nondisjunction happens in meiosis II, sister chromatids do not separate. If a cell has a diploid number of six (2N = 6) before meiosis, how many chromosomes will be in each of the four daughter cells if one pair of chromosomes experiences nondisjunction during meiosis I?
Two cells will have 4 chromosomes, two cells will have 2 chromosomes.
Reciprocal translocation
Two different types of chromosomes exchange pieces, thereby producing two abnormal chromosomes carrying translocations.
SMC protein? Describe two examples.
Two examples of SMC proteins are condensin and cohesin, which play different roles in metaphase chromosome structure. The function of condensin is to promote the proper compaction of metaphase chromosomes, while the function of cohesin is to promote the binding (i.e., cohesion) between sister chromatids.
Why does a female with one X chromosome exhibit a syndrome, knowing that if two X chromosomes are present one will be inactive?
Two weeks of fertilization -> you need two copies of X chromosome for development. Because the Barr body is not entirely inactive as well.
Deficiency
Used to describe a missing region of a chromosome.
Type I Topoisomerase
Usually monomeric proteins. Induce transient single-strand breaks into the double helix and changes supercoils one at a time
Terminal deletion
When a normal chromosome has broken into two separate pieces. The piece without the centromere is lost and degraded.
Metaphase chromosome are highly compacted
When cells prepare to divide, the protein filaments come closer together and form a more compact scaffold for anchoring the radial loops. This additional level of compaction greatly shortens the overall length of a chromosome and produces a diameter of 700 nm. End of prophase -> sister chromatids are heterochromatic. The overall size of a metaphase chromosome is much smaller than a chromosome territory found in the cell nucleus during interphase Structure of metaphase chromosomes determined by nuclear matrix proteins (scaffold forming) and by histones (needed to compact radial loops).
How to write karyotype
Write normal amount of chromosomes then comma sex chromosomes ex: 46, XX 46, XY
XYY individuals would most likely arise from nondisjunction in
XX x XXYY Separate normally in meiosis I and separate them differently in meiosis II
Fluorescence in situ hybridization
You can detect changes and see transmission of chromosomes
Amphidiploid
Zebroid
Allopolyploid
ex: Triticum aestivum, which is an *allohexaploid* Six sets of chromosomes and from three different species.
The more supercoiled it is...
faster it goes on a gel
Circular chromosomal DNA
~475 micrometers. -> Compaction -> goes to 40 micrometers -> supercoiled and looped -> 2 micrometers Supercoiling is independent of each other.
