Genetics Exam 3 Notes, Quizzes and Homework Review

What are some likely causes of rearrangements?

DNA Damage (Chromosomal breaks) Repeated sequences throughout the genome play a role in rearrangements DNA polymerase can introduce deletions and duplications during replication DNA polymerase can skip and switch from one chromosome to another causing translocations

Can the Environment determine sex?

Yes, it's called Environmental Sex Determination

Chimerism

You may have someone else's genome in many of your cells! Cells with different genetic origins •Natural chimeras •Microchimerism •Artificial chimeras: organ transplants, animal-human-chimeras for research

If you're missing a chromosome

You're Dead.

The AYE locus (A a) is maternally imprinted.Expression of the rare defective allele acauses medical problems.This affected man has genotype Aa. Which allele is expressed and which parent did he inherit this allele from?

a, his father

Barr-bodies

'Mostly' inactivated (heterochromatic) X-chromosomes located on the nuclear membrane of mammalian cells containing more than 1 X chromosome.

You are investigating a crime scene, you gather DNA evidence, and compare the leading suspects DNA with the DNA on the murder weapon. When comparing the D12S391 VNTR allele from the 2 samples, you conclude that both the crime scene DNA and the lead suspect DNA are both homozygous for the 15 repeat allele, which is prevalent in 2.9% of the population. What is the probability that the genotype's are a match by random chance?

0.00084

Joe Schmo recently had a genetic analysis on his genome performed. It turns out his odds ratio for cardiovascular disease is 2.7 times greater than the average person. If the probability of getting cardiovascular disease is 2%, what is Joe Schmo's probability?

0.02 * 2.7 = 0.054 = 5.4%

If the mutation rate is 1x10-8 per bp per generation, how many mutations will a 200 kb segment acquire in 100 generations (~2,500 years)? (Answer using a numerical value with no units)

0.2

The SNP rs573014 is located in the BRCA2 gene. From the HapMap project website, we can see that in the CEU population (Utah residents with European ancestry), the frequency of the C allele is 0.74 and the frequency of the T allele is 0.26. What is the expected frequency of people heterozygous for this SNP in this population?

0.38

A man has a condition where all of his gametes undergo nondisjunction of the sex chromosomes in meiosis I, but meiosis II proceeds normally. He mates with a woman who produces all normal gametes. What is the probability that the fertilized egg will develop into a child with Turners syndrome (XO)? Assume that all gametes and zygotes are viable. (write your answer as a decimal, for example for 1/4 type 0.25)

0.5

Describe 2 different methods used for DNA fingerprinting.

1) The RFLP (Restriction Fragment Length Polymorphism) method utilizes restriction enzymes to cut an entire genome into fragments. Because of SNPs and VNTR polymorphisms, each individuals genome fragments will vary, and thus a unique genetic fingerprint can be created. To visualize these fragments they are separated by gel electrophoresis and subsequently transferred to nitrocellulose paper where the fragments can then be radio-labeled or fluorescently labeled and visualized via a technique called southern blot analysis. 2) The PCR method utilizes the PCR technique to amplify known VNTR sequences in the genome. Because VNTR sequences are quite variable in the population, assessing a number of VNTR locations (CODIS utilizes 13 VNTRs which are used in forensics) make it possible to uniquely identify an individual. The fragments of interest are PCR'd using known primers and the fragments are then run on a gel and the VNTRs can be identified by their size.

What is needed for a functional chromosome?

1. Signals recognized by DNA replication proteins ('origins' where DNA replication starts and 'telomeres' at the chromosome ends). 2. A 'centromere' signal that creates an attachment point for the fibers that pull replicated chromosomes apart in cell division. 3. Genes (Without a functional centromere and/or telomeres the chromosomes will be lost)

Two chromosomes have the following segments, where • represents the centromere: K L M • N O P Q R S T U V • W X Y Z Match the type of chromosome mutation with the chromosomal variations: 1.) K L M • N O P O P Q R S T U V • W X Y Z 2.) K L M • N O P Q R S T U V • W Z 3.) K L M • N O P Q R S T X Y U V • W X Y Z 4.) K L M • N O P R Q Q R S T U V • W X Y Z 5.) K L M • N O P Q R S T X W • V U Y Z 6.) K L M • N O R Q P S T U V • W X Y Z 7.) K L M • N O P Q R Y Z S T U V • W X 8.) K L M • N O P Y Z S T U V • W X Q R

1.) Tandem Duplication 2.) Deletion 3.) Displaced Duplication 4.) Reverse Duplication 5.) Pericentric Inversion 6.) Paracentric Inversion 7.) Nonreciprocal Translocation 8.) Reciprocal Translocation

Joe Schmo's odds ratio for colon cancer is 2.0 times greater than the average person. If his probability for getting colon cancer is 1.4%, what is the probability for the average person?

1.4% / 2.0 = 0.7%

How many biological ancestors did you have 10 generations ago? (Assume they were all different people.)

1024

Joe Schmo's SNP analysis shows that his risk of Colorectal Cancer is 2.10 times greater than average person. These numbers are the 'odds ratios' for his genotypes relative to the average person. The average risk of Colorectal cancer is 1.20%. What is Joe Schmo's risk of Colorectal cancer?

2.5%

The AYE locus (A a) is maternally imprinted. Expression of the rare defective allele a causes an affected phenotype. What is the chance that the child (?) will be affected?

25%

Trisomy

2n + 1

Monosomy

2n - 1

If the mutation rate is 1x10^-8 per bp per generation, how many mutations will a 1 Mb segment acquire in 400 generations (~10,000 years)?

4

The gene A locus has two common alleles (A1 and A2). The frequency of A1 = 70% and the frequency of A2 = 30%. What is the likelihood that an individual is heterozygous (A1A2)?

42%

HapMap tells us that people of African ancestry living in the Southwest USA have a 98% frequency of T and a 2% frequency of A at the rs1157699 SNP. What percent of these people are homozygous for the T allele?

96%

Which of the following statements are true? [CHOOSE ALL THAT APPLY]

A haplotype can refer to a short segment of a chromosome Examining SNP's on a haplotype can be informative about a person's ancestry

Genome-Wide Association Studies

A means of discovering which genotypic differences effect phenotypic differences of interest (disease, physical attributes, etc.) HapMap and SNP-typing made this possible. A genome-wide association study assigns each SNP a prediction for the phenotype ('odds ratio') SNP-phenotype connections identified by GWAS have made SNP-typing useful for an individuals risk assessment

20% - 40% of women with Turner Syndrome have an X chromosome derived from their father. Which of the following are potential causes of this situation? (Choose ALL that apply.)

A non-disjunction error in maternal Meiosis I. A non-disjunction error in maternal Meiosis II.

A human oocyte resulting from a non-‐disjunction event that occurred in meiosis I of the sex chromosomes, is fertilized by a normal sperm. What 4 possible outcomes could result for the developing embryo (in other words, what possible genetic abnormalities could result)?

A non-‐disjunction event in meiosis I of the sex chromosomes would leave the oocyte either with an extra X or not X's. The 4 possible outcomes in the fertilized embryo would be as follows XXX: Female w/ extra X (2 barr bodies) (Called Triple-‐X syndrome) XXY: Male w/ extra X (1 barr body) Klinefelter Syndrome X0: Female w/ only 1 X (no barr bodies) Turner's Syndrome Y0: Embryonic Lethal

Non-allelic homologous recombination

A recombination event that occurs in the wrong place between chromosomes Between repeated sequences that are not alleles In meiosis or as a consequence of DNA damage Creates deletions and duplications

A man is found to have two X chromosomes and no Y chromosomes. DNA testing (by PCR) reveals that he has a functional copy of the SRY gene. How could this situation have arisen? (Choose ALL that apply)

A translocation of a segment of the Y chromosome in his father

Repeated sequences throughout the genome play a role in rearrangements

A60 kb segment of one human chromosome These repeats can be found on every human chromosome

You carry a rare allele that is maternally imprinted. You have a son and a daughter, both of whom are expecting little ones in the very near future. a) What is the likelihood that your children's children will express the rare allele if they are both boys? b) What is the likelihood that your children's children will express the rare allele if they are both girls?

ANSWER (A): Because it is maternally imprinted, your daughter's son will have 0% chance of expressing the allele. You son's son will have a 25% chance (½ * ½). ANSWER (B): Because it is maternally imprinted, your daughter's daughter will have 0% chance of expressing the allele. You son's daughter will have a 25% chance (½ * ½).

In gel electrophoresis, which of the following DNA fragments would travel the farthest distance from the sample well?

AT (The smaller it is, the farther the distance)

Variable Number Tandem Repeats (VNTRs)

Allows for PCR based DNA fingerprinting Our genomes consist of many regions with tandem repeats that differ significantly between individuals. 5 Different alleles in the population for a VNTR locus Individuals can easily be distinguished by PCRing these regions and subjecting the fragments to gel electrophoresis VNTR loci are a result of mutations which change the repeat number

Chromosomal Rearrangements

Alteration of gene loci within or between chromosomes.

You have discovered a gene that enables organisms to accumulate gold in their tissues by concentrating trace amounts found in normal soil. You want to transfer this gene into a plant. Order the steps below that would accomplish this.

Amplify the gold gene with PCR. Digest the gold gene and a Ti plasmid with appropriate restriction enzymes. Insert the gold gene into the Ti plasmid. Transfer the recombinant Ti plasmid into Agrobacterium tumefaciens. Infect the plant with the Agrobacterium strain. Use a selectable marker to identify plant cells that have integrated the recombinant plasmid into their genome.

The HapMap project provides

An extensive, freely available SNP consortium

Genomic Imprinting

An extreme form of epigenetic regulation inherited from your parents.

Genetic Testing can be used in which of the following ways? [CHOOSE ALL THAT APPLY]

Ancestry Pharmaceutical Toxicity Pharmaceutical Efficacy Disease Diagnosis Disease Screening

One segment of chromosome 15 includes genes that are paternally imprinted and genes that are maternally imprinted. Inherit deletion from mother => Inactive alleles from father => ?

Angelman Syndrome

You are a breeder of animals with an X-linked coat-color gene, one allele of which gives black fur and another of which gives white fur. If you cross a black-colored female with a white-colored male, what would their male and female offspring look like (hint: remember what a Barr body is and how Barr body formation could affect this phenotype)?

Answer: Their male offspring would be all black, while their female offspring would be mottled, owing to X-inactivation: XbXb × XwY → males: XbY (black) females: XbXw (some fur patches black, some white)

Which of the following statements regarding non-disjunction are true? [Choose all that apply]

Autosomal non-disjunction is more common in females than in males. Sex chromosome non-disjunction is more common in males than in females.

Brad and Janet have a child with Down syndrome. Haplotype analysis of a chromosome 21 segment of the parents show that Brad is C/J, and Janet is K/M. Which of the following haplotypes are possible for the child? (The analysis cannot detect the number of copies of each haplotype.) (Check ALL that apply)

C/M J/M C/K/M C/J/K

Cells that are aneuploid due to mis-segregation are often

Cancerous

Polyploidy is common in plants: Tetraploid plants are usually large and robust In agriculture, polyploidy is often induced using mitotic inhibitors

Cells are larger and thus fruit is larger. Absolute gene dosage is doubled, but relative gene dosage is normal.

Genetic Test

Check for common mutations in one or a few known genes •PCR or a specially designed DNA-typing chip •Widely available, relatively inexpensive Check for rare or unknown mutations in one or a few known genes •By DNA sequencing of one or more genes •Less widely available, quite expensive

NHEJ Repair can

Create deletions, inversions, and translocations

Synteny (look this word up!) is disrupted by which of the following? (Choose ALL that apply)

Deletions Duplications Inversions Translocations

Viable Human Trisomies of autosomes

Down Syndrome (Trisomy 21) Patau Syndrome (Trisomy 13) Edwards Syndrome (Trisomy 18)

Viable aneuploidies:

Down syndrome (trisomy 21), trisomies 13 and 18, and especially Turner syndrome are often mosaic.

Restriction enzyme

Enzymes that cut a DNA molecule at a particular sequence.

Summary of the causes of Chromosome Rearrangements

Errors by DNA polymerase can create/delete repeats and template switching can create translocations. Non-allelic homologous recombination (NAHR) and Non-homologous end-joining (NHEJ) can result in deletions, duplications, inversions, and translocations. Transposable elements create insertions and cause gene disruptions. The creation of Non-functional chromosomes lacking telomeres or centromeres will be lost over generations as will the accompanying genes. Rearrangements can be of little consequence if chromosomes are not lost and novel joints are in non-gene regions. Disruptions in the novel joint can lead to hybrid genes (either good or bad). Rearrangements affect meiosis and can lead to infertility.

Diploid gametes can result from

Errors in meiosis I Errors in meiosis II

True or False Every somatic cell inside your body has the exact same genome.

False Many cells are mosaic (meaning mutations have accrued making their genomes different from the initial genome inherited in the fertilized embryo). It's also possible you could be chimeric for someone else's genome.

True of False Because of the high demand, DNA sequencing is much more expensive now than it was 10 years ago

False Next gen sequencing has driven the cost down dramatically

True or False The B gene locus is maternally imprinted. You inherit allele B from your mother and allele b from your father, therefore you will express the B allele inherited from your mother.

False no, you will express the b allele that you inherited from your father since the B allele you inherited from your mother is imprinted in you (inactivated/turned off).

True or False Cells within the same organisms are capable of differentiating into specific cell types because they are able to select which genes they inherit from stem cells.

False No, they all in theory inherit the same genes (genomes), however they express these genes differently depending on their local environment (i.e. hormones and other cell signaling turning on/off genes/transcription factors)

True or False An extra chromosome in a diploid organism is generally not problematic, but a missing chromosome is generally very problematic.

False, both will be problematic. One reason being that they both will alter gene dosage which will affect biochemical pathways/cellular processes.

True or False Males are XY and females are XX for all sexually reproducing animals.

False, there are numerous types of sex determining mechanisms in the animal kingdom.

Platypus Sex Determination (an unusual phenomenon)

Females = 10 X's Males = 5 X's & 5 Y's

Sex Determination - XX-X0 System

Females = XX Males = X0

Sex Determination - XX-XY System

Females = XX Males = XY

Sex Determination - ZZ-ZW System

Females = ZW Males = ZZ

Triploidy can arise via

Fertilization of haploid to a diploid gamete Double fertilization

Which of the following is not a useful genomic marker typically utilized to differentiate individuals in forensic testing?

GFP

Which of the following methods are often employed to assess gene function? [CHOOSE ALL THAT APPLY]

Gene knock-in CRISPR/Cas9 gene editing RNAi Gene knock-out

Mammals turn off one copy of the X chromosome in females. What occurs during transcription?

Genes for male-specific transcription factors stay off. Female tissues develop. (NO SRY) Male-specific transcription factors are on. These turn on genes causing male tissue development. (SRY IS ON)

If a small region of a chromosome containing a non-essential gene is completely deleted, and an organism has two identical chromosomes with this deletion, then the organism

Has no alleles of that gene.

Aneuploid

Having an incomplete or overcomplete set of chromosomes Any deviation from a euploid

Euploid

Having complete set(s) of chromosomes Nothing more and nothing less n, 2n, 3n, etc where n = complete set Humans n = 23, Drosophila n = 4, etc.

Polyploid

Having more complete sets of chromosomes than an ancestor Triploid (3n), Tetraploid (4n), Hexaploid (6n), Octaploid (8n)

Susan has an older brother and a younger sister. Whose cells might she be microchimeric for? (Choose all that apply.)

Her mother Her brother

Which of the following are forms of or mechanisms of epigenetic regulation? (CHOOSE ALL THAT APPLY)

Histone Methylation Cytosine Methylation Genomic imprinting

Which of the following characteristics is not an important feature of a cloning plasmid in traditional restriction cloning?

Histone Proteins

Complete polyploidy is often lethal and thus rare in animals

However, animal somatic cells are often polyploid (especially 'terminally differentiated' cells).

Why are sex chromosome aneuploidy more likely to be viable?

Mammals already have a gene dosage mechanism in place to account for differing sex chromosomes Nondisjunction between the X and Y chromosomes in male meiosis I is more common than other aneuploidies Meiotic errors arise more often in the mother than the father, and increases with maternal age

True chimerism:

Individuals containing cells that originated from different zygotes.

Transposable elements create

Insertions and Gene Disruptions

Human gene expression has been optimized over evolutionary time and is dependent on how many copies of the genome?

It is dependent on 2 copies of the genome.

Mosaics for aneuploidies:

Many aneuploidies that are non-viable when present in all cells are viable when present in only a subset of cells.

Edwards Syndrome (Trisomy 18)

Many severe physical defects

Patau Syndrome (Trisomy 13)

Many severe physical defects

Epigenetics

Mechanisms of gene regulation that can be stably inherited through mitosis and (sometimes) meiosis, but can be established and released without changing the DNA sequence.

Why do reciprocal translocations cause infertility? (Choose ALL that apply)

Meiotic Errors

Which of the following techniques are capable of detecting SNPs? [CHOOSE ALL THAT APPLY]

Microarray Sequencing

Aneuploidy can arise by

Mitotic Errors Meiotic Errors

What are some likely causes of polyploidy?

Mitotic errors can double ploidy Meiotic errors can cause polyploidy Fertilization error can cause polyploidy

Down Syndrome (Trisomy 21)

Moderate and variable physical defects and mental retardation

Name and describe all of the known complete human monosomic conditions.

Monosomy X is the only one (Turner Syndrome X0) All other monosomies are embryonic lethal.

If you've got an extra chromosome

Most of the time, you're dead.

Mosaicism

Most of your cells really aren't diploid!!! Within an organism, theoretically all the cells should have the same exact genetic material, but in reality most cells in an adult deviate from the genome contained in the original fertilized embryo due to mutations accrued over time. •Somatic mutations make us all mosaic •Chromosomal mosaicism is common •Many tissues are normally mosaic

In predicting our ability to detect ancestral sequences, what one important factor have we neglected?

Mutation

You decide to send your DNA to get a DTC (direct to consumer) genetic test and find out that almost all of the sequence variants found in your exome were already known from other studies. However some variants had not been reported previously. Which of the following statements are likely explanations for these? (Choose ALL that apply.)

New mutations that arose in the germline of one of your grandparents SNVs from previous ancestors

Genic Sex Determination

No sex chromosomes, genes determine sex

A woman with normal vision, whose father has sex-linked color blindness, marries a man with normal vision. They have a son who has Klinefelter syndrome and is color blind. Describe precisely what kind of event could have caused his Klinefelter syndrome.

Nondisjunction must have occurred in the mother during meiosis II, when sister chromatids normally separate. With Klinefelter syndrome, the boy has an XXY karyotype. Since both of his X chromosomes contain the allele for color blindness, he likely has two copies of one homolog of his mother's X chromosome containing the allele for color blindness.

Consider a specific VNTR allele present in a woman who lived 300 years ago. Her VNTR allele has been inherited by 250 descendants alive today, by way of 150 now-deceased descendants. Assuming a VNTR copy number mutation rate of 10-3 per generation, how many new length variants of this allele would be found among these descendants?

None

NonHomologous End Joining (NHEJ)

Occurs during repair of double stranded DNA breaks When DNA is damaged and single strand breaks occur it's not a big deal, DNA repair enzymes can fix them easily. When DNA is damaged and double strand breaks occur, chromosome fragments are created. Without sequence complementarity, double stranded breaks have no guide for repair. The correct ends can join, but so can incorrect ends.

SNPs

Our genomes vary from our neighbors by 1 in 1000 nucleotides and many of those differences are at a single nucleotide. Allows for fingerprinting via Restriction Fragment Length Polymorphism (RFLP) analysis

Which of the following techniques will not assess gene expression?

PCR

The recognition sequences for many restriction enzymes are

Palindromic.

Which of the following statements are true concerning modern day farming and agriculture?

Polyploid plants tend to have larger and more robust fruit. Polyploidy in plants is induced by treating plants cells with drugs that disrupt mitosis.

One segment of chromosome 15 includes genes that are paternally imprinted and genes that are maternally imprinted. Inherit deletion from father => Inactive alleles from mother => ?

Prader-Willi Syndrome

Which of the following reasons could explain why a monoploid individual does not survive? (Choose ALL that apply)

Recessive lethal mutations cannot be masked by dominant alleles. They do not have the appropriate absolute gene dosages.

Tetraploidization can

Restore fertility to an infertile diploid hybrid plant

2 individuals are suspected to have ancestral history with one another. What type of genetic analysis could provide strong evidence to support this claim?

SNP analysis of haplotypes throughout the genome would provide this evidence. The larger the spans of DNA sequences that show identical SNPs between the individuals, the more closely related the individuals are.

Microarrays (DNA-Chips) perform millions of experiments simultaneously

SNP-Chips are specialized microarrays that are capable of genotyping ~106SNP positions from one individual.

Cytosine methylation of DNA in human cells usually results in: (Choose all that apply)

Silencing of transcription

The restriction enzyme HindIII cuts DNA at the 6-base recognition sequence 5'-AAGCTT-3'. Calculate the frequency of occurrence of this sequence. (Assume a 40% GC content.) (Input your answer as a numerical value, not a percentage or fraction. For example if your answer was 1/4 you would input 0.25--NOT 25 or 25%)

Subtract 40 from 100, this would be what percent AT have since the 40 is given. Since AT is 60, A by itself is 30. After that, it will be 30/100 x 30/100 x 20/100 x 20/100 x 30/100 x 30/100 = 0.000324.

Some genes that are expressed in the fetal stage are never expressed again in that individual's life. What do you think is the most common mechanism for preventing the expression of such genes (HINT: consider what mechanism would require the least maintenance)?

Such genes are permanently silenced, typically via heterochromatic packaging. This is more efficient than relying on repression or post-transcriptional regulation.

Which of the following is NOT a way in which gene expression is regulated in our cells?

Targeted Mutation Control

Haplotype

The 'haploid genotype' of a short segment of a chromosome The 'haploid genotype' of a short segment of a chromosome that has been inherited intact from an ancestor.

The restriction enzyme SmaI cuts DNA at the 6-base recognition sequence 5'-CCCGGG-3'. Calculate the frequency of occurrence of this sequence. (Assume a 50% GC content.) (Input your answer as a numerical value, not a percentage or fraction. For example if your answer was 1/4 you would input 0.25--NOT 25 or 25%)

The 6-nucleotide sequence would then occur with a frequency of (1/4)^6, which would equal 0.0002.

The Y chromosome carries what?

The Y chromosome carries a few of those critical genes located on the X as well as critical genes for maleness (SRY gene).

Rearrangements are usually harmless to the cell and individual provided the following are true

The altered chromosomes segregate appropriately at the next mitosis. No genes have been lost (on fragments lacking a centromere or telomere). The novel joint(s) (location where the 2 segments break and reconnect) does not disrupt a gene.

In 60-80% of women with Turner syndrome, their one X chromosome came from their mother. In 50% of men with Klinefelter syndrome, one of their X chromosomes came from their father. In which parent were the errors that caused the aneuploidies in these men and women?

The errors were in paternal Meiosis I for Klinefelter & either I or II for Turner.

This is a two-part question about single-gene genetic testing. Huntington's disease is a severe neurodegenerative disease caused by an autosomal dominant mutation in the HTT gene. One exon of this gene contains a variable number of tandem CAG repeats (each specifying glutamine). When the number of glutamines in this part of the protein exceeds 36 the protein's function is altered, causing the symptoms of Huntington's by a poorly understood mechanism. These mutant alleles have high penetrance - people with these alleles almost always get the disease. A woman with two siblings who have Huntington's is considering having children; she does not want them to have Huntington's disease. Since the symptoms of Huntington's don't often appear until mid-life, the woman does not know if she has the mutated HTT allele. Her doctor orders a genetic test of this gene. Part 1: How should her DNA be analyzed? (Choose all that apply.) Part 2: What information will the test provide? (Choose all that apply.)

The length of the CAG repeat segments in both alleles should be determined. Whether the woman has a mutated HTT allele. Whether the woman will likely develop Huntington's disease.

The majority of the X genes are only carried where?

The majority of the X genes are only carried on the X and there must be a mechanism to normalize gene dosage between the sexes!

DNA methylation is

The most common mechanism of genomic imprinting

The PCR based method

The predominant mode of analysis CODIS analysis of 5 markers from an individual Automated capillary electrophoresis has made the analysis fast and nearly error free

The Combined DNA Index System (CODIS) is used

To specifically identify individuals 13 VNTR DNA loci Highly polymorphic (quite variable) in most populations On many chromosomes

Regulation of Gene Expression

Transcriptional control can be 1)Sequence independent •Epigenetic •Stable 2)Sequence dependent •Less Stable •More dynamic

mRNA regulation can be achieved at the level of (Choose ALL that apply)

Translation Life span (degradation) Processing Transport.

Which of the following chromosomal rearrangements have the potential to disrupt genes and/or gene expression. [Choose all that apply]

Translocations Duplications Deletions Inversions

Down Syndrome is the result of an extra chromosome 21. Which of the following terms describes this type of condition.

Trisomy

True or False Genomics integrates genome sequencing with bioinformatics to understand the function of the genome

True

True or False Given the Hardy-Weinberg equation of (p^2 + 2pq + q^2). The 2pq represents the percent of the population that is heterozygous at a given locus.

True

True/False Most biochemical pathways involve genes contained on many chromosomes.

True

True or False A single microarray can assess the expression of millions of genes simultaneously.

True Other types of microarrays are capable of assessing millions of SNP's simultaneously

Two common sex-chromosome aneuploidies in humans:

Turner Syndrome in Women (45 XO) Klinefelter Syndrome in Men (47 XXY)

A plasmid used as a cloning vector in E. coli must have

Unique restriction sites An ori sequence A selectable marker.

In triploid meiosis chromosomes are

Unpaired or Mispaired

There are many critical genes located on the X chromosome, how many X's must we all have at least?

We all must have at least 1 X.

Which of the following helps explain why DNA can be used as forensic evidence? [Choose all that apply]

We shed thousands of skin cells every minute. DNA is very stable. We have techniques in the lab that can reliably copy even tiny amounts of DNA. Each cell that we shed has enough genetic material to identify us.

Which of the following would be suitable techniques to assess the protein levels in a sample (Choose all that apply)?

Western Blot ELISA

When is testing a single gene relatively inexpensive? (Choose all that apply)

When there's a large market for the test When it's a common mutation in livestock

Which of the following are valuable resources that HapMap provides? (Choose all that apply.)

Where SNPs are located in the genome. The frequencies of SNP alleles in different populations.

Almost all females mammals have patches of cells with different active X chromosomes. Calico Cats are XOXo.

XO allele is black Xo allele is orange Almost always female (XXY males are the exception).

Assuming a GC content of 50%, what would be the average sized fragment of a DNA molecule exposed to the restriction enzyme SpeI that cuts the DNA sequence ACTAGT?

~4,000 bp

If the mutation rate is 1x10-8 per bp per generation, how many mutations will a 10 kb segment acquire in 400 generations (~10,000 years)?

less than 0.1

Which of the following techniques/technologies are capable of assessing gene expression? (Choose all that apply)

qPCR ELISA Microarray RT-PCR Western Blot Northern Blot

Functions of Gene Regulation

•All our cells contain the same genes. •Different cells and tissues differ in which genes they express. •These differences are created and maintained by gene regulation, not by changes in DNA sequence. •Some gene regulation has evolved to respond fluidly to changing conditions within the lifetime of a single cell. •Other regulation needs to be stable.

Haplotype Summary

•Ancestral Haplotypes can be passed down for many generations. •Random recombination shortens ancestral haplotypes over generations, but short haplotypes are stable over many, many generations. •Mutations can change ancestral haplotypes, but the effect is small over thousands of years. •The polymorphisms on these haplotypes can be used to determine relatedness. •These haplotypes within populations can give us insight into inheritance of complex traits.

Functions of epigenetic regulation

•Cells that are terminally differentiated •Specialized progenitor cells => Stem cells that give rise to specific cell types. •Stably differentiated dividing cells. •X inactivation. •Genomic Imprinting (more on this later).

Impact of chromosomal rearrangements on genes and genomes

•Changes in genome size - Gene duplications, Gene deletions •Infertility (gametes with chromosome errors) •Gene disruptions - Breaks occur within genes •New hybrid genes - 2 genes regions fusing together.

Summary of Recombinant Techniques

•DNA makes great evidence as it is stable, unique, and hard to get rid of. •2 Common DNA fingerprinting methods include the RFLP (utlizing SNPs and restriction enzymes) and PCR-based methods (utilizing VNTRs). •By analyzing many VNTRs one can be certain of an individuals identity. •The Hardy-Weinberg Principle can be applied to DNA fingerprint analysis

Novel Joints and their consequences

•If the joint is in a non-gene region, it's of minimal to no consequence. •If the joint is in a gene, it can alter gene function! •Fusing a gene with a non gene region => Non-functional gene •Fusing 2 genes in opposite directions => Non-functional genes •Fusing 2 genes in the correct orientation ? •Hybrid genes can arise!

Summary of Genome Wide Association Studies

•Microarrays such as SNP-chips provide a means to collect genomic information cheaply and quickly. •The HapMap project provides free access to a global consortium of known SNPs in several populations all over the world. •GWAS associates phenotypic differences with genotypes (odds ratios)

Aneuploidy Summary

•Often seen in terminally differentiated cells. •Many cancers are aneuploid. •Complete aneuploids arise by errors in meiosis I or II. •More often in the mother, due to prolonged oocyte arrest in Meiosis I. •Most are inviable (except 13, 18 and 21). •Risk increases with maternal age. •Sex-chromosome aneuploidies are well-tolerated due to X-inactivation. •Turner and Klinefelter Syndromes are common sex-chromosome aneuploidies.

Summary of Polyploidy

•Polyploids have more complete sets than their ancestor •They arise by mitotic and meiotic errors and by mating of related species •Usually inviable in mammals but are very common in plants •Polyploids are valuable for farming as they are large and robust. •Triploids are infertile because of chromosome mispairing in meiosis.

What are the chances that 2 individuals could have the same genotype at random?

•Siblings have 1 in 70 million chance. •Unrelated individuals have less than 1 in a trillion chance. •The Hardy-Weinberg Equation can be used to calculate this.

Just how stable (or unstable) are VNTRs?

•The repeat-number mutation rate for VNTR loci was 1×10−3 per gamete per generation •95% of mutations were gains or losses of one repeat •Repeat gains were more frequent than losses •Longer alleles were more mutable •4 times as many mutations occurred in males as in females

Summary for Genetic Testing

•They can test for the presence of known mutations associated with diseases/syndromes •Diagnostic •Screening => Odds Ratio •Some are gene-specific others are gene panels. •Often used to test the health of a baby during pregnancy as well as for in vitro fertilization. •Can be used to determine pharmaceutical efficacy and toxicity. •Can help explain the cause of an unknown disease/disorder. •Most genetic test must be prescribed by a doctor, but Direct-To-Consumer (DTC) tests are starting to emerge. •Used to study ancestry.