Exam 4: Principles of Genetic Variation

Classical class I and class II HLA proteins are both highly polymorphic heterodimers polymorphic heterodimers that help lymphocytes to recognize peptide antigens but they differ in many ways. Which, if any of the following statements, is true?

The programmed rearrangements at immunoglobulin loci in B cells and in T-cell receptor loci in T cells that are required for antibody and T-cell receptor diversity are cell-specific. What precisely does that mean?

List three types of chemical reaction that cause damage to DNA, and illustrate your answer with examples.

List three ways in which an unrepaired double-stranded DNA break can be highly dangerous to the cell in which it occurs.

With reference to aberrant methylation of bases which of the following statements, if any, is false?

On the diagram below, identify the covalent bonds that break when hydrolytic attack results in deamination.

Our immunoglobulins, T-cell receptors and HLA proteins are thought to belong to one large superfamily of proteins based on their structures as well as their functions. In what ways do the structures of these three sets of proteins resemble each other?

What are the essential differences between base excision repair and nucleotide excision repair and what types of DNA damage are they dedicated to repairing?

Some of our DNA polymerases have a proofreading function. What is meant by this and how common is it.

List the major health consequences that arise as our DNA damage response and DNA repair systems become defective.

The C $\rightarrow$ T transition is, by some distance, the most common base substitution in human (and vertebrate) DNA. What makes it so common?

What is meant by balanced and unbalanced structural variation?

What is meant by non-classical DNA-dependent DNA polymerases? What roles do they play in our cells?

Most types of DNA damage are repaired by mechanisms that typically involves excising bases or nucleotides and then resynthesizing DNA. But certain types of DNA damage are directly reversible. Give two examples.

Outline the four broad classes of chemical damage to DNA.

Which, if any, of the following observations are consistent with the effect of purifying selection, and which, if any, are consistent with the effect of positive selection? a) Human populations that are accustomed to high-starch diets have comparatively higher copy numbers of the α-amylase gene. b) Telomere DNA sequences in vertebrates have tandem TTAGGG repeats c) Humans show very high levels of heterozygosity at the classical HLA loci. d) Human populations that live in more northerly latitudes have a high frequency of pale skin color. e) Human calmodulin and an ortholog in Drosophila each have 149 amino acid differences and differ at just four amino acid positions.

The human HLA-DRB1 and the chimpanzee Patr-DRB1 gene are orthologs. At the protein level, the human HLA-DRB1*0701 and HLA-DRB1*0302 alleles show 31 amino acid differences out of 270 amino acid positions. But human HLA-DRB1*0702 and the chimpanzee Patr-DRB1*0702 proteins are so closely related that they differ at only 2 positions out of the 270. What does the difference between these two pairwise comparisons tell us about the origins of HLA polymorphism?

Which, if any, of the following statements, is false? a) As a result of many post-zygotic changes in the DNA of our cells, each of us is a genetic mosaic. b) The vast majority of the post-zygotic DNA changes are random mutations. c) The vast majority of the post-zygotic DNA changes do not affect gene expression. d) Some post-zygotic DNA changes are programmed to occur in a very limited number of cell types.

On the diagram below, identify the covalent bonds that break when hydrolytic attack results in depurination.