Exam 7: Genetic Variation Producing Diseasecausing Abnormalities in Dna and Chromosomes

The number of cell divisions needed to make human gametes differs extensively between men and women and also between different men. Explain these differences.

Interpret the following examples of chromosome karyotypes. a) 47,XX,+mar. b) 45,XY,der(13;14)(q10:q10) . c) 46,XX,del(15)(q11q13). d) 46,XY,t(3;17)(q26q23)

Give two examples of genes where loss-of-function and gain-of-function mutations result in different disease phenotypes.

Which, if any, of the following statements is false?

What is the major natural role of the nonsense-mediated decay mechanism in our cells?

Regarding chromosome nomenclature, explain the following terms: a) distal b) proximal c) acentric chromosome d) derivative chromosome

What is meant by aneuploidy, and how does it occur?

Fill in the blanks using numbers. Depending on our ethnic background, each of us carries about ___1___or so mutations that would be expected to result in loss of gene function (with an average of ___2____ genes that are homozygously inactivated), plus about ____3____ missense variants that severely damage protein structure. When you factor in additional mutations in noncoding DNA, a normal person might be expected to have a total of over ____4____ damaging DNA variants.

Genetic variation can cause disease by causing a gene product to have an altered sequence of amino acids or ribonucleotides, or by altering the amount of gene product that is made. Describe the different ways in which genetic variation leads to a change in the amount of gene product.

Two groups of human disorders involve expansion of tandem trinucleotide repeats in coding DNA to give gene products with abnormally long polyglutamine or polyalanine repeats. The pathogenic mechanisms have rather different characteristics, however in the way that the trinucleotide repeats expand. In what ways do they differ?

What is a synonymous substitution and when does it not mean a silent mutation?

In terms of its contribution to pathogenesis which of the following mutant proteins is the odd one out, and why is it the exception?

How can a missense mutation with a dominant-negative effect result in greater loss of protein function and more severe disease than a full length gene deletion at the same gene locus?

Match the descriptions of a type of mutation given in a) to d) with one of the possible mutations listed in i) to iv).

Fill in the blanks using single words or with one or two letters. The most commonly used method in human chromosome banding is known as ___1___-banding, when the chromosomes are treated with trypsin and then stained with the ____2____ dye. The ____2____ dye binds preferentially to ___3____-rich regions in DNA and the staining produces a series of alternating ____4____ bands that are ____2___-positive and ___3____-rich and ____5____ bands that are ____2___-negative and ___6____-rich. The ____4____ bands have a generally ____7____ content of genes, whereas the ____5____ bands have a ____8____ content of genes.

Regarding mutations, which of the following statements, if any, is false?

Concerning disorders resulting from unstable expansion of tandem oligonucleotide repeats, which, if any of the following statements is false.

"The pathogenesis of sickle cell anemia is due to aberrant protein aggregation. Explain how.

Why should cysteine be the least mutable amino acid?

The genetic code that is used in our mitochondrial differs from the "universal" genetic code in the case of four codons. What are these codons and how does their interpretation differ between nuclear DNA and mitochondrial DNA?