Foundations 1 Week 3 Flashcards
If a given allele frequency is represented as x, what is the genotype frequency of being homozygous ‘not x’?
(1-x)^2. The allele frequency by definition of being ‘not x’ has to be 1-x; therefore, the genotype frequency of being homozygous for ‘not x’ is (1-x)^2.
What is the difference between penetrance and expressivity?
Penetrance is the proportion of people with a certain allele (allele frequency) who actually have a phenotype, while expressivity is a measure of degree to which the phenotype or trait is expressed.
In Tay Sachs Disease, a homozygous mutation in the HEXA gene abrogates the function of hexosaminidase A. However, antibodies recognizing a subunit of hexosaminidase show ample levels of the subunit even in Tay Sachs patients. How might this be possible?
Hexosaminidase A is made up of an α subunit (encoded by HEXA) and a β subunit (encoded by HEXB) to form a heterodimer; thus, an antibody that recognizes the β subunit would still detect presence of the protein in Tay Sachs patients, who have hexosaminidase B protein present (β homodimer), but no hexosaminidase A.
Deficiencies in galactokinase and galactose-1-phosphate uridyl transferase impair galactose metabolism, but their phenotypes are highly different. Why is deficiency of galactokinase much less toxic in comparison?
Loss of galactokinase also results in build-up of galactose but not in the build-up of gal-1-P, which causes liver damage and anemia.
A nonsense mutation in a gene encoding a component of a structural protein impedes the function of the protein. If this gene is autosomal, what is the most likely phenotypic pattern of inheritance of this mutation and why?
This would most likely be a dominant negative mutation that by definition must have an autosomal dominant pattern of inheritance. The presence of a single copy of this mal-functioning component is enough to affect the structure of the final protein, thus effecting a phenotype.
What is the difference between dominant negative mutations and haploinsufficiency?
Dominant negative refers to a mutation in which the defective copy of the gene interferes with the function of the unaffected copy of the gene. Haploinsufficiency refers to when the unaffected copy of the gene alone is not enough to produce a wild type phenotype.
Of the three most common autosomal trisomies, which has the lowest incidence?
Trisomy 13
Which of these strategies are more likely to promote double strand break repair through homologous repair rather than non-homologous end joining? a) Nicking only 1 strand rather than both b) Arresting the cell at interphase and introducing the double strand breaks then c) Using CRISPR rather than zinc finger nucleases or TALENs d) Including template strands in the reaction
D. Inclusion of a template strand increases the chances of homology directed repair which depends on the presence of a template. Nicking only 1 strand will promote a different mode of DNA repair entirely. Arresting the cell at interphase is more likely to promote NHEJ; HDR has a greater chance of occurring during the mitotic phase. The basic forms of all 3 mechanisms generate double strand breaks without influencing the rate of NHEJ or HDR occurring.
What is the function of the guide RNA during CRISPR-Cas9 gene editing?
The guide RNA is homologous to the target sequence of Cas9 cleavage, thus giving the enzyme its specificity of targeting
How do the phenotypes of the sons and daughters of a father with an X-linked dominant allele differ from a father with an X-linked recessive allele?
For an X-linked dominant allele, all daughters will be affected but no sons will be affected. For an X-linked recessive allele, all daughters will be carriers and none of the sons will be affected.
