8.23.16 Lecture

Question 1

Genetic variation defines ___ (phenotypic variation) and ethnic differences, provides us with markers of ___, and defines susceptibility to disease.

Answer 1

Inter-individual differences; disease

Question 2

What is the general format of mutation notation?

Answer 2

Type of sequence, nucleotide number, nucleotide, > replacement nucleotide

Question 3

What are the abbreviations for the 5 types of sequence?

Answer 3

g: genomic
c: cDNA
m: mitochondrial
r: RNA
p: protein

Question 4

The nucleotide is capitalized for which type of sequence? Lowercase for which type of sequence?

Answer 4

Genomic; RNA

Question 5

In introns, a mutation is noted as ___#, where the donor splice site G is assigned position ___.

Answer 5

IVS (Intervening Sequence); +1

Question 6

How are deletions and insertions notated?

Answer 6

By start and stop nucleotide # separated by _ then del or ins followed by affected nucleotides

Question 7

How are translated mutant sequences notated?

Answer 7

Original aa in 3 letter code, position in protein, replacement aa or X for stop codon

Question 8

What are polymorphisms?

Answer 8

Variant sequences (not necessarily deleterious) occurring at an allele frequency >1%

Question 9

What are the 5 types of typical polymorphisms?

Answer 9

1. Single nucleotide polymorphisms (SNP; 2 alleles)
2. Simple insertions or deletions (indols; 2 alleles)
3. Short tandem repeat sequences (STRP; 5+ alleles)
4. Variable number tandem repeat sequences (VNTR; 5+ alleles)
5. Copy number polymorphisms (CNP; 2 alleles)

Question 10

What are three examples of polymorphisms?

Answer 10

ABO, Rh, and MHC

Question 11

How are ABO blood groups defined?

Answer 11

By glycosyltransferase that adds either N-acetylgalactosamine residues (A) or D-galactose residues (B) or no sugars (O) to the H-antigen on RBC.

Question 12

What are the phenotypes, attached sugars, inheritances modes, and antibodies in serum for the 4 blood groups?

Answer 12

O - no sugar - recessive inheritance - anti-A, anti-B
A - N-acetylgalactosamine - dominant inheritance, anti-B
B - galactose - dominant inheritance, anti-A
AB - both types of sugar - co-dominant inheritance - neither

Question 13

What is the universal blood donor?

Answer 13

O

Question 14

What is the universal blood recipient?

Answer 14

AB

Question 15

The Rhesus factor, expressed on RBC, is encoded on chromosome ___. Mutations are inherited ___.

Answer 15

1; autosomal recessive

Question 16

What are the two Rhesus phenotypes, the corresponding presence of Rh-D polypeptide on RBC surface, mode of inheritance, and antibodies Rh-D in serum?

Answer 16

Rh negative - Rh-D polypeptide absent - recessive inheritance - antibodies to Rh-D present

Rh positive - Rh-D polypeptide present - dominant inheritance - antibodies to Rh-D absent

Question 17

What are MHC class I and class II and what do they do?

Answer 17

Major histocompatibility complexes; define expression of human lymphocyte antigen (HLA) needed to present antigen to specific T-cells.

Question 18

MHC complexes are encoded on which chromosome?

Answer 18

6p

Question 19

Matching ___ is pivotal for transplants.

Answer 19

HLA

Question 20

The MHC cluster is inherited as a haplotype - what does this mean?

Answer 20

These genes are mapped in close proximity to another another and are thus inherited together; very dense part of the genome, highly polymorphic, many alleles

Question 21

Disregarding crossing over, siblings have a ___ chance of sharing both alleles of the MHC haplotype.

Answer 21

25%

Question 22

Knowing ___ and ___ frequencies in a population allows us to calculate risk.

Answer 22

Genotype; allele

Question 23

What does the Hardy-Weinberg equilibrium do?

Answer 23

Describe the relationship between allelic frequencies and genotype frequencies in a stable population

Question 24

What is the Hardy-Weinberg equilibrium equation?

Answer 24

(p+q)^2 = p^2 + 2pq + q^2; p and q must remain constant, p + q = 1

Question 25

What is the Hardy-Weinberg equilibrium equation for 3 possible alleles?

Answer 25

(p+q+r)^2

Question 26

Disease frequency = ?

Answer 26

q^2

Question 27

How does the Hardy-Weinberg equilibrium change for sex-linked diseases?

Answer 27

Genotype frequency = allele frequency in males

Question 28

What are the 4 conditions necessary for Hardy-Weinberg Equilibrium?

Answer 28

1. Large population (not influenced by chance fluctuations)
2. Random mating (no preference based on phenotype similarities)
3. No mutation (no conversion of P allele to Q allele)
4. No selection (all genotypes are equally capable of mating/producing offspring)

Question 29

Generally, random mating means what 3 things?

Answer 29

1. No stratification (subpopulation exists that remains genetically separate)
2. No assortative mating (choice of mate determined by common trait)
3. No consanguinity

Question 30

What are the three major exceptions to Hardy-Weinberg equilibrium?

Answer 30

1. Gene flow: slow movement of genes between populations
2. Genetic drift: chance changes with the environment favoring a genetically defined subpopulation
3. Founder effect: small population with different allele frequency breaks away from general popualtion

Question 31

What is fitness?

Answer 31

Ability to procreate

Question 32

Reduced fitness occurs in conditions that affect the ability of diseased individuals to ___.

Answer 32

Procreate

Question 33

f (fitness) usually = ___ in dominant disease

Question 34

For a population in equilibrium, the new mutation rate (mu) = ?

Answer 34

sq; s (selection coefficient selection against mutation) = 1-f

Question 35

What is positive selection of heterozygotes?

Answer 35

In a balanced polymorphism, forces exist to remove affected alleles from the population as well as to maintain them. In this situation, equilibrium is affected by a heterozygous advantage favoring viability over homozygotes.

Question 36

What is an example of positive selection of heterozygotes?

Answer 36

Heterozygosity for sickle cell allele offers protection from malaria and beta-thalassemia

Question 37

What are AIMs?

Answer 37

Ancestry Informative Markers - alleles that show large differences among populations of different geographic origins