Genetic Variation

Question 1

Isozymes

Answer 1

Distinguishable proteins (sequence based) with the same or similar enzymatic activity (substrate specificity)

Question 2

Isoforms

Answer 2

Proteins with similar functional and/or structural properties that may be derived from different genes or from alternative splicing/post-translational modification of the same genes.

Question 3

Polymorphism

Answer 3

Occurrence of two or more allelic traits in a population with frequencies > 1-2% (relatively stable; can’t be accounted for by new, random mutation)

Question 4

single nucleotide polymorphisms (SNPs)

Answer 4

• Substitution of one base for another
• Synonymous/conservative = no change in AA but can still mess with splice sites, TF factor binding, or other mechanisms that rely on nucleotide sequence
• VERY common: every 100-200 bp

Question 5

Heterozygosity

Answer 5

• Nucleotide on one allele different from the nucleotide on the other allele (for almost all genes, both alleles are expressed)

Question 6

How frequent is heterozygosity?

Answer 6

Every 250-500 bp (up to 6-12 million sites in an individual)

Question 7

Disease predisposition

Answer 7

Polymorphism that leads to susceptibility for disease under certain conditions

Question 8

How are polymorphisms detected at the protein and genetic levels?

Answer 8

Protein: electrophoretic mobility, Km, thermostability, biophysical properties

Gene: exon sequencing (SNPs and STRs)

Question 9

Short Tandem Repeats (STRs)

Answer 9

Microsatellite regions consisting of 2-6bp sequences repeating 3-100 times.

Length of STRs associated with the presence of certain polymorphisms

Question 10

What are the possible consequences of polymorphism?

Answer 10

• No phenotypic effect
• Normal variation
• Disease susceptibility
• Disease (if monogenic)

Question 11

Principle of Segregation

Answer 11

Sexually reproducing organisms possess genes that occur in pairs but only one member of this pair is transmitted to offspring

Question 12

Principle of Independent Assortment

Answer 12

Genes at different loci are transmitted independently

Question 13

Dominance and recessivity

Answer 13

The effects of one allele may mask those of another allele

Question 14

Genotype frequency

Answer 14

Number of heterozygotes or homozygotes in a population

Question 15

Allele frequency

Answer 15

Number of times an allele is present (+2 for homozygotes and +1 for heterozygotes) out of the total number of alleles in a population (2n)

Question 16

Hardy-Weinberg Principle

Answer 16

In an ideal population the relative proportions of different genotypes remain constant from one generation to another

Question 17

Hardy-Weinberg Equations

Answer 17

p^2 + 2pq + q^2 = 1 and p+q=1

Question 18

What do p and q represent?

Answer 18

Allele frequencies (dominant and recessive)

Question 19

What do p^2, 2pq, and q^2 represent?

Answer 19

Genotype frequencies (homozygotes and heterozygotes)

Question 20

False Assumptions of Hardy-Weinberg

Answer 20

• Random mating (stratification, assortative mating, consanguinity)
• Constant allele frequencies (genetic drift/founder effect, gene flow, mutation and selection -> heterozygote advantage)

Question 21

Linkage

Answer 21

Two loci are considered linked if they are transmitted together; probability of being transmitted together depends on physical distance between the loci

Question 22

What are the 3 ways two loci can be related in terms of linkage?

Answer 22

• Unlinked: nonrecombinant = recombinant
• Completely linked: nonrecombinant only
• Partially linked: nonrecombinant > recombinant

Question 23

Recombination frequency

Answer 23

Percent recombination seen between two loci in a large series of meioses; can infer distance between two loci

Question 24

Genetic distance

Answer 24

• Unit measure of recombination (centiMorgan)

- 1 crossing over/100 meioses = 1% recombination = 1 cM ~ 1Mb

Question 25

Determining phase

Answer 25

Figuring out which alleles came from which parents

Question 26

Haplotype

Answer 26

combination of alleles on each chromosome

Question 27

Linkage analysis

Answer 27

Can be used to trace the inheritance of one trait (or disease) by presence of a linked trait and to identify unknown disease genes in a family

Question 28

Logarith of the odds

Answer 28

• Used to determine the likelihood that two loci are linked
• Equation: log of (likelihood of observing pedigree data if the loci are linked at a particular recombination frequency) / (likelihood of observing pedigree data if the loci are unlinked - recombination frequency = 0.5)
• LOD > 3 means 1000x more likely that the loci are linked than that they are associating by chance

Question 29

Linkage disequilibrium

Answer 29

• Non-random association of alleles at different loci

- Blocks of polymorphism inherited together, though you would expect lots of recombination between them

Question 30

Genome wide association studies

Answer 30

• Test for altered frequencies of particular alleles or haplotypes in affected individuals compared with controls
• Examines particular alleles or haplotypes for their contribution to the disease
• Looks for polymorphism associated with phenotype, but doesn’t determine cause