Population Genetics/Looking for Genes

Question 1

Hardy Weinberg principle & equilibrium

Answer 1

p² + 2pq + q²= 1

Equilibrium: gene frqs dont change across generations

Question 2

The incidence of an AR disorder is ___.

The frequency of carriers is ____.

Ex) Sickle cell

Answer 2

Incidence_AR = q²

Frequency of carriers = 2pq = 2q if q is small enough

Question 3

The incidence in an AD disorder is ___

Answer 3

IncidenceAD= heterozygous rate = 2pq =2p

Thus, the incidence of an AD disorder is ~twice the gene/allele frq

Question 4

The incidence of red-green colorblindness in a man is ____.

The incidence of red-greenc olorblindness in a woman is ___.

Note: RG colorblindness is a X-linked recessive disorder

Answer 4

Incidence_man = q

Incidence_woman= q²

Question 5

The incidence of carrier females in an X-linked recessive disorder is

Answer 5

2pq, but if q is small, then 2q (just like AR)

Question 6

Assortative mating (non-random mating) has what impact on genotype frequency?

Answer 6

Increase homozygote frq

Decrease heterozygote frq

Question 7

Inbreeding has what effec ton genotype frquency?

Answer 7

Increase homozygotes, but does not impact allele frqs

Question 8

Selection

Answer 8

Change in the gene or genotype frq from one generation to the next due to differential survival and/or reproduction

Question 9

Genetic drift

Answer 9

chance fluctuations from gen to gen in a small population due to random sampling among gametes

2nd major force in evolution

Question 10

Linkage analysis

Answer 10

Uses family data to identify genes of large effect by looking for cosegregation of marker with trait

Good for rare alleles causing Mendelian disease

Question 11

Association studies

Answer 11

Uses population data to find common variants/genes of small effect by looking for higher prevalence of a specific allele in cases

Good for common variants implicated in common disease

Question 12

Syntenic loci

Answer 12

Loci are far apart on the same chromosome; one of the ways you can have no linkage

Question 13

No linkage results in what ratio of nonrecombinant to recombinant?

Answer 13

Nonrecombinant = Recombinant

Question 14

Complete linkage results in what ratio of nonrecombinant to recombinant?

Answer 14

All nonrecombinants

Question 15

Linkage, but not complete results in what ratio of nonrecombinant to recombinant?

Answer 15

Mostly nonrecombinants, some recombinants occur because sometimes crossover happens between em

Question 16

When does crossover happen?

Answer 16

After prophase 1 of meiosis

Question 17

Recombination fraction (theta)

Answer 17

Probability that an odd number of crossover events will take place between 2 loci or the proportion of recombinant gametes

Question 18

What method is used to fine genes in large effect in loaded pedigrees?

Answer 18

Linkage analysis

Question 19

Limitations of linkage analysis

Answer 19

• May only find genes for familial cases (small portion)
• May be heterogeneity between families
• Doesn’t address gene-gene interactions or gene-environment interactions
• May not have a good pedigree or know the mode of inheritance for a disorder
• May be specific to only some families or ethnic groups

Question 20

What method of finding genes looks for susceptibility genes?

Answer 20

Susceptibility genes are genes of small effect –> association analysis

Question 21

Strengths of association analysis

Answer 21

Just uses populationd ata

Cost-effective

Can assess the role of a candidate gene

Question 22

Limitations of association analysis

Answer 22

• Identifies genes of small effect, but can’t determine effect size
• Only one part of the story
• Doesn’t address gene-gene interactions or gene-environment interactions, etc

Question 23

Which type of study is often used in direct to consumer testing?

Answer 23

ASsociation studies form teh base for many reports of susecptibility genes

Question 24

Increased relative risk seen with an allele at a particular locus does NOT prove that

Answer 24

The allele or even the locus is involved with disease pathogenesis

Question 25

Questions to think about when told “a gene for __ has been discovered”

Answer 25

• Was it found by linkage or association analysis? (Large effect or small effect)?
• If association, what is the relative risk? (How much susceptibility is thought to be attributable to this locus?)
• What percent of cases may be affected ?
• Is it just found for familial cases?
• Heterogeneity? (Is this the only causal gene?)
• What populationw ass tudied?

Question 26

Women who are BRAC1 or BRAC2 positive have an 80% risk of getting breast cancer in comparison tot he general population’s risk. So this is a gene of __ effect

Answer 26

large effect.

However, tehse gense are prominent in ~50% of familial cases of brast cancer and explain only 5% of all cases.