Population Genetics/Looking for Genes Flashcards
Hardy Weinberg principle & equilibrium
p2 + 2pq + q2= 1
Equilibrium: gene frqs dont change across generations
The incidence of an AR disorder is ___.
The frequency of carriers is ____.
Ex) Sickle cell
IncidenceAR = q2
Frequency of carriers = 2pq = 2q if q is small enough
The incidence in an AD disorder is ___
IncidenceAD= heterozygous rate = 2pq =2p
Thus, the incidence of an AD disorder is ~twice the gene/allele frq
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
Incidenceman = q
Incidencewoman= q2
The incidence of carrier females in an X-linked recessive disorder is
2pq, but if q is small, then 2q (just like AR)
Assortative mating (non-random mating) has what impact on genotype frequency?
Increase homozygote frq
Decrease heterozygote frq
Inbreeding has what effec ton genotype frquency?
Increase homozygotes, but does not impact allele frqs
Selection
Change in the gene or genotype frq from one generation to the next due to differential survival and/or reproduction
Genetic drift
chance fluctuations from gen to gen in a small population due to random sampling among gametes
2nd major force in evolution
Linkage analysis
Uses family data to identify genes of large effect by looking for cosegregation of marker with trait
Good for rare alleles causing Mendelian disease
Association studies
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
Syntenic loci
Loci are far apart on the same chromosome; one of the ways you can have no linkage
No linkage results in what ratio of nonrecombinant to recombinant?
Nonrecombinant = Recombinant
Complete linkage results in what ratio of nonrecombinant to recombinant?
All nonrecombinants
Linkage, but not complete results in what ratio of nonrecombinant to recombinant?
Mostly nonrecombinants, some recombinants occur because sometimes crossover happens between em
When does crossover happen?
After prophase 1 of meiosis
Recombination fraction (theta)
Probability that an odd number of crossover events will take place between 2 loci or the proportion of recombinant gametes
What method is used to fine genes in large effect in loaded pedigrees?
Linkage analysis
Limitations of linkage analysis
- 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
What method of finding genes looks for susceptibility genes?
Susceptibility genes are genes of small effect –> association analysis
Strengths of association analysis
Just uses populationd ata
Cost-effective
Can assess the role of a candidate gene
Limitations of association analysis
- 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
Which type of study is often used in direct to consumer testing?
ASsociation studies form teh base for many reports of susecptibility genes
Increased relative risk seen with an allele at a particular locus does NOT prove that
The allele or even the locus is involved with disease pathogenesis
Questions to think about when told “a gene for __ has been discovered”
- 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?
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
large effect.
However, tehse gense are prominent in ~50% of familial cases of brast cancer and explain only 5% of all cases.
