Exam #5: Population Genetics Flashcards
Polymorphism
Different forms of a gene in at least 1% of the population
Example of a highly polymorphic gene
HLA (Human Leukocyte Antigen) & cytochrome p450
Example of a non-polymorphic gene
Histones
How many deleterious recessive mutations does the average person carry?
3
How many nucleotide polymorphisms are there between unrelated humans?
Approximately 6 million, which works out to 1/1,000 base pairs
Describe polymorphisms in the context of race.
- 90% of genetic variation can be found within populations considered a race
- Only 10% of that variation is unique to the race
What are the four characteristics of an ideal population?
1) Large population size
2) Equal fitness of offspring (ability to reproduce)
3) Random mating
4) No influx or new alleles by migration or mutation
What did Hardy & Weinberg derive in their formula?
Proof that in ideal populations allele frequencies do not change over time
What are the four disturbances that can occur in the Hardy Weinberg equilibrium?
1) Genetic Drift (population is small)
2) Selection (fitness of offspring is unequal)
3) Assortative mating (mating is nonrandom)
4) Population bottlenecks & founder effect
Which of the four disturbances in the Hardy Weinberg equilibrium will NOT change the expected allele frequency over time; rather, the expected ratio of homozygosity & heterozygosity?
Non-random (assortative) mating will increase the frequency of homozygosity
f(a)
mutant
f(A)
wild-type
aa & AA=
f(a)^2 or f(A)^2
f(a) & f(A) heterozygotes
2*f(a)xf(A)
Carrier frequency in recessive diseases
2 x square root of prevalence
Allele frequency in x-linked recessive diseases
Fraction of males that are affected
Genetic Drift
- Statistical variation that can lead to the disappearance or multiplication of rare alleles
- Consequence of small population size?
Selection
- Over time will reduce the number of mutant alleles in a population
- HOWEVER, at some point the frequency of mutant alleles will stabilize at a low level
- Loss of mutant alleles will equal the appearance of spontaneous mutations, resulting in equilibrium
Heterozygote Advantage
Being heterozygous for a mutant allele confers some selective advantage (protection against something else)
CFTR Heterozygote Advantage
Protection from Typhoid Fever
Hemoglobin B/ Sickle Cell Anemia Heterozygote Advantage
Protection from Malaria
Hemoglobin B/ Beta- Thalassemia Heterozygote Advantage
Protection from Malaria
HFE/ Hemochromatosis Heterozygote Advantage
Protection from Plague
Assortative Mating
- Non-random mating
- Selection of partners based on a specific genetic trait
What effect does the mating of genetically similar individuals have?
Increases the degree of homozygosity in a population beyond what is predicted
In a first cousin marriage, what is the risk of having a child with a genetic disease?
5%, 2% above the risk to the general population
Founder Effect
- Population is wiped out by a catastrophic event
- Population has to recover from a small founder population, which can amplify rare alleles
Ellis van Creveld Syndrome
- Caused by a mutation in the EVC gene
- Example of the founder effect in Older Amish of Lancaster County, PA
- Symptoms include: shortening of limbs, postaxial polydactyly & heart defects
Ashkenazi Jews
Tay-Sachs Disease
French Canadians (Quebec)
Tyrosinemia
GWAS
- Genome wide association study
- millions of single nucleotide polymorphisms (SNPs) are analyzed
Odds Ratio
- Describes the strength of association between a SNP & disease
- NOTE, SNPs are not necessarily disease causing; rather, they lie outside coding regions that are and show linkage with the mutation that contributes to the disease
Why are young, genetically isolated populations the key to success for association studies?
Linkage disequilibrium between a disease trait & genetic markers scattered all over the genome
