Lecture 9b Flashcards
What is a single nucleotide polymorphism (SNP)?
Change in one base at a site compared to the most common WT allele. If change is in coding region, it may change the amino acid. If change is in noncoding region, it may affect gene regulation. SNPs are found by comparing DNA sequences of many individuals or by using a microarray. SNPs arise via point mutation.
What is a microsatellite?
A simple short motif repeated a variable number of times
- represents a special class of indel
- More alleles (# of repeats) than SNPs
- Higher mutation rate than SNPs
- Detectable as differences in length of DNA fragment by running a gel (heterozygote individuals have 2 products with different sizes, homozygotes have one)
- Number of instances of the repeat may vary
What are 5 types of chromosomal variation?
Inversion, translocation, deletion, duplication, and transposable element
What is a haplotype?
The combination of alleles at multiple loci on the same chromosomal homolog. Two homologous chromosomes that share the same allele at each of the loci under consideration have the same haplotype. If two chromosomes have different genotypes at even one of the loci in question, then they have different haplotypes
- Phylogenetic relationship between haplotypes can be determined
- Haplotypes serve as markers for gene flow
- Can be associated with disease or response to treatment
What is genetic diversity? How do you calculate it?
The probability that two alleles drawn at random from the gene pool will be different. It is (more or less) the expected proportion of heterozygotes.
GD = 1 - (sum of probability of each possible homozygote) = chance of being heterozygous
If p is equal to the frequency of an allele then GD = 1 -(p1^2 + p2^2 … + pn^2)
What is nucleotide diversity? How do you calculate it?
ND = # of SNPs / total bases = how often you see changes in DNA sequence
What is linkage disequilibrium?
Nonrandom association between two loci. Haplotype frequency should be the product of allele frequencies. If that is not true then there is linkage disequilibrium.
LD = P(AB) - P(A)P(B)
P(AB) = actual observed
P(A) and P(B) = independent chance of A and B
What cause linkage disequilibrium?
- Recent mutation which hasn’t had time to equilibrate
- Selection that maintains the combination
What is the neutral theory of molecular evolution?
At the molecular level, most change is caused by genetic drift of neutral mutants. Deleterious mutations are quickly eliminated by selection on organisms. Neutral mutations do not affect fitness of organisms. Ex. protein sequence changes but function doesn’t.
“The neutral theory of molecular evolution proposed that most mutations in DNA or amino acid replacements between species are functionally neutral or nearly neutral and fixed by random genetic drift. The assumption of neutrality offers a baseline expectation of how DNA should change over time when natural selection is absent.”
If purifying selection is so strong, why do deleterious alleles like sickle cell persist?
Heterozygote advantage in areas with malaria. Variation in sickle incidence matches environment, not tribe.
WT: AA
Heterozygote: AS
Homozygote sickle: SS (lowest fitness)
