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Flashcards in Genetic Analysis of Complex Traits Deck (27):
1

genetically complex trait

any phenotypic trait that exhibits evidence for familial aggregation and genetic involvement but is not inherited in an easily determined manner

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diseases with genetic components

cancer

diabetes mellitus

polycystic ovary syndrome

atherosclerosis

cardiovascular disease

autoimmune disease

neurological disease

psychiatric disease

asthma

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Hardy Weinberg Equilibrium

describes the relationship between gene freqeuencies and genotype frequencies in random mating populations

A = p and a = q = (1-p)

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

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Hardy-Weinberg Equilibrium Conditions

population is infinitely large

random mating (no population stratification, assortative mating, consanguinity or inbreeding)

no mutation, migration, and random drift

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Why does selection not remove deleterious mutations from the gene pool?

vast majority of the deleterious mutations are in the unaffected heterozygote

heterozygote selective advantage

new mutations introduced

lethal autosomal dominant traits have a high rate of de novo mutations

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linkage analysis

looking within a pedigree to see who is inheriting a disease and marker together, look for cosegregation

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parametric analysis

LOD scores, assume explicit mode of inheritance, Mendelian traits

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nonparametric analysis

affected sib pairs - no assumption about mode of inheritance, complex traits

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assortment of two alleles on the same chromosome

unlinked, completely linked, and partially linked

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genetic map

map of the relative locations of loci along a chromosome based on recombination frequencies, distance measured in centiMorgans

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map distance

number of units or centiMorgans between two loci

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map function

mathematical expression that describes the relationship between observed percent recombination and centiMorgans

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map unit

a measure of distance between two genetically linked loci, usually 1% recombination correpsonds to one map unit

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physical map

ordered set of genomic DNA clones demarcated with restriction endonuclease recognition or sequence tagged sites, the distance between sites is measured in base pairs

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LOD score

also known as Z score - logarithm of the ratio of the likelihood of linkage (H1) versus the likelihood of no linkage (H0)

LOD = Log10[L(H1)/L(H0)]

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LOD scores for linkage

linkage is assumed when the LOD score exceeds 3.6, and it can excluded when the score is less than -2.0

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recombination fraction

number of recombinant meiotic produces divided by the total number of meiotic products

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affected sip pair test

test for linkage by counting transmissions from heterozygous parents taht are shared by affected children

excess sharing of >50% indicates linkage, test significane by chi-squared

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association study

study based on the comparison of the frequency of a specific allele or haplotype in affected and unaffected individuals in a population

identify polymorphisms that may be linked with a specific disease trait

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haplotype

a unique combination of genetic markers present on a chromosome

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linkage equilibrium

when the frequency of each allele within a haplotype is the same as the frequency of that allele in the population as a whole (random assortment)

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linkage disequilibrium

a measure of the association of alleles on a chromosome, two loci are in linkage disequilibrium when their alleles are not randomly associated

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HapMap project

characterize common genetic variation across the genome in three major world populations

1 variant across every 5kb across the genome - phase I

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haplotypes between YRI, CEU, and CHB+JPT

most of the haplotypes are very similar, but the YRI group is a little older and therefore have slightly varying haplotypes

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proxy SNPs

20% of SNPs have >20 perfect proxies

60% have >5 perfect proxies

20% have no perfect proxies

varies by population

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htSNPs

haplotype tagged SNPs

a subset of SNPs which account for the majority of genetic variation in a given genomic fragment

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genome-wide association studies (GWAs)

260,000-474,000 SNPs capture all common SNPs in Phase I data set in caucasions