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11 Cards in this Set
- Front
- Back
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Linkage mapping |
1. Collect families with children affected. Test variety of genetic markers. 2. Identify markets that assort with disease allele - disease allele near marker |
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Linkage |
Tendency of alleles close together on same chromosome to transmit together Violates Mendel's Law of Independent Assortment |
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Why would patient w risk allele be unaffected? Or vice versa? |
Phenocopy Early death Incomplete penetrance Crossover |
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Crossover |
Generates nonparental/recombinant haplotype Chance of crossover depends on distance between loci - linked loci do not recombine (excess of nonrecombinants) |
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Linkage vs Nonlinkage |
Linkage - excess of nonrecombinants Nonlinkage - one quarter of each genotype |
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Phase |
Must have three generation pedigree |
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LOD score |
Log (odds of linkage/odds of no linkage) Odds of non linkage = (0.5)^NR * (0.5)^R Odds of linkage = (0.9)^NR * (0.1)^R Lod > 3.6 required to establish linkage, low enough p value that 5% probability seen by chance in genome screen |
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Genome wide linkage scan |
Run using markers across genome Use markers that are heterozygous or multiallelic Short tandem repeats are useful BC multiple alleles, but difficult to genotype Use SNPs Linkage gets us to region but not particular gene |
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Genetic association |
Specific allele rather than just a marker associated with disease across many families E.g. allele odds ratio - how much does risk increase with a certain allele Heterozygous odds ratio - how much does risk increase w heterozygous instead of homozygous state? For continuous traits - use regression |
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Linkage disequilibrium |
Alleles at two loci appear together in a large population more frequently than expected Alleles were continuously inherited together in a haplotype over generations and through populations. |
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Haplotyping and indirect association |
Haplotypes share alleles. We can sequence a single known polymorphism ("tag variant") to identify haplotype and assume sequence rather than sequencing entire block of DNA. |
