复杂疾病的遗传学演示文稿.ppt

* * * * * * * * * * * * * Sib Pair Analysis By random segregation sib pairs share 0, 1 or 2 parental haplotypes 1/4, 1/2 and 1/4 of the time, respectively. (B) Pairs of sibs who are both affected by a dominant condition share one or two parental haplotypes for the relevant chromosomal segment. (C) Pairs of sibs who are both affected by a recessive condition share both parental haplotypes for the relevant chromosomal segment. Affected sibling-pair（患病同胞对） analysis Suggested Criteria for Reporting Linkage Category of linkage Expected No. of occurrences by chances in a whole genome scan Range of approximate p value Range of approximate lod scores Suggestive 1 7 x 10-4 – 3 x 10-5 2.2 - 3.5 Significant 0.05 2 x 10-5 – 4 x 10-7 3.6 - 5.3 Highly significant 0.001 3 x 10-7 5.4 Confirmed 0.01 in a search of a candidate region that gave significant linkage in a previous independent study Lod score: 3.6 for IBD testing of affected sib pairs, 4.0 for IBS Given that the loci are truly linked, with recombination fraction q, the likelihood of a meiosis being nonrecombinant is 1 - θ and the likelihood of it being recombinant is θ. If the loci are in fact unlinked, the likelihood of a meiosis being either recombinant or nonrecombinant is 1/2. Family AThere are five recombinants and one nonrecombinant. The overall likelihood, given linkage, is (1 - θ)5. θ The likelihood given no linkage is (1/2)6 The likelihood ratio is (1 - θ)5. θ / (1/2)6 The lod score, Z, is the logarithm of the likelihood ratio. Family BII1 is phase-unknown. If she inherited A1 with the disease, there are five nonrecombinants and one recombinant. If she inherited A2 with the disease, there are five recombinants and one nonrecombinant. The overall likelihood is 1/2 [(1 - θ)5. θ / (1/2)6] + 1/2 [(1 - θ). θ 5 / (1/2)6]. This allows for either possible phase, with equal prior probability. The lod score, Z, is the logarithm of the likelihood ratio. Family CAt this point nonmasochists turn to the computer. Geno