《遗传学》课件-第6章 多基因遗传病.ppt

重组值的计算 连锁（ linkage ） 位于同一条染色体上的基因或者遗传标记，它们在减数分裂产生配子的时候，如果倾向于把处在同样染色体上的等位基因共分离到同一个配子中去，这时基因或遗传标记之间的关系称为连锁。 问题：什么是紧密连锁？强连锁？不连锁？ Linkage Disequilibrium (LD) The preferential occurrence of a disease gene is associated with specific alleles of linked markers. LD is the non-random association between alleles at two loci. The extent of LD is typically measured by D’. 连锁不平衡 Linkage Analysis (Study) Linkage studies typically use families with multiple affected individuals ideally including three or more generations to identify genetic regions that are more likely to be inherited with a disease or biological response than would be expected by random chance. LOD Score: Maximum－likelihood LOD score method for estimating recombination frequency between a trait and a marker, or two markers Positive LOD scores favor the presence of linkage, whereas negative LOD scores indicate that linkage is less likely. LOD = Z = log10 (1-θ)NR x θR 0.5(NR+R) probability of birth sequence with a given linkage value probability of birth sequence with no linkage = log10 θ= R / (NR + R) Linkage Analysis By convention: LOD = 3.0 ? linkage. 3 LOD =1.0 ······ linkage. 1.0 LOD = -2.0 ······ larger population LOD -2.0 no linkage 单倍型（haplotype） 单倍型：同一条染色体上紧密相连的两个或两个以上多态 位点的状态的组合。 Phenotype Black eye GATATTCGTACGGA-T Brown eye GATGTTCGTACTGAAT Black eye GATATTCGTACGGA-T Blue eye GATATTCGTACGGAAT Brown eye GATGTTCGTACTGAAT Brown eye GATGTTCGTACTGAAT Haplotypes AG- 2/6 GTA 3/6 AGA 1/6 SNP SNP SNP h2 VG = VA+ VD+ VI hN2 = ( VA+ VD+ VI) + VE VA X 100% 计算定义要记住，书上P103-106的计算不作要求。 Emphasize If a trait has a heritability of 0.5, it means that the phenotypic variation is 50% due to genetic variation. It does not imply that the trait is 50% caused by genetics. Inheritance Features of Polygenic Disease Runs in a family Increases the risk when closer between proband/patient and relatives Differs between nationalities Increases