Basics of Linkage Analysis课件.ppt

An example of ML estimation Single marker, dominant disease All genotypes known 1,3 2,4 2,3 1,4 1,2 1,4 1,2 3,4 1,2 Paternal haplotype combinations Haplotype combinations of children, assuming unlinked loci Basics of Linkage Analysis Idea of Linkage Analysis Types of Linkage Analysis Parametric Linkage Analysis Nonparametric Linkage Analysis Conclusions Basics of Linkage Analysis Idea of Linkage Analysis Types of Linkage Analysis Parametric Linkage Analysis Nonparametric Linkage Analysis Conclusions Gene mapping problem L?hde: Morgan Genetics Tutorial. /morganwebframes/level1/page2/karyotype.html Linkage Analysis One of the two main approaches in gene mapping. Uses pedigree data. Genetic linkage and linkage analysis Two loci are linked if they appear closeby in the same chromosome. The task of linkage analysis is to find markers that are linked to the hypothetical disease locus Complex diseases in focus ? usually need to search for one gene at a time Requires mathematical modelling of meiosis Meiosis and crossover Number of crossover sites is thought to follow Poisson distribution. Their locations are generally random and independent of each other. The simple idea ? DIS Marker L(? |data ) Find that maximises ? Recombination fraction Obtain measure for degree of evidence in favour of linkage (LOD score) 1 2 2 2 1 3 4 3 1 3 4 2 2 1 3 3 4 1 Father Mother Child Polymorphic loci whose locations are known Point mutations (SNP) or lengths of repetitive sequences Inherited together with the chromosomal segments Markersandinheritance Markers and information Two individuals share same allele label ? they share the allele IBS (identical by state) Two individuals share an allele with same grandparental origin ? they share an allele IBD (identical by descent) IBS sharing can easily be deduced from genotypes. IBD sharing provides more information. One can try to deduce IBD sharing based on family structure and inheritance. Markers and information 1,2 2,3 1,2 1,3 T