Folien

Haplotype sharing uses two sources of information about identity between two subjects in contrast to association. In association an identical SNP allele indicates a common founder for that allele, because the mutation frequency is low enough to ignore the possibility of two identical separate mutations to the same allele. Haplotypes can be identical by state and identical by descent. Identity by descent means that there is a common founder for a haplotype and that there have not been recombinations and mutations for all subsequent markers on a haplotype. If two haplotypes share many markers, a recent common founder is likely. Even with current high density snp marker sets from Illumina or Affymetrix most snp's will not be observed and genetic effects of most snp's will be observed indirectly. The number of different haplotypes observed surrounding an snp allel is much lower than would be expected if there was free recombination. This is caused by non-recombination since the haplotype was present in a common founder. The presence of unobserved disease alleles can be inferred from qualitatively different haplotypes and from length differences. The latter is especially important if disease mutations are young relative to the non-disease associated variant or when the disease allele is rarer and has less independent introductions in a population. A major problem is whether the information derived from haplotypes is really useful given the extra noise added by haplotype inference and given the extra effort of typing a father-mother-child trio with one affected individual. Current whole genome screens have been designed as case-control studies. However results are mixed and haplotype sharing tests need to be applied in order to see if they contribute to finding reliable genetic signals.