Long-range, high-throughput haplotype determination via haplotype-fusion PCR and ligation haplotyping.
Ligation Haplotyping is a robust, novel method for experimental determination of haplotypes over long distances, which can be applied to assaying both sequence and structural variation. The simplicity and efficacy of the method for genotyping large chromosomal rearrangements and haplotyping SNPs over long distances make it a valuable and powerful addition to the methodological repertoire, which will be beneficial to studies of population genetics and evolution, disease association and inheritance, and genomic variation. We illustrate the versatility of the method both by genotyping a Yp paracentric inversion, found in approximately 60% of Northwest European males, that strongly influences the germline rate of infertility-causing XY translocations and by haplotyping two autosomal SNPs that lie 16.4 kb apart on chromosome 7, and which influence an individual's susceptibility to systemic lupus erythematosus.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK. djt@sanger.ac.uk
Daniel J
DJ
Turner
Chris
C
Tyler-Smith
Matthew E
ME
Hurles
D007446:Chromosome Inversion; D011088:DNA Ligases; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D011088:DNA Ligases