Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies.

ABSTRACT

The study of complex genetic traits in humans is limited by the expense and difficulty of ascertaining populations of sufficient sample size to detect subtle genetic contributions to disease. Here we introduce an application of a somatic cell hybrid construction strategy called conversion that maximizes the genotypic information from each sampled individual. The approach permits direct observation of individual haplotypes, thereby eliminating the need for collecting and genotyping DNA from family members for haplotype-based analyses. We describe experimental data that validate the use of conversion as a whole-genome haplotyping tool and evaluate the theoretical efficiency of using conversion-derived haplotypes instead of conventional genotypes in the context of haplotype-frequency estimation. We show that, particularly when phenotyping is expensive, conversion-based haplotyping can be more efficient and cost-effective than standard genotyping.