Genome partitioning and whole-genome analysis.
Standard DNA marker-based approaches to mapping genes that influence complex traits typically consider a limited number of hypotheses. Most of these hypotheses concentrate on the effect of a single individual locus (or relatively few loci) on the trait of interest. Although of tremendous importance scientifically, such hypotheses do not accommodate the full range of genetic phenomena that may contribute to phenotypic expression. We present novel approaches to complex trait analysis that make as complete use of marker information as is possible. The proposed methodologies can be used to entertain a wide variety of hypotheses, including those that engage, for example, the contribution of a particular chromosome, genome-wide heterozygosity, and multiple genomic regions, to phenotypic expression. We consider a number of possible extensions of the proposed methods as well as their limitations. Although we discuss many methodological details in the context of quantitative trait locus mapping involving sampling units such as human pedigrees and hybrids resulting from crosses between inbred strains of model organisms, our procedures can be easily adapted to standard sibpair and other sampling unit-based designs. Ultimately, the proposed approaches not only have the potential to increase power to identify individual loci that harbor trait-influencing genes, but also present a framework for testing a number of hypotheses about the nature of the genetic determinants of phenotypes in general.