PAG-VI: POSITIONAL CLONING OF COMPLEX TRAIT LOCI - A UTOPIA?

PAG-VI  Plant & Animal Genome VI Conference

Town & Country Hotel, San Diego, CA, January 18-22, 1998.


S10

POSITIONAL CLONING OF COMPLEX TRAIT LOCI - A UTOPIA?

RUEDI FRIES

    Lehrstuhl fuer Tierzucht, Technische Universitaet Muenchen, Alte Akademie 12, 85350 Freising-Weihenstephan, GERMANY

Important traits of farm animals are mostly of a complex nature. The term complex refers to any phenotype that does not exhibit classic Mendelian recessive or dominant inheritance attributable to a single locus (Lander and Schork, Science 265: 2037-2048, 1994). The complexity is based on the effects of multiple loci (and their interactions) and / or high environmental noise. The first steps of positional cloning of complex trait loci consist of (1) the judicious choice of an animal material ensuring maximum homogeneity and (2) the application of phenotyping approaches that reveal robust 'endophenotypes' (e.g., physiological parameters). Both careful selection of the animal material (including the establishment of suitable crosses) and 'endophenotyping' will often reduce the complexity to an extent allowing straightforward positional, especially positional (comparative) candidate gene cloning. However, a major obstacle to positional cloning of complex trait loci is the lack of mapping precision that can be achieved with conventional linkage analysis. Population-wide analysis of linkage disequilibrium and the revival of the candidate gene approach using DNA-chip-based genotyping open new perspectives for systematic high-resolution mapping of complex traits loci and their 'topical' cloning.


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