High-resolution quantitative trait locus mapping for body weight in mice by recombinant progeny testing

A major obstacle to the positional cloning of quantitative trait loci (QTLs ) lies in resolving genetic factors whose allelic effects are blurred by en vironmental and background genetic variation. We investigate a fine-mapping approach that combines the use of an interval-specific congenic strain wit h progeny testing of recombinants for markers flanking a QTL. We apply the approach to map a murine QTL with an approximately 20% effect on growth rat e by progeny testing 39 recombinants in a 12 cM region of the X chromosome. We use a likelihood analysis in an attempt to maximize the information on QTL map location and effect. The major X-linked effect is mapped to an appr oximately 2 cM region flanked by markers about 5 cM apart, outside which LO D support for the QTL drops extremely steeply by about 80. Nearly unambiguo us assignment of the QTL genotypic state is obtained for each recombinant. The resolution of individual recombinants in the region is therefore suffic iently high to facilitate the positional cloning of the locus, although pro gress has been hampered because the genomic region containing the QTL shows an exceptionally low level of polymorphism in comparison with recent studi es.