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

Published online by Cambridge University Press:  08 June 2001

XIAOJUN LIU
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
FIONA OLIVER
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK
STEVE D. M. BROWN
Affiliation:
MRC UK Mouse Genome Centre and Mammalian Genetics Unit, Harwell, Oxfordshire OX11 ORD, UK
PAUL DENNY
Affiliation:
MRC UK Mouse Genome Centre and Mammalian Genetics Unit, Harwell, Oxfordshire OX11 ORD, UK
PETER D. KEIGHTLEY
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK

Abstract

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A major obstacle to the positional cloning of quantitative trait loci (QTLs) lies in resolving genetic factors whose allelic effects are blurred by environmental and background genetic variation. We investigate a fine-mapping approach that combines the use of an interval-specific congenic strain with 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 rate 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 approximately 2 cM region flanked by markers about 5 cM apart, outside which LOD support for the QTL drops extremely steeply by about 80. Nearly unambiguous assignment of the QTL genotypic state is obtained for each recombinant. The resolution of individual recombinants in the region is therefore sufficiently high to facilitate the positional cloning of the locus, although progress has been hampered because the genomic region containing the QTL shows an exceptionally low level of polymorphism in comparison with recent studies.

Type
Research Paper
Copyright
© 2001 Cambridge University Press