International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

MONDAY OCTOBER 18

3.30pm – 3.45pm

IN-SILICO MAPPING - USE OF INFERRED HAPLOTYPES TO DEFINE QTLS

Pletcher MT1, McClurg P1, Batalov S1, Su A1, Bogue M3, Mural R2, Paigen B3, Wiltshire T1

1 GNF, San Diego, United States, 2 Celera Genomics, Rockville, United States, 3 The Jackson Laboratory, Bar Harbor, United States

Single nucleotide polymorphisms (SNPs) that occur between mouse strains may produce a specific functional change in a gene leading to phenotypic variation but are more often simply markers for an ancestral haplotype.  In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purposes of dissecting genetic traits.  The goal of in-silico mapping is to identify which haplotype patterns track with a specific phenotype with the idea that the tracking haplotype contains a causative mutation.  For in silico mapping to be successful, a dense SNP map is required and multi-strain phenotypes data well defined. In mouse, the current SNP data has lacked the density across the genome and coverage of enough strains to properly achieve this goal.  To remedy this, 467,015 allele calls were produced for 10,917 evenly spaced SNP loci across 48 inbred mouse strains.  Phenotype data for multiple strains is now available through the Phenome project.  Use of the SNP set with statistical models that considered unique patterns within blocks of 3 SNPs as fixed haplotypes could successfully map known single gene traits and a cloned quantitative trait gene.  Application of these methods to high density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL).  Also, examining the SNP data in this manner allows for QTL regions to be refined by reviewing the haplotype structures such that candidate genes are then more readily identified.  We have examined a candidate gene Adcy7for an HDL phenotype in this manner and characterized polymorphisms within the gene.

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