International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Oral Presentation

Wednesday 20 November

12:00 - 12:15 HRS


T Wiltshire

Co-Authors: 2) Pletcher M, 1) Barnes W, 1) Tarantino L, 1) Cooke M, 3) Wu H, 4) Smylie K, 1) Santrosyan A, 1) Batalov S, 5) Copeland N, 5) Jenkins N, 2) Kay S, 1) Fletcher C.
Institutions: 1) Genomics Institute of the Novartis Research Foundation, 2) The Scripps Research Institute, 3) Phenomix, 4) Sequenom Inc, 5) NCI –Frederick Cancer and Research Development Center

Positional cloning in the mouse is routinely constrained by time-consuming traditional methods of genotyping and genetic mapping, and is one of the bottlenecks in developing high-throughput approaches for positional cloning and positional candidate identification of gene mutations.  The use of single-nucleotide polymorphisms (SNPs) as genetic markers are an attractive option for positional cloning of single gene traits and genetic dissection of complex phenotypes and quantitative trait loci (QTLs).  SNPs are abundant between inbred mouse strains and are well suited for rapid high-throughput genotyping.  Here we report the identification of 12,900 SNPs across 2384 loci in eight inbred strains, the development of a dense integrated SNP map, and the analysis of haplotypes shared between strains.  An anchor set of 388 SNPs has been genetically mapped to the mouse BSB dataset and all loci mapped with respect to a physical location from both the Celera and Ensembl genome assemblies.  We have also investigated procedures for rapid genotyping of mutant mice from an N-ethyl-N- nitrosourea (ENU) mutagenesis screen.  Using multiplexing of assays and pooling of DNAs comprehensive genome scans can be completed in several days and we demonstrate how SNP methodologies, mutation analysis and expression analysis have been used to identify the genes responsible for ENU-induced phenotypes

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