Nature Genetics
24, 381 - 386 (2000)
doi:10.1038/74215
Large-scale discovery and genotyping of single-nucleotide polymorphisms
in the mouseKerstin Lindblad-Toh1, Ellen Winchester1, Mark J. Daly1, David G. Wang1, 2, Joel N. Hirschhorn1, 3, Jean-Philippe Laviolette1, Kristin Ardlie1, David E. Reich1, Elizabeth Robinson1, Pamela Sklar1, 4, Nila Shah5, Daryl Thomas5, Jian-Bing Fan5, Thomas Gingeras5, Janet Warrington5, Nila Patil5, Thomas J. Hudson1, 6
& Eric S. Lander1, 71
Whitehead Institute/MIT Center for Genome Research,
Whitehead Institute for Biomedical Research, Cambridge,
Massachusetts, USA. 2
Bristol-Myers Squibb, P.O. Box 5400,
Princeton, New Jersey, USA. 3
Division of Endocrinology, Children's Hospital,
Boston, Massachusetts, USA. 4
Department of Psychiatry, Massachusetts General Hospital
, Boston, Massachusetts, USA. 5
Affymetrix, Inc., Santa Clara,
California, USA. 6
Montreal Genome Centre, McGill University Health Centre,
Montréal, Québec, Canada. 7
Department of Biology, Massachusetts Institute of Technology
, Cambridge, Massachusetts, USA.
Correspondence should be addressed to Kerstin Lindblad-Toh kersli@genome.wi.mit.edu or Eric S. Lander lander@wi.mit.eduSingle-nucleotide polymorphisms (SNPs) have been the focus of much attention
in human genetics because they are extremely abundant and well-suited for
automated large-scale genotyping. Human SNPs, however, are less informative
than other types of genetic markers (such as simple-sequence length polymorphisms
or microsatellites) and thus more loci are required for mapping traits. SNPs
offer similar advantages for experimental genetic organisms such as the mouse,
but they entail no loss of informativeness because bi-allelic markers are
fully informative in analysing crosses between inbred strains. Here we report
a large-scale analysis of SNPs in the mouse genome. We characterized the rate
of nucleotide polymorphism in eight mouse strains and identified a collection
of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density
oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the
mouse genome, providing a first-generation SNP map of the mouse. We have also
developed a multiplex genotyping procedure by which a genome scan can be performed
with only six genotyping reactions per animal.
|
