International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Oral Presentation

Sunday 17 November

13:45 - 14:00 HRS


K Lindblad-Toh
Whitehead Institute

Co-Authors: Wade C, Zody MC, Kirby A, Kulbolkas EJ, Lander ES , Daly MJ
Institutions: Whitehead Institute/MIT Center for Genome Research

Many commonly used inbred laboratory mouse strains are widely known to have originated from a mixed but limited founder population in a small number of labs.  However, the dramatic effect this breeding history may have had on patterns of genetic variation among these strains has not previously been explored.  Here we present an analysis of the fine structure of variation using data from both long finished sequences and genome-wide shotgun sequencing.  When the recently assembled C57BL/6J genome sequence is aligned with sequence from other strains, we observe long segments of either extremely high (~1 SNP/200-250 bp) or extremely low (~1 SNP/20,000 bp) polymorphism rate.   In all strain-to-strain comparisons examined, roughly one-third of the genome falls into long, high SNP-rate regions consistent with estimated divergence rates between M. m. domesticus and either M. m. musculus or M. m. castaneus.  This suggests that the genomes of these inbred strains are, as previously suggested, mosaic with half of the genome falling in segments larger than 2Mb and a 20-25% contribution from non-domesticus sources.  Furthermore, when many inbred lab strains are compared locally, nearly every strain contains one of only two distinct haplotypes that persist over long distances.  These observations have a dramatic impact on how these strains can be utilized in the design and interpretation of positional cloning experiments.

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