A catalog of nonsynonymous polymorphism on mouse chromosome 16

Numerous phenotypic traits differ among inbred mice, and the genetic diversity of inbred strains has been exploited in studies of quantitative trait loci (QTL). Sequencing the mouse genome has resulted in improved tools for the study of QTL, but a comprehensive catalog of sequence variants between strains would be of great value in identifying and testing potentially causative alleles. A/J DNA was included in the Celera shotgun sequence of the mouse genome and C57BL/6 DNA was sequenced by an international consortium. We have resequenced A/J and B6 DNA to cover nearly all of the protein-coding portions of mouse Chromosome 16, revealing that there are 106 nonsynonymous substitutions in 74 of the 779 genes on the chromosome. The pattern of substitution is more similar to the spectrum of benign polymorphism in the human population than it is to human disease-causing mutations. In mouse, polymorphic variants tend to be associated with one another on large haplotypes; this pattern also holds true for nonsynonymous polymorphism. However, sufficient fragmentation of haplotypes is present to suggest that only a very-high-resolution haplotype map will enable effective inference of alleles in additional strains.