| Popis: |
The impact of heterozygosity as an intrinsic mutagen in mammals is unknown. In plant models, existent heterozygosity increases the local de novo meiotic mutation rate. Mice offer study of this phenomenon given well-established genomic technologies and strains with known, diverse genomic landscapes of heterozygosity. High resolution genotyping arrays assay heterozygous single-nucleotide polymorphic (SNP) loci and copy number variants (CNVs). Using a J statistic for spatial analysis, 60.9% of autosomes from 707 publicly available array samples have nonrandom spatial associations between heterozygous SNP loci and CNVs. By crossing C57BL/6J inbred mice to DBA/2J inbred mice, heterozygous SNP loci and de novo CNVs were analyzed. Of 43 de novo CNVs in F2 mice compared to both F1 and F2 heterozygous SNP landscapes, 33 and 7 were found to co-localize with heterozygous SNP loci, respectively. Heterozygosity may be an overlooked meiosis-linked contributor to CNV mutagenesis, affecting models of disease risk prediction and evolution. |
