Significant gene content variation characterizes the genomes of inbred mouse strains
Significant gene content variation characterizes the genomes of inbred mouse strains
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DOI：
10.1101/gr.6754607
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发表时间：
2007-12-01
期刊：
影响因子：
7
通讯作者：
Kassner, Paul D.
中科院分区：
文献类型：
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作者：
Cutler, Gene;Marshall, Lisa A.;Kassner, Paul D.
基因组片段拷贝数变异（CNVs）对遗传多样性的贡献不如单核苷酸多态性（SNPs）了解得多。虽然比snp频率低，但CNVs具有更大的影响表型的潜力。在这项研究中，我们进行了迄今为止最全面的小鼠CNVs调查，分析了42个小鼠表型组优先菌株的基因组。这项基于微阵列比较基因组杂交（CGH）的分析鉴定出2094个假定的CNVs，当将单个小鼠菌株与参考菌株C57BL/ 6J进行比较时，51个CNVs中平均有10 Mb的DNA。这种数量的变异导致菌株之间的基因含量可能相差数百个基因。这些基因包括大家族的成员，如主要的组织相容性和信息素受体基因，但也有许多单基因，包括由于缺失或扩增而导致预期表型后果的基因。利用全基因组关联分析，我们证明了复杂的多基因表型，如食物摄入，可以与特定拷贝数的变化相关。
The contribution to genetic diversity of genomic segmental copy number variations ( CNVs) is less well understood than that of single-nucleotide polymorphisms ( SNPs). While less frequent than SNPs, CNVs have greater potential to affect phenotype. In this study, we have performed the most comprehensive survey to date of CNVs in mice, analyzing the genomes of 42 Mouse Phenome Consortium priority strains. This microarray comparative genomic hybridization ( CGH)- based analysis has identified 2094 putative CNVs, with an average of 10 Mb of DNA in 51 CNVs when individual mouse strains were compared to the reference strain C57BL/ 6J. This amount of variation results in gene content that can differ by hundreds of genes between strains. These genes include members of large families such as the major histocompatibility and pheromone receptor genes, but there are also many singleton genes including genes with expected phenotypic consequences from their deletion or amplification. Using a whole-genome association analysis, we demonstrate that complex multigenic phenotypes, such as food intake, can be associated with specific copy number changes.