生物谷：美国的研究人员希望通过对15只常用于生物医药研究的小鼠的DNA进行研究来帮助科研人员确定出与环境疾病敏感性相关的基因。目前这些数据被存放在了基因变异数据目录之下，即小鼠基因组单体型图谱（将染色体分隔成许多小的片段），从而帮助研究人员找出小鼠中影响健康和疾病的基因和遗传变异。这个单体型图谱公布在7月29日的《自然》杂志上，该图谱首次完整描述了小鼠基因组测序和SNP计划的分析数据。该研究计划由美国环境卫生科学研究院进行。
这些数据使研究人员能够比较一个小鼠与另外一个小鼠的遗传组成，并进行必要的遗传分析来确定出一些个体对疾病更敏感的原因。这项研究成果使人们向着了解对人类对环境毒素的个体敏感性前进了一步。研究人员还希望开放环境疾病药物的制药企业将能够利用这些数据。
这项研究详细地描述了用于确定出15个小鼠的基因组中分布的827万个高质量的SNP的方法。SNP即单核苷酸多态性是发生在DNA序列中的单个核苷酸的遗传变异。
研究人员利用将第一种小鼠C57BL/6J进行DNA测序，并将它们作为进行其他四种野生型和11种实验室常用小鼠测序的标准参照。研究人员利用寡核苷酸芯片来寻找人类基因组中的常见DNA变异。
这种芯片分析了标准参照小鼠株的25.7亿个碱基对中的14.9亿个碱基对。然后，这些数据被用于开发单体型图谱（含有40898个片段）。
NTP（National Toxicology Program）计划是一项以NIEHS为总部的多研究机构合作进行的计划。NTP计划希望能够探索这些小鼠株对不同环境试剂的反应。该研究的数据可登陆http://www.ncbi.nlm.nih.gov/SNP/获得。
原始出处:
Nature advance online publication 29 July 2007 | doi:10.1038/nature06067; Received 14 April 2007; Accepted 5 July 2007; Published online 29 July 2007
A sequence-based variation map of 8.27 million SNPs in inbred mouse strains
Kelly A. Frazer1, Eleazar Eskin2, Hyun Min Kang3, Molly A. Bogue4, David A. Hinds1, Erica J. Beilharz1, Robert V. Gupta1, Julie Montgomery1, Matt M. Morenzoni1, Geoffrey B. Nilsen1, Charit L. Pethiyagoda1, Laura L. Stuve1, Frank M. Johnson5, Mark J. Daly6,7, Claire M. Wade6,7 & David R. Cox1
Perlegen Sciences, 2021 Stierlin Court, Mountain View, California 94043, USA
Department of Computer Science and Department of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California 92093, USA
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Center for Human Genetic Research, Massachussets General Hospital, 185 Cambridge St, Boston, Massachusetts 02114, USA
Correspondence to: Kelly A. Frazer1 Correspondence and requests for materials should be addressed to K.A.F. (Email: frazer.kelly@scrippshealth.org).
A dense map of genetic variation in the laboratory mouse genome will provide insights into the evolutionary history of the species1 and lead to an improved understanding of the relationship between inter-strain genotypic and phenotypic differences. Here we resequence the genomes of four wild-derived and eleven classical strains. We identify 8.27 million high-quality single nucleotide polymorphisms (SNPs) densely distributed across the genome, and determine the locations of the high (divergent subspecies ancestry) and low (common subspecies ancestry) SNP-rate intervals2, 3, 4, 5, 6 for every pairwise combination of classical strains. Using these data, we generate a genome-wide haplotype map containing 40,898 segments, each with an average of three distinct ancestral haplotypes. For the haplotypes in the classical strains that are unequivocally assigned ancestry, the genetic contributions of the Mus musculus subspecies—M. m. domesticus, M. m. musculus, M. m. castaneus and the hybrid M. m. molossinus—are 68%, 6%, 3% and 10%, respectively; the remaining 13% of haplotypes are of unknown ancestral origin. The considerable regional redundancy of the SNP data will facilitate imputation of the majority of these genotypes in less-densely typed classical inbred strains to provide a complete view of variation in additional strains.
