生物谷：美國的研究人員希望通過對15只常用于生物醫(yī)藥研究的小鼠的DNA進(jìn)行研究來幫助科研人員確定出與環(huán)境疾病敏感性相關(guān)的基因。目前這些數(shù)據(jù)被存放在了基因變異數(shù)據(jù)目錄之下,，即小鼠基因組單體型圖譜（將染色體分隔成許多小的片段）,，從而幫助研究人員找出小鼠中影響健康和疾病的基因和遺傳變異,。這個單體型圖譜公布在7月29日的《自然》雜志上,，該圖譜首次完整描述了小鼠基因組測序和SNP計劃的分析數(shù)據(jù),。該研究計劃由美國環(huán)境衛(wèi)生科學(xué)研究院進(jìn)行,。
這些數(shù)據(jù)使研究人員能夠比較一個小鼠與另外一個小鼠的遺傳組成,，并進(jìn)行必要的遺傳分析來確定出一些個體對疾病更敏感的原因,。這項研究成果使人們向著了解對人類對環(huán)境毒素的個體敏感性前進(jìn)了一步。研究人員還希望開放環(huán)境疾病藥物的制藥企業(yè)將能夠利用這些數(shù)據(jù),。
這項研究詳細(xì)地描述了用于確定出15個小鼠的基因組中分布的827萬個高質(zhì)量的SNP的方法,。SNP即單核苷酸多態(tài)性是發(fā)生在DNA序列中的單個核苷酸的遺傳變異。
研究人員利用將第一種小鼠C57BL/6J進(jìn)行DNA測序,，并將它們作為進(jìn)行其他四種野生型和11種實驗室常用小鼠測序的標(biāo)準(zhǔn)參照,。研究人員利用寡核苷酸芯片來尋找人類基因組中的常見DNA變異。
這種芯片分析了標(biāo)準(zhǔn)參照小鼠株的25.7億個堿基對中的14.9億個堿基對,。然后,，這些數(shù)據(jù)被用于開發(fā)單體型圖譜（含有40898個片段）。
NTP（National Toxicology Program）計劃是一項以NIEHS為總部的多研究機(jī)構(gòu)合作進(jìn)行的計劃,。NTP計劃希望能夠探索這些小鼠株對不同環(huán)境試劑的反應(yīng),。該研究的數(shù)據(jù)可登陸http://www.ncbi.nlm.nih.gov/SNP/獲得。
原始出處:
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: [email protected]).
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.
