外显子测序揭示罕见遗传疾病的致病原因
美国华盛顿大学的研究人员首次成功地利用“外显子测序(exome quencing)”技术，发现了一种一个与孟德尔疾病（单基因疾病）相关的基因。这篇以“Exome quencing identifies the cau of a mendelian disorder”为题的研究报告发表在11月13日关于张飞的故事Nature Genetics杂志上。
学生自我评价200字孟德尔疾病是由单个位点或基因的突变造成的，如囊肿性纤维化，镰刀状细胞病等。在基因组中，所有能编码蛋白质的基因区域都称为外显子，虽然外显子只占基因组的1%，但在这1%的基因组中，发现了超过85%的突变都能导致孟德尔疾病。因此，科学家现在开始选择编码蛋白质的外显子作为研究对象，这或将成为一种研究遗传性疾病与基因之间关系的有效方式。
该课题组对米勒综合症(Miller syndrome)进行研究，米勒综合曾是一种导致患者口、眼、耳、足等畸形的遗传病。研究人员发现米勒综合症患者患病的原因是由于DHODH基因发生了基因突变。
原始出处：
奇怪的理发屋
Nature Genetics 13 November 2009 | Corrected online: 22 November 2009 | doi:10.1038/ng.499
Exome quencing identifies the cau of a mendelian disorder
Sarah B Ng1,10, Kati J Buckingham2,10, Choli Lee1, Abigail W Bigham2, Holly K Tabor2,3, Karin M Dent4, Chad D Huff5, Paul T Shannon6, Ethylin Wang Jabs7,8, Deborah A Nickerson1, Jay Shendure1 & Michael J Bamshad1,2,9
屏居
We demonstrate the first successful application of exome quencing to discover the gene for a rare mendelian disorder of unknown cau, Miller syndrome (MIM%263750). For four affected individuals in three independent kindreds, we captured and quenced coding regions to a mean coverage of 40 and sufficient depth to call variants at 97% of each targeted exome. Filtering against public SNP databas and eight HapMap exomes for genes with two previously unknown variants in each of the four individuals identified a single candidate gene, DHODH, which encodes a key enzyme in the pyrimidine de novo biosynthesis pathway. Sanger quencing confirmed the prence of DHODH mutations i
volterran three additional families with Miller syndrome. Exome quencing of a small number of unrelated affected individuals is a powerful, efficient strategy for identifying the genes underlying rare mendelian disorders and will likely transform the genetic analysis of monogenic traits.现代重生
1 Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
2 Department of Pediatrics, University of Washington, Seattle, Washington, USA.
3 Treuman Katz Center for Pediatric Bioethics, Seattle Children's Hospital, Seattle, Washington, USA.
4 Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
古典吉他曲>白酒英文5 Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
6 Institute of Systems Biology, Seattle, Washington, USA.
7 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
8 Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
9 Seattle Children's Hospital, Seattle, Washington, USA.
10 The authors contributed equally to this work.
