美国斯托瓦斯医学研究所开发出了一种名为“全基因组测序法”的果蝇突变基因测序法。研究人员称，在寻找果蝇突变基因上该方法能大幅减少时间和精力。相关研究发表在5月出版的《遗传学》杂志上。

据介绍，研究人员是通过测定果蝇突变后所产生的复合乙基甲（EMS）来绘制突变果蝇的基因图谱的。该结果将有助于对复合乙基甲的突变诱导机制以及使用基因工具来防止在同源染色体分裂后的基因重组的理解。

据了解，由于果蝇的基因可以被人工插入、删除或修改，可以被随机突变为人们所感兴趣的人类疾病特性以供研究，果蝇经常被用于对普通生物过程和人类疾病的研究。但要从大量的果蝇基因中寻找出带有研究人员所感兴趣的特定的突变基因却可谓是一个旷日持久的浩大工程，并且还有不少突变所导致的相关疾病尚未被发现。

该研究所称，新的方法大幅降低了在寻找突变果蝇上的障碍。负责该研究的斯科特·霍利研究员说，这种方法将会改变现有的果蝇基因遗传学。传统的测序方法的效率往往比较低，而这种“全基因组测序法”无论在时间还是在成本上都更胜一筹。除其他的潜在用途外，这种方法还能准确地发现那些被几个基因同时控制的具有遗传特性的分子。

该所分子生物学系主任卡伦·斯戴林·汉普顿说，如果根据复杂的显型特征，传统的绘制方法需要数月甚至一年的时间。而新的方法要获得科学家们感兴趣的突变基因只需要几个星期的时间，这种新一代基因测序技术的应用将是激动人心的。

推荐原始出处：

Genetics, Vol. 182, 25-32, May 2009, doi:10.1534/genetics.109.101998

Identification of EMS-Induced Mutations in Drosophila melanogaster by Whole-Genome Sequencing

Justin P. Blumenstiel*,, Aaron C. Noll, Jennifer A. Griffiths, Anoja G. Perera, Kendra N. Walton, William D. Gilliland, R. Scott Hawley, and Karen Staehling-Hampton,1

* Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, Kansas 66045,  Stowers Institute for Medical Research, Kansas City, Missouri 64110 and  Department of Physiology, Kansas University Medical Center, Kansas City, Kansas 66160
1 Corresponding Author: Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110.

Next-generation methods for rapid whole-genome sequencing enable the identification of single-base-pair mutations in Drosophila by comparing a chromosome bearing a new mutation to the unmutagenized sequence. To validate this approach, we sought to identify the molecular lesion responsible for a recessive EMS-induced mutation affecting egg shell morphology by using Illumina next-generation sequencing. After obtaining sufficient sequence from larvae that were homozygous for either wild-type or mutant chromosomes, we obtained high-quality reads for base pairs composing 70% of the third chromosome of both DNA samples. We verified 103 single-base-pair changes between the two chromosomes. Nine changes were nonsynonymous mutations and two were nonsense mutations. One nonsense mutation was in a gene, encore, whose mutations produce an egg shell phenotype also observed in progeny of homozygous mutant mothers. Complementation analysis revealed that the chromosome carried a new functional allele of encore, demonstrating that one round of next-generation sequencing can identify the causative lesion for a phenotype of interest. This new method of whole-genome sequencing represents great promise for mutant mapping in flies, potentially replacing conventional methods.