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迈向通用正向遗传学:利用线虫的基因组草图序列鉴定影响外阴发育的突变

Toward Universal Forward Genetics: Using a Draft Genome Sequence of the Nematode To Identify Mutations Affecting Vulva Development.

作者信息

Besnard Fabrice, Koutsovoulos Georgios, Dieudonné Sana, Blaxter Mark, Félix Marie-Anne

机构信息

École Normale Supérieure, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Biologie de l'École Normale Supérieure, Paris Sciences et Lettres Research University, 75005, France

Institute of Evolutionary Biology, University of Edinburgh, EH8 9YL, United Kingdom.

出版信息

Genetics. 2017 Aug;206(4):1747-1761. doi: 10.1534/genetics.117.203521. Epub 2017 Jun 19.

Abstract

Mapping-by-sequencing has become a standard method to map and identify phenotype-causing mutations in model species. Here, we show that a fragmented draft assembly is sufficient to perform mapping-by-sequencing in nonmodel species. We generated a draft assembly and annotation of the genome of the free-living nematode , a distant relative of the model We used this draft to identify the likely causative mutations at the -3 locus, which affect vulval development. The locus encodes the ortholog of , and we further show that mutants also have an unsuspected vulval-development phenotype. In a virtuous circle, we were able to use the linkage information collected during mutant mapping to improve the genome assembly. These results showcase the promise of genome-enabled forward genetics in nonmodel species.

摘要

基于测序的定位已成为在模式物种中定位和鉴定导致表型突变的标准方法。在此,我们表明,一个片段化的草图组装足以在非模式物种中进行基于测序的定位。我们生成了自由生活线虫基因组的草图组装和注释,该线虫是模式生物的远亲。我们利用这个草图鉴定了影响阴门发育的-3位点可能的致病突变。该位点编码的直系同源物,并且我们进一步表明突变体也具有未被怀疑的阴门发育表型。在一个良性循环中,我们能够利用在突变体定位过程中收集的连锁信息来改进基因组组装。这些结果展示了在非模式物种中基于基因组的正向遗传学的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c79e/5560785/9262a30b5f7d/1747fig1.jpg

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