Genome-wide consequences of deleting any single gene.
Genome-wide consequences of deleting any single gene.
复制标题
DOI：
10.1016/j.molcel.2013.09.026
复制
发表时间：
2013-11-21
期刊：
影响因子：
16
通讯作者：
Hardwick, J. Marie
中科院分区：
文献类型：
--
作者：
Teng, Xinchen;Dayhoff-Brannigan, Margaret;Cheng, Wen-Chih;Gilbert, Catherine E.;Sing, Cierra N.;Diny, Nicola L.;Wheelan, Sarah J.;Dunham, Maitreya J.;Boeke, Jef D.;Pineda, Fernando J.;Hardwick, J. Marie
染色体片段的丢失或重复可能导致与癌症相关的进一步基因组变化。然而，尚不清楚是否只有选定的基因子集负责推动进一步的变化。为了确定基因组中任何给定基因的扰动是否足以驱动随后的遗传变化，我们分析了酵母敲除集合中功能后果的二次突变。与野生型不同，大多数基因敲除菌株被发现具有一种额外的突变基因，影响营养反应和/或热应激诱导的细胞死亡。此外，同一基因的独立敲除通常会导致同一次要基因发生突变。基因组测序鉴定出几种人类肿瘤抑制同源物的获得性突变。因此，任何单个基因的突变都可能导致基因组失衡，其后果足以驱动适应性遗传变化。这使遗传分析变得复杂，但这是在进化过程中失去最初在压力下获得的功能单位的逻辑结果。
Loss or duplication of chromosome segments can lead to further genomic changes associated with cancer. However, it is not known if only a select subset of genes is responsible for driving further changes. To determine if perturbation of any given gene in a genome suffices to drive subsequent genetic changes, we analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat-stress-induced cell death. Moreover, independent knockouts of the same gene often evolved mutations in the same secondary gene. Genome sequencing identified acquired mutations in several human tumor suppressor homologs. Thus, mutation of any single gene may cause a genomic imbalance with consequences sufficient to drive adaptive genetic changes. This complicates genetic analyses, but is a logical consequence of losing a functional unit originally acquired under pressure during evolution.
登录
查看更多内容
影响因子：
9.8
作者：
Levy SF;Ziv N;Siegal ML
通讯作者：
Siegal ML
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Laurie, Cathy C.;Laurie, Cecelia A.;Rice, Kenneth;Doheny, Kimberly F.;Zelnick, Leila R.;McHugh, Caitlin P.;Ling, Hua;Hetrick, Kurt N.;Pugh, Elizabeth W.;Amos, Chris;Wei, Qingyi;Wang, Li-E;Lee, Jeffrey E.;Barnes, Kathleen C.;Hansel, Nadia N.;Mathias, Rasika;Daley, Denise;Beaty, Terri H.;Scott, Alan F.;Ruczinski, Ingo;Scharpf, Rob B.;Bierut, Laura J.;Hartz, Sarah M.;Landi, Maria Teresa;Freedman, Neal D.;Goldin, Lynn R.;Ginsburg, David;Li, Jun;Desch, Karl C.;Strom, Sara S.;Blot, William J.;Signorello, Lisa B.;Ingles, Sue A.;Chanock, Stephen J.;Berndt, Sonja I.;Le Marchand, Loic;Henderson, Brian E.;Monroe, Kristine R.;Heit, John A.;de Andrade, Mariza;Armasu, Sebastian M.;Regnier, Cynthia;Lowe, William L.;Hayes, M. Geoffrey;Marazita, Mary L.;Feingold, Eleanor;Murray, Jeffrey C.;Melbye, Mads;Feenstra, Bjarke;Kang, Jae H.;Wiggs, Janey L.;Jarvik, Gail P.;McDavid, Andrew N.;Seshan, Venkatraman E.;Mirel, Daniel B.;Crenshaw, Andrew;Sharopova, Nataliya;Wise, Anastasia;Shen, Jess;Crosslin, David R.;Levine, David M.;Zheng, Xiuwen;Udren, Jenna I.;Bennett, Siiri;Nelson, Sarah C.;Gogarten, Stephanie M.;Conomos, Matthew P.;Heagerty, Patrick;Manolio, Teri;Pasquale, Louis R.;Haiman, Christopher A.;Caporaso, Neil;Weir, Bruce S.
通讯作者：
Weir, Bruce S.
影响因子：
56.9
作者：
Hillenmeyer, Maureen E.;Fung, Eula;Giaever, Guri
通讯作者：
Giaever, Guri
影响因子：
13.6
作者：
Ferretti, E;De Smaele, E;Gulino, A
通讯作者：
Gulino, A