Whole genome analyses reveal no pathogenetic single nucleotide or structural differences between monozygotic twins discordant for amyotrophic lateral sclerosis
Whole genome analyses reveal no pathogenetic single nucleotide or structural differences between monozygotic twins discordant for amyotrophic lateral sclerosis
复制标题
全基因组分析显示，肌萎缩侧索硬化症不一致的同卵双胞胎之间没有致病性单核苷酸或结构差异
DOI：
10.3109/21678421.2015.1040029
复制
发表时间：
2015
影响因子：
2.8
通讯作者：
R. Pamphlett
中科院分区：
文献类型：
--
作者：
Karyn Meltz Steinberg;Thomas J. Nicholas;D. Koboldt;Bing Yu;E. Mardis;R. Pamphlett
The contribution of genetic and environmental factors to the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unclear. To investigate the genetic component of the disease, we performed whole genome sequencing on ALS discordant monozygotic twins. Illumina whole genome sequencing on white blood cell DNA of five ALS-discordant monozygotic twin pairs (10 samples in total) yielded ∼30x coverage per individual. All single nucleotide variants, indels, and structural variants (copy number variants, inversions and translocations) were called and evaluated for functional consequence, evolutionary conservation, population frequency and overlap with known ALS associated variants and genes. Results showed that no validated discordant coding or regulatory single nucleotide variants or indels were found, and nor were any genome-wide discordant structural variants detected. Concordant variants of particular interest were: 1) two rare, highly-conserved heterozygous non-synonymous variants in SYT9 and EWSR1, genes previously associated with ALS (out of 2044 rare heterozygous variants detected); 2) three rare homozygous missense variants; and 3) three novel copy number deletions that overlapped genes. In conclusion, no convincing coding or regulatory nucleotide or genome-wide structural differences were found between ALS discordant monozygotic twins. The results suggest that more work is needed to elucidate possible environmental, epigenetic, oligogenic and somatic genetic factors that could underlie susceptibility to sporadic ALS.
登录
查看更多内容
影响因子：
3.5
作者：
Couthouis, Julien;Hart, Michael P.;Gitler, Aaron D.
通讯作者：
Gitler, Aaron D.
DOI：
10.1056/nejmoa0903840
发表时间：
2009-09-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Mardis ER;Ding L;Dooling DJ;Larson DE;McLellan MD;Chen K;Koboldt DC;Fulton RS;Delehaunty KD;McGrath SD;Fulton LA;Locke DP;Magrini VJ;Abbott RM;Vickery TL;Reed JS;Robinson JS;Wylie T;Smith SM;Carmichael L;Eldred JM;Harris CC;Walker J;Peck JB;Du F;Dukes AF;Sanderson GE;Brummett AM;Clark E;McMichael JF;Meyer RJ;Schindler JK;Pohl CS;Wallis JW;Shi X;Lin L;Schmidt H;Tang Y;Haipek C;Wiechert ME;Ivy JV;Kalicki J;Elliott G;Ries RE;Payton JE;Westervelt P;Tomasson MH;Watson MA;Baty J;Heath S;Shannon WD;Nagarajan R;Link DC;Walter MJ;Graubert TA;DiPersio JF;Wilson RK;Ley TJ
通讯作者：
Ley TJ
影响因子：
7
作者：
Abyzov, Alexej;Urban, Alexander E.;Gerstein, Mark
通讯作者：
Gerstein, Mark
影响因子：
9.8
作者：
Bruder, Carl E. G.;Piotrowski, Arkadiusz;Dumanski, Jan P.
通讯作者：
Dumanski, Jan P.