Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis.
Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis.
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肌萎缩性侧硬化症中6,500个全基因组序列的结构变异分析。
DOI：
10.1038/s41525-021-00267-9
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发表时间：
2022-01-28
影响因子：
5.3
通讯作者：
Al-Chalabi A
中科院分区：
文献类型：
--
作者：
Al Khleifat A;Iacoangeli A;van Vugt JJFA;Bowles H;Moisse M;Zwamborn RAJ;van der Spek RAA;Shatunov A;Cooper-Knock J;Topp S;Byrne R;Gellera C;López V;Jones AR;Opie-Martin S;Vural A;Campos Y;van Rheenen W;Kenna B;Van Eijk KR;Kenna K;Weber M;Smith B;Fogh I;Silani V;Morrison KE;Dobson R;van Es MA;McLaughlin RL;Vourc'h P;Chio A;Corcia P;de Carvalho M;Gotkine M;Panades MP;Mora JS;Shaw PJ;Landers JE;Glass JD;Shaw CE;Basak N;Hardiman O;Robberecht W;Van Damme P;van den Berg LH;Veldink JH;Al-Chalabi A
肌萎缩侧索硬化症(ALS)的风险有很大的遗传贡献，遗传率估计高达60%。孟德尔变异和小效应变异都已被发现，但与其他疾病的共同之处是，这些变异只解释了一小部分遗传性。基因组结构变异可能是这种无法解释的遗传性的部分原因。因此，我们调查了一组25个ALS基因的结构变异与ALS风险和表型之间的关联。正如预期的那样，C9orf72基因的重复扩增被鉴定为与ALS相关。另外两个与肌萎缩侧索硬化症相关的结构变异被鉴定出来：VCP基因的倒位和ERBB4基因的插入。所有这三个变异都与ALS风险增加和疾病表达的特定表型模式相关。呼吸性ALS患者中超过70%的人携带ERBB4插入，而普通人群中的这一比例为25%，这表明呼吸性ALS可能是一种独特的基因亚型。
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
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影响因子：
14.5
作者：
Chio, Adriano;Borghero, Giuseppe;Sabatelli, Mario
通讯作者：
Sabatelli, Mario
DOI：
10.1016/s1474-4422(14)70219-4
发表时间：
2014-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Al-Chalabi A;Calvo A;Chio A;Colville S;Ellis CM;Hardiman O;Heverin M;Howard RS;Huisman MHB;Keren N;Leigh PN;Mazzini L;Mora G;Orrell RW;Rooney J;Scott KM;Scotton WJ;Seelen M;Shaw CE;Sidle KS;Swingler R;Tsuda M;Veldink JH;Visser AE;van den Berg LH;Pearce N
通讯作者：
Pearce N
DOI：
10.1038/nrg.2015.25
发表时间：
2016-04
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Carvalho CM;Lupski JR
通讯作者：
Lupski JR
影响因子：
11
作者：
Gijselinck I;Van Mossevelde S;van der Zee J;Sieben A;Engelborghs S;De Bleecker J;Ivanoiu A;Deryck O;Edbauer D;Zhang M;Heeman B;Bäumer V;Van den Broeck M;Mattheijssens M;Peeters K;Rogaeva E;De Jonghe P;Cras P;Martin JJ;de Deyn PP;Cruts M;Van Broeckhoven C
通讯作者：
Van Broeckhoven C
影响因子：
11
作者：
Dols-Icardo, Oriol;Garcia-Redondo, Alberto;Clarimon, Jordi
通讯作者：
Clarimon, Jordi