CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.
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DOI：
10.1371/journal.pone.0189591
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Gerdhem P
中科院分区：
文献类型：
--
作者：
Einarsdottir E;Grauers A;Wang J;Jiao H;Escher SA;Danielsson A;Simony A;Andersen M;Christensen SB;Åkesson K;Kou I;Khanshour AM;Ohlin A;Wise C;Ikegawa S;Kere J;Gerdhem P
最初通过遗传连锁分析对具有特发性脊柱侧凸常染色体显性遗传的瑞典家系进行了研究，优先考虑基因组区域进行进一步分析。这揭示了 1 号染色体上的一个位点，该位点具有所有受影响个体共有的假定风险单倍型。随后对两名受影响的个体进行了外显子组测序，发现了 CELSR2 基因中的罕见非同义变异。该变体是 rs141489111，外显子 21 (NM_001408) 中的 c.G6859A 变化，导致预测的 p.V2287I (NP_001399.1) 变化。该变异存在于所有受影响的谱系成员中，但外显率降低。对 1739 名瑞典-丹麦脊柱侧弯病例和 1812 名对照的 CELSR1-3 标记变异进行分析，发现与 rs2281894（CELSR2 中常见的同义变异）显着相关（p = 0.0001）。这种关联并未在日本和美国的病例对照队列中得到复制。未发现与 CELSR1 或 CELSR3 变异相关。我们的研究结果表明，CELSR2 中的一种罕见变异是显性隔离家庭特发性脊柱侧凸的病因，并进一步强调了 CELSR2 的常见变异在瑞典-丹麦人群中对特发性脊柱侧凸的普遍易感性。两种变体都位于高度保守的 GAIN 蛋白结构域中，该结构域是 CELSR2 自身蛋白水解所必需的，表明其功能重要性。
A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1007/978-1-4939-0366-5_2
发表时间：
2014-01-01
期刊：
PROTEIN STRUCTURE PREDICTION, 3RD EDITION
影响因子：
--
作者：
Kaellberg, Morten;Margaryan, Gohar;Xu, Jinbo
通讯作者：
Xu, Jinbo
影响因子：
2.8
作者：
Grauers, Anna;Rahman, Iffat;Gerdhem, Paul
通讯作者：
Gerdhem, Paul