Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82.
Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82.
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斑秃中的全外显子组测序鉴定了KRT82中的罕见变体。
DOI：
10.1038/s41467-022-28343-3
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发表时间：
2022-02-10
影响因子：
16.6
通讯作者：
Christiano AM
中科院分区：
文献类型：
--
作者：
Erjavec SO;Gelfman S;Abdelaziz AR;Lee EY;Monga I;Alkelai A;Ionita-Laza I;Petukhova L;Christiano AM
Alopecia areata is a complex genetic disease that results in hair loss due to the autoimmune-mediated attack of the hair follicle. We previously defined a role for both rare and common variants in our earlier GWAS and linkage studies. Here, we identify rare variants contributing to Alopecia Areata using a whole exome sequencing and gene-level burden analyses approach on 849 Alopecia Areata patients compared to 15,640 controls. KRT82 is identified as an Alopecia Areata risk gene with rare damaging variants in 51 heterozygous Alopecia Areata individuals (6.01%), achieving genome-wide significance (p = 2.18E−07). KRT82 encodes a hair-specific type II keratin that is exclusively expressed in the hair shaft cuticle during anagen phase, and its expression is decreased in Alopecia Areata patient skin and hair follicles. Finally, we find that cases with an identified damaging KRT82 variant and reduced KRT82 expression have elevated perifollicular CD8 infiltrates. In this work, we utilize whole exome sequencing to successfully identify a significant Alopecia Areata disease-relevant gene, KRT82, and reveal a proposed mechanism for rare variant predisposition leading to disrupted hair shaft integrity. Common variants have been discovered to be associated with Alopecia Areata; however, rare variants have been less well studied. Here, the authors use whole-exome sequencing to identify associated rare variants in the hair keratin gene KRT82. Further, they find that individuals with Alopecia Areata have reduced expression of KRT82 in the skin and hair follicle.
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影响因子：
6.5
作者：
Hedstrand, H;Perheentupa, J;Kämpe, O
通讯作者：
Kämpe, O
DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
鉴定基于序列的研究中罕见的因果变异：VPS13B的方法和应用，VPS13B是Cohen综合征和自闭症的基因。
影响因子：
4.5
作者：
Ionita-Laza I;Capanu M;De Rubeis S;McCallum K;Buxbaum JD
通讯作者：
Buxbaum JD