Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease.
Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease.
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DOI：
10.3390/genes12060922
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发表时间：
2021-06-16
期刊：
影响因子：
3.5
通讯作者：
Hadley Miller N
中科院分区：
文献类型：
--
作者：
Terhune EA;Wethey CI;Cuevas MT;Monley AM;Baschal EE;Bland MR;Baschal R;Trahan GD;Taylor MRG;Jones KL;Hadley Miller N
青少年特发性脊柱侧凸（AIS）是一种脊柱侧弯>10°并伴有旋转，影响人群中2-3%的健康儿童。众所周知，AIS具有重要的遗传成分，尽管通过GWAS和下一代测序方法在无关个体中鉴定出少数风险基因座，但该疾病的潜在病因在很大程度上仍然未知。在这项研究中，我们对23个多代家庭中的受影响个体进行了外显子组测序，假设罕见，低频率，致病变异的发生将共同发生在远亲，受影响的个体中。对所有测序的家族成员共有的不常见的、潜在的破坏性变异进行生物信息学过滤，发现23个家族的1160个基因中有1448个变异，其中132个基因由两个或更多个家族共有。有10个基因为>4个家系所共有，没有基因为所有家系所共有。基因富集分析表明，在细胞骨架和细胞外基质相关的过程中的变体的富集。这些数据支持这样一种模型，即AIS是一种高度多基因疾病，不同家族谱系的受影响个体之间共享的含有变异的基因很少。这项工作为进一步探索家族性AIS遗传学研究提供了新的资源。
Adolescent idiopathic scoliosis (AIS) is a lateral spinal curvature >10° with rotation that affects 2–3% of healthy children across populations. AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown. In this study, we performed exome sequencing of affected individuals within 23 multigenerational families, with the hypothesis that the occurrence of rare, low frequency, disease-causing variants will co-occur in distantly related, affected individuals. Bioinformatic filtering of uncommon, potentially damaging variants shared by all sequenced family members revealed 1448 variants in 1160 genes across the 23 families, with 132 genes shared by two or more families. Ten genes were shared by >4 families, and no genes were shared by all. Gene enrichment analysis showed an enrichment of variants in cytoskeletal and extracellular matrix related processes. These data support a model that AIS is a highly polygenic disease, with few variant-containing genes shared between affected individuals across different family lineages. This work presents a novel resource for further exploration in familial AIS genetic research.
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特发性脊柱侧弯的斑马鱼模型将脑脊液流缺陷与脊柱曲率联系起来。
DOI：
10.1126/science.aaf6419
发表时间：
2016-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grimes DT;Boswell CW;Morante NF;Henkelman RM;Burdine RD;Ciruna B
通讯作者：
Ciruna B
影响因子：
2.8
作者：
Hawasli, Ammar H.;Hullar, Timothy E.;Dorward, Ian G.
通讯作者：
Dorward, Ian G.
DOI：
10.1186/1748-7161-1-2
发表时间：
2006-03-31
期刊：
Scoliosis
影响因子：
--
作者：
Asher MA;Burton DC
通讯作者：
Burton DC
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
DOI：
10.1016/j.jsbmb.2009.04.010
发表时间：
2009-08-01
影响因子：
4.1
作者：
Esposito, T.;Uccello, R.;Varriale, B.
通讯作者：
Varriale, B.