Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.
Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.
复制标题
矢状位和异位性无综合征性颅缝闭合相关候选区域的靶向测序。
DOI：
10.3390/genes13050816
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发表时间：
2022-05-03
期刊：
影响因子：
3.5
通讯作者：
Boyadjiev, Simeon A.
中科院分区：
文献类型：
--
作者：
Justice, Cristina M.;Musolf, Anthony M.;Cuellar, Araceli;Lattanzi, Wanda;Simeonov, Emil;Kaneva, Radka;Paschall, Justin;Cunningham, Michael;Wilkie, Andrew O. M.;Wilson, Alexander F.;Romitti, Paul A.;Boyadjiev, Simeon A.
颅缝早闭（CS）是一种主要的出生缺陷，其中一个或多个颅骨缝过早融合。我们之前对矢状面非综合征型CS（sNCS）进行了全基因组关联研究（GWAS），确定了20p12.3上BMP 2下游和7p14.3上BBS 9内含子的关联;对3q 29上DLG 1中插补变异的分析也具有全基因组显著性。我们用GWAS跟踪了这项工作，发现了20q13.31上内含子与BMP 7的显著关联。在本研究中，我们对3q 29、7p14.3和20p12.3上的相关区域进行了测序，包括83个sNCS亲子三人组中靠近这些区域的两个候选基因（BMP 2和BMPER），并对80个mNCS亲子三人组中7p14.3和20q13.2-q13.32上的区域进行了测序。如果先证者携带至少一个拷贝的最高相关GWAS变异（sNCS的rs 1884302 C等位基因; mNCS的rs6127972 T等位基因），则从原始GWAS队列中选择这些儿童-父母三联体。在这些靶向区域中测序的许多变体被强烈预测为在颅面发育或骨形态发生中涉及的转录因子的结合位点内。富含多于一个三重体并且被预测为对基因功能有害的变体优先用于功能研究。
Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.
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DOI：
10.1002/ajmg.a.38159
发表时间：
2017-05
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Lattanzi W;Barba M;Di Pietro L;Boyadjiev SA
通讯作者：
Boyadjiev SA
影响因子：
3
作者：
Hong, Chang-Soo;Devotta, Arun;Lee, Young-Hoon;Park, Byung-Yong;Saint-Jeannet, Jean-Pierre
通讯作者：
Saint-Jeannet, Jean-Pierre
影响因子：
9.8
作者：
Li, Bingshan;Leal, Suzanne M.
通讯作者：
Leal, Suzanne M.
影响因子：
4.6
作者：
Aguiar, Diego P.;Sghari, Soufien;Creuzet, Sophie
通讯作者：
Creuzet, Sophie
影响因子：
9.8
作者：
He, Zongxiao;O'Roak, Brian J.;Leal, Suzanne M.
通讯作者：
Leal, Suzanne M.