Linkage disequilibrium analysis identifies an FGFR1 haplotype-tag SNP associated with normal variation in craniofacial shape
Linkage disequilibrium analysis identifies an FGFR1 haplotype-tag SNP associated with normal variation in craniofacial shape
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DOI：
10.1016/j.ygeno.2005.02.002
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发表时间：
2005-05-01
期刊：
影响因子：
4.4
通讯作者：
van Daal, A
中科院分区：
文献类型：
--
作者：
Coussens, AK;van Daal, A
据报道，FGFR 1和TWIST 1的突变会影响颅骨缝融合的时间，导致颅缝早闭和面部畸形。我们筛选了非病理性人群中可能与正常颅面变异相关的遗传多态性。我们在FGFR 1中发现了17个单核苷酸多态性（SNP），其中6个是新的（g.8591855G -> A，g.8593685G -> A，g.8602303C -> T，g.8602475A -> G（p，Ile 293 Val），g.8605849C -> T，g.8607868G -> A）。在TWIST 1中未发现SNP。FGFR 1 SNP单倍型重建高加索，亚洲，澳大利亚土著和非洲裔美国人的人口。所有群体共享两个连锁不平衡区块，每个区块有一个单倍型标签SNP（htSNP）标记。发现htSNP g.8592931G -> C与所有人群的头指数具有显著的负相关性（R =-0.187，p = 0.036），在亚洲人和女性中具有更大的相关性。这一发现是一个起点，在确定一组单核苷酸多态性，可以基因分型，以确定正常和疾病的颅面表型。(c)2005年爱思唯尔公司All rights reserved.
Mutations in FGFR1 and TWIST1 have been reported to affect the timing of calvarial suture fusion resulting in craniosynostosis and facial abnormalities. We screened nonpathologic populations for genetic polymorphisms that may associate with normal craniofacial variation. We identified 17 single-nucleotide polymorphisms (SNPs) in FGFR1, 6 of which were novel (g.8591855G -> A, g.8593685G -> A, g.8602303C -> T, g.8602475A -> G (p,Ile293Val), g.8605849C -> T, g.8607868G -> A). No SNPs were found in TWIST1. FGFR1 SNP haplotypes were reconstructed for Caucasian, Asian, Australian Aboriginal, and African American populations. All populations shared two linkage disequilibrium blocks, with one haplotype-tag SNP (htSNP) tagging each block. The htSNP g.8592931G -> C was found to have a significant negative correlation with the cephalic index for all populations (R = -0.187, p = 0.036), with larger correlations in Asians and females. This finding is a starting point in the identification of a set of SNPs that can be genotyped to determine both normal and disease craniofacial phenotypes. (c) 2005 Elsevier Inc. All rights reserved.