Linkage disequilibrium analysis identifies an FGFR1 haplotype-tag SNP associated with normal variation in craniofacial shape

摘要: Mutations in FGFR1 and TWIST1 have been reported to affect the timing of calvarial suture fusion resulting craniosynostosis facial abnormalities. We screened nonpathologic populations for genetic polymorphisms that may associate with normal craniofacial variation. identified 17 single-nucleotide (SNPs) FGFR1, 6 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 found TWIST1. SNP haplotypes reconstructed Caucasian, Asian, Australian Aboriginal, African American populations. All shared two linkage disequilibrium blocks, one haplotype-tag (htSNP) tagging each block. The htSNP g.8592931G-->C was a significant negative correlation cephalic index all (R = -0.187, p 0.036), larger correlations Asians females. This finding is starting point identification set can be genotyped determine both disease phenotypes.