title: Linkage disequilibrium analysis identifies an FGFR1 haplotype-tag SNP associated with normal variation in craniofacial shape.
abstract: 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.
authors.affiliation: Cooperative Research Centre for Diagnostics, Queensland University of Technology, GPO Box 2434, Brisbane, QLD 4001, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Coussens
authors.forename: Angela
authors.initials: A
authors.lastname: van Daal
mesh_terms: D001741:Black or African American; D044466:Asian People; D001483:Base Sequence; D002508:Cephalometry; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D005145:Face / Q000033:anatomy & histology*; D040461:Gene Components; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012886:Skull / Q000033:anatomy & histology*; D044465:White People
chemical_list: D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1