title: X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts.
abstract: As part of an international consortium, case-parent trios were collected for a genome-wide association study of isolated, non-syndromic oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP). Non-syndromic oral clefts have a complex and heterogeneous etiology. Risk is influenced by genes and environmental factors, and differs markedly by gender. Family-based association tests (FBAT) were used on 14,486 single nucleotide polymorphisms (SNPs) spanning the X chromosome, stratified by type of cleft and racial group. Significant results, even after multiple-comparisons correction, were obtained for the Duchenne muscular dystrophy (DMD) gene, the largest single gene in the human genome, among CL/P (i.e., both CL and CLP combined) trios. When stratified into groups of European and Asian ancestry, stronger signals were obtained for Asian subjects. Although conventional sliding-window haplotype analysis showed no increase in significance, selected combinations of the 25 most significant SNPs in the DMD gene identified four SNPs together that attained genome-wide significance among Asian CL/P trios, raising the possibility of interaction between distant SNPs within the DMD gene.
authors.affiliation: Johns Hopkins University, Baltimore, MD 21205-2103, USA.
authors.forename: Poorav J
authors.initials: PJ
authors.lastname: Patel
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Munger
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Tanda
authors.initials: T
authors.lastname: Murray
authors.forename: Margaret
authors.initials: M
authors.lastname: Rose
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Redett
authors.forename: Sheng C
authors.initials: SC
authors.lastname: Jin
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.forename: Yah-Huei
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ye
authors.forename: Vincent
authors.initials: V
authors.lastname: Yeow
authors.forename: Samuel
authors.initials: S
authors.lastname: Chong
authors.forename: Sun H
authors.initials: SH
authors.lastname: Jee
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked / Q000502:physiology*; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012306:Risk; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers