X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts

作者：Patel Poorav J; Beaty Terri H^*; Ruczinski Ingo; Murray Jeffrey C; Marazita Mary L; Munger Ronald G; Hetmanski Jacqueline B; Wu Tao; Murray Tanda; Rose Margaret; Redett Richard J; Jin Sheng C; Lie Rolv T; Wu Chou Yah Huei; Wang Hong; Ye Xiaoqian; Yeow Vincent; Chong Samuel; Jee Sun H; Shi Bing; Scott Alan F

来源：European Journal of Oral Sciences, 2013, 121(2): 63-68.

DOI：10.1111/eos.12025

• case-parent trios
• Duchenne muscular dystrophy (DMD)
• family-based association
• oral clefts
• X-linked

As part of an international consortium, caseparent 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.

• 出版日期2013-4