Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa, IA, USA.
Department of Orthodontics, University of Dundee, Dundee, UK.
Hum Mol Genet. 2019 Mar 15;28(6):1038-1051. doi: 10.1093/hmg/ddy402.
Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.
口腔颌面部裂是一种常见的发育障碍，会造成严重的临床、经济和心理问题。我们在撒哈拉以南非洲人群中，使用约 1700 万个标记物，对单纯腭裂（CPO）和唇裂伴或不伴腭裂（CL/P）进行了全基因组关联分析。经过复制和综合分析，我们在染色体 2（接近 CTNNA2）和 19（接近 SULT2A1）上鉴定到了与 CPO 相关的新的全基因组显著的基因座。在小鼠中的 Sult2a1 原位杂交显示 SULT2A1 在腭中胚层细胞、腭嵴和融合腭的腭上皮中有表达。在我们的研究中，先前报道的 8q24 是 CL/P 最显著的基因座，我们复制了包括 PAX7 和 VAX1 在内的几个先前报道的基因座。
