Shiang R, Lidral A C, Ardinger H H, Buetow K H, Romitti P A, Munger R G, Murray J C
Department of Biological Chemistry, University of California, Irvine.
Am J Hum Genet. 1993 Oct;53(4):836-43.
Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. We carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3' untranslated region of the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using chi 2 analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3' untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P.
遗传分析和组织特异性表达研究支持转化生长因子α（TGFA）在颅面发育中发挥作用。先前的研究已证实，TGFA等位基因与人类非综合征性唇裂伴或不伴腭裂（CL/P）有关联。我们进行了一项回顾性关联研究，以确定TGFA基因的特定等位基因变体是否也与单纯腭裂（CPO）有关联。通过单链构象多态性分析检测了针对TGFA cDNA的12组重叠引物的PCR产物。在TGFA基因的3'非翻译区鉴定出4个TGFA的DNA多态性位点。通过卡方分析，在CPO的病例和对照人群中对这些变体以及先前鉴定出的TGFA的限制性片段长度多态性（RFLP）进行了特征分析。确定了TGFA等位基因与CPO之间存在显著关联，这进一步支持了该基因作为颅面发育遗传决定因素之一的作用。对这些变体的序列分析揭示，在先前与反义转录本相关的3'非翻译区内，彼此相距30 bp的位置存在一组三个可变位点。这些研究扩展了TGFA在颅面形态发生中的作用，并支持了非综合征性CL/P形式背后的一种相互关联机制。
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