Genetic Factors in Birth Defects

大约20个主要的畸形已经被确定用于未来的调查。从先天畸形登记处和适当的对照对象中挑选了感兴趣的主要出生缺陷病例。来自登记处的数据已经与该州的新生儿筛查计划联系起来，以识别用于提取DNA的滤纸样本。已经为许多项目挑选了样本并提取了DNA。 第一批报告已经完成，并已提交出版。其中两项目前正在审查中。此外，其他三个项目的基因分型工作现已完成，这三个项目分别是先天性横隔疝、肢体缺陷和胎儿酒精综合征。对这些数据的分析正在进行中。其他项目的样本正在确定，正在进行DNA提取，或正在进行单核苷酸多态(SNPs)基因分型。 首批完成的项目是关于脐膨出和先天性巨结肠。脐膨出调查发现，病例与转钴胺2(维生素B12)受体基因之间存在关联。如果得到证实，这一发现表明B12在预防脐膨出方面可能是有用的，也可能解释之前的工作，即母亲使用多种维生素与降低脐膨出风险之间存在关联。这项研究还发现了与同型半胱氨酸代谢相关的其他基因与脐膨出之间的关联。这些发现表明，同型半胱氨酸代谢(与维生素B12有关)可能与脐膨出有因果关系。 第二个已完成的项目检查了与神经组织迁移和先天性巨结肠相关的基因。通过测序，发现了一种以前被报道与先天性巨结肠有关的基因的新变种。还发现了其他与迁徙有关的潜在重要基因。 识别病例和从银行获取样本以提取DNA的工作仍在继续。还在审查数据，以确定罕见的缺陷，以便通过不同的方法进行研究。DNA将通过大规模阵列进行分析，以识别拷贝数变异。

Approximately 20 major malformations have been identified for future investigations. Cases with the major birth defects of interest have been selected from the Congenital Malformations Registry along with suitable control subjects. Data from the Registry have been linked with the state's Newborn Screening Program to identify filter paper samples for DNA extraction. Samples have been selected and DNA has been extracted for many projects. The first reports have been completed and have been submitted for publication. Two are currently under review. In addition genotyping is now complete for three other projects, congenital diaphragmatic hernia, limb defects, and fetal alcohol syndrome. Analysis of these data is underway. Samples for other projects are being identified, undergoing DNA extraction, or being genotyped for single nucleotide polymorphisms (SNPs. The first completed projects are on omphalocele and Hirschsprung's disease. The omphalocele investigation found an association between being a case and the transcobalamin 2 (vitamin B12) receptor gene. If confirmed, this finding suggests that B12 may be useful in preventing omphaloceles and may also explain previous work that showed an association between maternal multivitamin use and reduced risk for omphalocele. This study also found a suggestive association between other genes related to homocysteine metabolism and omphalocele. These findings suggest that homocysteine metabolism (which is related to vitamin B12) could be causally related to omphalocele. The second completed project examined genes related to migration of neural tissue and Hirschsprung's disease. New variants of a gene previously reported to be related to Hirschsprung's disease,RET, were found by sequencing. Other potentially important genes involved in migration were also found. Work is continuing to identify cases and obtain samples from the bank for DNA extraction. Data are also being reviewed to identify rare defects for study by a different approach. DNA will be analyzed by large scale arrays to identify copy number variants.