Genetic Studies of Clubfoot (ITEV)

描述（由申请人提供）：马蹄内翻足或特发性马蹄内翻足（ITEV）是五种最常见的出生缺陷之一，在美国每年影响约4，000名新生儿。虽然这些儿童的矫形护理有所改善，但长期问题仍然存在，医疗保健费用很高。研究表明，ITEV是一种复杂的疾病，分离分析和家庭研究表明，遗传因素在ITEV的发展中起着重要的病因作用。只有一个环境因素，母亲在怀孕期间吸烟，有牵连。我们假设，一个小数目的基因占相当大的比例ITEV，这些基因可以在一个定义的人口。现在的挑战是确定遗传位点，以及环境暴露的影响。为了完成这一任务，重要的是要有一个明确的人口和方法来检测关联和不关联的联系。为了实现这些目标，我们已经确定和特点的多重ITEV家庭和单纯ITEV三人组，包括两个大的ITEV家庭，这是最大的ITEV人口中存在的资源。我们将对我们的ITEV数据集进行高密度SNP基因组扫描，以识别可能含有ITEV基因的染色体区域，并随后询问这些区域和候选基因。我们拥有独特的ITEV人群，并采用适当的方法进行这项研究。研究阶段为：1）继续确定多重家庭和种族多样的亲子三人组，2）高密度SNP全基因组扫描，3）收集验证性（单纯三人组和病例对照）数据集以测试新鉴定的基因。本研究的结果将为鉴定导致ITEV表型的基因提供必要的数据。高风险基因型的识别可以导致在选定的人群中制定预防计划，并可能建议基于基因的预防策略。

DESCRIPTION (provided by applicant): Clubfoot or idiopathic talipes equinovarus (ITEV) is one of the five most common birth defects, affecting approximately 4,000 newborns each year in the US. While the orthopedic care of these children has improved, longterm problems persist and the health care costs are significant. Studies suggest that ITEV is a complex disorder with segregation analyses and family studies indicating that genetic factors play an important etiologic role in the development of ITEV. Only one environmental factor, maternal smoking during pregnancy, has been implicated. We postulate that a small number of genes account for a substantial fraction of ITEV and that these genes can be identified in a defined population. The challenge now is to identify the genetic loci and, later, the effect of environmental exposures. To accomplish this task, it is important to have a well-defined population and the methodology to detect linkage with and without association. Towards these goals, we have identified and characterized multiplex ITEV families and simplex ITEV trios including two large ITEV families, a resource which is among the largest ITEV population in existence. We will perform a high-density SNP genome scan on our ITEV dataset to identify chromosomal regions that may harbor ITEV genes with subsequent interrogation of these regions and candidate genes. We are in a position with our unique ITEV population and with the methodology in place to undertake this study. The study phases are: 1) continued ascertainment of multiplex families and ethnically diverse parent child trios, 2) high density SNP genome-wide scan 3) collection of confirmatory (simplex trios and case-control) datasets to test newly identified genes. The results of this study will provide data essential to the identification of the gene(s) contributing to the ITEV phenotype. Identification of high-risk genotypes can lead to the development of prevention programs in selected populations and may suggest gene-based prevention strategies.