IDENTIFICATION OF MATERNAL AND FETAL GENETIC FACTORS IN PRETERM BIRTH

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 早产，或在怀孕37周前分娩的婴儿，是早产的结果，它影响到全球约10%的怀孕，目前在美国，这一数字正在上升到12%。尽管技术进步，但早产导致发病率和死亡率持续居高不下，在美国，每1000名活产婴儿中就有7名在出生后的第一个月死亡。在欠发达国家，即使在怀孕32周时出生的婴儿死亡率也高达80%。这一问题的严重性对穷人和少数群体的影响尤其严重，对个人、家庭和社会的影响是毁灭性的，迫使对病因进行调查，从而改善治疗和预防。虽然早产的一些特定原因已被确认，如双胎妊娠、早产前胎膜破裂和宫颈关闭不全，但仍有一大群人可以被认为是自发的。潜在的诱因包括感染、压力、营养不良、药物滥用、代谢失衡和遗传因素。双胞胎研究表明，遗传因素构成了这种风险的40%，而早产的唯一最佳预测因素是先前的早产。虽然有许多方法可以确定早熟等复杂性状的因果机制，但遗传研究不仅提供了验证先前怀疑的病因的机会，而且还提供了识别以前没有预料到的全新因素的机会。 研究早产儿遗传因素的一个主要挑战是风险病例尚未确定，因为可能是母亲和她的子宫，婴儿胎盘单位，或者两者一起，这使得即使是基础病例对照研究也很难进行。这些研究人员组建了一个跨学科的调查团队，包括产科医生、儿科医生、数量遗传学家和分子生物学家，以采取全面的遗传学方法来确定早产的潜在遗传原因。他们将使用一个全面的家庭收集计划，其中婴儿或母亲都可以被作为潜在病例进行研究，并将标准候选基因研究与非常强大的三代病例-父母三合一方法结合起来，利用全面的全基因组搜索来识别可能导致早产的多个基因。然后，基因识别可以为潜在生物学机制的研究提供支持，确认旧的靶点，最重要的是，确定预防和治疗策略的新靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Premature birth, or the delivery of an infant before 37 weeks gestation, is the result of preterm labor and it affects approximately 10% of pregnancies world-wide with growing numbers now at 12% in the United States. In spite of advances in technology, prematurity results in continued high-rates of morbidity and mortality with 7 per 1,000 live-born infants dying in the first month of life in the United States. Mortality is as high as 80% in infants born even at 32 weeks gestation in less developed countries. The enormity of this problem which disproportionately affects the poor and minority groups, is devastating in its impact on individuals, families, and society, compels investigations into etiologies that may lead to improvements in treatment and prevention. While some specific causes of prematurity are recognized, such as twin pregnancies, preterm pre-labor rupture of membranes, and cervical incompetence, a large group remains which can be considered spontaneous. Potential initiators of this include infection, stress, poor nutrition, substance abuse, metabolic imbalances, and inherited factors. Twin studies suggest that genetic factors underlie 40% of this risk and the single best predictor for preterm delivery is a previous preterm birth. While there are many approaches to identifying causal mechanisms in complex traits such as prematurity, genetic investigations afford the opportunity to not only validate previously suspected etiologies, but to identify entirely new factors not previously anticipated. A major challenge in studying genetic factors in prematurity is that the risk case is not yet established as it might be either the mother and her uterus, the infant placental unit, or the two together, and this makes even basic-case control studies difficult to undertake. These investigators have assembled a team of interdisciplinary investigators including obstetricians, pediatricians, quantitative geneticists, and molecular biologists to undertake a comprehensive genetic approach to identifying underlying genetic causes of prematurity. They will use a comprehensive family collection scheme in which either the infant or the mother can be studied as potential cases and incorporate standard candidate gene studies coupled to a very powerful three generation case-parent triad approach utilizing comprehensive genome-wide searches to identify the multiple genes likely contributing to prematurity. Gene identification can then serve to feed studies of underlying biological mechanisms, confirm old targets and, most importantly, identify new targets for prevention and treatment strategies.