Genetics of Brain Development

大脑发育的遗传学

• 批准号: 6988940
• 负责人: Maximilian Muenke
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6988940
• 关键词: cholesterol; clinical research; congenital brain disorder; developmental genetics; developmental neurobiology; disease /disorder etiology; family genetics; gene environment interaction; genetic polymorphism; genetic susceptibility; human genetic material tag; human pregnant subject; human subject; neurogenesis; neurogenetics; patient oriented research; pregnancy

A study of the complex genetics of brain development has been undertaken with an emphasis on those genes that cause the most common structural forebrain anomaly in humans, holoprosencephaly (HPE). This malformation of the brain can result from either environmental or genetic causes. It is the aim of these investigations to determine the genes responsible for both normal and abnormal brain development through the study of patients with this disorder. Mutations in six such genes has been shown by us to be responsible for approximately one quarter of familial and sporadic cases of HPE (Roessler et al. 1996,1997; Brown et al., 1998; Wallis et al., 1999; Gripp et al., 2000; Ming et al., 2002; dela Cruz et al., 2002). Other genes either related to the hedgehog pathway or located at defined genetic loci may also contribute to HPE and are the subject of active investigation. We anticipate that many genes important for normal brain development will be identified in the search for genetic causes of HPE. In addition, the aim of these investigations is to identify environmental factors that contribute to HPE. Animal models have shown that low maternal cholesterol causes brain anomalies in some offspring. The findings are now being tested in epidemiological studies where low maternal serum cholesterol during pregnancy is correlated with birth outcome.

对大脑发育的复杂遗传学的研究已经开始，重点是那些导致人类最常见的结构性前脑异常的基因，前脑无裂畸形（HPE）。这种大脑畸形可能是由环境或遗传原因造成的。这些研究的目的是通过对这种疾病患者的研究来确定负责正常和异常大脑发育的基因。我们已经证明，六个这样的基因中的突变与大约四分之一的家族性和散发性HPE病例有关（Roessler等，1996，1997; Brown等，1998;沃利斯等人，1999; Gripp等人，2000; Ming等人，2002年; J.C. Cruz等人，2002年）。其他与hedgehog通路相关或位于特定遗传位点的基因也可能导致HPE，并且是积极研究的主题。我们预计，在寻找HPE的遗传原因时，将确定许多对正常大脑发育重要的基因。此外，这些调查的目的是确定影响HPE的环境因素。动物模型表明，母体胆固醇低会导致某些后代的大脑异常。这些发现现在正在流行病学研究中进行测试，在这些研究中，怀孕期间母亲血清胆固醇低与出生结局相关。