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; 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.

已经对大脑发育的复杂遗传学进行了一项研究，重点是引起人类最常见的结构前脑异常的基因，Holoproscomencephaly（HPE）。大脑的这种畸形可能是由环境或遗传原因引起的。这些研究的目的是通过研究这种疾病的患者来确定负责正常和异常脑发育的基因。我们已经证明，六个这样的基因的突变是HPE的大约四分之一的家族性和零星病例（Roessler等，1996,1997； Brown等，1998; Brown等，1998; Wallis等，1999; Gripp et al。，2000; Ming等，2002; Dela Cruz等，2002; Dela Cruz等，2002）。其他与刺猬途径相关的基因或位于定义的遗传基因座也可能有助于HPE，并且是主动研究的主题。我们预计，在寻找HPE的遗传原因时，将确定许多对正常脑发育重要的基因。此外，这些调查的目的是确定对HPE有助的环境因素。动物模型表明，低母胆固醇在某些后代会导致脑异常。现在，在流行病学研究中对这些发现进行了测试，在流行病学研究中，怀孕期间低母生血清胆固醇与出生结果相关。