GENETIC ANALYSIS OF HUMAN DEVELOPMENTAL ABNORMALITIES

人类发育异常的遗传分析

• 批准号: 6162622
• 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/6162622
• 关键词: chromosome aberrations; congenital brain disorder; developmental genetics; embryogenesis; gene expression; gene mutation; genetic disorder; human subject; steroid biosynthesis; structural genes

Genetic studies of structural anomalies in humans help to better understand the underlying basis for normal and abnormal embryological development. We have studied the most common brain anomaly in humans, holoprosencephaly (HPE), a structural defect of the developing forebrain and midface. HPE is a genetically heterogeneous disorder associated with various chromosomal anomalies. Recently, mutations in the human Sonic Hedgehog (SHH) gene were shown to cause familial forms of HPE. Furthermore, anomalies in the cholesterol biosynthesis were found in a genetic syndrome associated with HPE. Thus, other yet unidentified HPE causing genes are postulated to be part of the SHH signaling pathway or are involved in the cholesterol biosynthesis. Lanosterol synthase (LS), is the key enzyme involved in the first step of the cholesterol synthesis. The LS gene has been mapped to human chromosome 21q22.3, a region known to be deleted in some HPE patients. Mutational analysis of the LS gene in HPE patients is now in progress to determine whether LS is another HPE candidate gene.

人类结构异常的遗传学研究有助于更好地 了解正常和异常胚胎学的潜在基础 发展我们研究了人类最常见的大脑异常， 前脑无裂畸形（HPE），一种发育中前脑的结构缺陷 和中脸HPE是一种遗传异质性疾病， 各种染色体异常最近，人类声波基因的突变 Hedgehog（SHH）基因被证明是引起家族性HPE的原因。 此外，在胆固醇生物合成中发现异常， 与HPE相关的遗传综合征。因此，其他尚未识别的HPE 致病基因被认为是SHH信号通路的一部分， 参与胆固醇的生物合成。羊毛甾醇合酶（LS）， 是参与胆固醇合成第一步的关键酶 合成. LS基因已定位于人类染色体21q22.3， 已知在一些HPE患者中缺失的区域。突变分析 HPE患者中的LS基因目前正在进行中，以确定LS是否 是另一个HPE候选基因。