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研究有助于改善 了解正常和异常胚胎学的基础 发展。我们研究了人类中最常见的大脑异常， Holoprosencephaly（HPE），发展前脑的结构缺陷 和中间。 HPE是一种遗传异质性疾病 各种染色体异常。最近，人类声音中的突变 刺猬（SHH）基因被证明引起家族形式的HPE。 此外，在A中发现了胆固醇生物合成中的异常 与HPE相关的遗传综合征。因此，其他未知的HPE 假设引起基因是SHH信号通路的一部分或 参与胆固醇生物合成。羊轮合酶（LS）， 是胆固醇第一步涉及的关键酶 合成。 LS基因已被映射到人类染色体21q22.3，a 已知在一些HPE患者中已删除的区域。突变分析 HPE患者中的LS基因现在正在进行中以确定LS是否是否 是另一个HPE候选基因。