GENETIC ANALYSIS OF HUMAN BRAIN DEVELOPMENT

描述：(改编自调查人员摘要)这是一项建议，以 识别和表征基因的产物是必需的 中枢神经系统的发育。我们的战略是确定 突变导致人类全前脑(HPE)的基因。HPE是 与大脑和面部中线发育异常有关。 严重类型的HPE表现为单脑室和睫状视，而 较轻的病例有智力发育迟缓和其他发育障碍。 家族性和散发性两种形式的HPE都存在。因此，私家侦探假设 HPE是由基因的改变引起的，这些基因的产物对 正常的早期大脑发育。为了解决这一假设，私家侦探 与HPA相关的几种形式的协同分子遗传学分析 21q22.3(HPE1)、2p21(HPE2)、 7q36(HPE3)和18p11.3(HPE4)。最近，HPE3被证明是由于 人类音速刺猬基因的突变。未来的努力将定向 针对五个特定目标：1)家族性遗传性疾病中人类SHH基因的MAP突变 和散发性HPE，2)检查这些疾病的生物学后果 SHH的突变，3)决定了SHH信号中的其他基因 途径是其他形式的HPE的候选者，4)筛选关键的 候选基因的HPE1和HPE4的染色体区域，以及5)使用 定位克隆以鉴定和鉴定HPE基因。

DESCRIPTION: (Adapted from Investigator's Abstract) This is a proposal to identify and characterize genes whose products are necessary for the development of the central nervous system. The strategy is to identify genes in which mutations cause holoprosencephaly (HPE) in humans. HPE is associated with abnormalities in midline development of the brain and face. Severe forms of HPE present with a single brain ventricle and cyclopia while milder cases have mental retardation and other developmental disabilities. Both familial and sporadic forms of HPE exist. Thus, the P.I. hypothesizes that HPE is caused by alterations in genes whose products are critical for proper early brain development. To address this hypothesis the P.I. has concerted molecular genetic analyses to those forms of HPA associated with cytogenetic deletions and translocations in 21q22.3 (HPE1), 2p21 (HPE2), 7q36 (HPE3), and 18p11.3 (HPE4). Recently, HPE3 was shown to be due to mutations in the human Sonic Hedgehog gene. Future efforts will be directed at five specific aims: 1) Map mutations in the human SHH gene in familial and sporadic HPE, 2) examine the biological consequences of the these mutations in SHH, 3) Determine whether other genes in the SHH signaling pathway are candidates for other forms of HPE, 4) Screen the critical chromosomal regions for HPE1 and HPE4 for candidate genes, and 5) Use positional cloning to identify and characterize HPE genes.