Identification of the gene for hereditary spinocerebellar degeneration and its usage for diagnosis.

遗传性脊髓小脑变性基因的鉴定及其诊断用途。

• 批准号: 09557020
• 负责人: YOSHIKI Takashi
• 金额: $ 3.9万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557020/
• 关键词: spinocerebellar degeneration; CAG triplet repeat; CACNL1A4; CACNLIA4; ポリグルタミン鎖; CAG反復配列; 遺伝子診断; spinocerebellar degeneration; CAG triplet repeat; CACNL1A4; CACNLIA4; ポリグルタミン鎖; CAG反復配列; 遺伝子診断

The dominantly inherited spinocerebellar ataxias are a cluster of genetically heterogeneous neuro-degenerative disorders. More than 500 people living in Hokkaido are affected with these diseases. Recent advances in molecular genetics have led to the identification of 7 loci named as SCAl to SCA7.Among them, abnormal expansions of the CAG trinucleotide repeat have been identified in the patients with SCAl, SCA2 and SCA3. Although number of patients exceeds 30 % in Japanese ataxic patients, the location and specific abnormalities of the gene for Holmes' ataxia were unknown when we started this research. Through two years research, we have clarified following evidences ;1) The responsible gene for the half of the patients with Holiness' ataxia in the Japanese are identical to that of SCA6.2) The responsible gene for SCA6 is a gene for alphalA - voltage dependent calcium channel (CACNL1A4) mapped at 19p13.3) An abnormal expansions of the CAG trinucleotide repeat located in the CACNL1A4 was observed in the patients with SCA6.4) The number of CAG repeat inversely correlated with age of onset.5) Strong linkage disequilibrium suggested that SCA6 in the Japanese in Hokkaido may derive from a single common ancestry.It should be solved in a future that why and how expanded CAG repeat, which translated into poly glutamine chain, causes a selective neuronal cell death.

主要遗传的脊椎发子共济失调是一组遗传性异质性神经差异疾病的簇。居住在北海道的500多人受到这些疾病的影响。分子遗传学的最新进展导致鉴定了7个位点为Sca7。尽管日本的共济失调患者的患者人数超过30％，但是当我们开始这项研究时，福尔摩斯共济失调基因的位置和特定异常是未知的。 Through two years research, we have clarified following evidences ;1) The responsible gene for the half of the patients with Holiness' ataxia in the Japanese are identical to that of SCA6.2) The responsible gene for SCA6 is a gene for alphalA - voltage dependent calcium channel (CACNL1A4) mapped at 19p13.3) An abnormal expansions of the CAG trinucleotide repeat located in the CACNL1A4 was observed in the patients with SCA6.4) The number of CAG repeat inversely correlated with age of onset.5) Strong linkage disequilibrium suggested that SCA6 in the Japanese in Hokkaido may derive from a single common ancestry.It should be solved in a future that why and how expanded CAG repeat, which translated into poly glutamine chain, causes a selective neuronal cell death.