LINKAGE ANALYSIS OF UNKNOWN GENETIC DISEASES

未知遗传疾病的连锁分析

• 批准号: 08307019
• 负责人: NIIKAWA Norio
• 金额: $ 20.8万
• 依托单位: NAGASAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08307019/
• 关键词: LINKAGE ANALYSIS; DISEASE LOCUS; MESOMELIC DYSPLASIA; ENGELMANN DISEASE; Paroxysmal kinetogenic choreoathetosis; FAMILIAL CATARACT; ATRIAL SPEPTAL DEFECT; POSITIONAL CLONING; 肢中部短縮型小人症

Genetic linkage analysis was performed in the following three autosomal dominant disorders : (1) familial cataracts ; (2) Camurati-Engelmann disease ; and (3) paroxysmal kinesigenic chorcoathetosis (PKC). The familial cataract is a new type of cataract observed in a family where 10 members are affected, Engelmann disease was found in two families in which a total of 17 members are affected, and PKC is a disease observed in three unrelated families where a total of 24 members are affected. After obtaining "informed consent', DNA samples were collected from the family members. DNA was amplified by PCR for 450 microsatellite marker loci, in order to know genotypes of the loci and parent-child transmission patterns. As results, the familial cataract locus is linked to chromosome 20 at a 33.9-cM region with the maximum lod score (Zmax) of 3.61 (theta = 0.00), while the Engelmann disease locus maps to another chromosome at a 26.3-cM region (region B) with Zmax of 5.78 (theta = 0.00, p = 0.90), and the PKC locus is assigned to a 17.3-cM region (region C) with Zmax of 6.077 (theta = 0.00, p = 0.90). The chromosomal localizations in these disorders provides useful positional information for further positional cloning of the disease genes.

对以下三种常染色体显性遗传病进行遗传连锁分析：(1)家族性白内障；(2) Camurati-Engelmann病；(3)阵发性动态性脉络疏松症（PKC）。家族性白内障是在一个家族中发现的一种新型白内障，该家族中有10人患病；恩格尔曼病在两个家族中发现，该家族中有17人患病；PKC是在三个无血缘关系的家族中发现的一种疾病，该家族中有24人患病。在获得“知情同意”后，从家庭成员那里收集DNA样本。对450个微卫星标记位点进行PCR扩增，了解其基因型及亲子传播模式。结果表明，家族性白内障基因座与20号染色体连接在33.9 cm区域，最大负荷评分（Zmax）为3.61 (θ = 0.00)，恩格斯曼病基因座与另一条染色体连接在26.3 cm区域（B区），Zmax为5.78 (θ = 0.00, p = 0.90)， PKC基因座连接在17.3 cm区域（C区），Zmax为6.077 （θ = 0.00, p = 0.90）。这些疾病的染色体定位为疾病基因的进一步定位克隆提供了有用的位置信息。

项目成果

Fujimoto M, Kantaputra PN, Ikegawa S et al.: "The gene for mesomelic dysplasia Kantaputra type is mapped to 2q24-q32." Journal of Human Genetics. 43. 32-26 (1998)

Fujimoto M、Kantaputra PN、Ikekawa S 等人：“中粒发育不良 Kantaputra 型的基因被映射到 2q24-q32。”

Yamada K,Tomita H,Yoshiura K et al.: "An Autosomal Dominant Posterior Polar Cataract Locus Maps to Human Chromosome 20." American Journal of Human Genetics. (in press). (1999)

Yamada K、Tomita H、Yoshiura K 等人：“常染色体显性后极白内障基因座映射到人类 20 号染色体。”