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.

在以下三种常染色体显性疾病中进行了遗传连锁分析：（1）家族性白内障； （2）Camurati-Engelmann病； （3）阵发性运动型薄膜病（PKC）。家族性白内障是一种在一个受影响的家庭中观察到的一种新型白内障，在两个家庭中发现了恩格尔曼疾病，其中总共有17名成员受到影响，而PKC是在三个无关的家庭中观察到的一种疾病。 24名成员受到影响。在获得“知情同意书”后，从家族成员中收集了DNA样品。DNA通过PCR扩增450个微卫星标记基因座，以了解基因座和亲子传播模式的基因型。结果，家族性白内障基因座为IS在33.9 cm区域的20号染色体链接，最高LOD评分（Zmax）为3.61（Theta = 0.00），而Engelmann病基因座映射到另一个染色体，位于26.3 cm区域（B区），Zmax为5.78（5.78）（ theta = 0.00，p = 0.90），将PKC基因座分配给17.3 cm区域（C区C），Zmax为6.077（Theta = 0.00，P = 0.90）。疾病基因的进一步位置克隆。

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。”