与亨廷顿病相关的基因座D4S111被确定为α-L-艾杜糖醛酸酶基因。

Huntington disease-linked locus D4S111 exposed as the alpha-L-iduronidase gene.

作者信息

MacDonald M E, Scott H S, Whaley W L, Pohl T, Wasmuth J J, Lehrach H, Morris C P, Frischauf A M, Hopwood J J, Gusella J F

机构信息

Neurogenetics Laboratory, Massachusetts General Hospital, Boston.

出版信息

Somat Cell Mol Genet. 1991 Jul;17(4):421-5. doi: 10.1007/BF01233067.

DOI:10.1007/BF01233067

PMID:1832239

Abstract

alpha-L-Iduronidase (IDUA) has been intensively studied due to its causative role in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of IDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4S111, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1 X 10(6) bp from the telomere, makes IDUA the most distal cloned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated from the HD candidate region, excluding a role for IDUA in this disorder.

摘要

α-L-艾杜糖醛酸酶（IDUA）因其在I型黏多糖贮积症（Hurler综合征、Scheie综合征和Hurler/Scheie综合征）中的致病作用而受到深入研究。人IDUA cDNA的近期克隆导致对该基因染色体定位的重新评估。IDUA先前被定位于22号染色体，现在已定位到4p16.3，即与亨廷顿舞蹈病（HD）相关的4号染色体区域。该区域一系列克隆DNA、物理图谱信息和遗传多态性数据的存在使得能够在4p的末端细胞遗传学带内快速对IDUA进行精细定位。发现IDUA与D4S111重合，D4S111是一个显示高度信息丰富的多等位基因DNA多态性的无名位点。该图谱位置距端粒1.1×10⁶ bp，使IDUA成为定位于4p的最远端克隆基因。然而，它位于已从HD候选区域中排除的4p16.3片段内，排除了IDUA在该疾病中的作用。