患有马查多-约瑟夫病的日本家系中的强连锁不平衡和单倍型分析。

Strong linkage disequilibrium and haplotype analysis in Japanese pedigrees with Machado-Joseph disease.

作者信息

Endo K, Sasaki H, Wakisaka A, Tanaka H, Saito M, Igarashi S, Takiyama Y, Sanpei K, Iwabuchi K, Suzuki Y, Onari K, Suzuki T, Weissenbach J, Weber J L, Nomura Y, Segawa M, Nishizawa M, Tsuji S

机构信息

Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University, Japan.

出版信息

Am J Med Genet. 1996 Sep 20;67(5):437-44. doi: 10.1002/(SICI)1096-8628(19960920)67:5<437::AID-AJMG1>3.0.CO;2-H.

DOI:10.1002/(SICI)1096-8628(19960920)67:5<437::AID-AJMG1>3.0.CO;2-H

PMID:8886159

Abstract

To identify the markers tightly linked to Machado-Joseph disease (MJD) and to investigate whether a limited number of ancestral chromosomes are shared by Japanese MJD pedigrees, a detailed linkage analysis employing D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1, D14S81, D14S265, D14S62, and D14S65 was performed. The results of multipoint linkage analysis as well as detection of critical recombination events indicate that the gene for MJD is localized in a 4-cM region between D14S280-D14S81. We found strong linkage disequilibria at AFM343vf1 and D14S81, and association of a few common haplotypes with MJD. These results indicate that there is an obvious founder effect in Japanese MJD and suggest the possibility of the existence of predisposing haplotypes which are prone to expansions of CAG repeats.

摘要

为了确定与马查多 - 约瑟夫病（MJD）紧密连锁的标记，并研究日本MJD家系是否共享有限数量的祖先染色体，我们使用D14S55、D14S48、D14S67、D14S291、D14S280、AFM343vf1、D14S81、D14S265、D14S62和D14S65进行了详细的连锁分析。多点连锁分析结果以及关键重组事件的检测表明，MJD基因定位于D14S280 - D14S81之间4厘摩的区域。我们在AFM343vf1和D14S81处发现了强连锁不平衡，以及一些常见单倍型与MJD的关联。这些结果表明日本MJD存在明显的奠基者效应，并提示存在易于CAG重复序列扩增的易感单倍型的可能性。