早发性阿尔茨海默病相关基因定位于14号染色体q24.3区域。

Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3.

作者信息

Van Broeckhoven C, Backhovens H, Cruts M, De Winter G, Bruyland M, Cras P, Martin J J

机构信息

Laboratory of Neurogenetics, Born Bunge Foundation, University of Antwerp, Belgium.

出版信息

Nat Genet. 1992 Dec;2(4):335-9. doi: 10.1038/ng1292-335.

DOI:10.1038/ng1292-335

PMID:1303290

Abstract

Genetic linkage studies with chromosome 21 DNA markers and mutation analysis of the beta-amyloid protein precursor gene located in 21q21.3 have indicated that early-onset Alzheimer's disease (EOAD) is a heterogeneous disorder for which at least one other chromosomal locus exists. We examined two extended histopathologically confirmed EOAD pedigrees, AD/A and AD/B, with highly informative short tandem repeat (STR) polymorphisms and found complete linkage of the disease to a (CA)n dinucleotide repeat polymorphism at locus D14S43 in 14q24.3 (Zmax = 13.25 at theta = 0.0). Using additional chromosome 14 STR polymorphisms we were able to delineate the region containing the EOAD gene to an area of, at most, 8.9 centiMorgans between D14S42 and D14S53, flanking D14S43 on both sides.

摘要

利用位于21号染色体的DNA标记进行的基因连锁研究以及对位于21q21.3的β-淀粉样蛋白前体基因的突变分析表明，早发性阿尔茨海默病（EOAD）是一种异质性疾病，至少还存在一个其他的染色体位点。我们用信息丰富的短串联重复序列（STR）多态性检测了两个经组织病理学确诊的EOAD家系，AD/A和AD/B，发现该疾病与位于14q24.3的D14S43位点的（CA）n二核苷酸重复多态性完全连锁（在θ = 0.0时，Zmax = 13.25）。利用额外的14号染色体STR多态性，我们能够将包含EOAD基因的区域划定在D14S42和D14S53之间，最多8.9厘摩的区域内，两侧以D14S43为侧翼。