Nechiporuk A, Fain P, Kort E, Nee L E, Frommelt E, Polinsky R J, Korenberg J R, Pulst S M
Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.
Am J Med Genet. 1993 May 1;48(1):63-6. doi: 10.1002/ajmg.1320480113.
Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.
阿尔茨海默病（AD）是一种导致全球痴呆的毁灭性神经退行性疾病。除了散发性AD形式外，家族性形式（FAD）也已被确认。已证明21号染色体（CHR）上淀粉样前体蛋白（APP）基因的突变在少数家系中会导致早发性AD。最近，在几个早发性FAD家系中已确定与14号染色体上的标记存在连锁关系。我们现在报告两个大型早发性FAD家系中14号染色体标记的对数优势分数。成对连锁分析表明，在这些家系中，该突变与位点D14S43和D14S53紧密连锁。然而，关于标记等位基因频率的假设对计算出的对数优势分数有重大且往往不可预测的影响。因此，当使用从文献或配偶群体中确定的标记等位基因频率对单个家系进行分析时，需要谨慎行事。
