Pulst S M, Fain P, Cohn V, Nee L E, Polinsky R J, Korenberg J R
Division of Neurology, Cedars-Sinai Medical Center, University of California, Los Angeles 90048.
Hum Genet. 1991 Jun;87(2):159-61. doi: 10.1007/BF00204173.
Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. The familial form (FAD) has been linked to markers on chromosome 21 in some families, most tightly to the loci D21S16 and D21S13 located close to the centromere of the long arm. In other families the FAD mutation has been excluded from the more telomeric D21S1/S11 region, but not from the centromeric region of chromosome 21. We identified two new restriction fragment length polymorphisms (RFLPs) for the locus D21S13 and have used these RFLPs for the analysis of one of the largest known early-onset FAD pedigrees. We calculated pairwise and multipoint lod scores for the loci D21S13, D21S110, and D21S11. Linkage to this region of chromosome 21 was excluded with maximum negative lod scores of -6.4 at D21S13 and D21S110. Thus, it is unlikely that the FAD mutation in this family is located in the region that has shown linkage in other FAD pedigrees. This result provides evidence for genetic heterogeneity of early-onset FAD or a location of FAD centromeric to D21S13.
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。在一些家族中，家族性形式（FAD）与21号染色体上的标记相关，最紧密的是与位于长臂着丝粒附近的D21S16和D21S13位点相关。在其他家族中，FAD突变已被排除在更靠近端粒的D21S1/S11区域，但未被排除在21号染色体的着丝粒区域。我们鉴定出了两个新的D21S13位点的限制性片段长度多态性（RFLP），并将这些RFLP用于分析已知的最大的早发性FAD家系之一。我们计算了D21S13、D21S110和D21S11位点的成对和多点连锁分数。在D21S13和D21S110处，以最大负连锁分数-6.4排除了与21号染色体该区域的连锁。因此，这个家族中的FAD突变不太可能位于在其他FAD家系中显示连锁的区域。这一结果为早发性FAD的遗传异质性或FAD位于D21S13着丝粒侧提供了证据。
