CLONING OF A GENE BEARING MISSENSE MUTATIONS IN EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE
CLONING OF A GENE BEARING MISSENSE MUTATIONS IN EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE
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DOI：
10.1038/375754a0
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发表时间：
1995-06-29
期刊：
影响因子：
64.8
通讯作者：
STGEORGEHYSLOP, PH
中科院分区：
文献类型：
--
作者：
SHERRINGTON, R;ROGAEV, EI;STGEORGEHYSLOP, PH
阿尔茨海默病的一些病例是作为常染色体显性遗传的。遗传连锁研究已经将与阿尔茨海默病的一种非常侵袭性形式的易感性相关的位点（AD 3）定位到染色体14q24.3。我们已经定义了一个最小的共分离区域包含的AD3基因，并分离出至少19个不同的转录本编码在这个区域内。这些转录本之一（S182）对应于一个新的基因，其产物被预测含有多个跨膜结构域，类似于一个完整的膜蛋白。已经发现五种不同的错义突变与早发性家族性阿尔茨海默病共分离。由于这些变化发生在该基因的保守结构域中，并且不存在于正常对照中，因此它们可能是AD3的病因。
Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred In conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.