Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17.
Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17.
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人类 21 号染色体的家族性阿尔茨海默病和唐氏综合症区域的 DNA 标记与小鼠 16 号和 17 号染色体的 DNA 标记的比较作图。
DOI：
10.1073/pnas.85.16.6032
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发表时间：
1988
影响因子：
11.1
通讯作者：
Gusella,JF
中科院分区：
文献类型：
--
作者：
Cheng,SV;Nadeau,JH;Tanzi,RE;Watkins,PC;Jagadesh,J;Taylor,BA;Haines,JL;Sacchi,N;Gusella,JF
小鼠16三体已被提议作为唐氏综合征（DS）的动物模型，因为该染色体含有来自人类染色体21的q22带的几个基因座的同源物。最近的映射缺陷导致家族性阿尔茨海默病（FAD）和基因座编码阿尔茨海默氏淀粉样β前体蛋白（APP）的人类染色体21促使更详细的检查的程度，这两个物种之间的连锁群的保护。使用匿名DNA探针和来自人类21号染色体的克隆基因，结合重组近交系和种间小鼠回交分析，我们已经确定小鼠16号染色体共享的连锁群不仅包括人类21号染色体的关键DS区域，还包括APP基因和FAD连锁标记。从匿名DNA位点D21S52延伸到ETS2，六个位点的连锁图在人中跨越39%的重组，但在小鼠中仅6.4%的重组。同线性的断裂发生在ETS2的远端，人类标记D21S56的同源物映射到小鼠17号染色体。在FAD区域的标记的连锁关系的保护表明，小鼠同源的FAD基因座可能映射到16号染色体，在这两个物种的相应区域的详细比较，可以促进识别这种疾病的主要缺陷。然而，人类21号染色体末端部分和小鼠16号染色体之间的同线性断裂表明，小鼠16号三体可能不代表DS的完整模型。
Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid beta precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, we have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.