NOVEL TRIPLET REPEAT CONTAINING GENES IN HUMAN BRAIN - CLONING, EXPRESSION, AND LENGTH POLYMORPHISMS
NOVEL TRIPLET REPEAT CONTAINING GENES IN HUMAN BRAIN - CLONING, EXPRESSION, AND LENGTH POLYMORPHISMS
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DOI：
10.1006/geno.1993.1232
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发表时间：
1993-06-01
期刊：
影响因子：
4.4
通讯作者：
ROSS, CA
中科院分区：
文献类型：
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作者：
LI, SH;MCINNIS, MG;ROSS, CA
含有三联重复序列的人类基因可能在长度上显着扩展并导致神经精神疾病，这解释了预期现象（在谱系中连续几代中严重程度增加或发病年龄提前）。为了鉴定具有三联重复序列的新基因，我们用含有CTG或CCG三联重复序列的寡核苷酸探针筛选人脑cDNA文库。40个克隆中有14个编码新的人类基因，其中8个插入片段已在两条链上测序。所有这些都含有重复序列，8个中的5个具有9个或更多个连续的完美重复序列。都在大脑中表达。染色体分配揭示了这些基因在多个常染色体和X染色体上的分布。此外，在两个基因的重复长度是高度多态性的，使他们有价值的索引连锁标记。我们预测存在许多含有三重重复序列的基因;用CTG探针筛选表明大约50-100个含有这种类型重复序列的基因在人脑中表达。由于其他疾病，如亨廷顿氏病，双相情感障碍，并可能其他，显示功能的预期，我们认为，这些新的人类基因与三联体重复是候选人，导致神经精神疾病。
Human genes containing triplet repeats may markedly expand in length and cause neuropsychiatric disease, explaining the phenomenon of anticipation (increasing severity or earlier age of onset in successive generations in a pedigree). To identify novel genes with triplet repeats, we screened a human brain cDNA library with oligonucleotide probes containing CTG or CCG triplet repeats. Fourteen of 40 clones encoded novel human genes, and 8 of these inserts have been sequenced on both strands. All contain repeats, and 5 of the 8 have 9 or more consecutive perfect repeats. All are expressed in brain. Chromosomal assignments reveal a distribution of these genes on multiple autosomes and the X-chromosome. Further, the repeat length in two of the genes is highly polymorphic, making them valuable index linkage markers. We predict that many triplet repeat-containing genes exist; screening with the CTG probe suggests approximately 50-100 genes containing this type of repeat are expressed in the human brain. Since additional disorders, such as Huntington's disease, bipolar affective disorder, and possibly others, show features of anticipation, we suggest that these novel human genes with triplet repeats are candidates for causing neuropsychiatric diseases.