A genetic mechanism implicates chromosome 11 in schizophrenia and bipolar diseases
A genetic mechanism implicates chromosome 11 in schizophrenia and bipolar diseases
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DOI：
10.1534/genetics.104.028217
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发表时间：
2004-08-01
期刊：
影响因子：
3.3
通讯作者：
Klar, AJS
中科院分区：
文献类型：
--
作者：
Klar, AJS
精神分裂症和双相人类精神障碍的原因尚不清楚。一种新的体细胞遗传模型假设染色体的两个拷贝的“沃森”和“克里克”DNA链非随机分离到特定的子细胞。这种定向的不对称细胞分裂导致了健康的、功能不对等的大脑半球的发育。染色体的遗传易位可能通过破坏偏向性链分离过程而引起疾病。只有一半的1号染色体和11号染色体易位携带者发生疾病，最近被解释为与模型一致的结果（KLAR 2002）。1号或11号染色体是否参与？易位断裂点会导致疾病吗？值得注意的是，从文献中发现的另外两个不相关的11号染色体易位同样导致了大约50%的携带者患病。总之，它们的断裂点位于三个不同的区域，跨越11号染色体的40%。因此，11号染色体是有牵连的，但断点本身不太可能引起疾病。结果表明，遗传引起的疾病的发展没有孟德尔基因突变。
The causes of schizophrenia and bipolar human psychiatric disorders are unknown. A novel somatic cell genetic model Postulated nonrandom segregation of "Watson" vs. "Crick" DNA chains of both copies of a chromosome to specific daughter cells. Such an oriented asymmetric cell division causes development of healthy, functionally nonequivalent brain hemispheres. Genetic translocations of the chromosome may cause disease by disrupting the biased strand-segregation process. Only one-half of chromosome 1 and 11 translocation carriers developing disease were recently explained as a result consistent with the model (KLAR 2002). Is chromosome 1 or 11 involved? Does the translocation breakpoint cause disease? Remarkably, two other unrelated chromosome 11 translocations discovered from the literature likewise caused disease in similar to50% of carriers. Together, their breakpoints lie at three distinct regions spanning similar to40% of chromosome 11. Thus, chromosome 11 is implicated but the breakpoints themselves are unlikely to cause the disease. The results suggest that the genetically caused disease develops without a Mendelian gene mutation.