CO-RECESSIVE INHERITANCE - A MODEL FOR DNA-REPAIR, GENETIC-DISEASE AND CARCINOGENESIS
CO-RECESSIVE INHERITANCE - A MODEL FOR DNA-REPAIR, GENETIC-DISEASE AND CARCINOGENESIS
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DOI：
10.1016/0167-8817(85)90031-8
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发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
LAMBERT, MW
中科院分区：
文献类型：
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作者：
LAMBERT, WC;LAMBERT, MW
提出了一些切除缺陷型着色性干皮病（XP）病例的遗传模型，其中性状（即，当且仅当个体在一组特定基因座中的一个以上基因座上对于缺陷等位基因是纯合或半合的时，才表达。该模型也可能适用于与DNA修复缺陷相关的某些其他疾病。该模型解释了XP的几个自相矛盾的方面，包括大量的互补组，尽管生物化学限制的DNA修复缺陷，XP和Cockayne综合征在XP的2个不同互补组中共存，一个家庭中XP严重程度明显不同的兄弟姐妹和另一个家庭中以X连锁方式传播疾病，存在一些似乎有DNA修复缺陷但没有临床XP的个体，以及与DNA修复机制中的显著缺陷相关但与内部癌症发病率的明显增加无关的疾病的看似矛盾。该模型预测，一般人群中有很大一部分是DNA修复机制中1个或多个缺陷基因的携带者。这些基因在许多人类癌症的病因学中可能是重要的。
A genetic model for some cases of excision-deficient xeroderma pigmentosum (XP) is propsed in which the trait (i.e., XP) is expressed if and only if the individual is homozygous or hemizygous for defective alleles at more than one of a specific set of loci. The model might also apply in some cases of certain other diseases associated with defective DNA repair. The model accounts for several paradoxical aspects of XP, including the large number of complementation groups despite the biochemically limited DNA-repair defect, the co-existence of XP and Cockayne''s syndrome in 2 different complementation groups of XP, siblings with markedly different degrees of severity of XP in one family and transmission of the disease in an X-linked manner in another, the existence of some individuals who appear to have the DNA-repair defect but not clinical XP, and the seeming paradox of a disease associated with a marked defect in a DNA-repair mechanism but not associated with an obvious increase in incidence of internal cancer. The model predicts that a large proportion of the general population is a carrier of 1 or more of these defective genes for DNA-repair mechanisms. Such genes may be important in the etiology of much of human cancer.