Melnick M, Shields E D
Lancet. 1976 Jan 24;1(7952):176-9. doi: 10.1016/s0140-6736(76)91277-0.
Contrary to the argument regarding the conservatism of the multifactorial threshold model for describing the inheritance of congenital malformations, little biological insight has resulted from the series of tautological, albeit grandiose, mathematical assumptions currently comprising the basis for this hypothesis. The working hypothesis of this presentation is to apply the "allelic restriction" model to the genesis of common human congenital malformations. New population data concerning isolated cleft palate closely fit the predictions of the proposed hypothesis. Recognising the heterogeneity of cleft palate as well as other common congenital malformations (namely, the difference between phenocopies, definable syndromes, and true hereditary cases), the "allelic restriction" model accords with the apparent greatly "reduced penetrance" of the heriditary cases. This model is meant to apply only to those congenital malformations which have both a high population frequency and a relatively small number of families showing an atypical type of vertical transmission.
与关于用于描述先天性畸形遗传的多因素阈值模型保守性的观点相反，目前构成该假说基础的一系列同义反复（尽管宏大）的数学假设几乎没有带来生物学上的见解。本报告的工作假说是将“等位基因限制”模型应用于常见人类先天性畸形的发生。关于孤立性腭裂的新人群数据与所提出假说的预测非常吻合。认识到腭裂以及其他常见先天性畸形的异质性（即表型模拟、可定义综合征和真正遗传性病例之间的差异），“等位基因限制”模型与遗传性病例明显大大“降低的外显率”相符。该模型仅适用于那些在人群中发病率高且显示非典型垂直传递类型的家庭数量相对较少的先天性畸形。
