Beaty T H, Maestri N E, Meyers D A, Murphy E A
Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
Am J Med Genet. 1987 Nov;28(3):631-45. doi: 10.1002/ajmg.1320280311.
We present the expected recurrence risks to a sib of an affected proband under 4 simple 2-locus epistatic models for various allele frequencies at both the disease locus and the epistatic locus. Four obvious epistatic models are considered: an autosomal recessive disease with both 1) dominant and 2) recessive masking by the epistatic locus, and an autosomal dominant disease again with both 3) dominant and 4) recessive masking. Expected recurrence risks to a sib of an affected proband and to a sib of an affected proband with another normal sib are presented in the absence of information on parental status. Similar risks are presented for the case where both parents are known to be phenotypically normal. These recurrence risks were calculated using a convenient matrix notation which allows sequential calculation of genotypic probabilities. In general, 2-locus epistatic models can give surprisingly low recurrence risks, and often these risks, especially for models of recessive diseases, fall into the range associated with a more general multifactorial model for liability.
我们给出了在4种简单的双基因座上位模型下，疾病基因座和上位基因座处不同等位基因频率时，受累先证者的同胞的预期复发风险。考虑了4种明显的上位模型：一种常染色体隐性疾病，上位基因座存在1）显性和2）隐性掩盖；以及一种常染色体显性疾病，同样存在3）显性和4）隐性掩盖。在没有父母状态信息的情况下，给出了受累先证者的同胞以及有另一个正常同胞的受累先证者的同胞的预期复发风险。对于已知父母表型均正常的情况，也给出了类似风险。这些复发风险是使用一种方便的矩阵表示法计算的，该方法允许顺序计算基因型概率。一般来说，双基因座上位模型可能会给出低得出奇的复发风险，而且这些风险，尤其是对于隐性疾病模型，往往落入与更一般的易感性多因素模型相关的范围内。
