Gershon E S, Goldin L R
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
J Psychiatr Res. 1987;21(4):541-50. doi: 10.1016/0022-3956(87)90103-8.
Analysis of the distribution of diagnoses in families (segregation analysis) has not, so far, advanced us toward the goal of resolving the inheritance of the major psychiatric disorders. Recent advances in genetics, particularly the development of new molecular genetic linkage methods, have made it, at least theoretically, feasible to scan the entire human genome, so that in a properly designed and executed set of studies it will be possible to demonstrate whether there exists single locus transmission for a particular disorder, and to map the locus. We present here an analysis of feasibility of moderate-sized pedigrees (approximately 15 persons, two generations) and affected-sib-pair sets in such studies. Eight to ten moderate-sized pedigrees are sufficient to perform definitive mapping under the tested conditions, of recessive or additive inheritance, low penetrance of the heterozygote, and a genetically homogeneous disorder. The affected-sib-pair method required 25 pairs of sibs to detect linkage under such conditions in a recessive model, and 45 in a dominant model. When there is genetic heterogeneity, moderate-sized pedigrees are much less useful, but the affected-sib-pair method retains considerable power.
到目前为止，对家族中诊断分布的分析（分离分析）尚未推动我们朝着解决主要精神疾病遗传问题的目标前进。遗传学的最新进展，特别是新的分子遗传连锁方法的发展，至少在理论上使扫描整个人类基因组成为可能，因此在一组设计合理且执行得当的研究中，有可能证明特定疾病是否存在单基因座传递，并绘制出该基因座的位置。我们在此分析此类研究中中等规模家系（约15人，两代）和患病同胞对集合的可行性。在隐性或加性遗传、杂合子低外显率以及遗传同质疾病的测试条件下，8至10个中等规模家系足以进行确定性定位。在隐性模型中，患病同胞对方法在此类条件下需要25对同胞来检测连锁，在显性模型中需要45对。当存在遗传异质性时，中等规模家系的作用要小得多，但患病同胞对方法仍具有相当大的效力。
