Martinez M
INSERM U 155, Château de Longchamp, Paris, France.
Rev Epidemiol Sante Publique. 1993;41(4):306-14.
The goal of this paper is to show how the information provided by genetic markers may help to delineate the genetic factors implicated in the aetiology of mental disorders. Family studies have provided good evidence for the involvement of genetic factors in the aetiology of two of the most common psychiatric diseases: affective disorders and schizophrenia. However, a single susceptibility gene responsible for all the familial resemblance for these diseases is unlikely. Analysis of the disease transmission in families has been, so far, unsuccessful in delineating a genetic component in their aetiology. With the recent development of molecular genetics a large number of genetic markers are now available. They allow an alternative investigation of the genetic aetiology of such disease. Indeed a non independent transmission of the disease is evidence for 1) the effect of at least one susceptibility gene and 2) the genetic localization of this gene on the same chromosome and near the marker. However, linkage strategies in psychiatric disorders face specific difficulties that should not be ignored. For such complex diseases, the observed disease correlations between relatives are likely due to the effect and to the interaction of both genetic and non genetic factors. Accurate analysis of genetic linkage requires consideration of residual (non-genetic) familial correlations in the joint segregation of the disease and the marker. Furthermore, focusing linkage strategies on markers of candidate genes would clearly enhance the power of the linkage test.
本文的目的是展示遗传标记所提供的信息如何有助于阐明与精神障碍病因相关的遗传因素。家族研究已为遗传因素参与两种最常见的精神疾病（情感障碍和精神分裂症）的病因提供了充分证据。然而，不太可能存在一个单一的易感基因导致这些疾病的所有家族相似性。到目前为止，对家族中疾病传递的分析在确定其病因中的遗传成分方面并不成功。随着分子遗传学的最新发展，现在有大量的遗传标记可用。它们为这类疾病的遗传病因提供了另一种研究方法。事实上，疾病的非独立传递是以下两点的证据：1）至少一个易感基因的作用；2）该基因在同一条染色体上且靠近标记的遗传定位。然而，精神障碍中的连锁策略面临一些不应被忽视的特殊困难。对于这类复杂疾病，亲属之间观察到的疾病相关性可能是由于遗传和非遗传因素的共同作用和相互作用。准确的遗传连锁分析需要在疾病和标记的联合分离中考虑残余（非遗传）家族相关性。此外，将连锁策略集中在候选基因的标记上显然会增强连锁检验的效力。
