Feingold Josué
Inserm U.393, Hôpital Necker Enfants-Malades, 149, rue de Sèvres, 75015 Paris, France.
Med Sci (Paris). 2005 Nov;21(11):927-33. doi: 10.1051/medsci/20052111927.
Common diseases are often familial, but they do not show in most families, a simple pattern of inheritance. In a few families these diseases may be caused by a mutation in a single gene. In most families these diseases are multifactorial, they result from a complex interaction between a genetic component which is often polygenic and many environmental factors. Two major, model free, methods are used to locate and identify susceptibility genes that predispose to multifactorial diseases. The first is a non parametric linkage analysis that relies on affected sib pairs, or an affected pedigree member, the second method is association studies which looks for increase frequency of particular alleles or genotypes in affected compared with unaffected individuals in the population. Most of the results have not been replicated, identifying susceptibility genes is proving much more difficult than most geneticists imagined 20 years ago. The main reason for this irreproducibility is genetic heterogeneity.
常见疾病往往具有家族性，但在大多数家族中，它们并不呈现简单的遗传模式。在少数家族中，这些疾病可能由单个基因突变引起。在大多数家族中，这些疾病是多因素的，它们是由通常为多基因的遗传成分与许多环境因素之间的复杂相互作用导致的。有两种主要的、无模型的方法用于定位和识别易患多因素疾病的易感基因。第一种是基于受累同胞对或受累家系成员的非参数连锁分析，第二种方法是关联研究，该研究寻找在人群中受累个体与未受累个体相比特定等位基因或基因型频率的增加。大多数结果尚未得到重复验证，事实证明，识别易感基因比大多数遗传学家20年前想象的要困难得多。这种不可重复性的主要原因是遗传异质性。
