Tienari P J, Terwilliger J D, Ott J, Palo J, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Genomics. 1994 Jan 15;19(2):320-5. doi: 10.1006/geno.1994.1064.
One of the major challenges in genetic linkage analyses is the study of complex diseases. We demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, we have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family members than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested.
基因连锁分析中的主要挑战之一是复杂疾病的研究。我们在此展示了双位点连锁分析在多发性硬化症（MS）中的应用，MS是一种具有复杂遗传模式的多因素疾病。在一组芬兰多重家庭中，我们之前已发现MS易感性与两个独立位点之间存在连锁的证据，这两个位点分别是位于18号染色体上的髓鞘碱性蛋白基因（MBP）和位于6号染色体上的HLA复合体。这组家庭提供了一个独特的机会，可在两个导致该疾病的位点的条件下进行连锁分析。在双性状位点/双标记位点分析中，另一个疾病位点的存在被参数化，并且与单疾病位点分析相比，该分析能更恰当地处理来自未患病家庭成员的信息。如在MS中所示例的那样，双位点分析可能是研究复杂性状易感性位点的一种强大方法，最适合用于分析特定候选基因，或用于已经存在或提示有连锁初步证据的情况。
