Affected sib pair method for searching major gene in multifactorial disease

The affected sib pair method to detect the effect of HLA-linked disease genes has been explained from a practical viewpoint. It is based on the assumption that HLA haplotypes as marker are used to trace the inheritance pattern of closely linked disease susceptibility genes. Looking at families in which two or more siblings had disease in question, the nonrandom zygotic assortment of HLA haplotypes would be a demonstration of disease gene. Application of affected sib pair method to Graves' disease had delineated that two genes, HLA-lined and Gm-linked, are responsible for manifestation of the disease as recessive inheritance with high penetrance.