CONSORTIUM-BACED LINKAGE ANALYSIS AND IDENTIFICATION OF GENES FOR SINGEL-GENE DISEASES

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This research aimed to collect many cases of single-gene disorders of unknown cause by a consortium from all of Japan and to map the disease loci and identify genes for the diseases. During a 5-year-period of the research, we performed linkage analysis of 14 such disorders (including genetic traits) and identified novel gene mutations in 8 disorders. The followings are the details of the diseases studied : (1)Retinitis pigmentosa : by linkage analysis, we assigned disease loci of 3 Japanese and 2 Thai families, and identified RPGR and NDP mutations, respectively ; (2)Engelmann disease : as a linkage analysis found two Engelmann disease families in which disease loci did not correspond the TGFB1 locus, we proposed the disease in the families is a new clinical entity, Engelmann disease type 2 ; (3)Familial hearing impairment : linkage analysis of a large family mapped the locus and identified a novel mutation ; (4)Van der Woude syndrome : the diseases of two families were both mapped to … More 1q32-q41, and mutations in IRF6 were identified in each family ; (5)Anosmia : we found two large Iranian families, and mapped the disease locus within a region between D18S452 and D18S475 ; (6)Familial ASD : linkage analysis of one large family led to the disease gene localization to 8p23-p22, and mutation analysis identified a one-base deletion in GATA4 ; (7)Spastic paraplegia : linkage analysis of one big family mapped the disease to 2p23 and mutation study identified a large intragenic deltion in SPG4 ; (8)Palmoplantar hyperhydrosis : linkage analysis of 11 families assigned the disease of three families to 14q11.2, but locus heterogeneity was evident ; (9)Epidermolysis bullosa : linkage and mutation analysis of one family identified a novel mutation in COL17A1 ; (10)Human earwax trait : linkage analysis mapped the earwax locus to 16p11.2-q12.1, and subsequent association study using SNPs identified a functional SNP in ABCC11 as the earwax determinant ; (11)Familial thrombocytopenia : linkage analysis mapped the disease between D17S950 and D17S1607 ; (12)Familial amyotropic lateral sclerosis : linkage analysis of one family mapped the disease to either 1p or 17q ; (13)and(14)Familial prognathism and Familial blepharoptosis : In neither diseases, disease loci were assigned, because of locus heterogeneity was evident. Less