[Molecular genetics of adrenoleukodystrophy].

Human Xq28 region harbors many disease genes including genes for adrenoleukodystrophy, Emery-Dreifuss muscular dystrophy, X-linked centronuclear myopathy, and nephrotic diabetes inspidus. The genes for the diseases, however, have not been identified. On the other hand, only small number of transcribed sequences including G6PD gene, Gdx, P3, factor VIII gene, red and green color pigment genes, GABRA3 gene, L1 adhesion molecule gene, QM gene and so on have been identified at Xq28. To identify the disease genes at Xq28 by positional cloning, it is essential to construct physical maps of the Xq28 region and to develop a strategy for identifying expressed genes. Macrorestriction maps of human Xq28 have been generated by pulsed field gel electrophoresis (PFGE). With the recent development of yeast artificial chromosomes (YACs), major efforts have been focused on the generation of contigs of YACs from Xq28. Recently, a putative ALD gene was identified. The gene named ALDP gene was partially deleted in 6 of 85 independent patients with ALD. In familial cases, the deletions segregated with the disease. The deduced protein sequence of ALDP shows significant sequence identity to a peroxisomal membrane protein of 70 K that is involved in peroxisome biogenesis and shares unexpected homology to ABC transporter gene.