Mapping of the human voltage-dependent anion channel isoforms 1 and 2 reconsidered

Eukaryotic porins or VDACs (Voltage-Dependent Anion-selective Channels) are integral membrane proteins forming large hydrophilic pores. Three function ing genes for VDAC isoforms have been detected in mouse and the correspondi ng cDNAs are known also in humans. Tissue-specific VDAC isoform 1 (HVDAC1) deficiency in human skeletal muscle is responsible of a rare mitochondrial encephalomyopathy, fatal in childhood. Since coding sequences are not affec ted in the patient, we focused our interest in the gene structure. HVDAC1 a nd 2 have been previously mapped at chromosomes Xq13-21 and 21, respectivel y. Screening of an human chromosome X cosmid library resulted only in the i solation of processed pseudogenes, finely mapped at Xq22 and Xp11.2. Here, we report the mapping of HVDAC1 to chromosome 5q31 and HVDAC2 to chromosome 10q22 by FISH. Exon/intron probes, designed on the basis of the mouse gene structures, were obtained by long extension PCR amplification using the wh ole genomic DNA as a template. The sequence of the probe extremities clearl y pointed to a genuine VDAC genomic sequence. Human and mouse regions where VDAC 1 and 2 genes were mapped are known to be synthetic, thus reinforcing the mapping of the human homologues. (C) Academic Press.