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The adrenoleukodystrophy-related gene (ALDR, ABCD2) is a candidate modifier gene and a potential therapeutic target for X-linked adrenoleukodystrophy (ALD), a severe neurodegenerative disease. The ALDR gene is the closest homologue of the ALD gene, which encodes a peroxisomal ABC transporter involved in the catabolism of very-long-chain fatty acids. Administration of fenofibrate upregulates ALDR expression in rodent liver. As a step toward understanding ALDR transcriptional regulation, the mouse and human 5′ regions were characterized. The human and mouse genes share a 500-bp conserved region that contains potential Sp1- and AP-2-binding sites but no TATA box. Analysis of the 5′-flanking region of ALDR using a luciferase reporter system revealed that 1.3 kb of human or mouse 5′-upstream region has functional promoter activity. In these transfection experiments, promoter activity of both human and mouse genes could be upregulated by 9-cis-retinoic acid and forskolin, while no effect of PPARα could be detected.

We report here on the identification and genomic mapping of a novel member of the family of the ATP-binding cassette (ABC) transporters, ABC7, conserved in mouse and in humans. The ABC7 gene encodes a protein with the typical features of half-transporters, such as those involved in translocation of antigenic peptides or in peroxisomal disorders. ABC7 shows a ubiquitous expression pattern and maps to the X chromosome both in mouse and in humans. The high sequence similarity to those of two yeast half-transporters supports once again the extreme evolutionary conservation of this family of proteins.

The family of ATP binding cassette (ABC) transporters or traffic ATPases is composed of several membrane-associated proteins that transport a great variety of solutes across cellular membranes. Two novel mammalian members of the family, ABC1 and ABC2, have been identified by a PCR-based approach. They belong to a group of traffic ATPases encoded as a single multifunctional protein, such as CFTR, STE 6, and P-glycoproteins. Their peculiar structural features and close relationship to ABC transporters involved in nodulation suggest that ABC1 and ABC2 define a novel subgroup of mammalian traffic ATPases.

We report the successful use of whole yeast artificial chromosomes (YACs) as probes for direct positional cloning of novel expressed sequences in a given genomic fragment. The class I region of the human major histocompatibility complex, in particular the chromosomal fragment spanning the HLA-E locus, was investigated. The screening of a cDNA library with a 210-kb-long YAC clone led to the identification of a new gene, positionally conserved in the major histocompatibility complex of the mouse genome and encoding a putative GTP binding protein. Although its precise function remains unknown, the interspecies conservation of both sequence and map position suggests a regulatory or functional link with the histocompatibility cluster.

The two classical minisatellite probes, 33.6 and 33.15, were used for in situ hybridization to human metaphase chromosomes. Surprisingly, a single major hybridization peak was observed with each probe, respectively at 1q23 for 33.6 and 7q35-q36 for 33.15. Hybridization to human DNA cleaved with "rare-cutter" enzymes and fractionated on pulsed-field gels also showed a fairly simple, largely monomorphic pattern which allows chromosomal assignment using somatic cell hybrids. Differences in hybridization stringency and degree of resolution account for most of the discrepancy between these results and the accepted view of minisatellites, i.e., a large number of unlinked loci spread over the genome. Our results nevertheless indicate the existence of particularly large and homologous loci on a particular chromosome for each of these probes.