The Human ATP-Binding Cassette (ABC) Transporter Superfamily

Abstract

Single nucleotide polymorphisms (SNPs) are likely to contribute to the study of complex genetic diseases. The genomic sequence of human chromosome 21q was recently completed with 225 annotated genes, thus permitting efficient identification and precise mapping of potential cSNPs by bioinformatics approaches. Here we present a human chromosome 21 (HC21) cSNP database and the first chromosome-specific cSNP map. Potential cSNPs were generated using three approaches: (1) Alignment of the complete HC21 genomic sequence to cognate ESTs and mRNAs. Candidate cSNPs were automatically extracted using a novel program for context-dependent SNP identification that efficiently discriminates between true variation, poor quality sequencing, and paralogous gene alignments. (2) Multiple alignment of all known HC21 genes to all other human database entries. (3) Gene-targeted cSNP discovery. To date we have identified 377 cSNPs averaging ∼1 SNP per 1.5 kb of transcribed sequence, covering 65% of known genes in the chromosome. Validation of our bioinformatics approach was demonstrated by a confirmation rate of 78% for the predicted cSNPs, and in total 32% of the cSNPs in our database have been confirmed. The database is publicly available at

The motor domains of ABC-transporters

“…The human genome encodes 48 ABC transporters (Dean et al 2001). These are divided into five different subfamilies:ABCA, ABCB, ABCC, ABCD and ABCG.…”

Mutational analysis of theABCC6 gene and the proximalABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE)

“…This protein is abundantly expressed in liver and kidney cell membranes, and to a lesser extent in tissues affected by PXE, including skin, retina and vessel walls (Kool et al, 1999;Bergen et al, 2000). MRP6 belongs to a family of transmembrane proteins which function as efflux transporters (Dean et al, 2001;Haimeur et al, 2004). The physiological function of MRP6 is still unknown, but recent reports suggest its implication in transmembrane transport of glutathionated metabolites (Belinsky et al, 2002;Ilias et al, 2002).…”

Age at onset: important marker of genetic heterogeneity in Alzheimer's disease

“…One of these is ABCA1, a gene which has been implicated in disorders of cholesterol transport. 9 This gene is of particular interest as the risk of AD is influenced by ApoE allelic status, a gene involved in cholesterol transport, and as recent studies have implicated cholesterol levels in the metabolism of the amyloid precursor protein. Within 1 LOD unit of the 15q22 region, there are nearly 200 known genes, including among others microtubule-associated protein kinases 1 and 5, and RAB11A which encodes a RAS-related GTPase.…”