Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells.
Alterations of the distal portion of the short arm of chromosome 1 (1p) are among the earliest abnormalities of human colorectal tumours. Recently, we have cloned the Aflatoxin B1 aldehyde reductase (AFAR) gene from a smallest region of overlapping deletion that is frequently (48%) hemizygously deleted in sporadic colorectal cancer. AFAR is expressed in a broad range of tissues. Its closely related rat protein is the major factor conferring resistance of rats towards aflatoxin B1-induced liver carcinogenesis. Here, we have identified cDNAs covering two additional human AFAR-related genes localized in close proximity to the previously described AFAR at 1p35-36. We have analysed their structure and tissue-related expression. One of them, AFAR3, carries a Selenocysteine-Insertion Element (SECIS)-like structure that during translation may recode an in-frame TGA-stop codon to a selenocysteine. Two additional AFAR-pseudogenes are localized at Xq25 and 1p12, respectively. AFAR exon sequences share an identity of DNA and amino acids of more than 78%. Also large blocks of intronic sequences can be up to 98.6% identical. Knowledge of the AFAR genes and their structure will be essential in genetic and functional studies, where discrimination of the genes and proteins is a prerequisite for evaluating their individual functions.
Praml
Christian
C
Division of Tumour Genetics B030, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Savelyeva
Larissa
L
Schwab
Manfred
M
D000449:Aldehyde Reductase / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics; D020451:Contig Mapping; D003360:Cosmids; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution
D003062:Codon; D018076:DNA, Complementary; D004247:DNA; C082765:aflatoxin B1 aldehyde reductase; D000449:Aldehyde Reductase