Evolutionary clues to the molecular function of fanconi anemia genes.
Fanconi anemia (FA) is an autosomal recessively inherited disease with diverse clinical symptoms including developmental anomalies, predisposition to neoplasia, and a deficiency of hematopoietic stem cells resulting in progressive aplastic anemia. FA is genetically heterogeneous with at least 8 genes being implicated on the basis of functional complementation studies. To date, six FA genes are known: FANCA, FANCC, FANCD2, FANCE, FANCF and FANCG, all of which encode orphan proteins sharing no homology to each other nor to any other known protein. In addition, they do not appear to possess any domains with homology to currently known protein domains, which makes a prediction about their molecular action difficult. Studying the molecular evolution of FA genes and their products using sensitive database search methods such as PSI-BLAST may provide novel insight into the nature of the FA pathway and its relationship to hematopoiesis, embryonic development and the origin of malignancies. Preliminary results of such an approach show that at least one FA protein, FANCG, may contain a known domain, suggesting that this protein is a member of the family of tetratricopeptide repeat-containing proteins.
Blom
Eric
E
Department of Clinical Genetics and Human Genetics, Free University Medical Center, Amsterdam, The Netherlands.
van de Vrugt
Henri J
HJ
de Winter
Johan P
JP
Arwert
Fré
F
Joenje
Hans
H
D000465:Algorithms; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D030562:Databases, Protein; D019143:Evolution, Molecular; D005199:Fanconi Anemia / Q000235:genetics*; D052241:Fanconi Anemia Complementation Group G Protein; D006801:Humans; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment
D004268:DNA-Binding Proteins; C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein