The Fanconi anemia gene network is conserved from zebrafish to human.
Fanconi anemia (FA) is a complex disease involving nine identified and two unidentified loci that define a network essential for maintaining genomic stability. To test the hypothesis that the FA network is conserved in vertebrate genomes, we cloned and sequenced zebrafish (Danio rerio) cDNAs and/or genomic BAC clones orthologous to all nine cloned FA genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL), and identified orthologs in the genome database for the pufferfish Tetraodon nigroviridis. Genomic organization of exons and introns was nearly identical between zebrafish and human for all genes examined. Hydrophobicity plots revealed conservation of FA protein structure. Evolutionarily conserved regions identified functionally important domains, since many amino acid residues mutated in human disease alleles or shown to be critical in targeted mutagenesis studies are identical in zebrafish and human. Comparative genomic analysis demonstrated conserved syntenies for all FA genes. We conclude that the FA gene network has remained intact since the last common ancestor of zebrafish and human lineages. The application of powerful genetic, cellular, and embryological methodologies make zebrafish a useful model for discovering FA gene functions, identifying new genes in the network, and identifying therapeutic compounds.
Titus
Tom A
TA
Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403, USA.
Selvig
Daniel R
DR
Qin
Baifang
B
Wilson
Catherine
C
Starks
Amber M
AM
Roe
Bruce A
BA
Postlethwait
John H
JH
D000595:Amino Acid Sequence; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D005199:Fanconi Anemia / Q000235:genetics*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000235:genetics*
D052236:Fanconi Anemia Complementation Group D2 Protein