Isolation of a Drosophila T-box gene closely related to human TBX1.

T-box genes, in all metazoans studied from nematode to man, exist in small gene families. They encode transcription factors with a novel, large, and highly conserved DNA binding domain termed the T-domain. In all cases studied, T-box genes have important developmental roles. Two familial diseases, Holt-Oram syndrome and ulnar-mammary syndrome, were recently shown to be caused by mutations in the human T-box genes TBX5 and TBX3, respectively. T-box genes were first identified in Drosophila and mouse. Two of the three known Drosophila T-box genes show a close sequence homology to mammalian genes. Similarities in the phenotypes of fly and mammalian mutants can be taken as evidence of functional conservation. We report here the isolation of a fourth Drosophila T-box gene, optomotor-blind-related gene-1 (org-1), closely related to mouse and human TBX1. We localized TBX1 to chromosomal band 22q11, confirming a recent report, and discuss TBX1 as a candidate gene for DiGeorge and related syndromes.