GENOMIC STRUCTURE OF TBX2 INDICATES CONSERVATION WITH DISTANTLY RELATED T-BOX GENES

TBX2 is a member of a recently discovered gene family of transcription factors, named T-box genes after the Brachyury or T gene. Mutations i n two of these family members, TBX5 and TBX3, have recently been shown to be responsible for the congenital abnormalities associated with Ho lt Gram syndrome and ulnar-mammary syndrome respectively, while mutati ons in T-box genes in other species also result in developmental abnor malities in the tissues where the gene is normally expressed. Thus, it likely that other T-box genes are responsible for additional human de velopmental anomalies. Here we report the exon/intron boundaries of TB X2 and a polymorphism within intron 2 of TBX2 that should be useful fo r exploring the involvement of this gene in human genetic disease. We further note that the exon/intron boundaries of TBX2 are highly conser ved within the T-box domain with those of both T and TBX5, as well as with a new human T-box gene and more distantly related genes from Caen orhabditis elegans and Drosophila. This observation should facilitate the analysis of the genomic structure of other members of this gene fa mily. It is also of interest that several members of this gene family have an additional intron that is variably present within members of a t least two different lineages of the T-box family. This observation h as implications regarding the evolution of T-box genes.