The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21.

Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal abnormalities in human hematological malignancies. Two distinct regions of minimal deletion have been identified by loss of heterozygosity studies at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD-2), suggesting the presence of one or more tumor suppressor genes. We have cloned sequences within RMD-2 and screened for novel genes using a combination of direct sequencing, cDNA library screening, and exon trapping. Sequences generated from a cosmid fragment, mapping within RMD-2, showed homology to the Drosophila tailless gene (tll). The human homologue of the Drosophila tailless gene (human tlx; MGMW-approved symbol, TLX) was subsequently cloned from a fetal brain cDNA library. The gene is a member of the steroid nuclear receptor superfamily and is homologous to tll genes from other species that are involved in brain development. TLX is predominately expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and D6S447, in a YAC clone that also contains marker D6S246. The contributions of this gene to human B-cell leukemia and to brain development are unknown at present.