Identification and characterization of the human homologue (RAI2) of a mouse retinoic acid induced gene in Xp22

We have identified a novel human gene during studies of a 1.3-Mb region of Xp22 between DXS418 and DXS999. A PAC contig spanning the region was constr ucted, sequenced, and analyzed by gene and exon prediction programs and by homology searches. Further investigation of predicted exons from PAC clone 389A20 led to the identification of a single-exon gene, designated RAI2 (re tinoic acid-induced 2). RAI2 mapped 28 kb centromeric to marker DXS7996, be tween DXS7996 and DXS7997, and was transcribed from centromere to telomere. Northern blot analysis and reverse transcription-polymerase chain reaction analysis revealed expression of a 2.5-kb transcript in four fetal tissues (brain, lung, kidney, and heart) and eight adult tissues (heart, brain, pla centa, lung, skeletal muscle, kidney, pancreas, and retina) but not in feta l or adult liver. The 530-amino-acid protein (57 kDa predicted mass) displa ys 94% homology with a mouse retinoic acid-induced gene product and contain s a novel proline-rich (39%) domain of 68 amino acids. Retinoic acid is inv olved in vertebrate anteroposterior axis formation and cellular differentia tion and has been shown to modulate gene expression controlling early embry onal development, suggesting a developmental role for RAI2. RAI2 remains a candidate gene for diseases mapping to the Xp22 region. (C) 1999 Academic P ress.