Walpole S M, Hiriyana K T, Nicolaou A, Bingham E L, Durham J, Vaudin M, Ross M T, Yates J R, Sieving P A, Trump D
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, United Kingdom.
Genomics. 1999 Feb 1;55(3):275-83. doi: 10.1006/geno.1998.5667.
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 constructed, 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 (retinoic acid-induced 2). RAI2 mapped 28 kb centromeric to marker DXS7996, between 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, placenta, lung, skeletal muscle, kidney, pancreas, and retina) but not in fetal or adult liver. The 530-amino-acid protein (57 kDa predicted mass) displays 94% homology with a mouse retinoic acid-induced gene product and contains a novel proline-rich (39%) domain of 68 amino acids. Retinoic acid is involved in vertebrate anteroposterior axis formation and cellular differentiation and has been shown to modulate gene expression controlling early embryonal development, suggesting a developmental role for RAI2. RAI2 remains a candidate gene for diseases mapping to the Xp22 region.
在对Xp22上位于DXS418和DXS999之间的1.3 Mb区域进行研究的过程中，我们鉴定出了一个新的人类基因。构建了一个跨越该区域的PAC重叠群，对其进行测序，并通过基因和外显子预测程序以及同源性搜索进行分析。对PAC克隆389A20预测的外显子进行进一步研究，导致鉴定出一个单外显子基因，命名为RAI2（视黄酸诱导基因2）。RAI2定位于标记DXS7996着丝粒侧28 kb处，在DXS7996和DXS7997之间，并且从着丝粒向端粒转录。Northern印迹分析和逆转录-聚合酶链反应分析显示，在四种胎儿组织（脑、肺、肾和心脏）和八种成人组织（心脏、脑、胎盘、肺、骨骼肌、肾、胰腺和视网膜）中表达一种2.5 kb的转录本，但在胎儿或成人肝脏中不表达。这个由530个氨基酸组成的蛋白质（预测分子量为57 kDa）与小鼠视黄酸诱导基因产物具有94%的同源性，并且包含一个由68个氨基酸组成的富含脯氨酸的新结构域（占39%）。视黄酸参与脊椎动物前后轴的形成和细胞分化，并且已被证明可调节控制早期胚胎发育的基因表达，这表明RAI2具有发育方面的作用。RAI2仍然是定位到Xp22区域疾病的候选基因。
