Identification and characterization of MTR1, a novel gene with homology tomelastatin (MLSN1) and the trp gene family located in the BWS-WT2 criticalregion on chromosome 11p15.5 and showing allele-specific expression

Alterations within human chromosomal region 11p15.5 are associated with the Beckwith-Wiedemann syndrome (BWS) and predisposition to a variety of neopl asias, including Wilms' tumors (WTs), rhabdoid tumors and rhabdomyosarcomas , To identify candidate genes for 11p15.5-related diseases we compared huma n genomic sequence with expressed sequence tag and protein databases from d ifferent organisms to discover evolutionarily conserved sequences. Herein w e describe the identification and characterization of a novel human transcr ipt related to a putative Caenorhabditis elegans protein and the trp (trans ient receptor potential) gene. The highest homologies are observed with the human TRPC7 and with melastatin 1 (MLSN1), whose transcript is downregulat ed In metastatic melanomas, Other genes related to and interacting with the trp family include the Grc gene, which codes for a growth factor-regulated channel protein, and PKD1/PKD2, involved in polycystic kidney disease. The novel gene presented here (named MTR1 for MLSN1- and TRP-related gene 1) r esides between TSSC4 and KvLQT1, MTR1 is expressed as a 4.5 kb transcript i n a variety of fetal and adult tissues. The putative open reading frame is encoded in 24 exons, one of which is alternatively spliced leading to two p ossible proteins of 872 or 1165 amino acids with several predicted membrane -spanning domains in both versions, MTR1 transcripts are present in a large proportion of WTs and rhabdomyosarcomas, RT-PCR analysis of somatic cell h ybrids harboring a single human chromosome 11 demonstrated exclusive expres sion of MTR1 in cell lines carrying a paternal chromosome 11, indicating al lele-specific inactivation of the maternal copy by genomic imprinting.