TTID: A novel gene at 5q31 encoding a protein with titin-like features

A deletion of the long arm of chromosome 5 is a recurring abnormality in ma lignant myeloid disorders. In previous studies, we identified an approximat ely 1-Mb segment in 5q31 that was deleted in all patients examined. As part of a positional cloning project to identify transcribed sequences in this region, we identified and characterized the TTID gene. This gene contains 1 0 exons that extend over 19 kb, The composite cDNA is similar to 2.3 kb and encodes a protein of 498 amino acids, with a predicted molecular mass of 5 5 kDa. The C-terminal half of this putative protein contains an internally repeated domain of 43 amino acids, which resembles the N-terminal half of a n immunoglobulin domain from the immense skeletal muscle protein titin. The TTID gene is expressed in multiple muscle tissue types as well as in thyro id gland and bone marrow. We evaluated the gene as a candidate tumor suppre ssor gene by searching for mutations in malignant myeloid disorders with ab normalities of chromosome 5. However, we detected no inactivating mutations . A single nucleotide change (G to A) was identified at nucleotide position 1889 in the untranslated region of the mRNA, which may represent a polymor phism. Therefore, TTID is unlikely to be the candidate tumor suppressor gen e involved in malignant myeloid disorders. (C) 1999 Academic Press.