TTID: A Novel Gene at 5q31 Encoding a Protein with Titin-like Features

• Published in: Genomics (San Diego, Calif.) Vol. 60; no. 2; pp. 226 - 233
• Main Authors: Godley, Lucy A., Lai, Fang, Liu, Jin, Zhao, Nanding, Le Beau, Michelle M.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.09.1999; Elsevier
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 5 - genetics; Cloning, Molecular; Connectin; Cytoskeletal Proteins; DNA Primers - genetics; DNA, Complementary - genetics; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes. Genome; Humans; Introns; Leukemia, Myeloid, Acute - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Molecular Weight; Muscle Proteins - chemistry; Muscle Proteins - genetics; Mutation; Myelodysplastic Syndromes - genetics; Polymorphism, Single-Stranded Conformational; Protein Kinases - chemistry; Protein Kinases - genetics; Proteins - chemistry; Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tissue Distribution; Genetic mapping; Human; Connectin; Domain structure; Nucleotide sequence; Homology; Gene organization; Chromosome B5; Gene expression; Polymorphism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1999.5912

A deletion of the long arm of chromosome 5 is a recurring abnormality in malignant myeloid disorders. In previous studies, we identified an approximately 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 10 exons that extend over 19 kb. The composite cDNA is ∼2.3 kb and encodes a protein of 498 amino acids, with a predicted molecular mass of 55 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 an immunoglobulin domain from the immense skeletal muscle protein titin. The TTID gene is expressed in multiple muscle tissue types as well as in thyroid gland and bone marrow. We evaluated the gene as a candidate tumor suppressor gene by searching for mutations in malignant myeloid disorders with abnormalities 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 polymorphism. Therefore, TTID is unlikely to be the candidate tumor suppressor gene involved in malignant myeloid disorders.