title: Small deletions in the regulatory 3' UTR of the human alpha-tropomyosin gene identified by differential display.
abstract: The differential display technique (DDT) was used to compare Fanconi anaemia (FA) fibroblasts with those of normal controls in a screen for genes involved in DNA repair, recognizing and handling damage or indicating cell cycle abnormalities as a result of genetic changes. The DDT revealed two different deletions of 5 and 11 bp at a single locus in the 3' untranslated region (UTR) of a gene known to encode human alpha-tropomyosin (TPM1) in FA cells. These small deletions were detected by analysis of shifted 900-bp long cDNA fragments on polyacrylamide gels. They were characterized as loss of GTTTT or TGTTTTGTTTT, respectively, in a region with five GTTTT tandem repeats. Since it was postulated that the 3' UTR of the TPM1 gene plays a regulatory role in cell differentiation and tumour suppression, the existence and possible patterns of deletions in a variety of normal donors was investigated. The heterogenous distribution of non-deleted, 5- and 11-bp deleted 3' UTR regions indicate a polymorphism of the TPM1 gene in this tandem repeat motif. Therefore the expression pattern of these mutations among FA and non-FA cells rendered any direct relationship to the putative DNA repair defect in FA unlikely. Of note, however, the fact remains that such deletions reportedly facilitate mRNA degradation and may bear significance in the TPM1 gene action. Finally, of further interest is the finding that even small deletions can be identified by DDT in addition to the identification of the differential expression patterns of genes.
authors.affiliation: Biotechnology Therapeutics, Research Center, Boehringer Mannheim GmbH, Penzberg, Germany.
authors.forename: S A
authors.initials: SA
authors.lastname: Planitzer
authors.forename: A W
authors.initials: AW
authors.lastname: Machl
authors.forename: D
authors.initials: D
authors.lastname: Schindler
authors.forename: M
authors.initials: M
authors.lastname: Kubbies
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004249:DNA Damage; D017931:DNA Primers; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017384:Sequence Deletion; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D014335:Tropomyosin