A domain of the thyroid adenoma associated gene (THADA) conserved in vertebrates becomes destroyed by chromosomal rearrangements observed in thyroid adenomas.
THADA, mapping to chromosomal band 2p21 is target gene of specific chromosomal rearrangements observed in thyroid benign tumors. Thus, it is one of the most common gene targets in chromosomal rearrangements in benign epithelial tumors. Nevertheless, nothing is known about the function of its protein. Therefore, we have analyzed the genetic structure of THADA homologous genes in selected vertebrates (Canis familiaris, Chlorocebus aethiops, Gallus gallus, and Mus musculus), which are not characterized up to now. The coding sequences of the mRNA of these species have been sequenced and analyzed revealing similarities to ARM repeat structures which indicates an involvement in protein-protein interactions. Using multiple alignments we identified the most conserved part of the protein (aa 1033-1415 Homo sapiens) with an identity of 70.5% between the most different organisms implying a putative important functional domain. The truncations observed in human thyroid adenomas disrupt this conserved domain of the protein indicating a loss of function of THADA contributing to the development of the follicular neoplasias of the thyroid.
Drieschner
Norbert
N
Center for Human Genetics, University of Bremen, Leobenerstr./ZHG, D-28359 Bremen, Germany.
Kerschling
Svenja
S
Soller
Jan T
JT
Rippe
Volkhard
V
Belge
Gazanfer
G
Bullerdiek
Jörn
J
Nimzyk
Rolf
R
D000236:Adenoma / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D002869:Chromosome Aberrations; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D018076:DNA, Complementary; D004285:Dogs; D015321:Gene Rearrangement; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D017386:Sequence Homology, Amino Acid; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger