ABSTRACT
Human sex chromosomes, which are morphologically and genetically different, share few regions of homology. Among them, only pseudoautosomal regions (PARs) pair and recombine during meiosis. To better address the complex biology of these regions, we sequenced the telomeric 400 kb of the long arm of the human X chromosome, including 330 kb of the human Xq/YqPAR and the telomere. Sequencing reveals subregions with distinctive regulatory and evolutionary features. The proximal 295 kb contains two genes inactivated on both the inactive X and Y chromosomes [ SYBL1 and a novel homologue ( HSPRY3 ) of Drosophila sprouty ]. The GC-rich distal 35 kb, added in stages and much later in evolution, contains the X/Y expressed gene IL9R and a novel gene, CXYorf1, only 5 kb from the Xq telomere. These properties make Xq/YqPAR a model for studies of region-specific gene inactivation, telomere evolution, and involvement in sex-limited conditions.
Subject(s)
Proteins/genetics , Telomere/genetics , X Chromosome/genetics , Y Chromosome/genetics , Base Composition , Blotting, Southern , Cell Line , Chromosome Mapping , Chromosomes, Artificial, Yeast , Dosage Compensation, Genetic , Humans , In Situ Hybridization, Fluorescence , Intracellular Signaling Peptides and Proteins , Membrane Proteins/genetics , Membrane Proteins/metabolism , Molecular Sequence Data , Proteins/metabolism , R-SNARE Proteins , Repetitive Sequences, Nucleic Acid , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Telomere/metabolism , X Chromosome/metabolism , Y Chromosome/metabolismABSTRACT
In order to clarify some of the molecular mechanisms involved in the pathogenesis of thyroid proliferating diseases we have investigated the role of TGF-beta in thyroid carcinoma, adenoma and multinodular goiter. TGF-beta 1 expression studies were carried out in surgically removed thyroid tissue isolated from 15 patients affected by multinodular goiter, 4 patients affected by papillary carcinoma and 4 patients affected by follicular adenoma. TGF-beta 1 gene expression, evaluated by Northern analysis, dramatically increased in malignant proliferating thyroid disease and decreased drasticly in multinodular goiter patients with respect to normal thyroid. Immunocytochemical analysis demonstrated that TGF-beta 1 is produced by an autocrine mechanism in the carcinoma and in the benign thyroid disease (multinodular goiter), whereas TGF-beta seems to be produced in adenoma tissues in both an autocrine and a paracrine fashion. This feature further supports the hypothesis that TGF-beta may contribute to regulation of thyrocyte growth and differentiation.
