title: Molecular characterization of a serine/threonine kinase in the DiGeorge minimal critical region.
abstract: The majority of patients with DiGeorge, velocardiofacial or conotruncal anomaly facial syndromes share a common genetic etiology, deletion of chromosomal region 22q11.2. This report describes a computational approach toward the identification and molecular characterization of a newly identified serine/threonine kinase from the minimal critical deleted region (MDGCR). A cosmid contig of the minimal critical region has been assembled and sequenced in its entirety. Database searches and computer analysis of one cosmid (111f11) for coding sequences identified two regions with high similarity to the mouse serine/threonine kinase, Tsk1. Our investigations demonstrate that one of these regions contains a testis-specific gene that undergoes differential splicing, while the other region is most likely a pseudogene. Northern blot analysis and cDNA cloning demonstrate that there is alternate processing of the 3'UTR without altering the conserved kinase domains within the open reading frame. Serine/threonine kinases can play a regulatory role and have been found to be expressed during early embryogenesis. Based on its position in the MDGCR and possible function, the gene reported here is a candidate for the features seen in the 22q11 deletion syndrome.
authors.affiliation: The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, The Department of Pediatrics, 19104, USA. egoldmuntz@email.chop.edu
authors.forename: E
authors.initials: E
authors.lastname: Goldmuntz
authors.forename: J
authors.initials: J
authors.lastname: Fedon
authors.forename: B
authors.initials: B
authors.lastname: Roe
authors.forename: M L
authors.initials: ML
authors.lastname: Budarf
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D003360:Cosmids; D004062:DiGeorge Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011544:Pseudogenes; D012333:RNA, Messenger / Q000235:genetics; D013737:Testis
chemical_list: D012333:RNA, Messenger; C097507:testis-specific protein kinase 1; D017346:Protein Serine-Threonine Kinases