title: Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.
abstract: DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and isolated and familial forms of conotruncal cardiac defects have been associated with deletions of chromosomal region 22q11.2. This report describes the identification, cloning, and characterization of the human TBX1 gene, which maps to the center of the DiGeorge chromosomal region. Further, we have extended the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1 is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes are transcription factors involved in the regulation of developmental processes. There is 98% amino acid identity between human and mouse TBX1 proteins overall, and within the T-box domain, the proteins are identical except for two amino acids. Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse. Additionally, using 3 'RACE, we obtained a differentially spliced message in adult skeletal muscle. Mouse Tbx1 has been previously shown to be expressed during early embryogenesis in the pharyngeal arches, pouches, and otic vesicle. Later in development, expression is seen in the vertebral column and tooth bud. Thus, human TBX1 is a candidate for some of the features seen in the 22q11 deletion syndrome.
authors.affiliation: The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chieffo
authors.forename: N
authors.initials: N
authors.lastname: Garvey
authors.forename: W
authors.initials: W
authors.lastname: Gong
authors.forename: B
authors.initials: B
authors.lastname: Roe
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Silver
authors.forename: B S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: M L
authors.initials: ML
authors.lastname: Budarf
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005326:Fetal Proteins / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D005784:Gene Amplification; D015870:Gene Expression / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*; D014981:Xenopus / Q000235:genetics; D000098908:Brachyury Protein
chemical_list: D004247:DNA; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D011506:Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C107397:ESS2 protein, human; C108625:TBX1 protein, human; C491573:Tbx1 protein, mouse