title: Novel alleles of the transforming growth factor β-1 regulatory region and exon 1.
abstract: Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiologic and pathogenic processes with pleiotropic effects. Regulatory activity for this gene has been shown for 3.0 kb between positions -2665 and +423 from its translational start site. At least 17 TGFB1 regulatory region and exon 1 alleles have been defined on the basis of 18 polymorphic sites. Polymorphisms in TGFB1's regulatory region have been associated with differential levels of expression of this cytokine and to genetic risk in cancer and transplantation. In this report, we present 19 novel TGFB1 regulatory region and exon 1 alleles: p018-p036. Amplification of TGFB1's regulatory region was performed with an in-house protocol, and novel alleles were defined by either allele-specific amplification and/or molecular cloning of the amplicons, followed by sequencing in isolation. Three of these novel alleles (p018, p019, and p020) are shown to be formed by novel combinations of the aforementioned known polymorphic positions. Another 16 novel alleles are shown to carry additional known and unknown single-nucleotide polymorphisms. Polymorphism in TGFB1's regulatory region could have an impact on important processes, including embryogenesis, hematopoiesis, carcinogenesis, angiogenesis, fibrosis, immune responses, and transplantation, making its characterization necessary.
authors: Anthony Nolan Research Institute, Royal Free Hospital, London, UK; Cancer Institute, University College London, Royal Free Campus, London, UK; Centro de Investigaciones en Hematología y Trastornos Afines (CIHATA), Universidad de Costa Rica, San José, Costa Rica.
authors: E
authors: E
authors: Arrieta-Bolaños
authors: J A
authors: JA
authors: Madrigal
authors: B E
authors: BE
authors: Shaw
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D003001:Cloning, Molecular; D004926:Escherichia coli; D005091:Exons / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D033581:Stem Cell Transplantation; D014019:Tissue Donors; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000502:physiology
chemical_list: D020121:5' Untranslated Regions; D011993:Recombinant Fusion Proteins; D053773:Transforming Growth Factor beta1
keywords: +29T>C; alleles; polymorphism; regulatory region; transforming growth factor β-1; −1347C>T