title: Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's Disease.
abstract: Potential roles for variants in the human BDNF gene in human brain disorders are supported by findings that include: (a) influences that this trophic factor can exert on important neurons, brain regions, and neurotransmitter systems, (b) changes in BDNF expression that follow altered neuronal activity and drug treatments, and (c) linkages or associations between genetic markers in or near BDNF and human traits and disorders that include depression, schizophrenia, addictions, and Parkinson's disease. We now report assembly of more than 70 kb of BDNF genomic sequence, delineation of 7 noncoding and 1 coding human BDNF exons, elucidation of BDNF transcripts that are initiated at several alternative promoters, identification of BDNF mRNA splicing patterns, elucidation of novel sequences that could contribute to activity-dependent BDNF mRNA transcription, targeting and/or translation, elucidation of tissue-specific and brain-region-specific use of the alternative human BDNF promoters and splicing patterns, identification of single nucleotide polymorphism (SNP), and simple sequence length polymorphism (SSLP) BDNF genomic variants and identification of patterns of restricted haplotype diversity at the BDNF locus. We also identified type 2 BDNF-locus transcripts that are coded by a novel gene that is overlapped with type 1 BDNF gene and transcribed in reverse orientation with several alternative splicing isoforms. Association studies of BDNF variants reveal no associations with Parkinson's disease. Comparisons between substance abusers and controls reveal modest associations. These findings increase interest in this diverse human gene.
authors.affiliation: Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program (NIDA-IRP), NIH, Department of Health and Human Services (DHHS), Baltimore, Maryland, USA.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
authors.forename: Donna
authors.initials: D
authors.lastname: Walther
authors.forename: Tomas
authors.initials: T
authors.lastname: Drgon
authors.forename: Oxana
authors.initials: O
authors.lastname: Polesskaya
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Strain
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: James H
authors.initials: JH
authors.lastname: Bower
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics*; D011061:Poly A / Q000235:genetics; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019966:Substance-Related Disorders / Q000235:genetics*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D022661:RNA, Untranslated; D011061:Poly A; D012313:RNA; D004247:DNA