Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease

Qing Rong Liu, Donna Walther, Tomas Drgon, Oxana Polesskaya, Timothy G. Lesnick, Kari J. Strain, Mariza De Andrade, James H. Bower, Demetrius M. Maraganore, George R. Uhl

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume134 B
Issue number1
DOIs
StatePublished - Apr 5 2005

Fingerprint

Brain-Derived Neurotrophic Factor
Substance-Related Disorders
Parkinson Disease
Genes
human brain-derived neurotrophic factor
Messenger RNA
Brain
Alternative Splicing
Brain Diseases
Genetic Markers
Haplotypes
Single Nucleotide Polymorphism
Neurotransmitter Agents
Exons
Schizophrenia
Protein Isoforms
Depression
Neurons

Keywords

  • Haplotype
  • Isoforms
  • Polymorphism
  • Promoters
  • Translation mechanism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease. / Liu, Qing Rong; Walther, Donna; Drgon, Tomas; Polesskaya, Oxana; Lesnick, Timothy G.; Strain, Kari J.; De Andrade, Mariza; Bower, James H.; Maraganore, Demetrius M.; Uhl, George R.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 134 B, No. 1, 05.04.2005, p. 93-103.

Research output: Contribution to journalArticle

Liu, Qing Rong ; Walther, Donna ; Drgon, Tomas ; Polesskaya, Oxana ; Lesnick, Timothy G. ; Strain, Kari J. ; De Andrade, Mariza ; Bower, James H. ; Maraganore, Demetrius M. ; Uhl, George R. / Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2005 ; Vol. 134 B, No. 1. pp. 93-103.
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