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

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  • Supplemental material including detailed PCR primers, and sequences of SSLPs is available on-line. The BDNF gene, isoform, and SSLP sequences in this study have been submitted to NCBI GenBank under accession numbers: BDNF gene, AF411339; BDNF1, AY054392; BDNF2A, AY054393; BDNF2B, AY054394; BDNF2C, AY054395; BDNF3, AY054396; BDNF4, AY054397; BDNF5, AY054398; BDNF6A, AY054399; BDNF6B, AY054400; BDNF7, AY054406, BT1B, AY513486; BT1C, AY054401; BT1A, AY054402; BT2B, AY054403; BT2D, AY054404; BT2A, AY054405; BT2C, AY054391. NCBI SNP Assay ID (MNBNIDA): ss13534842 and ss4323247.

  • This article is a US Government work and, as such, is in the public domain in the United States of America.

  • §

    This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

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. Published 2005 Wiley-Liss, Inc.

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