Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease
Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's disease
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DOI：
10.1002/ajmg.b.30109
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发表时间：
2005-04-05
影响因子：
2.8
通讯作者：
Uhl, GR
中科院分区：
文献类型：
--
作者：
Liu, QR;Walther, D;Uhl, GR
人类BDNF基因变异在人类大脑疾病中的潜在作用得到以下发现的支持：（a）该营养因子可对重要的神经元、脑区和神经递质系统施加的影响，（B）神经元活性改变和药物治疗后BDNF表达的变化，和（c）BDNF中或附近的遗传标记与人类特征和疾病（包括抑郁症、精神分裂症、成瘾和帕金森病）之间的联系或关联。我们现在报告了超过70 kb的BDNF基因组序列的组装，描述了7个非编码和1个编码人BDNF外显子，阐明了在几个替代启动子处启动的BDNF转录物，鉴定了BDNF mRNA剪接模式，阐明了可能有助于活性依赖性BDNF mRNA转录、靶向和/或翻译的新序列，阐明替代性人BDNF启动子和剪接模式的组织特异性和脑区域特异性用途，鉴定单核苷酸多态性（SNP）和简单序列长度多态性（SSLP）BDNF基因组变体，以及鉴定BDNF基因座处的限制性单倍型多样性模式。我们还确定了2型BDNF基因座转录本，其由与I型BDNF基因重叠的新基因编码，并与几种选择性剪接异构体反向转录。BDNF变体的关联研究显示与帕金森病没有关联。药物滥用者和对照组之间的比较显示出适度的关联。这些发现增加了人们对这种多样的人类基因的兴趣。2005年出版Wiley-Liss，Inc.（匕首）
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 I 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.(dagger)