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全基因组单核苷酸变异在基因组区域的分布及其与重度抑郁症的关系。

Whole-genome single nucleotide variant distribution on genomic regions and its relationship to major depression.

作者信息

Yu Chenglong, Baune Bernhard T, Licinio Julio, Wong Ma-Li

机构信息

Mind and Brain Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia; School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.

出版信息

Psychiatry Res. 2017 Jun;252:75-79. doi: 10.1016/j.psychres.2017.02.041. Epub 2017 Feb 20.

DOI:10.1016/j.psychres.2017.02.041
PMID:28258043
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5730269/
Abstract

Recent advances in DNA technologies have provided unprecedented opportunities for biological and medical research. In contrast to current popular genotyping platforms which identify specific variations, whole-genome sequencing (WGS) allows for the detection of all private mutations within an individual. Major depressive disorder (MDD) is a chronic condition with enormous medical, social and economic impacts. Genetic analysis, by identifying risk variants and thereby increasing our understanding of how MDD arises, could lead to improved prevention and the development of new and more effective treatments. Here we investigated the distributions of whole-genome single nucleotide variants (SNVs) on 12 different genomic regions for 25 human subjects using the symmetrised Kullback-Leibler divergence to measure the similarity between their SNV distributions. We performed cluster analysis for MDD patients and ethnically matched healthy controls. The results showed that Mexican-American controls grouped closer; in contrast depressed Mexican-American participants grouped away from their ethnically matched controls. This implies that whole-genome SNV distribution on the genomic regions may be related to major depression.

摘要

DNA技术的最新进展为生物学和医学研究提供了前所未有的机遇。与目前流行的识别特定变异的基因分型平台不同,全基因组测序(WGS)能够检测个体内所有的私人突变。重度抑郁症(MDD)是一种具有巨大医学、社会和经济影响的慢性疾病。通过识别风险变异,从而增进我们对MDD发病机制的理解,基因分析可能会改善预防措施,并推动新的、更有效的治疗方法的开发。在这里,我们使用对称化的库尔贝克-莱布勒散度来衡量25名人类受试者12个不同基因组区域上全基因组单核苷酸变异(SNV)的分布,以测量它们的SNV分布之间的相似性。我们对MDD患者和种族匹配的健康对照进行了聚类分析。结果显示,墨西哥裔美国对照组聚集得更近;相比之下,抑郁的墨西哥裔美国参与者与他们种族匹配的对照组分开聚类。这意味着基因组区域上的全基因组SNV分布可能与重度抑郁症有关。

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本文引用的文献

1
Single-nucleotide variant proportion in genes: a new concept to explore major depression based on DNA sequencing data.基因中的单核苷酸变异比例:基于DNA测序数据探索重度抑郁症的新概念。
J Hum Genet. 2017 Apr;62(5):577-580. doi: 10.1038/jhg.2017.2. Epub 2017 Feb 2.
2
The Genetic Architecture of Major Depressive Disorder in Han Chinese Women.中国汉族女性重度抑郁症的遗传结构
JAMA Psychiatry. 2017 Feb 1;74(2):162-168. doi: 10.1001/jamapsychiatry.2016.3578.
3
The PHF21B gene is associated with major depression and modulates the stress response.
基因组范围内位置效应在……中对异质基因表达的影响图谱 。 你提供的原文似乎不完整,“in.”后面应该还有具体内容。
Biotechnol Biofuels. 2017 Jul 18;10:189. doi: 10.1186/s13068-017-0872-3. eCollection 2017.
PHF21B基因与重度抑郁症相关,并调节应激反应。
Mol Psychiatry. 2017 Jul;22(7):1015-1025. doi: 10.1038/mp.2016.174. Epub 2016 Oct 25.
4
Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder - Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study).重度抑郁症认知维度的临床、功能及生物学关联——认知功能与情绪研究(CoFaM研究)的原理、设计与特点
Front Psychiatry. 2016 Aug 26;7:150. doi: 10.3389/fpsyt.2016.00150. eCollection 2016.
5
Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.一项基于大规模人群的研究中的外显子组测序揭示了LIPG基因中一种与抑郁症状相关的罕见Asn396Ser变体。
Mol Psychiatry. 2017 Apr;22(4):634. doi: 10.1038/mp.2016.141. Epub 2016 Aug 9.
6
Identification of 15 genetic loci associated with risk of major depression in individuals of European descent.在欧洲血统个体中鉴定出15个与重度抑郁症风险相关的基因位点。
Nat Genet. 2016 Sep;48(9):1031-6. doi: 10.1038/ng.3623. Epub 2016 Aug 1.
7
Sparse whole-genome sequencing identifies two loci for major depressive disorder.稀疏全基因组测序确定了重度抑郁症的两个基因座。
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J Theor Biol. 2015 May 7;372:135-45. doi: 10.1016/j.jtbi.2015.02.026. Epub 2015 Mar 5.
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Kullback-Leibler divergence for detection of rare haplotype common disease association.用于检测罕见单倍型与常见疾病关联的库尔贝克-莱布勒散度
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