基因组拷贝数变异载体的皮层下大脑变化
Kuldeep Kumar1, Claudia Modenato1, Clara Moreau1
1Centre de Recherche du CHU Sainte-Justine, University of Montreal, Montreal (Kumar, Harvey, Huguet, Jean-Louis, Douard, Martin, Younis, Tamer, Dumas, Jacquemont); Mila-Quebec AI Institute, University of Montreal, Montreal (Dumas); Laboratoire de Recherche en Neuroimagerie, Department of Clinical Neurosciences (Modenato, Martin-Brevet, Lippé, Draganski), and Service des Troubles du Spectre de l'Autisme et Apparentés (Maillard, Rodriguez-Herreros, Pain), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Human Genetics and Cognitive Functions, Institut Pasteur, and Université de Paris, CNRS UMR 3571, Paris (Moreau); Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles (Kushan, Bearden); School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (Silva, Linden); Centre for Neuropsychiatric Genetics and Genomics (Silva, van den Bree, Owen, Hall), Division of Psychological Medicine and Clinical Neurosciences, School of Medicine (van den Bree, Owen, Hall), and Neuroscience and Mental Health Innovation Institute (van den Bree, Linden, Hall), Cardiff University, Cardiff, U.K.; Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Draganski); Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey (Ching, Moreau, Thompson); Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia (Schultz, Almasy); Lifespan Brain Institute, Children's Hospital of Philadelphia and Penn Medicine, Philadelphia (Schultz, Almasy); Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Almasy); Department of Psychiatry, Harvard Medical School, Boston, and Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston (Glahn); Department of Biomedical Engineering, Duke University, Durham, N.C. (Isaev); Department of Biomedical Engineering, Oregon Health and Science University, Portland (Ragothaman); Department of Psychology, Georgia State University, Atlanta (Turner); Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago (Alpert, Wang); Department of Psychiatry and Behavioral Health, Ohio State University Wexner Medical Center, Columbus (Wang); Department of Psychiatry and Behavioral Sciences and Department of Psychology, Stanford University, Stanford (Ho); Orygen, National Centre of Excellence in Youth Mental Health, Parkville, Australia, and Centre for Youth Mental Health, University of Melbourne, Melbourne (Schmaal); NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, and University of Oslo, Oslo (Sønderby, Andreassen); Department of Medical Genetics, Oslo University Hospital, Oslo (Sønderby); K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo (Sønderby, Andreassen); Department of Biomedical Engineering, Illinois Institute of Technology, Chicago (Gutman).
副本数变异 (CNVs) 影响大脑结构,影响神经发育障碍 (如自闭症和精神分裂症) 的风险. 这些遗传变化在皮层下大脑区域显示出不同的模式,为疾病发展提供了洞察力.
科学领域:
- 神经遗传学 神经遗传学
- 神经成像是一种神经成像.
- 精神病学遗传学 精神病学遗传学
背景情况:
- 副本数变异 (CNV) 是神经发育和精神疾病 (NPD) 的已知的遗传风险因素,包括自闭症谱系障碍 (ASD) 和精神分裂症.
- 不同的CNVs对皮下大脑结构的确切影响及其与疾病风险的相关性仍然不完全理解.
研究的目的:
- 为了研究与NPD相关的各种CNV如何影响皮质下大脑结构.
- 探索 CNV 相关的大脑变化与疾病风险水平之间的关系.
主要方法:
- 在 675 个 CNV 载体和 782 个控制器中使用协调的 ENIGMA 协议来表征皮层下结构 (体积,厚度,表面图).
- 分析了11个特定的CNV,并将结果与现有的ENIGMA数据对六种NPD (ASD,精神分裂症,多动症,强迫症,双相情感障碍,严重抑郁症) 进行了比较.
主要成果:
- 所有研究的CNV都在至少一个皮质下测量尺度上表现出改变,其中海马和杏仁核最常受到影响.
- 形状分析揭示了体积分析中没有明显的亚区域性变化,确定了一个共同的维度,对海马/桃体和骨/骨产生了相反的影响.
- CNV对皮下测量的影响与它们对认知和ASD和精神分裂症风险的已知影响相关.
结论:
- 与CNV相关的皮质下变化部分反映了在NPD中看到的变化,但也表现出独特的模式.
- 特定的CNV与成人发病或ASD相关,提供了对差异风险的洞察力.
- 调查结果解决了为什么不同的CNV会给同一NPD带来风险,为什么单一的CNV会增加不同NPD的风险.
更多相关视频
相关概念视频
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Single Nucleotide Polymorphisms-SNPs
Genome Copying Errors
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Mutations


