| 1 | 摩尔。精神病学2010年6月15日：637-46 |
|---|---|
| PMID | 19546859 |
| Title | 注意力缺陷多动障碍中发现的罕见结构变体优先与神经发育基因相关。 |
| 抽象的 | 注意缺陷多动症(ADHD)a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism,精神分裂症and Tourette syndrome, including A2BP1,AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD. |
| SCZ Keywords | 精神分裂症 |
| 2 | PLoS Genet. 2010 May 6: e1000962 |
| PMID | 20502679 |
| Title | 癫痫中全基因组的拷贝数变化：特发性广义和局灶性癫痫中的新型敏感性基因座。 |
| 抽象的 | 癫痫是一种最常见的神经细胞ological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and精神分裂症。尚未进行癫痫拷贝数变化的全基因组研究。我们已经将全基因组寡核苷酸阵列比较基因组杂交应用于具有各种特发性，非静脉癫痫的517个人群。我们在8.9％的受影响的个体中检测到一个或多个罕见的遗传CNV，其中2493个对照中不存在。五个人有两个罕见的CNV。我们确定了以前与其他神经发育障碍有关的基因中的CNV，其中包括两种缺失AUTS2and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or精神分裂症。In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism,精神分裂症和癫痫。 |
| SCZ Keywords | 精神分裂症 |
| 3 | 细胞遗传学。基因组res。2011 -1 135：228-40 |
| PMID | 22085975 |
| Title | 解散了复杂疾病的无数基因组学，特别关注自闭症，癫痫和精神分裂症。 |
| 抽象的 | Analyses of structural genome variation by array-CGH have dramatically enhanced our ability to detect copy number variations (CNVs). De novo CNVs and those co-segregating with disease in a family are generally interpreted as pathogenic. Yet, often CNVs, such as recurrent microdeletions in region 15q13.3, are not so clearly pathogenic. Here we discuss potential confounding mechanisms that may lead to the phenotypic pleiotropy of CNVs, such as unmasking of recessive alleles by hemizygous deletions, interaction of CNVs with other loci and genes, genetic epistasis, allelic exclusion, and somatic mosaicism. We illustrate some of these mechanisms with a detailed analysis of recent studies of CNVs involving MCPH1,AUTS2，CNTNAP2和GRIN2B中的突变。接下来，我们将讨论这些发现的临床影响，并敦促工人避免“诊断性宿命论”（即，在发现单个CNV后停止所有遗传研究），并应对下一代测序技术实施可能造成的一些未来挑战。 |
| SCZ Keywords | 精神分裂症 |
| 4 | Transl Psychiatry 2011 -1 1: e34 |
| PMID | 22832608 |
| Title | 在老年男性的后代中，从头拷贝数的变体增加。 |
| 抽象的 | 较老的父亲的后代患神经发育障碍的风险增加，例如精神分裂症and autism. In light of the evidence implicating copy number variants (CNVs) with精神分裂症and autism, we used a mouse model to explore the hypothesis that the offspring of older males have an increased risk of de novo CNVs. C57BL/6J sires that were 3- and 12-16-months old were mated with 3-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, 7 distinct CNVs were identified in a set of 12 offspring and their parents. Competitive quantitative PCR confirmed these CNVs in the original set and also established their frequency in an independent set of 77 offspring and their parents. On the basis of the combined samples, six de novo CNVs were detected in the offspring of older sires, whereas none were detected in the control group. Two of the CNVs were associated with behavioral and/or neuroanatomical phenotypic features. One of the de novo CNVs involvedAUTS2（自闭症易感性候选2），其他CNV包括与之相关的基因精神分裂症，自闭症和大脑发育。这是第一个实验证明，即老年男性的后代具有从头cnvs的风险增加。我们的结果支持以下假设：较老的父亲的后代患有神经发育障碍的风险增加，例如精神分裂症和自闭症在雄性种系中从头产生。 |
| SCZ Keywords | 精神分裂症 |
| 5 | Cell 2012 Apr 149: 525-37 |
| PMID | 22521361 |
| Title | 测序染色体异常揭示了神经发育基因座，可在诊断边界赋予风险。 |
| 抽象的 | 平衡的染色体异常（BCA）代表了神经发育障碍（NDDS）中单基因中断的相对尚未开发的储层。我们对自闭症或相关NDD患者的BCA进行了测序，揭示了四个一般类别中33个基因座的破坏：（1）先前与异常神经发育相关的基因（例如，例如，AUTS2, FOXP1, and CDKL5), (2) single-gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, and SNURF-SNRPN), (3) novel risk loci (e.g., CHD8, KIRREL3, and ZNF507), and (4) genes associated with later-onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, and ANK3). We also discovered among neurodevelopmental cases a profoundly increased burden of copy-number variants from these 33 loci and�a significant enrichment of polygenic risk alleles from genome-wide association studies of autism and精神分裂症。Our findings suggest a polygenic risk model of autism and reveal that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. |
| SCZ Keywords | 精神分裂症 |
| 6 | Cell Rep 2014 Dec 9: 2166-79 |
| PMID | 25533347 |
| Title | Cytoskeletal regulation by AUTS2 in neuronal migration and neuritogenesis. |
| 抽象的 | Mutations in the Autism susceptibility candidate 2 gene (AUTS2）蛋白质被认为在神经元细胞核中起作用，与多种精神病疾病有关，包括自闭症谱系障碍，智力障碍和精神分裂症。在这里，我们证明了细胞质AUTS2参与细胞骨架和神经发育的调节。免疫组织化学和分级研究表明AUTS2不仅在细胞核中定位，而且还将其定位在细胞质中，包括在发育中的大脑中的生长锥中。AUTS2激活Rac1诱导层状脂蛋白，但下调CDC42以抑制丝状霉菌。我们的功能丧失和救援实验表明细胞质AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These findings suggest that cytoplasmicAUTS2充当Rho家族GTPases的调节剂，促进大脑发育，并深入了解人类精神疾病的病理学AUTS2突变。 |
| SCZ Keywords | 精神分裂症 |
| 7 | Int J Mol Sci 2014 -1 15：19406-16 |
| PMID | 25347278 |
| Title | 协会研究确定了用于精神分裂症的新敏感基因（AUTS2）。 |
| 抽象的 | 精神分裂症（SCZ）是一种严重且令人衰弱的精神障碍，而SCZ风险仍然难以捉摸的具体遗传因素。自闭症易感性候选者2（AUTS2) gene has been reported to be associated with autism, suicide, alcohol consumption, and heroin dependence. We hypothesized thatAUTS2might be associated with SCZ. In the present study, three polymorphisms (rs6943555, rs7459368, and rs9886351) in theAUTS2gene were genotyped in 410 patients with SCZ and 435 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forced PCR-RFLP methods. We detected an association between SCZ and the rs6943555 genotype distribution (odds ratio (OR)=1.363, 95% confidence interval (CI): 0.848-2.191, p=0.001). The association remained significant after adjusting for gender, and a significant effect (p=0.001) was observed among the females. In the present study, rs6943555 was determined to be associated with female SCZ. Our results confirm previous reports which have suggested that rs6943555 might elucidate the pathogenesis of精神分裂症并在其病因中发挥重要作用。 |
| SCZ Keywords | 精神分裂症 |
| 8 | 摩尔。Psychiatry 2014 Jun 19: 652-8 |
| PMID | 24776741 |
| Title | De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. |
| 抽象的 | 精神分裂症is a serious psychiatric disorder with a broadly undiscovered genetic etiology. Recent studies of de novo mutations (DNMs) in精神分裂症and autism have reinforced the hypothesis that rare genetic variation contributes to risk. We carried out exome sequencing on 57 trios with sporadic or familial精神分裂症。在零星的三重奏中，我们观察到无义DNM的比例增加了约3.5倍（0.101 vs 0.031，经验P = 0.01，Benjamini-Hochberg经过的Benjamini-Hochberg校正P = 0.044）。这些突变在高度排名的不足概率的基因中明显更可能发生（p = 0.0029，校正后p = 0.006）。还发现潜在功能后果的DNM在预测罕见变化的基因中发生（p = 2.01�10（ - ）（5），校正后p = 2.1�10（ - ）（3））。具有DNM的基因与与自闭症有关的基因重叠（例如，AUTS2, CHD8 and MECP2) and intellectual disability (for example, HUWE1 and TRAPPC9), supporting a shared genetic etiology between these disorders. Functionally CHD8, MECP2 and HUWE1 converge on epigenetic regulation of transcription suggesting that this may be an important risk mechanism. Our results were consistent in an analysis of additional exome-based sequencing studies of other neurodevelopmental disorders. These findings suggest that perturbations in genes, which function in the epigenetic regulation of brain development and cognition, could have a central role in the susceptibility to, pathogenesis and treatment of mental disorders. |
| SCZ Keywords | 精神分裂症 |
| 9 | PLoS ONE 2015 -1 10: e0145979 |
| PMID | 26717414 |
| Title | 自闭症易感性候选者的杂合破坏2导致情绪控制和认知记忆受损。 |
| 抽象的 | Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and精神分裂症。我们先前证明了细胞质AUTS2acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of theAUTS2小鼠中的基因导致神经元迁移和神经发生缺陷，在Rac1信号途径失活引起的发育中的大脑皮质中，这表明这表明AUTS2is required for neural development. In this study, we conducted a battery of behavioral analyses onAUTS2杂合突变小鼠检查AUTS2在成人认知大脑功能中。AUTS2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired inAUTS2mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate thatAUTS2is critical for the acquisition of neurocognitive function. |
| SCZ Keywords | 精神分裂症 |