微卫星D6S1960和D6S274多态性与精神分裂症的关联研究

目的探讨江西地区汉族人群微卫星D6S1960和D6S274遗传多态性与精神分裂症的关系。方法对符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的174例精神分裂症患者进行微卫星D6S1960和D6S274多态性的检测,以174名健康体检者为正常对照组。结果患者组和正常对照组D6S1960位点的273bp等位基因的检出率分别为21.55%(75/348)和11.78%(41/348),两者的差异有统计学意义(X2=11.93,P0.01);两组D6S274位点的172bp等位基因检出率分别为11.78%(41/348)和4.60%(16/348),差异也有统计学意义(X2=11.93,P0.01)。两组间其他等位基因的检出率差异无统计学意义(P0.05)。结论 6号染色体短臂D6S1960和D6S274附近可能存在精神分裂症的易感基因。     

5个精神分裂症家系的12个遗传标志分析

目的通过5个精神分裂症同胞对家系的12个遗传标志的检测和分析,探索不同染色体上遗传标志与精神分裂症之间的联系。方法按照美国精神障碍诊断与统计手册第3版修订本的精神分裂症诊断标准,选择5个同胞对精神分裂症家系,采用PCR-RFLP、小卫星和微卫星DNA的Amp- FLP技术,观察12个遗传标志MAOACA、MAOBTG、MAOBI2、DXS7、D6S296、D6S274、D6S470、D6S260、 SCA1、D9S175、DAT1和APOE的分布。结果从各遗传标志的等位基因在家系成员中分布及复等位基因传递不平衡检验(TDT),未见明显关联现象。结论12个国内、外资料曾表明与精神分裂症有关联的遗传标志,经5个同胞对精神分裂症家系成员中检测和分析,未见明显的连锁和关联。     

同胞精神分裂症与5-羟色胺2A受体基因的关联分析

目的 探讨慢性精神分裂症患者的受累同胞和散发性精神分裂症与5-羟色胺2A受体基因(5-HT2A)T102C多态性的关联。方法 先用严格的纳入标准收集共患慢性精神分裂症的同胞60对(120例)和散发性精神分裂症120例,分别与正常同胞60对(120名)和120名正常人对照,采用聚合酶链反应(PCR)扩增及MspI内切酶酶切技术,检测各组的5-HT2A受体基因的基因型和等位基因的频率分布。结果 60对共患慢性精神分裂症的受累同胞组5-HT2A受体基因A1／A1基因型频率显著高于正常同胞组(X2=5.58,P<0.05),经配对比较,患者同胞组共有A1／A1基因型也显著多于正常同胞组(X2=3.94,P<0.05),而散发性精神分裂症与正常人对照组各基因型和等位基因的构成差异均无显著性意义。结论 共患慢性精神分裂症的同胞与5-HT2A受体基因A1／A1型关联,A1／A1纯合子易患精神分裂症,散发性精神分裂症可能与5-HT2A受体基因无关联。     

难治性精神分裂症与细胞色素P4502D6基因多态性相关性研究

目的 探测难治性精神分裂症与细胞色素P4502D6基因多态性关系。方法 用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术分析92例难治性精神分裂症患者的CYP2D6基因多态性,并以92例正常人作为对照。结果 在难治性精神分裂症组和对照组中,等位基因C、T及基因型T/T的差异具有非常显著性和显著性（P=0.002;P=0.002;P=0.014）。结论 本组样本中CYP2D6C188T基因多态性与难治性精神分裂症关联。提示CYP2D6C188T突变可能是难治性精神分裂症发病因素之一,本组中国汉族人中22号染色体长臂（22q13.1）可能存在难治性精神分裂症易感性基因。     

精神分裂症与微卫星DNA D3S1358的多态性的关联研究

目的　通过对微卫星DNAD3S135 8多态性的分析 ,了解精神分裂症与D3S135 8有关等位基因的关联情况。方法　对 32名精神分裂症患者和 12 3名随机人群采用PEProfilerplus系统进行PCR复合扩增 ,然后用ABI310型基因分析系统对扩增产物进行电泳和基因检测。结果　两组D3S135 8等位基因频率符合Hardy Weinberg平衡定律 (P >0 .0 5 ) ;精神分裂症组D3S135 8 14的检出率为 12 .5 % ,对照组的检出率为 4 .4 7% ,两者有统计学显著差异 (P <0 .0 5 ) ;精神分裂症组D3S135 8 17的检出率为 9.38% ,对照组检出率为 2 0 .73% ,显著低于对照组 (P <0 .0 5 ) ;其他各等位基因检出率两组无统计学显著差异(P >0 .0 5 )。结论　D3S135 8某些等位基因与精神分裂症的发病有关 ,在第 3号染色体上可能存在与精神分裂症相关的易感或抗性基因。     

山东省某地区精神分裂症患者6号染色体的基因组扫描研究

目的在6号染色体上寻找与精神分裂症的关联区域，进而定位精神分裂症的致病基因。方法在6号染色体采用问隔10cM（厘摩）遗传距离的20个微卫星遗传标记，分别对山东省潍坊市东部地区119例精神分裂症患者和119名正常对照者的DNA混合样本进行基因组扫描，比较两组每个等位基因峰值比率的差异。结果患者组D6S289和D6S460两个遗传位点上的等位基因频率分别为0．121和0．200，高于对照组（分别为0．046和0．157，P〈0．01），而患者组D6S1610遗传位点的等位基因频率（0．087）低于对照组（0．161，P〈0．01）。结论山东省潍坊市东部地区的精神分裂症患者中存在与6号染色体的关联区域，致病因子（基因或调控因子等）可能位于其中。     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。     

中国人D13S296位点多态性检测及肝豆状核变性的基因诊断

目的评估中国人群肝豆状核变性(HLD)基因(WND)侧翼短重复序列(STR)位点D13S296的基因多态性及其临床应用价值.方法采用聚合酶链反应(PCR)、变性聚丙烯酰胺凝胶电泳和银染法分析98名无血缘关系中国人D13S296的片段长度多态性;并对19个HLD家系进行STR多态性分析.结果D13S296有18个等位片段,长度范围为106～140bp,多态信息含量(PIC)为0.906.共检出8例症状前患者,10例基因携带者及14例正常人,4例未能确定.基因诊断率达88.87%.结论D13S296在中国人群是较优秀的多态性标记,对HLD基因诊断有较重要的临床应用价值.     

精神分裂症同胞家系的6号染色体基因组扫描研究

目的：通过对6号染色体进行候选区域的基因组扫描，探索精神分裂症的遗传易感基因。方法：以分布于6号染色体的28个微卫星标记在137个精神分裂症同胞家系样本中进行候选区域的基因扫描，采用受累同胞对分析方法，结合诊断分类，量表及必要的临床资料。通过GENEHUNTER ，MAPMAKER／SIBS等软件系统进行质量性状及数量性状的非参数连锁分析。结果：结合诊断分类的质量性状连锁分析未发现阳性结果。结合阳性和阴性症状量表（PANSS）的Haseman Elston数量性状连锁分析，结合PANSS－P分析所得最大Lod值为1．39，位于D6S1960附近，结合PANSS－G和PANSS－N所得最大Lod值分别为2．50和1．56，位于D6S291附近，变异因素数量性状分析与Haseman-Elason分析结果一致，即在相应的数量性状分析中，在D6S1960和D6S291附近，位点本身的遗传效应有明显作用的趋势。结论：6号染色体短臂可能存在精神分裂症的易感基因。     

多巴胺D5受体基因多态性与精神分裂症的关联研究

目的　探讨昆明地区汉族人群多巴胺D5受体 (DRD5 )基因多态性与精神分裂症的关系。方法　对 79例精神分裂症患者 (患者组 )和 75名正常对照者 (对照组 )采用聚合酶链反应 (PCR)扩增DRD5基因二核苷酸多态性片段 ,并通过聚丙烯酰胺凝胶电泳对PCR扩增产物进行多态性分型鉴定。比较患者组与对照组DRD5基因各等位基因分布频率。结果　 ( 1)患者组与对照组之间等位基因分布的差异无显著性 ( χ2 =12 2 6 ,P >0 0 5 )。 ( 2 )女性患者比男性患者及对照组 14 0bp等位基因有更高的分布频率 ;与男性患者比较 ,相对危险度 (RR) =2 73( χ2 =5 33,P <0 0 5 ) ;与对照组比较 ,RR =2 0 1( χ2 =4 5 9,P <0 0 5 )。结论　未发现汉族人群中DRD5基因多态性与精神分裂症存在明显关联 ,但该基因多态性可能影响不同性别间的疾病易感性     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的 探讨主动攻击行为与D6S1043、D12S391基因座等位基因或基因型的关联情况.方法 采用PCR结合毛细管电泳的方法对江苏地区103例男性主动攻击行为者(研究组)和159例健康男性(对照组)的外周静脉血样进行D6S1043、D12S391基因座的基因型分析,观察两组在D6S1043、D12S391基因座的等位基因及基因型分布差异,以推测与主动攻击行为相关的易感因素和(或)抗性因素.结果 D6S1043、D12S391基因座均符合遗传平衡定律(Hardy-Weinberg定律)(P＞0.05);在两个群体中D6S1043基因座的基因型12-19的频率分布差异有统计学意义(P =0.000 4,OR=7.511,95％CI:2.084 ～ 27.066),但等位基因频率分布无差异(P ＞0.05/n);在D12S391基因座上未发现分布存在显著差异的等位基因及基因型(P ＞0.05/n).结论 D6S1043基因座的基因型12-19可能为主动攻击行为的易感因素.     

Co-expression of cyclin D1 and phosphorylated ribosomal S6 proteins in hemimegalencephaly

Hemimegalencephaly (HMEG) is a developmental brain malformation highly associated with epilepsy. Balloon cells (BCs) and cytomegalic neurons (CNs) are frequently observed in HMEG specimens. Cytomegaly in developmental brain malformations may reflect in aberrant activation of the mTOR and β-catenin signaling cascades, known regulators of cell size. We hypothesized that there is aberrant co-expression of phospho-ribosomal S6 (P-S6) protein, a downstream effector of the mTOR cascade, as well as cyclin D1, a downstream effector of the β-catenin pathway, in BCs and cytomegalic neurons in HMEG. We hypothesized that mutations in PTEN (a cause of HMEG associated with Proteus syndrome), TSC1 or TSC2 (tuberous sclerosis complex) genes, which are known to modulate β-catenin and mTOR signaling could cause sporadic HMEG. Expression of cyclin D1, phospho-p70 S6 kinase (P-p70S6K, another mTOR cascade kinase), P-S6, MAP2, NeuN, or GFAP was determined by immunohistochemistry in HMEG brain tissue (n = 7 specimens). Cyclin D1, P-p70S6K, and P-S6 proteins were co-localized in BCs and CNs in the enlarged hemisphere but not in the unaffected hemisphere or in morphologically normal tissue. Cyclin D1 and P-S6 proteins were not detected in GFAP-labeled astrocytes. Sequencing of PTEN, TSC1, and TSC2 genes in cytomegalic cells co-expressing cyclin D1 and P-S6 proteins did not reveal mutations. Selective expression of cyclin D1 and P-S6 in cytomegalic cells in HMEG suggests co-activation of the β-catenin and mTOR cascades. PTEN, TSC1, or TSC2 gene mutations were not detected suggesting that sporadic HMEG is distinct from HMEG associated with Proteus syndrome or tuberous sclerosis complex.     

CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with Major Depression

Objective

Cytochrome P450 (CYP) enzymatic activity, which is influenced by CYP genetic polymorphism, is known to affect the inter-individual variation in the efficacy and tolerability of antidepressants in major depressive disorder (MDD). Escitalopram is metabolized by CYP2D6, and recent studies have reported a correlation between clinical outcomes and CYP2D6 genetic polymorphism. The purpose of this study was to determine the relationship between the CYP2D6 P34S polymorphism (C188T, rs1065852) and the efficacy of escitalopram treatment in Korean patients with MDD.

Methods

A total of 94 patients diagnosed with MDD were recruited for the study and their symptoms were evaluated using the 21-item Hamilton Depression Rating scale (HAMD-21). The association between the CYP2D6 P34S polymorphism and the clinical outcomes (remission and response) was investigated after 1, 2, 4, 8, and 12 weeks of escitalopram treatment using multiple logistic regression analysis and χ² test.

Results

The proportion of P allele carriers (PP, PS) in remission status was greater than that of S allele homozygotes (SS) after 8 and 12 weeks of escitalopram treatment. Similarly, P allele carriers exhibited a greater treatment response after 8 and 12 weeks of escitalopram treatment than S allele homozygotes.

Conclusion

Our results suggest that the P allele of the CYP2D6 P34S polymorphism is a favorable factor in escitalopram treatment for MDD, and that the CYP2D6 P34S polymorphism may be a good genetic marker for predicting escitalopram treatment outcomes.     

Analysis of allelic association between D6S461 marker and multiple sclerosis in Ashkenazi and Iraqi Jewish patients

A genetic factor contributing to multiple sclerosis (MS) disease risk is evident by the increased prevalence of disease among siblings of probands. A recent genome screen on Canadian sib pairs suffering from MS identified linkage between the genetic marker D6S461 and MS, and showed disequilibrium in transmission of its 260-bp allele from heterozygous parents to affected siblings (Ebers et al., 1996). The present study examined the allelic segregation of this marker among MS patients of Iraqi Jewish and Ashkenazi origin, two homogeneous ethnic groups that differ considerably from Caucasians. The frequency of the 260-bp allele reached 28.3% among Iraqi MS patients (n=30) and 25.2% among the Ashkenazi patients (n = 121) compared with 19.6% (n=28) and 21.3% (n=115) in respective origin-matched controls (for the combined data set, p=0.18). A secondary analysis of the frequency of the 260-bp allele in clinical subgroups showed a frequency of 38.1% among patients with juvenile MS (i.e., onset by 21 yr of age) of Ashkenazi origin (n=21, p=0.019) and 38.8% in the combined pool (n=27, p=0.0045). Most (90%) of the juvenile MS patients belonged to the relapsing-remitting subgroup, which itself showed a frequency of 28.5% of the 260-bp allele (n=121, p=0.045). The results suggest that the D6S461 region may contain a locus contributing to an early onset of relapsing-remitting MS.     

CSA6D: Channel-Spatial Attention Networks for 6D Object Pose Estimation

Cognitive Computation - 6D object pose estimation plays a crucial role in robotic manipulation and grasping tasks. The aim to estimate the 6D object pose from RGB or RGB-D images is to detect...     

CYP 2D6 polymorphism and antipsychotic therapy

One of the most challenging problems in clinical psychiatry are inter-individual differences in clinical response to antipsychotic treatment. Several studies were investigating the impact of the polymorphic cytochrome P450 2D6 gene (CYP 2D6) on the psychopathological and extrapyramidal symptoms, but the results were conflicting. There is a lack of clinical studies of the impact of CYP2D6 polymorphism on therapeutic efficacy, especially in the long-term treatment of schizophrenia. The aim of the presentation was to evaluate the impact of CYP2D6 genotype on psychopathological and extrapyramidal symptoms in a group of Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, who were receiving long-term maintenance therapy.