偏执型精神分裂症患者GRIN1基因-855G/C与-1140G/A位点的遗传多态性

目的探讨GRIN1基因启动子区两个单核苷酸多态性位点-855 G/C、-1140 G/A遗传多态性与偏执型精神分裂症的相关性及法医学意义。方法采用PCR限制性片段长度多态性(restriction fragment length polymorphism,RFLP)结合PAGE法对中国北方汉族183例健康无关个体和172例偏执型精神分裂症患者GRIN1基因5′端的-855 G/C和-1140 G/A位点多态性进行检测,采用χ2检验人群中基因型分布是否符合Hardy-Weinberg平衡定律,并比较两组人群中基因型和等位基因频率分布的差异。结果两组群体基因型分布符合Hardy-Weinberg平衡定律。-855 G/C位点基因型分布在对照组女性和实验组女性间的差异具有统计学意义(P0.05),-1140 G/A位点基因型和等位基因频率分布在对照组和实验组间及两组女性间差异具有统计学意义(P0.05)。结论 GRIN1基因启动子区-1140 G/A位点单核苷酸多态性可能与精神分裂症存在相关性;精神分裂症发生的遗传学因素可能存在性别倾向,可为精神分裂症的司法鉴定提供参考。     

GRIN1基因-855G／C和-1140G／A位点遗传多态性

谷氨酸（glutamate．Glu）是哺乳动物脑内重要的兴奋性神经递质．Glu通过作用其受体发挥着重要的生物学功能。Glu受体基因存在单核苷酸多态性（single nueleotide polymorphism．SNP）,为探讨其在法医学中的应用价值．本研究调查了Glu受体基因之一GRIN1启动子区域-855G／C与-1140G／A2个SNP位点在中国北方汉族群体中的频率分布。     

DRD5基因遗传多态性与精神状态的相关性及法医学意义

多巴胺是人类神经系统中重要的神经递质,通过与受体结合发挥生物学作用。当编码受体的基因异常时,可能导致精神疾病的发生。多巴胺受体有5种类型,分别为DRD1、DRD2、DRD3、DRD4、DRD5。DRD5是精神疾病的一个重要候选基因。DRD5受体基因上的rs7655090、rs1850744、(TC)n与精神疾病可能相关联;同时也存在矛盾的研究结果,表明精神疾病可能为多因素、多位点、多基因复制遗传疾病。DRD5基因的SNP具有较好的遗传多态性,可为法医学个人识别与亲权鉴定提供新的遗传标记及为司法精神病鉴定提供参考性遗传学指标。     

胆囊收缩素基因-45C/T多态性与精神分裂症的关联

目的 探讨精神分裂症人群胆囊收缩素(cholecystokinin,CCK)基因-45C/T位点遗传多态性及其法医学意义.方法采用双向等位基因特异性PCR方法对中国北方汉族群体207例精神分裂症患者(患者组)和202例健康个体(对照组)CCK基因-45C/T位点多态性进行检测.采用X<'2>检验对照组人群中基因型分布是...     

人类酪氨酸羟化酶基因SNP多态性与精神疾病的相关性

目的通过调查人类酪氨酸羟化酶（tyrosine hydroxylase,TH）基因的部分SNP在正常及疾病群体中的分布,探讨TH基因与精神疾病的相关性。方法采用DNA测序和实时荧光定量PCR技术,选择正常人、精神分裂症患者、抑郁症患者群体及部分精神分裂症患者家系的DNA为样本,对TH基因外显子3中的G334A和内含子9中的C5162G两个SNP位点进行分析。结果（1）G334A位点G和A的等位基因频率分布分别为：正常人群0.214和0.786;精神分裂症群体0.133和0.867;抑郁症群体0.116和0.884。（2）C5162G位点C和G的等位基因频率分布分别为：正常人群0.961和0.039;精神分裂症群体0.962和0.038;抑郁症群体0.959和0.041。结论G334A基因频率的分布在正常人群与精神分裂症和忧郁症群体之间的差别均有统计学意义,而C5162G基因频率的分布无统计学意义。     

中国北方汉族群体TPH2基因5′和3′端SNP位点遗传多态性

目的调查中国北方汉族群体TPH2基因5′和3′端SNP位点遗传多态性并探讨其法医学应用价值。方法测序分析244例中国北方健康无关个体TPH2基因5′端905 bp和3′端1 104 bp两个靶片段的序列特征和6个SNP位点(rs4570625、rs11178997、rs11178998、rs41317118、rs17110747和rs41317114)的遗传多态性,应用Haploview v4.2软件进行统计分析。结果 244例中国北方汉族个体6个SNP位点基因型分布均符合Hardy-Weinberg平衡定律,在92922位点检测到1例C/T变异,TPH2基因5′端3个SNP位点(rs4570625、rs11178997和rs11178998)和3′端3个SNP位点(rs41317118、rs17110747和rs41317114)分别显示出高度连锁不平衡,获得了TPH2基因6个SNP位点的群体遗传学参数。结论中国北方汉族群体TPH2基因5′和3′端序列呈现出高度遗传多态性,可作为相关疾病关联分析的遗传学指标,同时可用于个体识别和亲权鉴定。     

多巴胺受体基因遗传多态性与精神分裂症的关联及法医学意义

精神分裂症是一种常见的多因子参与的复杂疾病,司法精神病学鉴定中对精神分裂症的涉及甚多,但无有效的生物学鉴定指标。研究表明,多巴胺神经递质功能紊乱可能在精神分裂症的发生及其主要症状中发挥重要作用。本文综述了多巴胺受体的分类、基因结构以及近年来关于多巴胺受体基因遗传多态性与精神分裂症的关联研究及其法医学意义。     

胆囊收缩素基因单核苷酸多态性与精神状态的关系及法医学意义

胆囊收缩素（cholecystokinin,CCK）是一种具有广泛生物学活性的脑肠肽,既是胃肠道主要调节激素之一,还广泛存在于中枢及外周神经系统中以神经递质或神经调质的形式发挥重要的生理作用。近年来国内外研究发现,CCK基因上存在多个单核苷酸多态性（single nucleotide polymorphisms。SNP）位点,其中一45C／T,-196G／A变异与多种精神状态如精神分裂症、抑郁症、自杀行为、帕金森病等存在一定的相关性。这些SNP多态性可应用于法医物证学的亲子鉴定和个人识别,并且可能成为某些特殊案例如涉及精神病鉴定、法医病理学的疾病鉴定、异常行为（自杀倾向等）鉴定的辅助指标之一。     

中国北方汉族人群FUT6基因3个SNPs遗传多态性

目的对中国北方汉族人群FUT6基因编码区序列特征及等位基因多态性进行调查。方法测序分析30例中国北方汉族人FUT6基因整个编码区序列并鉴定其单倍型,采用复合PCR与复合限制性内切酶结合的RFLP法分析FUT6基因rs778805（C370T）、G855A及rs61147939（C907G）3个SNPs遗传多态性;应用Haploview4.1软件进行相关统计分析。结果 30例测序样本中共检出8个SNPs和6种单倍型,149例中国北方汉族个体C370T、G855A、C907G基因型分布均符合Hardy-Weinberg平衡。杂合度分别为0.544、0.416、0.510;多态信息含量为0.375、0.372、0.367;个人识别能力为0.600、0.651、0.603;非父排除率为0.187、0.186、0.183。PCR-RFLPs检出13种基因型,单倍型变异度为0.646。Haploview4.1软件分析表明3个SNPs处于连锁不平衡状态。结论中国北方汉族人群FUT6基因编码区序列呈现出高度多态性;C370T、G855A、C907G位点多态性分布良好,但处于连锁不平衡状态。     

SNRPN基因rs220030位点的分型及甲基化亲缘相关性

目的建立变性梯度凝胶电泳(denaturing gradient gel electrophoresis,DGGE)技术与焦磷酸测序技术对小核核糖核蛋白多肽N(small nuclear ribonucleoprotein polypeptide N,SNRPN)基因rs220030位点的分型方法。建立应用焦磷酸测序技术分析CpG甲基化状态的方法,探讨rs220030位点用于亲缘等位基因判定的可行性。方法应用DGGE技术对97例上海地区汉族家系血样rs220030位点进行分型,同时应用焦磷酸测序技术对其中25例血液来源的家系样本的rs220030位点分型,并对两种方法在SNP分型结果上进行比较。通过重亚硫酸盐修饰联合焦磷酸测序技术分析随机2组家系样本rs220030位点上游CpG甲基化状态,判断甲基化是否有亲缘相关性。结果经DGGE检测97例家系血样rs220030位点分型结果为C纯合子20例,T纯合子29例,C/T杂合子48例。经焦磷酸测序检测25例血液来源的家系样本结果与DGGE检测结果一致。经重亚硫酸盐修饰联合焦磷酸测序技术分析,2组血液来源的家系子代的rs220030位点上游CpG甲基化状态均与母亲较相似。结论相比DGGE技术,焦磷酸测序技术更精确、方便,适合大样本、高通量SNP分型。重亚硫酸盐修饰联合焦磷酸测序技术可以精确分析CpG甲基化状态。rs220030位点可用于亲缘等位基因判定。     

Experimental long-distance haplotyping of OCA2-HERC2 variants

The regulatory HERC2 SNP, rs12913832, is strongly associated with blue and brown eye colour. However, eye colour in heterozygous rs12913832 individuals is observed to vary greatly. Missense mutations in OCA2, such as rs1800407 and rs74653330, are associated with lighter eye colour in some but not all heterozygous rs12913832 individuals. Determining the physical linkage of these variants might help to further explain eye colour variation. So far, experimental haplotyping of these variants has been challenging because the genomic distance between them (∼ 135 kb) exceeds the fragment lengths produced by commonly used DNA isolation kits. The aim for this study was to explore novel methods for long distance haplotyping to assess associations between OCA2-HERC2 haplotypes and eye colour. DNA was isolated from frozen blood samples collected from Norwegians that are known to be heterozygous for both HERC2 rs12913832 and OCA2 SNPs, either rs1800407 (n = 23) or rs74653330 (n = 17), using the newly commercially available Monarch® HMW (heigh molecular weight) DNA Extraction Kit (New England BioLabs_inc). We successfully isolated DNA fragments up to 210 kb, which were long enough to haplotype OCA2-HERC2 loci by droplet digital PCR (ddPCR). Three haplotypes were observed in the study population: rs12913832:A-rs1800407:T in 22/23 individuals, rs12913832:A-rs1800407:C in 1/23 individuals and rs12913832:A-rs74653330:T in 16/16 individuals. As expected, all individuals with the rs12913832:A-rs74653330:T haplotype had intermediate to blue eye colour. However, the rs12913832:A-rs1800407:T haplotype was observed in both blue and brown-eyed individuals, suggesting more research is needed.     

线粒体 DNA突变与心肌病关系的研究进展

人类某些疾病与线粒体DNA(mtDNA)基因组缺陷有关.本文就mtDNA突变与缺血性心肌病和肥厚型心肌病关系的研究加以回顾.目前的研究大多认为心肌缺血缺氧致氧化磷酸化紊乱,产生氧自由基损伤mtDNA,以及缺氧致氧化磷酸化过度诱导而损伤mtDNA,慢性损伤积累终致mtDNA片断缺失或点突变,主要表现出mtDNA5.0kb、7.4kb缺失及细胞色素b(cytb)基因上C15452A点突变;tRNA基因保守序列突变,致肌肉收缩蛋白合成缺陷,缺陷的收缩蛋白持续而无效的收缩可能会增加心肌对ATP的代谢需求,因此导致心肌肥厚.     

Molecular variants associated with flavor perceptions and ancestral proportions of Ecuadorian populations

The perception of taste is determined by several factors, including genetics, which at the same time is related with the diet and diseases in different populations. We aimed to identify the frequency of six single nucleotide polymorphisms (rs307355, rs35744813, rs713598, rs1726866, rs10246939 and rs11091046) involved in the perception of sweet, bitter and salty flavor in Ecuadorian mestizo population. It was found that the presence of the T allele of rs307355 and rs35744813 is associated with decreased ability of subjects to carry out specific discrimination of sweetness, this is particularly interesting given the correlation found (p = 0.0022) between sucrose perception and family history of cancer and diabetes. Furthermore, rs713598, rs1726866 and rs10246939 do not influence the ability to perceive the bitter taste. Concerning the perception of the salty taste, rs11091046 does influence the capacity of detecting it more easily. This theoretical knowledge of the genetic influence on taste perception can contribute to the understanding of eating habits and their impact on human health.     

H-抗原缺乏分泌型个体FUT1及FUT2等位基因的分子基础

一例H-缺乏分泌型个体被发现。其血清学表现为：红细胞上无A、B、H抗原；唾液中有B、H抗原分泌；血清中检出了抗A抗体。推测其为类孟买OHmB型。在该个体FUT1等位基因编码区上发现两处单碱基突变（T460C、G1042A）。这两个点变异，将导致两个氨基酸的置换（Y154H、E348K）。同时也破坏了限制性内切酶RsaⅠ和AvaⅠ的作用部位。用PCR－RFLP法可检出此两种变异。用PCR－RFLP法证实，该个体为T460C、G1042A变异的纯合子。在136例随机个体中未能查出上述变异。将该FUT1基因转染COS－7细胞未能检出α2－FUT活性及证实H抗原的表达。该个体的FUT2基因与野生型一致。     

Correlation between Genetic Variants and Polymorphism of Caveolin and Sudden Unexplained DeathCSCD

Objective: To explore the genetic variation sites of caveolin (CAV) and their correlation with sudden unexplained death (SUD). Methods: The blood samples were collected from SUD group (71 cases), coronary artery disease (CAD) group (62 cases) and control group (60 cases), respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exonintron splicing region of CAV1 and CAV3 using PCR. The type of heritable variation of CVA was confirmed and statistical analysis was performed. Results: A total of 4 variation sites that maybe significative were identified in SUD group, and two were newfound which were CAV1:c.45C>T (T15T) and G4V7:C.512G>A (R171H), and two were SNP loci which were CAVl:c.246C>T (rs35242077) and CAV3:C.990T (rsl008642) and had significant difference (P<0.05) in allele and genotype frequencies between SUD and control groups. Forementioned variation sites were not found in CAD group. Conclusion: The variants of CAV1 and CAV3 may be correlated with a part of SUD group. © 2017 by the Editorial Department of Journal of Forensic Medicine.     

焦磷酸测序分析短片段牙釉质蛋白基因进行性别鉴定

目的采用焦磷酸测序技术分析短片段牙釉质蛋白基因进行性别鉴定并用于骨骼及腐败生物检材的检测。方法应用blast软件,确定牙釉质蛋白基因(Amel)上1段含有3个SNP位点及1个插入/缺失(indel)位点的序列作为待测靶序列,设计引物,扩增该段序列,应用焦磷酸测序技术分析扩增序列,进行性别鉴定。对方法进行准确性、灵敏度、种属特异性的测试,并用于对骨骼和高度降解DNA的检测。结果 PCR产物分别为44bp(Amel X)和45bp(Amel Y),女性测序结果为:G/G,T/T,…/…,C/C,男性测序结果为:G/T,T/A,…/C,C/A,分型图谱清晰。应用本文方法检测100份已知性别的DNA样本,结果均正确无误,方法最低DNA模板量为0.5ng,具有较好的人类种属特异性。用于高度降解DNA分析,较IdentifilerTM试剂盒具有更高的成功率且骨骼样本也得到清晰的分型结果。结论本文采用焦磷酸测序技术分析Amel的方法在法医学性别鉴定中有较好的应用价值。