维吾尔族人群CX3CR1基因多态性特征及其意义

HIV辅助受体CX3CR1的249I280M单倍型与AIDS病程加速有关，而CX3CR1的SNP在我国尚无人研究。选择维吾尔族正常人标本的98份，HIV感染者血样21份。采取PCR－RFLP分析方法，分别用AclI和BsmBI确定249和280密切子是否发生基因突变，行列表χ^2检验法进行统计处理。结果发现249I和280M基因频率分别为15．8％和13．8％，正常人与HIV感染者无差别，群体及性别分布符合Hardy-Weinberg平衡。CX3CRI基因249I280M单倍型频率为13．8％，接近高加索入。CX3CR1基因SNP与CCR5－△32之间无连锁关系，但CX3CR1的249I和280M之间存在明显的连锁关系（P＜0．05）。由于249I280M单倍型与AIDS病程加速相关，维吾尔族249I280M单倍型比例与高加索人接近，而且249I和280M之间连锁程度更高，这种现象在维吾尔族AIDS病的预防和治疗方面的意义值得深入研究。     

新疆维吾尔族乙型肝炎病毒慢性无症状携带者的乙型肝炎病毒基因型测定

目的;研究新疆维吾尔族乙型肝炎病毒（HBV）慢性无症状携带者的HBV基因型分布。方法：利用限制性片段长度多态性（RFLP）分析技术,由限制性内切酶AvaⅡ和DpnⅡ作用于HBV DNA前S区扩增片段建立的简便的HBV基因型分型方法,对52例HBeAg阳性的新疆维吾尔族HBV慢性无症状携带者的HBV进行基因型测定。结果：D基因型57．7％（30／52）,C基因型30．8％（16／52）,B基因型11．5％（6／52）,无A、E和F型。结论：新疆维吾尔族HBV慢性无症状携带者的HBV基因型以D型为优势,为我国HBV基因型分布提供了新的资料,并为建立中国人HBV基因库提供依据。     

CRELD1基因多态性与新疆维吾尔族先天性心脏病相关性研究

目的研究CRELD1基因单核苷酸多态性与新疆维吾尔族先天性心脏病的关系。方法选择112例新疆维吾尔族先天性心脏病患者和112例年龄、性别匹配的对照者。选择CRELD1基因的6个SNPs（m3894571、~3846167、m2302785、m279552、m17050660、m279551）,应用TaqManSNP基因分型的方法进行基因分型,分析CRELD1基因单核苷酸多态性与新疆维吾尔族先天性心脏病的相关性。结果患者年龄和性别在入选样本时进行了匹配,所以在分析时进行了剔除。对先心病患者母亲的年龄、文化程度、忧虑情绪、饮食状况等基本情况进行单因素分析,结果显示年龄、文化程度、忧虑情绪、饮食状况等因素与先心病发生有关联。病例组与对照组CC、CT及TT基因型频率分别为74．35％、22．28％、3．37％和83．03％、16．07％、0．90％,两组比较无统计学差异（r=5．488,P〉0．05）。两组均以CC型为主,等位基因以C占优势,病例组TT基因型频率高于对照组,但是差异无统计学意义（P〉0．05）,而CT、CT＋TT基因型频率和携带T等位基因频率高于对照组,有统计学意义（P〈0．05）。应用Logistic回归分析先心病主要相关因素：母亲年龄、文化程度、忧虑情绪、饮食状况对结果的影响,rs3894571CT、CT＋TT、CT、等位基因T因素进入回归方程。结论CRELD1基因核苷酸多态性与新疆维吾尔族先天性心脏病有相关性。     

β地中海贫血IVS-Ⅱ-654(C→T)的基因鉴定

目的：总结新疆１６例β地中海贫血ＩＶＳⅡ６５４（Ｃ→Ｔ）的基因分析结果。方法：应用聚合酶链式反应和寡核苷酸探针杂交。结果：对新疆１６例β地中海贫血先证者进行基因分析，鉴定为ＩＶＳⅡ６５４（Ｃ→Ｔ）基因突变，均为杂合子，其中汉族１１例，回族４例，维吾尔族１例。回族中这种突变类型属首次报道。结论：本文结果对了解这一突变类型在我国的分布特点提供了有意义的资料     

PCR检定eNOS基因VNTR多态性

目的：建立eNOS基因基因VNTR多态性的PCR分析方法。方法：按eNOS基因VNTR位点侧翼序列设计引物，自健康献血者基因组DNA扩增VNTR片段，琼脂糖凝电泳分析扩增片段的长度和数目，鉴定VNTR基因型。结果与结论：在208名健康献血者中鉴定出6／5杂合、5／5纯合、5／4杂合和4／4纯合4种VNTR基因型，等位基因的分布频率与日本人相似，但与美国黑人存在显著差异。     

CCR7基因rs3136685多态性与中国北方汉族人群冠心病的关系

目的 探讨趋化因子CCR7基因单核苷酸多态位点rs3136685多态性与中国北方汉族人群冠心病的关系.方法 连续收集2010年3月—2011年12月沈阳军区总医院心内科住院患者578例,其中病例组(经冠状动脉造影证实一支或多支血管狭窄50％以上)287例,对照组(冠状动脉造影正常且没有其他粥样硬化证据)291例.冠心病组根据血管病变支数分为3个亚组:单只病变组(n=104),双支病变组(n=89)和3支病变组(n=94).提取患者血液白细胞基因DNA,采用直接测序法测定趋化因子CCR7基因rs3136685单核苷酸多态位点的基因型,并进行基因型和等位基因与冠心病及冠心病病变程度的相关性分析.结果 CCR7基因rs3136685单核苷酸多态性共检测到3种基因型,即GG型、AG型和AA型,在病例组的分布频率分别为42.9％、45.6％、11.5％,在对照组分别为43.0％、44.3％、12.7％,两组基因型分布皆符合Hardy-Weinberg平衡定律,3种基因型在两组间的分布差异无统计学意义(P＞0.05).A等位基因在病例组及对照组的分布频率分别为34.3％、34.9％,差异亦无统计学意义(P＞0.05).亚组分析显示,CCR7基因rs3136685单核苷酸多态性的基因型和等位基因频率在单支病变、双支病变及3支病变3个亚组间差异无统计学意义(P＞0.05).结论 CCR7基因rs3136685单核苷酸多态性与中国北方汉族人群冠心病的发病及疾病严重程度可能无相关关系.     

人体组织激肽释放酶基因5′端调控序列点突变的检测

目的 探讨一种能有效检测组织激肤释放酶基因启动子区点突变的实验技术。方法 提取16例外周血的人基因组DNA，经PCR反应扩增出目标启动子区后，与寡核苷酸探针杂交，并进行测序，比较2种方法的准确性。结果 12例为纯合子，无G碱基插入；4例杂交结果阳性，其中2例为杂合子；2种方法结果吻合。结论 与测序法相比，本文ASO法经济、简便、灵敏度和准确率高，适合做大规模人群检测。     

无胶筛分毛细管电泳与琼脂糖电泳检测ApoB_100基因点突变的比较

目的：无胶筛分毛细管电泳与琼脂糖电泳两种方法检测ＡｐｏＢ１００基因点突变的比较。方法：聚合酶链反应（ＰＣＲ）扩增ＡｐｏＢ１００基因的２６号外显子，ＸｂａⅠ酶切后，分别用常规琼脂糖电泳和无胶筛分毛细管电泳对比检测了４３例标本。结果和结论：毛细管电泳的突变检出率明显高于琼脂糖凝胶电泳，是一种研究基因突变与高脂血症关系更有效的分析手段。     

DNA损伤在电离辐射诱导凋亡中的重要性:重度联合免疫缺陷突变和DNA倍体对小鼠淋巴细胞系辐射敏感性的影响

目的 :通过研究重度联合免疫缺陷 ( scid)突变和 DNA倍体对电离辐射诱导小鼠淋巴细胞系凋亡敏感性的影响 ,判定 DNA损伤是否是凋亡的关键始动因子。方法 :采用γ射线 ( 1 3 7　 Cs,剂量率约为 0 .9Gy/ min)或DNA相关的 1 2 5 　 I衰变 (细胞在培养基内培育约 2 4小时 ,其中含 5 0～ 10 0 Bq/ m l的 1 2 5 　 I-碘代脱氧尿苷 )比较野生型及 scid纯合或杂合突变小鼠前 B和前 T细胞系在照射后致死的敏感性和凋亡产生速率。用小鼠前 T细胞系假 2倍体和倍体克隆研究 DNA倍体的不同对细胞的辐射敏感性和凋亡的影响。应用荧光显微镜观察凋…     

乙型肝炎病毒基因型测定

目的研究新疆维吾尔族乙型肝炎病毒(HBV)慢性无症状携带者的HBV基因型分布.方法利用限制性片段长度多态性(RFLP)分析技术,由限制性内切酶AvaⅡ和DpnⅡ作用于HBVDNA前S区扩增片段建立的简便的HBV基因型分型方法,对52例HBeAg阳性的新疆维吾尔族HBV慢性无症状携带者的HBV进行基因型测定.结果D基因型57.7%(30/52),C基因型30.8%(16/52),B基因型11.5%(6/52),无A、E和F型.结论新疆维吾尔族HBV慢性无症状携带者的HBV基因型以D型为优势,为我国HBV基因型分布提供了新的资料,并为建立中国人HBV基因库提供依据.     

三个民族正常妊娠产前产后凝血功能的调查分析

目的　观察 3个民族妇女正常妊娠产前产后凝血功能的差别。方法　采用OPTON4PLUS型血凝分析仪对 300例 3个民族妇女正常妊娠产前产后凝血酶原时间 (PT)、部分凝血活酶时间 (APTT)、凝血酶时间 (TT)及纤维蛋白原 (FIB)、血小板计数 (BPC)进行检测。结果　汉族与维吾尔族、回族与维吾尔族妇女产前APTT,PT,TT,FIB,BPC有显著性差异,产后凝血检测指标各项相比差异均无显著性。汉族与回族妇女产前产后之间的常规凝血检测指标各项相比差异均无显著性。结论　3个民族妇女间正常妊娠产前凝血功能多项指标存在差异,医师在诊断 3个民族妊娠晚期妇女相关疾病时应充分考虑其民族的特殊性。     

Statistical and population genetics issues of two Hungarian datasets from the aspect of DNA evidence interpretation

When the DNA profile from a crime-scene matches that of a suspect, the weight of DNA evidence depends on the unbiased estimation of the match probability of the profiles. For this reason, it is required to establish and expand the databases that reflect the actual allele frequencies in the population applied. 21,473 complete DNA profiles from Databank samples were used to establish the allele frequency database to represent the population of Hungarian suspects. We used fifteen STR loci (PowerPlex ESI16) including five, new ESS loci. The aim was to calculate the statistical, forensic efficiency parameters for the Databank samples and compare the newly detected data to the earlier report. The population substructure caused by relatedness may influence the frequency of profiles estimated. As our Databank profiles were considered non-random samples, possible relationships between the suspects can be assumed. Therefore, population inbreeding effect was estimated using the FIS calculation. The overall inbreeding parameter was found to be 0.0106. Furthermore, we tested the impact of the two allele frequency datasets on 101 randomly chosen STR profiles, including full and partial profiles. The 95% confidence interval estimates for the profile frequencies (pM) resulted in a tighter range when we used the new dataset compared to the previously published ones. We found that the FIS had less effect on frequency values in the 21,473 samples than the application of minimum allele frequency. No genetic substructure was detected by STRUCTURE analysis. Due to the low level of inbreeding effect and the high number of samples, the new dataset provides unbiased and precise estimates of LR for statistical interpretation of forensic casework and allows us to use lower allele frequencies.     

Application of a mitochondrial DNA control region frequency database for UK domestic cats

DNA variation in 402 bp of the mitochondrial control region flanked by repeat sequences RS2 and RS3 was evaluated by Sanger sequencing in 152 English domestic cats, in order to determine the significance of matching DNA sequences between hairs found with a victim’s body and the suspect’s pet cat. Whilst 95% of English cats possessed one of the twelve globally widespread mitotypes, four new variants were observed, the most common of which (2% frequency) was shared with the evidential samples. No significant difference in mitotype frequency was seen between 32 individuals from the locality of the crime and 120 additional cats from the rest of England, suggesting a lack of local population structure. However, significant differences were observed in comparison with frequencies in other countries, including the closely neighbouring Netherlands, highlighting the importance of appropriate genetic databases when determining the evidential significance of mitochondrial DNA evidence.     

一种国产基因芯片用于乙型肝炎病毒P基因突变的检测

目的：验证国产基因芯片检测HBV—P基因突变的准确性和敏感性。方法：选择14例服用拉米夫定48周时HBV—DNA定量检测仍阳性的慢性乙型肝炎病人的血清标本，用HBV基因突变检测基因芯片检测患者血清中HBV—DNA聚合酶基因，观察发生YMDD变异的情况。同时用聚合酶链反应(PCR）技术扩增上述血清标本中编码HBV—DNA聚合酶的P基因片段并直接测序，以对比检查P基因发生YMDD变异的情况。结果：14例患者血清标本用基因芯片均检出HBV—DNA，9例为野生株，5例发生YMDD变异，其中3例为M552I(YIDD)变异，2例为M552V(YVDD)变异，同时均伴有L528M变异。与用PCR扩增产物直接测序的结果完全相同。结论：国产HBV基因突变检测芯片具有特异性强、灵敏性高、快速、简便等优点，可以替代繁琐的DNA序列测定和分析，可作为临床监测HBV—DNA变异的常规方法。     

Development of the nine X-STR loci typing system and genetic analysis in three nationality populations from China

This study is to develop a new multiplex polymerase chain reaction (PCR) system that simultaneously amplifies the nine X-chromosome short tandem repeats loci in the same PCR reaction, and to explore their polymorphism and mutation rate among three nationality populations from China. These loci included DXS6854, DXS9902, DXS6809, GATA172D05, HPRTB, DXS7423, DXS6807, DXS8378, and DXS8377. The samples of 890 (484 males and 406 females) unrelated individuals from Guangdong Han population, Xinjiang Uigur, and Inner-Mongolia Mongol were successfully analyzed using this multiplex system. The allele frequencies and mutation rates of the nine loci were investigated, and the comparison of allele frequency distribution among different populations was performed. There were 87 alleles for all the loci, and six to 18 alleles for each locus observed by our new multiplex PCR system. Polymorphism information content was 0.4998–0.9101, and power of discrimination in females was 0.6518–0.9846. Five cases with mutation of above loci were detected in 5,310 meioses. Pair-wise comparisons of allele frequencies distribution showed significant differences for most loci among different populations. Our results indicate that this multiplex system is very useful for identification analysis, and that the information about polymorphism and mutation rate is necessary for forensic application in three nationality populations from China.     

HIV—1型辅助受体研究进展

简述了ＨＩＶ－１辅助受体的发现过程及辅助受体ＣＣＲ－５在ＨＩＶ－１感染及发病过程中的作用。大量数据分析表明染色体上两个拷贝ＣＣＲ－５基因缺失突变能保护个体不受ＨＩＶ－１感染，而携带一个拷贝ＣＣＲ－５基因突变的受感染个体，其发病过程较缓慢。     

20例散发性激素耐药型肾病综合征儿童NPHS2和WT1基因突变分析

目的 初步分析散发性激素耐药型肾病综合征(SRNS)JL童的NPHS2和WT1基因突变及其特点.方法选择20例南方汉族散发性SRNS儿童作为实验组,另选50例尿检正常的南方汉族成年人作为对照组.应用PCR、DNA直接测序法、PCR/限制性片段长度多态性进行NPHS2和WT1基因突变分析.结果 对20例SRNS儿童NPHS2和WT1基因的全部外显子及其周围的部分内含子进行检测,未发现NPHS2和WT1致病突变,但检测到2个已报道的NPHS2基因多态性(102G>A和954T>C)和6个WT1基因变异(5'-UTR-7G>T、126C>T、IVS3+16G>A、WS5-64A>G、903A>G和IVS7-32C>A).其中,IVS5-64A>G为新发现的WT1基因多态性.与对照组比较,实验组的1个NPHS2基因多态性(102G>A)和6个WT1基因多态性的基因型频率和等位基因频率差异无统计学意义(P>0.05).结论 NPHS2和wn基因突变不是本研究散发性SRNS儿童的主要致病原因.     

Genetic data on three complex STRs (ACTBP2, D21S11 and HUMFIBRA/FGA) in the Galician population (NW Spain)

The allele frequency distributions of three complex STRs, ACTBP2 (SE33), D21S11 and HUMFIBRA/ FGA in the population of Galicia were investigated. Analysis was carried out under denaturing conditions and fluorescent detection in the ALF DNA sequencer and typing was made by comparison with sequenced allelic ladders. No significant deviations from Hardy-Weinberg equilibrium were observed. No significant differences were found between our data and other Caucasian population data. ACTBP2 seems to be one of the most informative and polymorphic STRs. Received: 5 October 1998 / Received in revised form: 18 December 1998     

Population data of 15 STR loci of Chinese Yi ethnic minority group

Allele frequency data and statistical parameters for D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA loci were determined in a sample of 120 healthy unrelated individuals of Chinese Yi ethnic minority group living in Yunnan province, China. We observed 132 alleles with allelic frequencies ranging from 0.0042 to 0.5333. The forensic statistical parameters from the data of all the loci showed high values. All loci were in accordance with Hardy-Weinberg equilibrium (p>0.05). The obtained frequency distributions were compared with previously published other population data, and significant differences were found between Yi population and Korean, Chinese Tibetan, Uigur, Ewenki, Han, Hui population at some STR loci. Our results of present study were valuable for forensic application and Chinese population genetic studies. These population data enriched Chinese genetic informational resources.     

DNA序列测定法与实时荧光PCR法检测YMDD突变结果的比较

目的比较DNA序列测定法与实时荧光法检测YMDD突变的结果,并对除YMDD突变之外的耐药相关基因突变及其意义进行讨论。方法收集89例慢性乙肝患者的92份血清样本,均用实时荧光PCR法做YMDD突变检测。采用巢式PCR法扩增HBV反转录酶(RT)基因,对PCR产物进行DNA双向测序,采用NTI软件比对结果,并对RT基因上其他11个已知耐药相关突变位点进行分析。结果在37份YMDD突变阴性的样本中,DNA测序法检测结果为33份M204M(未突变)、1份M204I、3份M204V;4份YMDD突变阳性样本均为突变/未突变序列共存;另检出7份样本存在ADV耐药相关突变,占18.9%(7/37)。在55份YMDD突变阳性样本中,DNA测序法检测到52份,阳性结果符合率为94.5%(52/55);另检出5例存在ADV或ETV耐药相关突变,占9.1%(5/55)。结论DNA序列测定法检测HBVRT基因耐药相关突变敏感性高,重复性好,与实时荧光PCR方法的检测结果有较高的符合率,可同时检出YMDD突变以外的各种耐药相关突变,有助于临床全面了解患者对核苷(酸)类似物的耐药情况,合理地制订抗HBV治疗方案。