重庆市汉族健康人群白细胞介素-1基因多态性的研究

为了了解白细胞介素-I基因在中国重庆市汉族健康人群中的分布及其与不同种族比较的特点,采用了聚合酶链反应-限制性片段长度多态（PCR—RFLP）的方法,对140名重庆市汉族健康者的IL-1B-511基因多态性和IL-1RN第2内含子可变数目串联重复序列多态性进行检测,并结合相关文献进行了不同种族间的分析比较。结果表明重庆市汉族健康人群中1L-1B-511的各基因型频率为C/T型0．58、形,型0．50、C/C型0,32,与西班牙白种人相比,重庆地区汉族人IL-1B,B-511等位基因频率存在明显差异（P〈0．05）。1L-1RN的各基因型频率为1／1型0．93、1／2型0．05、1／4型0．01、4／4型0．01,与西班牙白种人及南非黑种人相比,重庆地区汉族人,IL-IRN等位基因频率存在明显差异（P〈0．05）。由此可以得出重庆地区汉族人群IL-1B-511位点存在C／T多态性和IL-1RN基因的第2号内含子存在可变数目串联重复序列多态性．其在不同种族间的分布存在着差异．     

云南汉族群体FIBRA、DHFRP2、ACTBP2基因座多态性及其法医学应用

采用Amp-FLP分型方法,调查云南汉族群体FIBRA、DHFRP2、ACTBP2基因座的遗传多态性,并将其应用于法医学实践。200份EDTA抗凝血采自昆明地区无血缘关系汉族个体,采用酚—氯仿法提取DNA;法医物证实际检案及亲子鉴定检材取自昆明医学院法医系物证教研室检案,各种动物血痕取自动物中心,采用酚—氯仿法或Chelex法提取DNA,PCR扩增,非变 性聚丙烯酰胺凝胶垂直板电泳,硝酸银染色分型。结果表明,FIBRA、DHFRP2、ACTBP2基因座分别观察到15、7、13个等位基因,基因型数分别是57、25、61。3个STR基因座的杂合度（H）分别为：0.8940、0.8174、0.9130;多态信息容量（PIC）分别是:0.8908、0.8045、0.9117;个人识别力（Dp）分别是：0.9733、0.9416、0.9772;非父排除率（Epp）分别是：0.7994、0.6542、0.8348,基因型频率分布均符合Hardy-Weinberg平衡。20个家系调查结果表明,3个基因组均符合孟德尔遗传规律。 Genetic Polymorphism of FIBRA,DHFRP2 and ACTBP2 and Their Forensic Application in Yunnan Han PopulationJING Qiang,NIE Sheng-jieDepartment of Forensic Medicine,Kunming Medical College,Yunnan Province 650031,ChinaAbstract:To investigate the genetic polymorphism of FIBRA,DHFRP2 and ACTBP2 in Yunnan Han population as well as their application in forensic science,EDTA-blood specimens were collected from 200 healthy individuals.The DNA were extracted either by the Chloro form,phenol method or by the Chelex-100 method.The PCR products were analyzed by PAG vertical electrophoresis,following by silver staining.All gene frequencies,discrimination power (DP),exclusion of paternity probability (EPP),heterozygosity (H),polymorphisms information content (PIC),matching probability (PM) as well as the Hardy-Weinberg test were calculated.The obtained data are beneficial in the understanding of population genetics of the three STR loci in Yunnan Han population and the results suggest that these loci are valuable genetic markers for paternity testing and personal identification in forensic science practice.Key words：short tandem repeat; Amp-FLP; genetic polymorphism     

中国南方汉族群体MPSI型Kpn I酶切位点的遗传多态性

为研究中国汉族群体IDUA基因Kpn I 酶切位点的遗传多态性以及该位点等位基因片段传递的规律,采用PCR-RFLP技术, 对162例无血缘关系的健康中国汉人的324条染色体进行检测,另又对5个家系16位成员进行同样的检测,然后用χ     

中国南方汉族群体MPSⅠ型KpnⅠ酶切位点的遗传多态性

为研究中国汉族群体IDUA基因球KｐｎⅠ酶切位点的遗传多态性以及该位点等位基因片段传递的规律,采用PCR－RFLP技术,对162例无血缘关系的健康中国汉人的324条染色体进行检测,另又对5个家系16位成员进行同样的检测,然后用X2检验进行统计学处理。结果表明,等位基因A1频率为0．17,等位基因A2频率为0．83,杂合率为29％;A1、A2的传递规律与理论上预计的完全符合。认为中国汉族群体IDUA基因KｐｎⅠ酶切位点也具有遗传多态性,并且与国外报道的无显著性差异;A1、A2在世代中的传递完全符合孟德尔遗传规律。     

贵州荔波封闭人群MTHFR基因多态性研究分析

目的 对贵州汉族、布依族亚甲基四氢叶酸还原酶（Methylenetetrahydrofolate Reductase,MTHFR）基因多态性进行研究,为贵州少数民族基因多态性数据库的建立提供相关数据。方法 应用聚合酶链式反应及限制性片段长度多态性检测贵州荔波汉族90例、布依族119例MTHFR基因两个单核苷酸（677及1298位）多态位点的基因频率及基因型频率。结果 汉族、布依族MTHFR 677位T等位基因的分布频率分别是22、8％,16．1％,x^2=1．561,P〉0．1;MTHFR 1298位C等位基因的分布频率分别是28．9％,39、1％,x^2=2．075,P〉0．1;677CT／1298AC双杂合子的分布频率分别是16．66％,22．7％。结论 MTHFRC 677T和A1298C多态性在中国南方和北方人群存在群体差异;贵州汉族与布依族此两位点无显著性差异。贵州荔波布依族MTHFR 1298位有较高的C等位基因频率。     

HLA－DRB1基因位点多态性的PCR－RFLP分析

设计并建立一套适合国内应用的改良ＰＣＲ－ＲＦＬＲ方法,分５组特异性扩增ＤＮＡ样品,随后进行酶切定型分析,准确检测了编码ＤＲ抗原特异性的ＨＬＡ－ＤＲＢ１基因位点的多态性,该法采用分组扩增,不发生与其它ＤＲＢ位点等位基因的交叉扩增,不仅适合纯合子的区分而且可以清楚准确地检测杂合子样品,已报道过的ＤＲＢ１位点编码的特异性组合都可以通过这个方法得到准确分析。所使用的Ⅱ类限制性内切酶均价格便宜、易购。     

云南汉族HLA-DRB1多态性分析及与9个汉族群体的比较

主要应用聚合酶链反应—微孔板杂交(Polymerase Chain Reaction and Microtitre Plate Hybridization,PCR-MPH)的方法对云南129个无亲缘关系的汉族样品进行了HLA-DRB1的遗传多态性分析,对MPH初分出的DRB1*15组的样品进行了单链构象多态（Single-Strand Conformation Polymorphism, SSCP）检测。共发现36种等位基因,其中等位基因频率大于0.05的有DRB1*1501(0.1240),DRB1*09012(0.0969),DRB1*08032(0.0930),DRB1*1202(0.0891),DRB1*1201(0.0814),DRB1 *1401(0.0775),DRB1 *0701(0.0620)。云南汉族HLA-DRB1等位基因频率与中国其他9个汉族群体进行χ²检验,结果显示与云南汉族比较χ²>10的有西安汉族（DR8,χ²=13.9712）、上海汉族（DR4,χ²=10.1632）、广东汉族（DR9,χ²=12.6121）和南京汉族（DR4,χ²=10.5796）。从遗传距离分析发现,在9个国内汉族群体中云南汉族与辽宁汉族有最近的距离（0.0541）,而与广东汉族最远（0.1851）。云南汉族在构成上可能与辽宁汉族更为接近,尽管地处南方,但已不属典型的南方汉族。这也可能因云南汉族与当地的少数民族存在基因交流,从而形成了一个较为特殊的群体。     

中国北方汉族人群肌型肌酸激酶基因（CKMM）A/G多态研究

为研究中国汉族群体CKMM基因NcoI 酶切位点的遗传多态性以及该位点的具体多态形式, 采用PCR-RFLP技术, 对306例无血缘关系的健康中国北方汉人的染色体进行检测,并对3种基因型的扩增产物进行基因测序。用卡方检验对所得等位基因频率、基因型频率与其他种族进行比较。结果NcoI 位点多态性测序结果为：A/G颠换; 等位基因频率是A=86%,G=14%;基因型频率为：A/A=74%, A/G=24% , G/G=2%;经卡方检验符合Hardy－Weinberg遗传平衡定律;认为中国汉族群体CKMM 基因NcoI酶切位点具有遗传多态性。其基因型频率和等位基因频率在男女间没有显著性差异,与欧美人群相比有极显著差异,而与韩国人相比没有显著性差异。     

中国南方汉族群体MPSI型Kpn I酶切位点的遗传多态性

为研究中国汉族群体IDUA 基因Kpn I 酶切位点的遗传多态性以及该位点等位基因片段传递的规律, 采用PCR-RFLP技术, 对162例无血缘关系的健康中国汉人的324条 染色体进行检测,另又对5个家系16位成员进行同样的检测,然后用χ2检验进行统计学处理。结果表明,等位基因A1 频率为0.17,等位基因A2 频率为0.83,杂合率为29%;A1 、A2 的传递规律与理论上预计的完全符合。认为中国汉族群体IDUA 基因 Kpn I 酶切位点也具有遗传多态性, 并且与国外报道的无显著性差异;A1、A2 在世代中的传递完全符合孟德尔遗传规律。Abstract:To investigate the genetic polymorphism of the Kpn I site in the α-L-iduronidase(IDUA) gene from a Han population in southern China and to study the mode of transmission of alleles, PCR-RFLP was used to analyze 324 chromosomes from 162 Chinese unrelated healthy Han individuals, and the analysis of the genotypes of 16 members in five families. To compare the frequencies and heterzygosity between Chinese Han population and Caucasians in Western by using χ2test. The frequency of allele 1 (450bp) was 0.17,allele 2 (390 plus 60 bp) 0.83, the heterozygosity was 29%.The genotypes of each member of all families detected was completely agreement with the theorical assessment. The locus of Kpn I in the IDUAgene from Han population has polymorphism. There is no significant difference between Chinese Han population and Caucasians in Western countries. The transmission of alleles was agreement with the Mendelian genetic law.     

乙醛脱氢酶2（ALDH2）基因研究进展及其与饮酒行为的关系

亚洲人群中普遍存在突变型的乙醛脱氢酶2（ALDH2*2）。此酶突变后活性缺失,导致乙醛在肝脏内大量累积使突变携带者在喝酒后会有脸红等不适反应,因此这可能影响他们的饮酒行为。由于ALDH2*2等位基因与饮酒行为相关,它也可能与酒精引起的肝脏损伤及某些癌症密切相关,而且,它在不同的亚洲人群中有不同的频率分布。近年来对ALDH2*2等位基因的序列结构、表达及其重要功能等有了更深入的了解,对ALDH2的多态性在研究方法、研究群体分布范围等都有很大进展。本文还讨论了不同地理分布、不同年龄结构、性别差异条件下,中国人群中ALDH2基因型频率与饮酒行为的关系。 Abstract: An atypical allele （ALDH2*2） in low Km aldehyde dehydrogenase (ALDH2), which is highly prevalent in Asian, may influence drinking behavior because of higher production of acetaldehyde in the liver. High alcohol sensitivity such as flushing after drinking has been shown to be mainly due to the atypical ALDH2 genotypes. The atypical allele is associated with alcohol-induced liver injury and some cancers. Recently, the researches on the polymorphisms not only in the gene itself but also its frequencies in different Asian populations have been made great progress. Three factors, including different sex, age and geography, were also analyzed with the genotypes of ALDH2 in Chinese populations.     

Human stomach alcohol and aldehyde dehydrogenases (ALDH): A genetic model proposed for ALDH III isozymes

Isozyme phenotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from human gastroendoscopic as well as surgical gastric biopsies were determined by starch gel electrophoresis and agarose isoelectric focusing. γγ ADH isozymes were expressed predominantly in the mucosal layer of the stomach, whereas ββ isozymes were in the muscular layer. In the 56 gastroendoscopic mucosal biopsies examined, the homozygous ADH₃ 1-1 phenotype was found in 75% of the samples, and the heterozygous ADH₃ 2-1 phenotype in 25%. Accordingly, the gene frequencies of the allelesADH ₃ ¹ andADH ₃ ² were calculated to be 0.88 and 0.12, respectively. Using a modified agarose isoelectric focusing procedure, gastric ALDH I, ALDH II, and up to five ALDH III forms could be clearly resolved. The ALDH III isozymes accounted for more than 80% of the total ALDH activities in gastric mucosa and exhibitedK _m values in the millimolar range for propionaldehyde atpH 9.0. Forty-five percent of the 55 gastroendoscopic biopsies studied lacked ALDH I isozyme. The complex gastric ALDH III isozyme phenotypes seen in these biopsies fall into three patterns. They can be interpreted by a genetic hypothesis, based on a dimeric molecule, in which there are two separate genes,ALDH _3a andALDH _3b, with theALDH _3b locus exhibiting polymorphism. The homozygous phenotypes ALDH_3b 1-1 and ALDH_3b 2-2 were found to be 4 and 76%, respectively, and the heterozygous ALDH_3b 2-1 phenotype 20%, of the total. Therefore, the allele frequencies forALDH _3b ¹ andALDH _3b ² were calculated to be 0.14 and 0.86, respectively. Several lines of biochemical evidence consistent with this genetic model are discussed. This work was supported by grants from the National Science Council, Republic of China, and the Institute of Biomedical Sciences, Academia Sinica.     

Genetic Diversity in Ralstonia solanacearum Strains from Mauritius using Restriction Fragment Length Polymorphisms

Race 1, biovar III of Ralstonia (synonym Pseudomonas ) solanacearum , causal organism of bacterial wilt, has been reported in Mauritius on several crops and plant species. The genetic relationship among 38 strains isolated from potato, tomato, bean and anthurium was determined by restriction fragment length polymorphisms (RFLPs). After hybridization with probe 5a67, five RFLP patterns could be distinguished. Types V and I were most commonly encountered. A common band of approximately 6.5 kb was found in 35 strains. Type I pattern consisted of only this band and was observed in 12 out of 16 anthurium strains tested. Type V was associated with 12 out of 16 potato strains and consisted of a band of approximately 3.3 kb in addition to the one observed in type I. RFLP patterns II, III and IV were less frequently encountered. The RFLP analysis showed that genetic diversity was present in race 1, biovar III strains. The relationship between the host and RFLP pattern is discussed.     

Genetics of ocular NAD+-dependent alcohol dehydrogenase and aldehyde dehydrogenase in the mouse: Evidence for genetic identity with stomach isozymes and localization ofAhd-4 on chromosome 11 near trembler

Electrophoretic and activity variation of the stomach and ocular isozyme of aldehyde dehydrogenase (designated AHD-4) was observed between C57BL/6J and SWR/J inbred strains of mice. The phenotypes were inherited in a normal mendelian fashion, with two alleles at a single locus (Ahd-4) showing codominant expression. The alleles assorted independently of those atAdh-3 [encoding the stomach and ocular isozyme of alcohol dehydrogenase (ADH-C₂)] on chromosome 3. Three chromosome 11 markers, hemoglobin -chain (Hba), trembler (Tr), and rex (Re), were used in backcross analyses which established thatAhd-4 is closely linked to trembler. The distribution patterns for stomach and ocular AHD-4 phenotypes were examined among SWXL recombinant inbred mice, and those for stomach and ocular ADH-C₂ among BXD recombinant inbred strains. The data provided evidence for the genetic identity of stomach and ocular ADH-C₂ and of stomach and ocular AHD-4.This research was supported in part by the U.S. Department of Energy under Contract DE-ACO5-84OR214000 with Martin Marietta Energy Systems, Inc. (to R.A.P.).     

Alcohol Dehydrogenases: Identification and Names for Gene Families

Plant gene products that have been described as `alcohol dehydrogenases' are surveyed and related to their CPGN nomenclature. Most are Zn-dependent medium chain dehydrogenases, including `classical' alcohol dehydrogenase (Adh1), glutathione-dependent formaldehyde dehydrogenase (Fdh1), cinnamyl alcohol dehydrogenase (Cad2), and benzyl alcohol dehydrogenase (Bad1). Plant gene products belonging to the short-chain dehydrogenase class should not be called alcohol dehydrogenases unless such activity is shown.     

Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: Implications for ethanol metabolism and cytotoxicity

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exhibit genetic polymorphism and tissue specificity. ADH and ALDH isozyme phenotypes from 39 surgical Chinese lung specimens were identified by agarose isoelectric focusing. The identity of the lung β-ADHs was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation,K _m values for NAD and ethanol, and inhibition by 4-methylpyrazole or 1,10-phenanthroline. The β₂ allele, coding for β₂ polypeptide, was found to be predominant in the lung specimens studied. The ADH activities in the lungs with the homozygous phenotype ADH₂ 2-2 (exhibiting β₂β₂) and ADH₂ 1-1 (exhibiting β₁β₁) and the heterozygous phenotype ADH₂ 2-1 (exhibiting β₂β₂, β₂β₁, and β₁β₁) were determined to be 999±77, 48±17, and 494±61 nmol/min/g tissue, respectively. Fifty-one percent of the specimens studied lacked the ALDH2 activity band on the isoelectric focusing gels. The activities in the lung tissues with the ALDH2-active phenotype and the inactive phenotype were determined to be 30±3 and 17±1 nmol/min/g tissue, respectively. These findings indicate that human pulmonary ethanol-metabolizing activities differ significantly with respect to genetic polymorphism at both theADH ₂ and theALDH ₂ loci. The results suggest that individuals with highV _max β₂-ADH and deficient in low-K _m mitochondrial ALDH2, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during alcohol consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite. This work was supported by Grants NSC 77-0412-B016-58 and NSC 80-0412-B016-21 from the National Science Council, Republic of China.     

Biochemical genetic variants in mice selectively bred for sensitivity or resistance to ethanol-induced sedation

The distribution of biochemical genetic variants was examined among eight inbred strains of mice, which served as contributors to a heterogeneous stock of mice (HS), and in short-sleep (SS) and long-sleep (LS) mice, selectively bred from the HS stock for differential ethanol sensitivity. Fifteen loci for enzymes of alcohol and aldehyde metabolism, as well as 12 other biochemical loci, were investigated. Thirteen of these loci exhibited allelic variation between strains, of which six were separately fixed in the SS and LS mice. Comparisons of genetic similarity coefficients, based upon the distributions of allelic variants for the loci examined, with behavioural sensitivities (sleep-time) to an acute dose of ethanol for the inbred and selected strains of mice, indicated no correlations between these data. This suggests that this collective group of loci are not useful indicators of the genes selectively bred in the SS and LS strains, which are responsible for the differential sensitivities to acute doses of ethanol.     

Gene markers for alcohol-metabolizing enzymes among recombinant inbred strains of mice with differential behavioural responses towards alcohol

The genetic variability of alcohol dehydrogenase (C₂ isozyme), aldehyde dehydrogenase (A₂ isozyme) and aldehyde oxidase (A₂ isozyme) has been examined among recombinant inbred strains of mice which have been previously studied concerning their differential behavioural responses towards alcohol. The results showed no correlation between biochemical phenotype for these loci and behavioural response.