中国20个民族中PGM_1及其亚型EsD、GLO1、AK、ADA和6-PGD酶型分布调查

调查了汉族、鄂伦春、赫哲、朝鲜、蒙古、羌、土家、苗、侗、畲、壮、纳西、傈僳、白、彝、景颇、哈尼、傣、维吾尔和塔吉克等20个民族的PGM_1及其亚型,EsD、GLO_1、AK、ADA和6-PGD等酶型的分布及基因频率。PGM_1及其亚型、EsD和GLO_1在中国各民族中是分布较好的,个人识别能力较高的酶。有12个民族查出有PQM_1~6基因,壮族的频率最高,PGM_1 6-1表型达4.15％。对在4174份血样中所检出的带有PGM_1~6基因的68份血样做亚型分析,在凝胶上PGM_1~6谱带均在同一位置上。EsD_1基因频率的总趋向是北方各民族高于南方。哈尼、傈僳、傣、纳西、畲、壮、侗和苗等民族EsD2-2表型达15％以上,哈尼族高达32.4％。GLO1~1基因频率塔吉克和维吾尔族为0.2927和0.2112,羌族为0.0583,其它各族在0.0714—0.1527。各民族AK~1、ADA和6-PGD~(?)基因频率均甚高。     

九个汉族群体和四个少数民族群体中腺苷酸激酶的遗传多态性

用淀粉凝胶电泳及特异的染色方法,调查了我国九个汉族和四个少数民族群体的腺苷酸激酶-1(AK1)的遗传多态性在这十三个群体中AK1*2频率都远低于AK1*1频率,未达到0.01的多态水平,分别为：兰州汉族0.0096,郑州汉族0.0023,呼和浩特汉族0.0024,西安汉族0.0025,漳州汉族0.0024,羌族0.0024;而在广东客家人、成都汉族、哈尔滨汉族、贵阳汉族以及哈尼族、瑶族、布依族中均为0。在兰州汉族群体中观察到国内第一例AK1*2-2表型。     

蒙古族、朝鲜族和壮族中腺苷酸激酶、腺苷脱氨酶、血清触珠蛋白、α_1-抗胰蛋白酶的多态性

调查了中国内蒙古的蒙古族、吉林的朝鲜族和广西壮族的红细胞腺苷酸激酶(AK)、腺苷脱氨酶(ADA)及血清触珠蛋白(Hp)、a_1-抗胰蛋白酶(a_1-AT)的遗传多态性。蒙古族、朝鲜族、壮族的基因频率:AK_1~1分别为0.9843、1.0000、1.0000;ADA~1分别为0.9529、0.9468、0.9573;Hp~1分别为0.2597、0.3152、0.3571;在a_1-AT中Pi~M分别为0.9953、0.9953、0.9928,Pi~s分别为0.0000、0.0000、0.0072,Pi~F分别为0.0047、0.0047、0.0000。x~2检验表明,三个民族各项指标的表型观察值都符合Hardy-Weinberg法则。     

云南23个少数民族人群腺苷酸激酶(AK1)多态分布调查

采用淀粉凝胶电泳法,对云南彝、白、哈尼、壮、傣、苗、傈僳、回、拉祜、佤、纳西、瑶、藏、景颇、布朗、普米、怒、阿昌、德昂、基诺、布依、独龙和苦聪人等23个少数民族人群的红细胞腺苷酸激酶(AK1)的多态分布进行了调查。结果,在23个人群中均未检出AK21纯合子。但在彝、回、景颇、布朗、怒和德昂6个民族中检出了AK21杂合子,AK21基因频率在这6个民族中的分布在0.0045-0.0446之间,其中,仅回族的AK21基因达多态水平。 Abstract:The investigation on the distribution of adenylate kinase(AK1)polyorphism in 23 ethnic groups in Yunnan province of China,including the minorities of Yi,Bai,Hani,Zhuang,Dai,Miao,Lisu,Hui,Lahu,Wa,Naxi,Yao,Tibetan,Jingro,Bulang,Pumi,Nu,Achang,Deang,Jino,Buyi,Dulong and Kucong people,was carried out,using starch gel electrophoresis.The results showed that no AK21,homozygote and other variations were found.But AK21 heterozygotes were found in the minorities of Yi,Hui,Jingpo,Bulang,Nu and Deang.The ranges of AK21 gene frequencies were 0.0045-0.0446.     

血管紧张素Ⅱ 1型受体基因A1166C多态性与新疆维吾尔族高血压相关性研究

目的:探讨新疆维吾尔族人群血管紧张素Ⅱ1型受体基因(AT1R)A1166C多态性与原发性高血压之间的关系,了解该基因多态在维吾尔族群体中的分布情况。方法:选择新疆维吾尔族原发性高血压病患者126例,正常血压者143例,应用多聚酶链反应、限制性片段长度多态性技术(PCR-RFLP)时入选样本进行基因分型。结果:AT1R基因A1166C多态符合Hardy-Weinberg平衡;AA、AC各基因型频率在维吾尔族病例组和对照组分别为73%、27%和74．8%、25．2%,差异无统计学意义(P＞0．05),C等位基因频率分别为13．5%和12．6%,差异亦无统计学意义(P＞0．05)。结论:AT1R基因A1166C多态可能不是新疆维吾尔族原发性高血压病的遗传易感指标。     

腺苷脱氨酶在我国九个民族中的多态分布

用沉粉胶电泳及特异染色的方法,对我国九个少数民族中红细胞腺苷脱氨酶(ADA)的多态分布进行了测定。ADA2基因频率在白族中最高(0.0735),土家族中最低(0.0300),二者差异显著。白族及土家族与其它民族(维吾尔0.0654、彝族0.0622、回族0.0610、藏族0.0547、满族0.0485、侗族0.0450、苗族0.0320)比较,差异均不显著。没有发现罕见表型。     

新疆维、哈、蒙古族-HTT基因启动子区多态性的研究

采用聚合酶链反应(PCR)技术,对我国新疆维吾尔族、哈萨克族和蒙古族三个正常群体5-HTT基因启动子区(5-HTTLPR)的一个插入/缺失多态性进行了研究。结果显示:5-HTTLPR等位基因及基因型频率分布在三个民族中没有较大差异,短片段等位基因S有较高的分布频率。X2检验证明,三个民族群体的基因型分布均符合Hardy-Weinberg平衡(P>0.05)。经分析,维吾尔族的观测杂合度(Hobs)、期望杂合度(Hexp)、多态信息量(PIC)分别为0.4167、0.4845和0.3759;哈萨克族的Hobs、Hexp和PIC分别为0.4141、0.4338和0.3396;蒙古族的Hobs、Hexp和PIC分别为0.4639、0.4386和0.3425。结果可为人类学、法医学鉴定及疾病的关联研究提供遗传学数据。     

α_1抗胰蛋白酶遗传类型在七个民族中的分布

调查了α_1-AT遗传类型在东北及内蒙古地区汉、蒙、朝鲜、满、达斡尔、鄂温克、鄂伦春等七个民族中的分布。计算了每个群体中的α_1-AT基因频率,经X~2检测证明七个群体α_1-AT表型分布均符合Hardy-weinberg法则。同时,将各少数民族人群α_1-ATM类型及变异型的基因频率与汉族人群进行了比较。     

云南10个民族红细胞酸性磷酸酶型分布调查

用淀粉凝胶电泳法对云南省汉族及9个少数民族的红细胞酸性磷酸酶(ACP_1)的表型分布进行了调查,检出A、BA和B3种表型,计算得云南汉、彝、白、傣、瑶、佤、哈尼、布朗、基诺和拉祜族ACP_1~A、ACP_1~B的基因频率依次为0.2067、0.7933;0.2406、0.7594;0.2341、0.7659;0.3750、0.6250;0.2300、0.7700;0.2727、0.7273;0.3594、0.6406;0.3036、0.6964;0.2381、0.76119和0.4474、0.5526。未发现ACP_1~C基因及其它稀有基因。研究表明,ACP_1表型的分布存在着一定的种族与民族差异。     

新疆地区维吾尔族和汉族人群CaSR基因多态性与草酸钙肾结石关系的研究

目的:探讨新疆地区维吾尔族和汉族草酸钙结石与钙敏感受体(calcium sensitive receptor,Ca SR)基因多态性之间的关系。方法:选择398例临床确诊泌尿系草酸钙结石患者(200例维吾尔族,198例汉族)和399例正常对照者(200例维吾尔族,199例汉族),应用Sna Pshot方法对Ca SR基因两位点(rs1042636,rs1801726)的基因型及等位基因频率进行检测,并分析其与草酸钙结石发病的相关性以及对血钙、24 h尿钙水平的影响。结果:各组2个位点的基因型分布均符合Hardy-Weinberg平衡。汉族结石组与汉族对照组及维吾尔族结石族与维吾尔族对照组rs1042636、rs1801726位点基因型分布及基因频率差异均无统计学意义(P0.05)。维吾尔和汉族rs1042636基因型及等位基因频率比较差异有统计学意义(P0.05),且维吾尔族人群携带rs1042636等位基因A的风险高于汉族人群(病例组中OR值=2.145,%95CI=[1.602~2.866],P0.01;对照组中OR值=1.773,%95CI=[1.332~2.359],P0.01),其中维/汉病例组中等位基因频率分别为A=278(69.5%)/204(51.5%),G=122(30.5%)/192(48.5%);维/汉对照组中等位基因频率分别为A=264(66.0%)/208(52.3%),G=136(34.0%)/190(47.7%)。而病例组和对照组rs1801726基因型频率差异无统计学意义(P0.05);汉族病例组、对照组发现GG+AG基因型较AA基因型有较高的尿钙水平(病例组:P=0.007和对照组:P=0.006),维吾尔族人群该位点与两项指标无相关性。结论:Ca SR基因2个基因位点rs1042636、rs1801726可能不是新疆地区维吾尔族和汉族草酸钙结石发病的危险因子,两族rs1042636基因多态性分布存在差异,rs1042636位点基因多态性能影响汉族人群尿钙排泄,可能汉族调节钙排泄的遗传因素之一。     

Synthesis of lipopolysaccharide O side chains by Pseudomonas aeruginosa PAO1 requires the enzyme phosphomannomutase.

We have cloned a lipopolysaccharide (LPS) biosynthetic gene from Pseudomonas aeruginosa PAO1 that complements the defect in the production and incorporation of LPS O side chains in the LPS-rough strain AK1012. This gene was characterized by pulsed-field gel electrophoresis, deletion and restriction mapping of the cloned DNA, and biochemical analysis of the protein product. The cloned DNA was found to map to the 7-to-11-min region of the P. aeruginosa chromosome, and the gene needed for complementation of the LPS-rough phenotype was contained on a 2.6-kb HindIII-SacI fragment. This same size restriction fragment contains the alginate gene algC, which encodes the enzyme phosphomannomutase (PMM) and also maps to this region of the P. aeruginosa chromosome. The LPS-rough strain AK1012 was deficient in PMM activity, and this activity was restored to parental levels when the cloned gene was transferred to strain AK1012. In addition, the cloned gene could complement the PMM deficiency in the algC mutant strain 8858, and the cloned algC gene could restore the LPS-smooth phenotype to strain AK1012. These results indicate that the gene we have cloned is equivalent to the alginate gene algC. We designate this gene pmm to emphasize that it encodes the enzyme PMM, which has been shown to be essential for alginate production, and we demonstrate that PMM activity is required for the LPS-smooth phenotype in P. aeruginosa PAO1.     

DNA mutation associated with the human butyrylcholinesterase K-variant and its linkage to the atypical variant mutation and other polymorphic sites.

Genomic DNA from two families exhibiting the K-variant phenotype of serum butyrylcholinesterase was amplified by PCR and sequenced to determine the molecular basis of this variant. The K-variant phenotype was found to be associated with a DNA transition from guanine to adenine at nucleotide 1615, which caused an amino acid change from alanine 539 to threonine (GCA----ACA; Ala539----Thr). There was a 30% reduction of serum butyrylcholinesterase activity associated with this mutation. Amplification and sequencing of DNA from a random sample of 47 unrelated people gave a frequency of .128 for the K-variant allele. Thus, 1 person in 63 should be homozygous for the K-variant, making the K-variant the most common butyrylcholinesterase variant. The K-variant mutation was also found to be present in 17 (89%) of 19 butyrylcholinesterase genes containing the point mutation which causes the atypical phenotype of butyrylcholinesterase (GAT----GGT; Asp70----Gly). The presence of the K-variant in the same molecule as the atypical variant does not contribute to the qualitative change in the atypical enzyme, but it most likely accounts for the approximately one-third reduction in Vmax of butyrylcholinesterase activity in atypical serum. Two additional point mutations located in noncoding regions of the gene were also observed to be in linkage disequilibrium with the K-variant mutation. As many as four different point mutations have been identified within a single butyrylcholinesterase gene. Inhibition tests of the enzyme in plasma are usually used to distinguish the K-variant from the usual enzyme when the former is present with the heterozygous atypical variant (AK phenotype vs. UA phenotype). Inhibition tests were performed on plasma enzyme from the four possible genotypic combinations of the heterozygous atypical mutation with or without the K-variant mutation on either allele; we found that the AK phenotype was caused by three genotypes (A/K, AK/K, and U/A) and that the UA phenotype was caused by two genotypes (U/A and U/AK).     

内蒙古鄂伦春、鄂温克、达斡尔族人三种酶型遗传多态性分析

用同步电泳分型的方法,对中国内蒙古鄂伦春族、鄂温克族、达斡尔族人506份血痕红细胞酶EAP、ADA、AK1遗传多态性进行了研究,被调查群体中均未检出上述三种酶型的变异型。被调查群体三种酶型基因频率范围分别为EAPA 0.2139～0.2280;ADA10.9500～0.9596;AK1 1.0～0.9963。 Abstract:In the paper the phenotype freguencies of the EAP,ADA and AK1 have been investigated by the emthod of typing of EAP-ADA-AK on the samemixed starch／agarose gel electrophresis among 3 nationalities in Inner Mongolia.(Oroqen,Ewenki and Dawuor.) The distribution of their typy frequencies varied with races. The gene freqrencies DP and CDP were also calculated.     

Red cell enzyme polymorphisms in three Iranian population samples: Tabriz,Yazd, Mashhad

Three population samples from Iran (Tabriz, Yazd, Mashhad) have been typed for four enzyme group polymorphisms: ACP1, ESD, AK, and PGD. The phenotype and allele frequencies are presented and compared with other Iranian populations. The AK allele frequencies do not show significant intergroup heterogeneity, whereas ACP1, ESD and PGD allele frequencies disclose obvious heterogeneity. The possible reasons therefore are discussed.     

Phylogenetic and disruption analyses of aspartate kinase of Deinococcus radiodurans

The extremely radioresistant bacterium Deinococcus radiodurans is evolutionarily closely related to the extremely thermophilic bacterium Thermus thermophilus. These bacteria have a single gene encoding an aspartate kinase (AK) that catalyzes the phosphorylation of L-aspartate. T. thermophilus has an aminoadipate pathway for lysine biosynthesis that does not use AK for lysine biosynthesis. Phylogenetic analysis in this study indicated that D. radiodurans AK has a different protein structure and a different evolutionary history from T. thermophilus AK. Disruption analysis of D. radiodurans AK indicated that D. radiodurans AK was not used for lysine biosynthesis but for threonine and methionine biosyntheses. A D. radiodurans AK disruption mutant exhibited a phenotype similar to a T. thermophilus AK disruption mutant, which indicates that these two AKs have different evolutionary origins, though their functions are not different.     

Red cell adenylate kinase phenotypes in the affective disorders

Summary The red cell adenylate kinase (AK) phenotype was determined by starch gel electrophoresis in 96 adult Caucasian subjects with affective disorders (24 with bipolar illness and 72 with unipolar illness). The phenotype frequencies and the gene frequencies of the bipolar group closely resembled that of the control subjects (180 subjects drawn from the population of a large institution for the mentally retarded), the unipolar group however, showed a significant increase in the frequency of the AK² allele.The significance of these results have been discussed in relation to the known genetic and biochemical findings in the affective disorders. It is suggested that the mechanism involved may be a reduction of the enzyme activity in the tissues of subjects with the AK 2:1 phenotype. This may present a selective disadvantage in the form of a decrease in control of energy metabolism in general, and control of adenine nucleotide levels in nervous tissue in particular.     

Tissue variability of the phosphotransferases adenylate kinase (EC: 2.7.4.3.) and pyruvate kinase (EC: 2.7.1.40.)

Summary Studies of the tissue variability of human AK and PK are reported. Homozygous probands of phenotype AK 1, show five electrophoretic positions with AK activity in different tissues and six positions with PK activity. In one of the 20 probands studied the brain, not however any other tissue, revealed a different zymogram. It can be followed therefore that different isozymes can be present in different tissues.Head: Prof. Dr. Dr. H. BaitschSupported by the Deutsche Forschungsgemeinschaft.     

Heterogeneity of long-term cultured activated killer cells induced by anti-T3 antibody

The present study has characterized the short term and long term cultured murine-activated killer (AK) cells that are induced by antibody directed against the epsilon-chain of T3 complex. The conventional lymphokine AK (LAK) cells were generated by culturing normal B6 spleen cells with purified human rIL-2. The alpha T3-induced AK cells (T3AK) were induced by culturing normal B6 spleen cells with alpha T3 and were then maintained in culture medium supplemented with human rIL-2 and/or alpha T3. After initial activation with alpha T3, lymphocyte proliferation and generation of cytotoxic effectors (T3AK) were noted, and these events were related to the endogenous production of IL-2 and IL-4. Addition of alpha IL-2 and/or alpha IL-4 suppressed both the proliferative response and the cytotoxic response induced by alpha T3. In comparing the T3AK cells with the conventional LAK cells, there were many similarities as well as some distinct differences. Both cells displayed a similar cytotoxic spectrum against a variety of tumor targets. The T3AK cells usually gave much higher levels of cytotoxic activity against susceptible targets. However, the susceptibility of different tumor targets to conventional LAK cells and T3AK cells varied. The time course for the generation of lytic activity also differed between the conventional LAK and T3AK cells. One distinct difference was their ability to survive in vitro. The conventional LAK cells survived in culture for only 1 wk. The T3AK cells could survive for at least 4 to 5 wk with active growth. The serologic phenotype of the LAK precursors was asialo GM1 (AsGM1+) cells, but the T3AK precursors could be either AsGM1+ or AsGM1-, depending on the target cell. The LAK effectors were both Lyt-2+ and Lyt-2-, but the short-term T3AK effectors were exclusively Lyt-2+. The long term T3AK cells (cultured for more than 2 wk) were found to consist of Lyt-2+ and Lyt-2- cells, and these subsets of T3AK cells showed different target specificities. These findings demonstrate the heterogeneity of LAK and T3AK cells, and this heterogeneous property may contribute to their diversity in specificity against different tumor targets and thus may affect their effectiveness in the immunotherapy of cancer.     

The adenylate kinase family in yeast: identification of URA6 as a multicopy suppressor of deficiency in major AMP kinase.

The gene URA6 encoding uridylate kinase (UK) from Saccharomyces cerevisiae was isolated as a multicopy suppressor of the respiratory-deficient phenotype of an S. cerevisiae mutant defective in the gene AKY2 encoding AMP kinase (AK). The URA6 gene also restored temperature resistance to two different temperature-sensitive mutations in the gene encoding Escherichia coli AK. By contrast, the gene encoding UK of Dictyostelium discoideum on a multicopy yeast shuttle plasmid, expressed under control of the constitutive yeast AKY2 promoter, failed to complement the deficiency in yeast, although such transformants expressed high UK activity. We show that yeast UK exerts significant AK activity which is responsible for the complementation and is absent in the analogous enzyme from D. discoideum. Since UK also significantly phosphorylates CMP (but not GMP), it must be considered an unspecific short-form nucleoside monophosphate kinase. Wild-type mitochondria lack UK activity, but import AKY2. Since multicopy transformation with URA6 heals the Pet- phenotype of AKY2 disruption mutants, the presence of AKY2 in the mitochondrial intermembrane space is not required to maintain respiratory competence. However, furnishing UK with the bipartite intermembrane space-targeting presequence of cytochrome c1 improves the growth rates of AKY2 mutants with nonfermentable substrates, suggesting that AK activity in mitochondria is helpful, though not essential for oxidative growth.