遗传药理学在治疗糖尿病和肥胖中的潜在作用

常见的遗传基因变异与常见代谢性疾病如1型和2型糖尿病、肥胖的风险相关。探索疾病从弱到中等程度的遗传易感性需要大样本，并在独立的有相同统计要素的一组人中再现一个这样的关联，且需要统计学的标准去发现一个真实的关联。此研究目的在于回顾现今对于常见基因变异如何影响代谢性疾病易感性及其治疗的认识。

Genetic Structure of the Oriental River Prawn (Macrobrachium nipponense) from the Yangtze and Lancang Rivers, Inferred from COI Gene Sequence

This study analyzed nueleotide sequences from the mitochondrial eytochrome oxidase submit （COI） gene region （450 bp） to investigate the genetic structure of the oriental river prawn （ Macrobrachium nipponense ） among nine populations from the Yangtze and Lancang Rivers. A total of 79 individuals were collected for this work. Eighty-nine nucleotides were found to be variable, resulting in 46 haplotypes. Among the nine populations, the population from Kunming shows the greatest level of variability （h = 1.000, π = 0.028）, whereas the population from Cbongqing exhibits the lowest level of variability （h = 0.700,π = 0.008）. Analysis of molecular variance suggested that of the total genetic diversity, 9.66% was attributable to inter-population diversity and the remainder （90.34%） to differences within populations. A molecular phylogenetic tree constructed using the Neighbor-joining （N J） method showed that the 46 haplotypes were assigned to two clades associated with geographic regions. These results provide basic information for the conservation and sustainable exploitation of this species.

Genetic Transformation in Triticeae Crops

Wheat, triticale, tritordeum, barley, oat and rye are the most important crops in human consumptions and industry in the world. Transformation technology supplies a new source of improving Triticeae crops. In the past decade, transformation of wheat crops has considerably progressed. Many transgenic plants of Triticeae crops with various genes were produced via nricroprojectile bombardment, Agrobacterium-mediated transformation, PEG-uptake DNA technique, electroporation, microinjection, injection inflorescence and silicone carbide. Integration and expression of transgenes, inheritance and variation of transgenic plants have been studied. Technical improvements of genetic transformation for wheat crops will be extensively useful in commerce and benefit significantly to human being in the world.

Genetic Variation Analysis of 3D Gene and Molecular Detection of Porcine Kobuvirus in 2013-2014

[Objective] This study aimed to investigate the prevalence and variation of porcine kobuvirus （PKV） in suckling piglets in China. [Method] In 2013-2014, 224 feces samples from suckling piglets with diarrhea in 27 pig farms of five provinces in China were collected to detect 3D genes of PKV with RT-PCR method; the sequences and genetic variation of 29 PKV 3D genes were analyzed. [Result] Total positive rate of PKV in feces samples from suckling piglets with diarrhea was 65.18% （146/224）; total positive rate of PKV in pig farms was 85,2% （23/27）; nucleotide sequences and the deduced amino acid sequences of 29 PKV 3D genes shared 87.0%-100% and 92.7%-100% homologies with six PKV-related 3D sequences, respectively. [Conclusion] PKV infection is prevalent in suckling piglets in China; PKV 3D genes exhibit high diversity.

Analysis of Genetic Variation and Population Structure of Starch Synthesis-related Genes in Indica Rice Cultivars

In this study, 34 molecular markers of starch synthesis-related genes were used to evaluate the genetic variation and population structure of 87 indica rice cultivars from different countries and regions. The results showed that a total of 80 alleles were amplified using 34 primer pairs, with an average of 2.5 alleles per locus. The allele number varied from 2 to 6 among various cultivars. Shannon＇s diversity index of molecular markers varied from 0.303 to 0.796, with an average of 0.539. Polymorphism information content （PIC） varied from 0.084 to 0.658, with an average of 0.295. The genetic similarity coefficients of 87 indica rice cultivars ranged from 0.265 to 0.990, indicating significant genetic differences of starch synthesis-related genes among different cultivars, but the variation frequency of alleles varied among different cultivars. Population structure analysis showed that these 87 indica rice cultivars were divided into three categories. Genetic differences were small within the same category but great among different categories. Moreover, indica rice cultivars with simple genetic components accounted for 39.1% and those with complex genetic background accounted for 60.9%. This study may not only provide theoretical basis for genetic improvement of rice starch quality, but also lay a solid foundation for subsequent association analysis of rice quality-related traits.

Genetic Variation of the ORF5 Gene of Porcine Reproductive and Respiratory Syndrome Virus in East China during 2008-2010

[Objective] A total of 260 swine samples of dead or sick pigs collected from 7 provinces （municipalities） Jiangsu, Anhui, Shanghai, Shandong, Zhejiang, Fujian and Jiangxi of China during 2008-2010 were detected for porcine reproductive and respiratory syndrome virus （PRRSV）. And the ORF5 genes of some isolates were amplified and sequenced for understanding the molecule epidemiology and the genetic evolution of PRRSV in East China. [Method] Using RT-PCR method, PRRSV was detected by RT-PCR from samples. The complete ORF5 genes of 36 PRRSV positive samples was amplified, sequenced and analyzed with other 15 strains available on GenBank. [Result] PRRSV was detected in 118/260 of the clinical samples, with a positive rate was 45.4%. Sequence analysis showed that the 36 isolates of this study belonged to the North American-type PRRSV strains and were closely related to the highly pathogenic PRRSV （HP-PRRSV） with 94.6%-100% amino acid sequence identities. The sequence analysis combined with the phylogenetic analysis indicated that all these North American-type PRRSV strains in East China were further divided into five subgenotypes, subgenotype Ⅲ showed closer identity with HPPRRSV; almost all subgenotypes were found to be variable in the primary neutralizing epitope; subgenotypes Ⅲ and IV had more glycosylation sites than others. Although these 36 isolates were collected from different provinces in East China, there were no obvious relations between the distribution of PRRSV and the region. [Conclusion] The PRRSV infection was widespread and HP-PRRSV was the popular strain in East China during 2008-2010. However some different genetic characteristics appeared in the genomes, the genetic evolution was relatively stable. There exists a cross-cutting phenomenon on the genetic relationship of PRRSV isolates obtained from different provinces. Subgenotypes IV and V only appeared in some provinces, but the distribution of PRRSV did not show apparent geographical characteristics.

早期乳腺癌芳香化酶抑制剂引起骨关节疼痛相关研究进展

芳香化酶抑制剂(Aromatase Inhibitors, AIs)药物治疗绝经后早期乳腺癌引起的不良反应,影响了患者的日常生活,最常见的就是骨关节疼痛和骨骼肌僵硬,简称为(AI-associated arthralgia, AIA)或AIs诱发的肌肉骨骼综合征(AI-associated musculoskeletal symptoms, AIMSS),AIA涉及多种临床因素和治疗方法,但是目前缺乏对AIA的统一定义及有效的评估工具,AIA没有得到最佳的管理与控制;有研究发现遗传基因变异也可能影响药物的疗效或毒性,目前越来越多的研究致力于寻找遗传生物标志物以改善风险预测、诊断和治疗。本文从AIA临床危险因素、治疗方法和其相关的单核苷酸多态性(Single Nucleotide Polymorphisms, SNP)几个方面出发,叙述了AIA相关研究进展,在帮助医生平衡内分泌治疗、提高患者依从性方面有重大意义。

类风湿性关节炎与肺间质性病变

类风湿性关节炎（RA）是一种以侵犯关节为主的自身免疫性疾病，也是最常见的一种风湿性疾病。类风湿性关节炎多见于女性，美国其发病率约为1％，我国发病率约0．4％-1％，75％的病人呈慢性过程。多发性、对称性的关节炎是其主要临床表现。RA以关节内的滑膜炎症起病，经久不愈则导致滑膜增厚、血管翳形成软骨及软骨下骨质破坏，最终关节发生畸形及强直。其发病可能与患者遗传基因变异有关，在外因如细菌、病毒、神经内分泌等因素作用下，机体免疫功能发生紊乱，引起机体损伤。类风湿因子（RF）及各种免疫介质的释放在本病的发展和延续中起重要作用。RA除关节病变外，还有下列表现常被忽略，如皮下结节、眼部炎症、心包炎、淋巴结肿大、脾肿大、皮肤血管炎（皮肤溃疡）、Felty综合症及胸膜、肺的病变。其肺部损害较为常见，据报告RA病人中21％具有呼吸道症状，39％的病人有胸部X线异常，两者兼有者占14％，说明RA有肺部改变者并不少见。类风湿性关节炎是临床上常见的疾病，它侵犯全身的结缔组织和血管，因肺脏有丰富的结缔组织和血管，故RA患者常同时伴有肺部损害。有作者认为其发病率为1．6％，47％。RA累及肺部时，以肺间质纤维化为多见，临床表现为咳嗽、咳痰、进行性呼。吸困难、乏力等，有称“类风湿肺炎”。

Differential response of root morphology to potassium deficient stress among rice genotypes varying in potassium efficiency

Disparity in the root morphology of six rice(Oryza sativa L.) genotypes varying in potassium(K) efficiency was studied with three K levels:5 mg/L(low),10 mg/L(moderate) and 40 mg/L(adequate) in hydroponic culture. Morphological parameters included root length,surface area,volume and count of lateral roots,as well as fine(diameter<0.2 mm) and thick(diameter>0.2 mm) roots. The results indicate that the root growth of all genotypes was reduced under low K,but moderate K deficiency increased the root length of the efficient genotypes. At deficient and moderate K levels,all the efficient rice genotypes developed more fine roots(diameter<0.2 mm) than the inefficient ones. Both fine root count and root surface area were found to be the best parameters to portray K stress in rice. In accordance with the root morphology,higher K concentrations were noted in shoots of the efficient genotypes when grown at moderate and deficient K levels,indicating that root morphology parameters are involved in root uptake for K and in the translocation of K up to shoots. K deficiency affected not only the root morphology,but also the root ultra-structure. The roots of high-efficient genotypes had stronger tolerance to K deficient stress for root membrane damage,and could maintain the developed root architecture to adapt to the low K growth medium.

Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Genomic and genetic alterations influence the progression of gastric cancer

Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

Population structure of the blacklegged tick Ixodes scapularis revealed by SSCP data using the mitochondrial Cyt b and the nuclear ITS1 markers

The population genetic structure of the blacklegged tick Ixodes scapularis was analyzed using 853 individual ticks collected from 12 sites along the eastern seaboard of the United States. PCR-based DNA single strand conformation polymorphism(SSCP) was used for analysis of one haploid locus, the mitochondrial cytochrome b(Cyt b), and one diploid locus, the internal transcribed spacer 1(ITS1) of nuclear ribosomal RNA. Seven haplotypes in the Cyt b locus and 13 genotypes in the ITS1 locus were identified. Population differentiation and isolation by distance were found. Distribution of haplotype and genotype frequencies across geographic regions suggests that two distinct populations exist along the Eastern Coast of the US. However, genetic variation among individuals within regions was large. This degree of variation suggests frequent gene flow between regions. Moreover, overall genetic diversity among individuals was much higher in ticks from the southern population.

Understanding biological functions through molecular networks

The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.

CLINICAL AND GENETIC ANALYSIS OF THREE FAMILIES WITH FAMILIAR AMYLOID POLYNEUROPATHY

Objective To study the clinical and genetic features of familiar amyloid polyneuropathy (FAP). Methods Three families of suspected FAP in China mainland and Macao were investigated on aspects of clinical manifestations, histological features, and gene analysis. Results All the 3 families had the clinical features of sensory and motor polyneuropathies, and notable vegetative nerve involvements. Affected cases of one family had ultrasound proved cardiomyopathy. Histological studies showed amyloid deposition in all the biopsy tissues of the affected cases of the 3 families, and anti-transthyretin antisera staining was positive in 3 cases of one family. Gene analysis confirmed that mutation types were amyloidogenic transthyretin (ATTR) Val30Met, Phe33Val, and Gly67Glu in the 3 families respectively. The ATTR Gly67Glu family had a shorter survival time due to the heart involvement compared with the other 2 families. Conclusion FAP is an autosomal dominant inherited disease, with its clinical manifestations related to the type of genetic mutation.

Analysis on Genomic Structure Changes and Diversity of Introgression Lines in Dongxiang Wild Rice(Oryza rufipogon Griff.)

[Objective] The aim of the study was to make research on genomic struc- ture variation and variety analysis of Dongxiang wild rice. [Method] Introgression groups of BC1F6 were based on donor of Oryza rufipogon Griff. and receptor of O. sativa sp. indica Kate. Strains of 239 in the group were analyzed on Polymor- phism with the help of 25 couples of SSR primers distributed in 12 pairs of chromo- somes. [Result] Gene fragments of O. rufipogon Griff. were found penetrated in the 25 microsatellite sites and most of the groups kept the parents of Xieqinzao B or DNA sequence of O. rufipogon Griff. The average rate of recurrent homozygous bands was 78.13% in the ILs, but the highest was 94.98% （amplified by primer RM131） and the lowest was 60.25% （RM171）. The average rate of donor homozy- gous bands was 13.37%, but the highest was 32.64% （RM171） and the lowest was 2.93% （RM1095）. There were numerous heterozygous sites in the population and the average heterozygosis rate was 5.62%, while the highest was 10.04%（RM401）. Moreover, we found some parental fragments were lost and some novel fragments were not detected in either parent in BC1F6 population. The average rate of lost bands was 2.88%, while the highest was 13.39% （RM311） and the lowest was 0 （RM401）. The average rate of new bands was 1%. The average of Nei＇s gene di- versity （He） and Shannon＇s Information index （I） were 0.276 and 0.457 respectively in high generation of introgression lines. [Conclusion] The study demonstrated that distant hybridization led to extensive genetic and epigenetic variations in high gener- ation of introgression lines, which expanded the base of genetic variation and laid an important foundation for rice improvement and germplasm innovation.

Microsatellite analysis of variation among wild, domesticated, and genetically improved populations of blunt snout bream （Megalobrama amblycephala）

In the present study, the genetic diversity of one selected strain （Pujiang No. 1）, two domesticated populations （GA and HX） and four wild populations （LZ, YN, SS and JL） of blunt snout bream （Megalobrama amblycephala） was analyzed using 17 microsatellite markers. The results showed that an average of 4.88-7.65 number of alleles （A）; an average of 3.20-5.33 effective alleles （Ne）; average observed beterozygosity （Ho） of 0.6985-0.9044; average expected beterozygosity （He） of 0.6501--0.7805; and the average polymorphism information content （PIC） at 0.5706-0.7226. Pairwise FST value between populations ranged from 0.0307-0.1451, and Nei＇s standard genetic distance between populations was 0.0938-0.4524. The expected heterozygosities in the domesticated populations （GA and HX） were significantly lower than those found in three wild populations （LZ, SS and JL）, but no difference was detected when compared with the wild YN population. Likewise, no difference was found between the four wild populations or two domesticated populations. The expected heterozygosity in Pujiang No. 1 was higher than the two domesticated populations and lower than the four wild populations. Regarding pairwise Fsr value between populations, permutation test P-values were significant between the GA, HX and PJ populations, but not between the four wild populations. These results showed that the expected beterozygosity in the selected strain of blunt snout bream, after seven generations of selective breeding, was lower than that of wild populations, but this strain retains higher levels of genetic diversity than domesticated populations. The genetic differences and differentiation amongst wild populations, domesticated populations and the genetically improved strain of blunt snout bream will provide important conservation criteria and guide the utilization of germplasm resources.

Analysis of molecular variation in porcine reproductive and respiratory syndrome virus in China between 2007 and 2012

In the present study, 89 porcine reproductive and respiratory syndrome virus(PRRSV) isolates in China during 2007 to 2012 were randomly selected from the GenBank genetic sequence database. Evolutionary characteristics of these isolates were analyzed based on the sequences of non-struc-tural protein 2(Nsp2) and glycoprotein 5(GP5). The genetic variations of the isolates were also compared with six representative strains. The results showed that a high degree of genetic diversity exists among the PRRSV population in China. Highly pathogenic PRRSV isolates, with a discon-tinuous deletion of a 30 amino acid residue in the Nsp2 region, remained the most dominant virus throughout 2007–2012 in China. Owing to the extensive use of representative vaccine strains, natu-ral recombination events occurred between strains. Three isolates – HH08, DY, and YN-2011 – were more closely related to vaccine strains than the other isolates. Both YN-2011 and DY were the evolu-tionary products of recombination events between strains SP and CH-1R. The results of the present study provide useful information for the epidemiology of PRRSV as well as for vaccine development.

Novel genetic variations of the p53R2 gene in patients with colorectal adenoma and controls

AIM: p53-Inducible ribonucleotide reductase small subunit 2 (p53R2) encodes a 351-amino-acid peptide, which catalyzes conversion of ribonucleoside diphosphates to the corresponding deoxyribonucleotides required for DNA replication and repair. A recent study reported that a point mutation (G/T) in the p53 binding sequence in a colon cancer cell line completely impaired p53R2 protein activity.METHODS: We screened the p53R2 gene coding regions and a regulatory region which contains a p53 binding sequence in 100 patients with colorectal adenoma and 100 control subjects using PCR, cold SSCP, and direct DNA sequencing.RESULTS: Although we did not identify genetic variation in all nine exons, four regulatory-region variants were found,of which three were single nucleotide polymorphisms (SNPs) (nt 1 789 C/G, nt 1 928 A/G, 1 933 T/C), and one was 20 bp insertion which replaced a ATTTT between nt 1 831 and 1 835. Additionally, we determined the frequency of these p53R2 variants in a recently concluded case-control study of incident sporadic colorectal adenomas (163 cases and 210 controls).CONCLUSION: Although more detailed functional characterizations of these polymorphisms remain to be undertaken, these polymorphic sites may be useful for identifying alleles associated with mis-splicing, additional transcript factors and, more generally, in cancer-susceptibility association studies.

Genetic variations of beta 2-adrenergic receptor gene are associated with essential hypertension in Xinjiang Kazakans

Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor （β2-AR）, ADRB2, gene with essential hypertension （EH） in Xinjiang Kazakans population.Methods A gender-matched case-control （271 hypertensive cases and 267 normotensive controls） study was used to investigate the associations of the four variations in the coding region of ADRB2 with EH. The genotypes of the variants were identified by the polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP） methods. Results 46 A〉G, 79 C〉G and 659 C〉G polymorphisms were common in the Kazakan population, but 491 C〉T was a mutation （frequency ofT allele was only 0.003） and only found in EH group. The fxequency distributions of genotypes and alleles for 659 C〉G between the EH and control groups was significantly different （P〈0.05）, while those for 46 A〉G and 79 C〉G polymorphisms were not statistically different. Logistic regression analysis suggested that the G allele of 659 C〉G polymorphism was a risk factor for hypertension （minor allele vs common homo; odds ratio, 13.240, 95% CI, 4.052-43.274; P〈0.05）. Covariance analysis showed that systolic and diastolic blood pressure levels in GG＋CG group of 659 C〉G were significantly higher than those in the CC group, but no significant difference of blood pressure were found between common homo and minor allele for 46 A〉G and 79C〉G polymorphisms. Haplotype analysis showed that two hyplotypes, HI： 46A-79C-491C-523C（48%）and H5：46A-79C-491C-659G, were associated with EH.Conelusion ADRB2 genetic variants may play independent roles in the molecular genetic mechanism of EH in Xinjiang Kazakans population （d Geriatr Cardio12010; 7：52-57）.

Genetic variants in telomere-maintenance genes and bladder cancer risk

Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere maintenance genes has been confirmed.Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes.Genetic variants in telomere maintenance genes may affect telomere length and stability,thus the increased cancer risk.This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.