中国人MTHFR基因多态性与神经管畸形遗传易感性

目的：应用分子生物学方法进行遗传流行病学研究, 探讨MTHFR基因多态性在神经管畸形的遗传易感性中的作用。方法：应用PCR?RFLP方法检测MTHFR热敏感性基因型;对18个NTD核心家庭进行以父母为对照的病例对照研究,计算TDT和HHRR;另外对31例NTD胎儿和62例正常成年人进行的成组病例对照研究,计算MTHFR纯合突变对NTD的比值比。结果：核心家庭分析结果：比值比OR=3.2,95％CI=1.120～11.169;TDT（χ2）=5.762,P<0.05,HHRR（成组χ2）=6.727,P<0.05;胎儿MTHFR纯合突变对NTD的相对危险度OR=3?21,P<0?05。结论：研究结果说明,突变等位基因在神经管畸形核心家庭中存在突变基因(T)的遗传失衡现象,胎儿MTHFR基因第677位核苷酸的多态性是中国人NTD遗传易感性因素之一。 Abstract：The objective of the study is to clarify the effect of MTHFR thermolabile polymorphism on genetic susceptibility of NTD in Chinese population.MTHFR genotypes were detected using PCR-RFLP analysis; 18 NTD nuclear families were analysed as case-parental control study,from which Transmitted Disequillibrium Test(TDT) and Haplotype-based Haplotype Relative Risk (HHRR) were calculated; 31 NTD fetuses and 62 adult controls were analysed for calculation of OR of homozygotic MTHFR.The results are as follow:Nuclear family analysis: OR=3.2( 95％CI=1.120～11.169);TDT（paired χ2）=5.762,P<0.05,HHRR（χ2）=6.727,P<0.05;homozygotic MTHFR of fetus vs adult control: OR=3.21,P<0.05. The 677th allele of MTHFR is abnormally transmitted in NTD nuclear families.Homozygotic MTHFR of the fetus may be a genetic factor of NTD in China.     

中国汉蒙两族人群MTHFR基因热敏感性多态性分布的比较

为比较中国蒙汉两族人群MTHFR基因第677位核苷酸多态性的分布情况,获得该位点多态性的群体遗传学数据,本研究应用PCR扩增技术, 其扩增产物用限制性核酸内切酶Hinf I消化后进行非变性聚丙烯酰胺凝胶电泳,分析蒙汉族人群中MTHFR基因第677位核苷酸基因型（野生型、杂合型和突变纯合型）的分布频率。结果表明,蒙族人群基因型构成以野生型为主,占45.6％,突变杂合型占39.2％,突变纯合型仅占15.2％,汉族人群基因型构成以突变杂合型为主,占55.7％,野生型仅占17.9％,突变纯合型占26.4％,明显高于蒙族人群。经χ2检验,两组基因型构成比具有显著性差异（P<0.001）;蒙族人群MTHFR 677T等位基因频率为34.8％,经u检验显著低于汉族人群（54.2％）的频率。据此认为,中国蒙族人群MTHFR热敏感性基因突变频率显著低于汉族人群,提示该基因多态性分布在中国不同民族人群中存在差异。 Abstract：The purpose of this study is to compare the genetic polymorphism distribution of the 677th nucleotide of MTHFR between the Mongolian population and the Hans of China,and to obtain the population genetic data of this polymorphism.Using PCR－RFLP method,the authors analyzed the genotypes of the 677th nucleotide of MTHFR in Mongolians and Hans.Results show that in Mongolian population,the proportion of wild type is 45.6％,proportion of heterozygotes is 39.2％ and that of homozygotes is 15.2％; While in Hans,proportions are wild type 17.9％,heterozygotes 55.7％ and homozygotes 26.4％.The ratios of genotypes are significantly different between Mongolian and Han populations(χ2－test,P<0.001).The 677th allele frequency in Mongolians is 34.8％,lower than that in Hans(54.2％,u－test,P<0.001).This suggests that the mutant MTHFR gene frequency is significantly higher in the Han population than in the Mongolian population in China.     

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip/palate in northern Venezuela

Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.     

MTHFR基因多态性与动脉粥样硬化性脑梗塞的关系

采用PCR-RFLP技术,检测了62例动脉粥样硬化性脑梗塞患者和79名对照者的C677T突变的基因型。结果发现, MTHFR基因C677T 突变型等位基因(V)频率在实验组和对照组中,有显著性差异(χ2＝4.41,P<0.05);三种基因型频率在两组人群中均无显著性差异。基因型频率的相对风险分析,AV基因型比AA基因型患脑梗塞风险高1.76倍;VV基因型比AA基因型患脑梗塞风险高3.25倍。结果表明, MTHFR基因C677T突变型等位基因与动脉粥样硬化性脑梗塞有一定的关联,突变基因型增加了动脉粥样硬化脑梗塞的发病风险。 Abstract:　In order to detect the relationship between MTHFRgene C677Tpolymorphism and arteriosclerotic cerebral infarction, this study examined the genotype of 62 patients with arteriosclerotic cerebral infarction and 79 control subjects by PCR-RFLP. The result showed that there was significance difference between patients and control subjects in V allele frequency of MTHFRgene C677Tmutation (χ2＝4.41,P<0.05) and there was no difference between patients and control subjects in genotype frequency of MTHFRgene C677Tmutation. The relative risk for arteriosclerotic cerebral infaction of heterozygote (AV/AA) was 1.76 and that of homozygote (VV/AA) was 3.25. The study confirmed an association between mutated allele of the MTHFRgene C677Tand arteriosclerotic cerebral infarction, mutated genotypes increased the risk of arteriosclerotic cerebral infarction.     

MTHFR基因C677T多态性与内蒙古汉族人群中冠心病的关系

目的:检测中国内蒙古汉族人群中MTHFR基因多态性与冠心病的关系.方法:研究组包括62例冠心病(coronary heartdisease,CHD)患者和120例正常对照人群,用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)分析C677T型突变.结果:677T/T基因型在冠心病人群中更普遍,是正常人群的3.4倍.结论:在内蒙古汉族人群中,677T/T基因型增加了个体患冠心痛的风险性.     

小麦体细胞无性系Glu-1基因突变体的遗传分析

对 Glu-1基因的Glu-Al和Glu-Bl位点都发生突变的1个小麦体细胞无性系后代的高分子量谷蛋白亚基组成进行的分析结果,进一步证实了体细胞无性系发生了基因突变, 且发现同源染色体的等位基因易发生相同突变,突变体多是纯合基因型。认为这是体细胞无性系变异稳定快的遗传根源。 Abstract:Evidence for specific gene mutation has been obtained in our previous research by analyzing high-molecular-weight glutenin subunits(HMW-GS)controlled by Glu-1 gene in wheat somaclons.On the basis of the result,the present study detected in the offspring of a HMW-GS somaclone the mutants at both Glu-A1 and Glu-B1 loci.The occurrence of gene mutation in wheat somaclones was further proved.The results showed that a allele on homologous chromosomes often mutated identically.Genotype of this kind mutation migh be pure.Thie is considered to be genetic reason for quickly stabilizing of somaclonal variation.     

Nonlinear maternal effects on personality in a rodent species with fluctuating densities

Consistent among individual variation in behavior,or animal personality,is present in a wide variety of species.This behavioral variation is maintained by both genetic and environmental factors.Parental effects are a special case of environmental variation and are expected to evolve in populations experiencing large fluctuations in their environment.They represent a non-genetic pathway by which parents can transmit information to their offspring,by modulating their personality.While it is expected that parental effects contribute to the observed personality variation,this has rarely been studied in wild populations.We used the multimammate mouse Mastomys natalensis as a model system to investigate the potential effects of maternal personality on offspring behavior.We did this by repeatedly recording the behavior of individually housed juveniles which were born and raised in the lab from wild caught females.A linear correlation,between mother and offspring in behavior,would be expected when the personality is only affected by additive genetic variation,while a more complex relationship would suggests the presence of maternal effects.We found that the personality of the mother predicted the behavior of their offspring in a non-linear pattern.Exploration behavior of mother and offspring was positively correlated,but only for slow and average exploring mothers,while this correlation became negative for fast exploring mothers.This may suggests that early maternal effects could affect personality in juvenile M.natalensis,potentially due to density-dependent and negative frequency-dependent mechanisms,and therefore contribute to the maintenance of personality variation.     

Association of β-fibrinogen gene -148C/T and -455G/A polymorphisms and coronary artery disease in Chinese population: A Meta analysis

The purpose of our study was to evaluate the correlation between the b-fibrinogen gene –148C/T and –455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta–analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the –148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the –455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differ-ences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in –148T allele carriers compared to the –148C/C wild-type homozygotes was 1.31 (95%CI: 0.94－1.84, P=0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in –455A allele carriers compared to the –455G/G wild-type homozygotes was 1.75 (95%CI: 1.24－2.46, P=0.001). Our results suggest the absence of an association between the b-fibrinogen gene –148C/T polymorphism and susceptibility to coronary artery disease and the possibility that –455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.     

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI) project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1) were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of Pac Bio,10? Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of597 participants and identified 24.85 million(M) single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677 T),we hypothesize that there exists a ‘‘comfort" zone for a high frequency of 677 T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.