clock基因rs1801260多态性与抑郁症的关联分析

目的:探讨clock基因与汉族人群抑郁症的关联。方法:用Snapshot SNP分型技术对155例抑郁症患者(其中包括133名抑郁症睡眠障碍者)和150名正常对照进行clock基因rs1801260位点分型,比较两组该基因多态性基因型和等位基因频率的差异。结果:与对照组相比,患者组rs1801260多态性的基因型和等位基因的频率差异无统计学意义(P0.05);对rs1801260多态性二种基因型C/T、T/T抑郁症的临床资料比较,显示HAMA总分差异具有统计学意义(t=2.012,P=0.047),其他各项没有明显差异(P0.05)。结论:clock基因rs1801260多态性可能与中国汉族抑郁症的发病无关联,但与抑郁症的焦虑程度可能关联。     

CACNB2基因多态性与原发性高血压的关联性研究

目的 探讨钙离子通道β2亚基基因(calcium channel β2 gene,CACNB2)多态性与温州汉族人群原发性高血压的相关性及应用荧光素酶报告基因技术检测rs7069292不同等位基因对基因表达的影响.方法 收集原发性高血压患者637例,以血压正常者600名作对照,采用飞行时间质谱分型技术对CACNB2基因rs2228645、rs2357928、rs7069292、rs7099380、rs10764319和rs11014166共6个SNP位点进行分型.构建CACNB2基因5’上游-2831 bp到-2460 bp的rs7069292的侧翼序列的荧光素酶报告基因载体.结果 高血压组rs7069292 CT基因型频率及C等位基因频率高于正常对照组(5.20％ vs.2.17％,2.59％ vs.1.08％,均P＜0.05),分型未发现rs7069292 CC基因型;含rs7069292 C等位基因的启动子活性与T等位基因相比明显增高,差异有统计学意义(P＜0.05);其余5个SNP位点各基因型频率及等位基因频率与对照组比较差异均无统计学意义(均P＞0.05).结论 CA CNB2基因rs7069292多态性与温州汉族人群原发性高血压病有关联,T＞C变异可能是CACNB2基因功能表达的一个影响因子.     

广西人群IL-22基因多态性分布特征及其与血脂的关系

目的:研究广西正常人群中白细胞介素22(IL-22)基因rs2227485C/T和rs2227491A/G位点的多态性分布特点和在不同人群间的分布差异,探讨不同基因型间常见血脂指标水平的差异。方法:采取多重单碱基延伸法(SNa Pshot)和DNA测序相结合的方法对280例广西人群IL-22基因的rs2227485C/T和rs2227491A/G位点进行基因分型检测,并用统计学方法比较各组间多态性分布的差异及不同基因型间血脂指标水平的差异。结果:rs2227485C/T存在CC、CT和TT 3种基因型,分布频率分别为17.1%、49.3%和33.6%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),其基因型及等位基因与国际人类基因组单体型图计划公布的意大利、北京、日本和墨西哥人群相比,差异有统计学意义(P0.05);rs2227491A/G存在AA、AG和GG 3种基因型,分布频率分别为16.1%、52.8%和31.1%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),基因型频率与意大利、日本和墨西哥人群之间的差异有统计学意义(P0.05),等位基因分布频率与其他4个人群相比差异均有统计学意义(P0.05)。rs2227491A/G位点3种基因型间的HDL-C和LDL-C差异有统计学意义(P0.05),其中HDL-C在AG/AA与GG组比较差异有统计学意义(P0.05),LDL-C在AG/GG和AA组比较差异有统计学意义(P0.05)。结论:IL-22基因rs2227485C/T和rs2227491A/G位点多态性在不同人群间存在着差异。rs2227491A/G多态性与血脂水平相关。     

缺氧诱导因子-3α基因rs3764609A / G 和rs3764611T / C 单核苷酸多态性在广西人群中的分布

目的:观察缺氧诱导因子-3α(HIF3A)在广西人群中的分布特点,并比较其与其他地区人群的分布差异。方法:采用SNPscan技术检测187例广西志愿者rs3764609A/G和rs3764611T/C位点基因分型,分析其基因型和等位基因频率在不同性别和组间的分布差异。结果:rs3764609A/G位点存在3种基因型GG、AG和AA,分布频率分别为14.4.%、53.5%和32.1%;rs3764611T/C位点存在3种基因型CC、CT和TT,其分布频率分别为16.0%、47.6%和36.4%。2个位点的基因型和等位基因频率在不同性别间差异均无统计学意义(P0.05)。与人类基因组计划(HapMap)公布的欧州人(CEU)、日本人(JPT)、约鲁巴人(YRI)和北京汉族人(HCB)人群的SNP分型数据相比,广西人群rs3764609和rs3764611基因型和等位基因频率与CEU、JPT和YRI差异均有统计学意义(P0.05),与HCB相比,rs3764609基因型频率差异有统计学意义,等位基因频率差异无统计学意义(P0.05);rs3764611基因型频率差异有统计学意义,等位基因频率差异无统计学意义。结论:广西人群HIF3A基因rs3764609A/G和rs3764611T/C基因多态性在不同人群间存在不同程度差异。     

中国广西人群中RTN4基因遗传多态性的研究

目的:研究RTN4基因rs2920891A/C和rs17046647A/G位点多态性在广西人群中的分布特征,比较不同人群的分布差异。方法:本实验采用多重单碱基延伸PCR(SNa Pshot)和DNA测序方法,对323例广西健康体检者RTN4基因的rs2920891A/C和rs17046647A/G位点基因型进行检测,并与国际人类基因组单体型图计划(Hap Map)公布的不同人群(北京、日本、欧洲及非洲人群)RTN4基因多态性数据进行比较。结果:在广西人群中,RTN4基因rs2920891A/C位点存在AA、AC、CC基因型及A、C等位基因,其等位基因频率在男女间的分布差异有统计学意义(P0.05),基因型及等位基因频率与日本、欧洲及非洲人群比较差异均有统计学意义(P0.05);rs17046647A/G位点存在AA、AG、GG基因型和A、G等位基因,基因型及等位基因频率在男女间比较差异无统计学意义(P0.05),而与日本、欧洲及非洲人群比较差异均有统计学意义(P0.01)。结论:中国广西人群中RTN4基因的rs2920891A/C和rs17046647A/G位点多态性与其他种族间存在差异性。     

广西人群miR-29b-2 基因rs1474742 A / C 和rs12401619 C / G 多态性 分布特征及其与血脂的关系

目的:探讨miR-29b-2基因单核苷酸位点rs1474742A/C和rs12401619C/G多态性在我国广西人群的分布情况,比较其与其他人群的多态性差异,并统计分析不同基因型的常见血脂检测项目水平。方法:SNPscan法对291例研究对象rs1474742A/C和rs12401619C/G位点进行分型,SPSS23.0软件统计分析。结果:rs1474742A/C具有AA、AC和CC基因型,广西人群rs1474742A/C基因型和等位基因频率与千人基因组计划公布的美国人、欧洲人、日本人、意大利人和中国汉族人的差异均有统计学意义(P0.01)。rs12401619C/G具有CC、CG和GG基因型,基因型频率和等位基因频率与美国人、欧洲人、日本人、意大利人和中国汉族人相比差异均有统计学意义(P0.01)。rs1474742A/C位点AC/AA和CC在LDL-C中差异具有统计学意义(P0.05)。结论:miR-29b-2基因rs1474742A/C和rs12401619C/G位点的多态性在不同人群中差异具有统计学意义。rs1474742A/C基因型与LDL-C水平相关。     

G72基因与抑郁症的关联研究

目的探讨抑郁症与G72基因多态性的关系，以及是否有混合家族史的抑郁症其G72基因多态性有无区别。方法应用聚合酶链反应技术分别检测符合《中国精神障碍分类与诊断标准》的100例元混合家族史抑郁症、50例有混合家族史抑郁症、86名正常对照的G72基因的单核苷酸多态性rs947267、rs2181953，并进行关联分析。结果（1）女性无混合家族史抑郁症组与对照组rs947267基因型及等位基因分布频率，差异均有统计学意义（P=0．017、P=0．008），基因型A／A、等位基因A、C的OR值分别为0．300（P=0.010）、0．456（P=0．008）、2．195（P=0．008），而男性差异均无统计学意义（P〉0．05）；（2）不同性别无混合家族史抑郁症组与对照组rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0．05）；（3）不同性别有混合家族史抑郁症组与对照组rs947267、rs2181953基因型及等位基因分布，差异均无统计学意义（P〉0.05）。结论G72基因多态性可能与女性无混合家族史的抑郁症患者存在关联，其中rs947267的C等位基因是危险因子。     

网状蛋白4基因rs2588519 T/C和rs7582359 A/G多态性在广西人群中的分布

目的研究广西人群中网状蛋白4(RTN4)基因rs2588519 T/C及rs7582359 A/G位点多态性的分布特征,对比分析不同种族间这两个位点基因型及等位基因频率的分布差异。方法运用多重单碱基延伸技术和DNA测序方法检测323例广西健康体检者的RTN4基因rs2588519 T/C及rs7582359 A/G位点基因型,分析其基因型及等位基因频率的分布,并对比HapMap(国际人类基因组单体型图计划)公布的欧洲人、日本人、非洲人和北京人的多态性数据。结果在广西人群中,RTN4基因rs2588519 T/C位点存在CC(53.0%)、TC(38.7%)、TT(8.3%) 3种基因型;rs7582359 A/G位点存在AA(7.4%)、AG(37.5%)、GG(55.1%) 3种基因型,这两位点的基因型及等位基因频率在男女间差异无统计学意义(P0.05)。rs2588519 T/C位点基因型与非洲人群比较差异具有统计学意义(P0.05),其等位基因则与欧洲人、日本人和非洲人差异具有统计学意义(P0.05);rs7582359 A/G位点基因型及等位基因与欧洲人、非洲人比较差异均有统计学意义(P0.05)。结论 RTN4基因rs2588519 T/C及rs7582359 A/G位点多态性分布存在不同程度的种族差异。     

IL-10基因启动子多态性与皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-10基因启动子-1082G/A(rs1800896)、-819C/T(rs1800871)、-592C/A(rs1800872)位点多态性与安徽皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照方法,用聚合酶链反应及直接基因测序法比较183例支气管哮喘组与151例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组IL-10基因启动子-1082G/A、-592C/A位点基因型与对照组相比有差异(P<0.05),其等位基因型频率在哮喘组和对照组间亦有差异(P<0.05)。而-819C/T位点基因型及等位基因型频率在哮喘组和对照组间均无差异(P>0.05)。结论:IL-10基因启动子rs1800896(-1082G/A)位点和rs1800872(-592C/A)位点的多态性可能与安徽皖南地区汉族哮喘相关;而rs1800871(-819C/T)位点的多态性可能与安徽皖南地区汉族哮喘无相关。     

广西壮族及汉族人群CD40配体基因rs3092923G/A和rs3092929A/C遗传多态性的研究

目的探讨CD40配体基因rs3092923G/A和rs3092929A/C多态性位点在广西壮族及汉族人群中的分布,同时比较其基因型及等位基因频率分布在不同种族人群之间以及同一种族不同性别之间存在的差异。方法采用单碱基延伸PCR的检测方法,分析201名广西汉族人和199名广西壮族人的CD40配体基因rs3092923G/A和rs3092929A/C多态性。结果在广西壮族人群中,CD40配体基因rs3092923G/A位点AA、AG与GG基因型频率和rs3092929A/C位点AA、AC与CC基因型频率均为86.4%、7.5%和6.0%,rs3092923G/A位点的A、G等位基因频率和rs3092929A/C位点的A、C等位基因频率均为90.2%、9.8%;在广西汉族人群中,CD40配体基因rs3092923G/A位点AA、AG与GG基因型频率和rs3092929A/C位点AA、AC与CC基因型频率均为93.0%、4.0%、3.0%,rs3092923G/A位点的A、G等位基因频率和rs3092929A/C位点的A、C等位基因频率均为95.0%、5.0%。将这2个多态性位点基因型分布频率在2个民族人群中比较,差异均无显著性(P均>0.05),而等位基因频率却有着显著性差异(P均<0.05)。另外,将这2个位点多态性分布频率在男女性别之间作比较,差异都没有显著性(P均>0.05)。进一步与人类基因组计划公布的4个人群相比,广西汉族人群的rs3092923G/A和rs3092929A/C 2位点基因型和等位基因频率与非洲、日本、欧洲和北京人群比较,差异都具有显著性(P均<0.05)。结论在广西地区壮族及汉族人群中存在着CD40配体基因多态性。广西汉族人群CD40配体基因多态性的分布频率同其他种族人群比较存在着显著性差异,这种差异可能是导致与CD40配体相关的疾病在不同种族人群间的临床表现以及发病率存在明显不同的原因之一。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.