Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders

Recently a linkage study on five Icelandic and two English pedigrees has provided evidence for a dominant gene for schizophrenia on 5q11-13 (ref. 1). In that study, families with bipolar illness were not included. Using the same probes, two similar but independent investigations on one Swedish pedigree and on fifteen Scottish families excluded linkage to schizophrenia. To evaluate whether the susceptibility gene on 5q11-13 is a common cause of schizophrenia in other populations, we examined five affected North American pedigrees using probes to the D5S39, D5S76 and dihydrofolate reductase loci. Two families in the present series had cases of bipolar disorder. We found that linkage can be excluded by multipoint analysis. These results, taken together, suggest that the disease gene on 5q11-13 does not account for most cases of familial schizophrenia.     

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2

Malignant hyperthermia (MH) is an inherited human skeletal muscle disorder and is one of the main causes of death due to anaesthesia. The reported incidence of MH varies from 1 in 12,000 in children to 1 in 40,000 in adults. MH is triggered in susceptible people by all commonly used inhalational anaesthetics; it is characterized by a profoundly accelerated muscle metabolism, contractures, hyperthermia and tachycardia. Susceptibility to MH (MHS) is predicted by contracture tests on muscle tissue obtained by biopsy. An almost identical disorder known as porcine MH exists in pigs. The genetics of the porcine syndrome have been extensively studied; the locus controlling expression of porcine MH is genetically linked to the glucose phosphate isomerase locus (GPI). In man, GPI has been mapped to the q12-13.2 region of chromosome 19 (refs 10-12). We have now investigated genetic linkage in several extended Irish pedigrees in which MHS is segregating as an autosomal dominant trait. Here we show linkage between MHS and DNA markers from the GPI region of human chromosome 19 with a maximum log likelihood ratio (lod score) of 5.65 at the CYP2A locus. These results indicate that human and porcine MH are most probably due to mutations in homologous genes, and also provide a potentially accurate and noninvasive method of diagnosis for MHS.     

ACE2、AT2R、eNOS基因与原发性高血压相关性研究

原发性高血压（EH）是一种由遗传因素和环境因素共同作用导致的严重危害人类健康的心血管疾病。高血压疾病基因的研究有助于高血压发病机制的探讨,对其早期预防和及时治疗具有十分重要的理论意义和巨大的临床应用前景。至今研究者们已经发现有一百多种基因与原发性高血压的发病有关,特别是内皮型一氧化氮合酶（eNOS）更是研究的热点。已经确定肾素血管紧张素系统（RAS）在调控心血管功能时发挥重要作用,最近又在该系统中新发现了两个成员——血管紧张素转换酶2（ACE2）和血管紧张素Ⅱ2型受体（AT2R）,但是对其研究报道较少。文章分别从eNOS,ACE2和AT2R的生物学特性和作用机制的情况,探讨其与原发性高血压的相关性。     

Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. FAD Collaborative Study Group

Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.     

Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q

Proximal spinal muscular atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). These different clinical forms have previously been attributed to either genetic heterogeneity or variable expression of different mutations at the same locus. Research has been hindered because the underlying biochemical defect is unknown, and there are insufficient large pedigrees with the most common and severe form (type I) available for study. Therefore, we have undertaken a genetic linkage analysis of the chronic forms of the disease (types II and III) as an initial step towards the ultimate goal of characterizing the gene(s) responsible for all three types. We report here the assignment of the locus for the chronic forms to the long arm of chromosome 5 (5q12-q14), with the anonymous DNA marker D5S39, in 24 multiplex families of distinct ethnic origin. Furthermore, no evidence for genetic heterogeneity was found for types II and III in our study, suggesting that these two forms are allelic disorders.     

Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene

PRIMARY hypertension is a polygenic condition in which blood pressure is enigmatically elevated; it remains a leading cause of cardiovascular disease and death due to cerebral haemorrhage, cardiac failure and kidney disease. The genes for several of the proteins involved in blood pressure homeostasis have been cloned and characterized, including those of the renin-angiotensin system, which plays a central part in blood pressure control. Here we describe the introduction of the mouse Ren-2 renin gene into the genome of the rat and demonstrate that expression of this gene causes severe hypertension. These transgenic animals represent a model for hypertension in which the genetic basis for the disease is known. Further, as the transgenic animals do not overexpress active renin in the kidney and have low levels of active renin in their plasma, they also provide a new model for low-renin hypertension.     

Localization of genes for lateral branch and female sex expression and construction of a molecular linkage map in cucumber (Cucumis sativus L. ) with RAPD markers

A cucumber ( Cucumis sativus L. ) molecular linkage map, including 79 random-amplified polymorphic DNAs (RAPD)and two genes , lb for lateral branch and f for female sex expression, is constructed from a cross between a line, S52, with weak lateral growing ability and staminate from Dabieshan Mountains area in China and another line, S06, with strong lateral growing ability and gynoecious from Europe. The map contains nine linkage groups and spans 1110.0 cM with an average distance of 13.7 cM between loci. The lb locus is located in a longer linkage group LG-2 and flanked by two markers, OP-Q5-1 and OP-M-2-2, at 9.3 cM and 15.9 cM, respectively. In the meantime, the RAPD loci, OP-Q5-2 and BC151, in a short linkage group were found to flank f at 13.7 cM and 13.4 cM,respectively. The construction of RAPD map has paved a way for further study of the genes for lateral branch, female sex expression and other agronomic traits in cucumber.     

Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage

Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci.     

高校教职工血压状况的测量与分析——以宝鸡文理学院为例

目的了解高校教职工血压水平及其分布特征,提高教职工对异常血压的预防意识。方法采用实验法和数理统计法,对宝鸡文理学院833名教职工的血压进行测量分析。结果教职工最佳血压人数比例为47.5%,高血压和低血压人数比例分别为16.6%和16.9%;女教职工最佳血压人数比例高于男教职工,为61.1%;20～29岁最佳血压人数比例最高,为75.0%;体育教师最佳血压人数比例最高,为60.7%。结论高校教职工异常血压存在一定比例,血压状况与性别、年龄和工作岗位有关。     

Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats.

The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.     

猪2号染色体MYOD1区域的RH定位和连锁定位

在已经定位的QTL区域中开展基因连锁定位是寻找候选基因的重要途径．运用比较基因组方法筛选出猪2号染色体上生长、胴体和肉质性状QTL区域中与肌肉发育相关的5个基因（MYOD1、LDHA、CSRP3、TEF-1和COPB1）,通过RH和连锁定位方法研究这5个基因的排列顺序和距离,并与人和小鼠基因的顺序进行了比较．结果表明这5个基因在猪2号染色体上的排列顺序和距离是：MYOD1（75．2cM）-LDHA（79cM）-CSRP3（83．8cM）-TEF-1（86．5cM）-COPB1（90cM）,猪与小鼠基因的顺序相同,而与人（TEF-1—COPB1-MYOD1-LDHA—CSRP3）的顺序不一致．本研究结果对于进一步开展这5个基因的功能研究奠定了基础．     

高血压的联合用药治疗

单一降压药治疗高血压,常因其局限性而力不能及.为了最大程度取得降压效果,必须联合用药,联合用药对于治疗高血压,尤其是中、重度高血压十分重要,它是治疗高血压的必然需要.也是业经证明了很有价值的治疗举措.     

太极拳运动对原发性高血压作用机制

目的:探讨太极拳对高血压的降压作用与机制.方法:经医院确诊为1级原发性高血压患者52例(男28例、女24例),平均收缩压150.4±7.7,舒张压96.8±5.4.陈式太极拳锻炼90d,2次/d,分别在6:30am(早餐前)和8:00pm(晚饭后)进行,每次40min;血浆NO浓度64.3±20.8.观察实验前、中、后动脉血压、血浆一氧化氮(NO)浓度.结果:90天的陈式太极拳练习使运动血压发生显著的下降(P<0.05),平均收缩压132.8±6.8,舒张压86.6±5.9,平均降幅收缩压18.05mmHg、舒张压9.9 mmHg;日平均降幅收缩压0.22 mmHg、舒张压0.13 mmHg;血浆NO浓度有显著增加(P<0.05),平均浓度为79.5±22.4.结论:太极拳运动对原发性高血压有明显的降低血压作用,降压效果男性略优于女性.太极拳的运动特性对大脑皮层以良好的刺激,调整中枢神经系统机能活动能力,提高血浆一氧化氮浓度,促进一氧化氮的合成与释放,增加血液循环系统功能;太极拳运动是原发性高血压患者的合适运动疗法.     

Expression ofBcl-2 in cells with different telomerase activities

Both telomerase andBcl-2 are important genes in controlling apoptosis. The activation of telomerase and the abnormal regulation ofBcl-2 are also closely related to carcinogenesis. However, little is known about the linkage between telomerase andBcl-2. The effect of activated telomerase on the expression ofBcl-2 has been investigated. It is demonstrated that in tumor and transformed cells with higher telomerase activity,Bcl-2 expression is significantly lower than that in telomerase negative or less telomerose activity cells. Further study showed that in the telomerase gene-transformed 2BS-fibroblasts,Bcl-2 expression is inhibited significantly while the exogenous telomerase catalytic subunit gene is re-expressed in fibroblasts. Results indicated that there might be a certain linkage between the expression of telomerase andBcl-2, and overexpression of exogenous telomerase gene might down regulate the expression ofBcl-2. They contributed equally to this work.     

A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.     

Isolation and polymorphic frequency detection of a novel STR on human chromosome 14q24.3

A single copy fragment (FD14-ca 1) cantaining 22 CA repetitive units was isolated with (CA)₁₅ oligonucleotide probe from a human chromosome 14q24.3 probe pool generated by microdissection, and proved to be a new short tandem repeat (STR) sequence through querying in GenBank of NCBI. The STR has 11 alleles in Chinese. and its polymorphic information content (PIC) is 0.85. Mendelian segregation was shown in 2 Chinese pedigrees with two generations; This STR has been accurately relocalized on chromosome 14q24.3 by fluorescencein situ hybridization (FISH). The accession numbers of this STR in GDB and Gnknk database are D14S1435 and G31413 respectively. This STR would be able to be regarded as a novel genetic marker which can increase the genetic map accuracy in this chromosome region and improve the gene diagnosis on some genetic diseases located in chromosome 14q24.3 band.     

辽宁汉族人群6个短串联重复序列基因座的遗传多态性

利用多重PCR和4色荧光(5-FAM,JOE,NED和ROX)自动化检测技术调查辽宁地区汉族人群CSF1PO,THO1,D16S539,2S1338,D19S433和TPOX等6个STR基因座多态性分布并计算该6个基因座的基因频率(Pi)、个体识别率(DP)、无偏倚期望杂合度(H)、多态性信息含量(PIC)和非父排除率(PE)．结果显示,6个STR基因座的基因型分布符合Hardy—Weinberg定律．6个STR基因座累积个体识别率(CDP)为0．99999948,累积非父排除率(CPE)为0．98927．6个STR基因座适合作为中国人群的遗传标记,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域．     

西藏大学学生高血压患病情况及危险因素分析

目的：了解西藏大学学生血压水平及青年人患高血压病的危险因素,为预防高血压病提供依据。方法：应用单纯随机抽样方法,抽取1038名学生进行血压、身高、体重的测量并进行标准化的问卷调查。高血压的诊断标准采用了2005年中国高血压防治指南标准。结果：西藏大学学生高血压病总患病率为5．02％（男生为9．0％,女生为1．7％,P=0．000）,男生和女生高血压的患病率有显著的统计学意义。经过Logiscic回归分析,性别、体质指数与高血压有相关性。结论：培养健康的生活方式、控制体重是预防和减少大学生高血压发生的主要措施。