bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Human Genome Project and the Role of Genetics in Health Care
Authors: van Ommen Gert-Jan B. 
Published: October 2004

Abstract
The Human Genome Project, the mapping of our 100000 genes and the sequencing of all of our DNA, will have major impact on biomedical resarch and the therapeutic and preventive health care. The tracing of genetic diseases to their molecular causes is rapidly expanding diagostic and preventive options, while the increased insights into molecular pathways open tremendous perspectives for pharmacological and genetic therapies. The design of animal model systems for the functional study of disease and development of bioinformatics and biostatistics to improve our pattern recognition abilities are greatly accelerating progress. However, the optimal value from the current explosion of ‘data mining’ possibilities will only be gained when the basic data are made and kept publicly accessible, at the same time preventing the jeopardisation of the protection of intellectual property, arising from downstream inventions. This is one of the goals of HUGO, the international Human Genome Organisation, established 9 years ago to assist coordinating data acquisition and exchange and societal implementation of the genome project. Additional points of major importance in this historic endeavour are the safe-guarding of a worldwide balance in the contribution and benefits to countries and population, the prevention of stigmatisation and discrimination of individuals and groups and the maintenance of respect for the priceless diversity of our world's cultures and traditons.
Population Genomics: Laying the Groundwork for Genetic Disease Modeling and Targeting
Authors: Gulcher Jeff , Stefansson Kari 
Published: October 2004

Abstract
The family has proven the most appropriate unit with which to study Mendelian diseases. There are, however, certain limitations on the use of the family as a fundamental unit in the study of common diseases, most of which are complex genetic diseases. The groups that are most likely to yield the genetics of complex diseases are isolated populations with strong founder effects. Therefore, access to such populations is proving to be a precious resource in the work on the genetics of common diseases. The Icelandic population is an excellent population for the study of the genetics of common diseases; it is genetically homogeneous, with founder effects for many traits, and the genealogy of the entire nation is well documented back to the founding days. Furthermore, the nature of the Icelandic national health care system facilitates the assignment of phenotypes in the search for disease genes.
Decode Genetics has begun to study of the genetics of 20 of the most common diseases in the Western parts of the world. The company has placed the groundwork for the construction of an encrypted database with information on the health care of the entire nation, genealogy of the entire nation, genotyping information with high density of markers on a large part of the nation (including typing for known disease genes), and resource use in the Icelandic health care system. The plan is to build the database with approval of participating individuals as well as Icelandic government and health care officials. The database will be used to model health care as viewed in the context of genetic predisposition to the development of disease. The database will also be used in the search for drug targets in complex diseases and in the solution of pharmacogenomic problems. Basing the company in Iceland directly benefits the population in terms of employment and return on investment as well as providing the health care system with an information resource which may be used in preventive medicine and in the optimization of health care in Iceland.
Signal Transduction Pathways and Modulation of Gene Activity
Authors: Weitzman Jonathan B. , Yaniv Moshe 
Published: October 2004

Abstract
Research over the last decade has provided us with much information about the mechanisms that integrate signal transduction pathways with specific gene expression programs. We discuss the types of mechanisms used by different pathways to modulate transcription factor activity, citing examples from diverse molecular systems. Careful regulation of these pathways is essential to maintain balanced transcriptional control. Understanding the mechanisms that control gene activity will enable us to intervene therapeutically in diseases associated with deregulated transcriptional activity.
Do Overexpressed Oncoproteins Cause Malignant Growth of Cancer Cells? – Studied by Antisense Oligonucleotides
Authors: Lin Shwu-Bin 
Published: October 2004

Abstract
Antisense oligonucleotides were used to demonstrate the importance of insulin-like growth factor II and α-fetoprotein for the growth of hepatoma cell lines. The level of insulin-like growth factor II was found to correlate positively with cell proliferative activity, whereas α-fetoprotein was not. We have developed an in vitro system for the screening of antisense oligonucleotides effective for inhibiting target protein production. Using this system, the effectiveness of antisense oligonucleotides can be determined even when a specific antibody or activity assay method is not available. These approaches will be useful for verifying the physiological role of other oncoproteins or proteins in living cells, and antisense oligonucleotides may be developed as new therapeutic agents.
Ethical and Legal Issues in the Procurement, Storage and Use of DNA
Authors: McQueen Matthew J. 
Published: October 2004

Abstract
At the risk of ignoring the benefits, the problems of genetic testing have been widely discussed. Many clinical laboratories are archival stores for human tissues and very few have formal policies and procedures for the use of this material. There is little evidence of planning or preparation of appropriate protocols for the safekeeping of the collected clinical material. The process of informed consent needs to be re-examined. The standard of what would be expected by a reasonable and prudent person poses challenging questions relating to confidentiality and privacy, control and ownership of the stored tissue and cells, withdrawing from a research study, length of storage of samples, the use of biological materials by other parties, and the use of biological materials for purposes other than those for which they were first obtained. There also needs to be a clear understanding of identifiable, non-identifiable and anonymous samples. Clinical laboratory staff and their professional organisations need to engage in the discussion and development around the ethical, legal and social issues raised by testing human DNA. Clinical research laboratories will be increasingly involved in DNA testing and will be asked for access to stored blood or tissue. It is essential that professional responsibility is understood and is then exercised in the presence of appropriate policies and procedures. There is also a paramount need to involve the public who are already demonstrating evidence of alienation from the world occupied by genetics research.
DNA Extraction and Stability for Epidemiological Studies
Authors: Visvikis Sophie , Schlenck Alexandra , Maurice Mickaël 
Published: October 2004

Abstract
During the last few years, an important development of molecular biology techniques has been observed in research and clinical laboratories, and consequently the availability of DNA is becoming essential for epidemiological studies. Several DNA extraction procedures have been proposed. However as the quantity and quality of the DNA extracted is very variable, standardization of the storage of samples, and of extraction procedures becomes essential.
Three steps will be considered. (i) Procedures of whole blood preservation prior to extraction which seem to affect yield and purity of the DNA extracted; (ii) DNA extraction procedures, which must be validated by a systematic DNA quality control using DNA molecular weight screening and spectrophotometric analysis, and also by verification that the DNA obtained is well adapted for molecular biology applications; (iii) the third important factor to study is the storage of DNA, since data on short-term (several months) and especially on long-term (several years) DNA stability is often missing and/or conflicting.
Detailed studies must be done in order to establish guidelines for proper handling of genetic material.
A Multilocus Genotyping Assay for Cardiovascular Disease
Authors: Cheng Suzanne , Pallaud Céline , Grow Michael A. , Scharf Stephen J. , Erlich Henry A. , Klitz William , Pullinger Clive R. , Malloy Mary J. , Kane John P. , Siest Gérard , Visvikis Sophie 
Published: October 2004

AbstractIn our efforts to develop diagnostic tests for complex multifactorial disorders, and to assist the research community in evaluating genetic markers for predisposition to cardiovascular disease, we have developed a prototype assay to genotype up to 35 variable sites among 15 genes. The candidate markers in this panel were selected from biological pathways likely to contribute to the development and progression of cardiovascular disease. Each sample is amplified in two multiplex polymerase chain reactions that are then hybridized to an array of immobilized oligonucleotide probes. The assay has been applied to a population-based cohort representing 238 families; allele frequencies observed among 455 unrelated parents from this cohort agree with available literature values. Data from a cohort of 142 lipid-clinic patients were used to explore locus associations with arterial occlusion, as measured by quantitative angiography. This prototype assay provides a research tool for studies to assess the association of multiple markers with disease, and for clinical studies to evaluate marker association with patient responsiveness to experimental therapies.
Quantification of Relative Expression of Genes with Homologous Sequences Using Fluorescence-Based Single-Strand Conformation Polymorphism Analysis – Application to Lactate Dehydrogenase and Cyclooxygenase Isozymes
Authors: Maekawa Masato , Sugano Kokichi 
Published: October 2004

Abstract
The combination of reverse transcribed-PCR and fluorescence-based single strand conformation polymorphism analysis has been proposed for the quantitative determination of ratio of mRNA molecules with homologous sequences. We applied this procedure to lactate dehydrogenase subunits M and H, and cyclooxygenase 1 and 2. We designed fluorescence labeled common PCR primers in the sequences highly homologous between two subunit and isozyme cDNAs, and performed reverse transcribed-PCR and fluorescencebased single strand conformation polymorphism analysis. PCR efficiency was almost the same for the different target sequences, so analysis of mixtures of known amounts of lactate dehydrogenase M and H revealed linear and precise proportions of lactate dehydrogenase M mRNA. It was shown that template concentrations and number of PCR cycles did not affect the determination of proportions of lactate dehydrogenase M to total lactate dehydrogenase. The procedure was applicable to a determination of cyclooxygenase-2 proportion; furthermore, the present procedure could be easily applied to investigation of expression levels of genes encoding mRNAs with homologous sequences.
A Simple PCR with Different 3′ Ends of the Third Primer for Detection of Defined Point Mutations: HCV Genotyping as an Example
Authors: Alavantić Dragan , Glisić Sanja , Radovanović Nataša , Romić Marija 
Published: October 2004

Abstract
In this article, we describe a useful modification of the polymerase chain reaction for amplification applicable to hepatitis C virus genotyping and determination of its subtypes. The method is fast, cheap and simple for detection of any known point mutation, and could be used in every laboratory with experience in polymerase chain reaction technique. We could differentiate hepatitis C virus subtype 1b from other subtypes and 2b from 2a and other subtypes as well. We could also differentiate hepatitis C type 3 using a type-specific oligonucleotide from 3a subtype, thus covering the most common hepatitis C virus (sub)types present in the European region.
Two Quantitative Methods for Imaging Samples in Molecular Biology
Authors: Tian Li 
Published: October 2004

Abstract
In this paper, we introduce two autoradiography imaging systems from Packard Instrument Company, that provide unmatched speed, accuracy, sensitivity, and resolving power for radioisotopic imaging in biomedical research. The first system is a direct nuclear imaging system, which provides fast and accurate nuclear counting without intermediate steps. Data are displayed in real time so that counting, imaging and data analysis can be done all at the same time. The second system is a new storage phosphor system that was designed with a unique optical assembly which provides high resolution imaging. With various types of phosphor screens, one can optimize the performance of this storage phosphor system with any radiolabel and any appropriate sample size. With these two systems, quantitative radioisotopic imaging becomes not only faster and easier, but also more consistent and accurate, providing researchers with a higher standard in molecular biology imaging.
Quantitative Detection of Hepatitis B Virus DNA with a New PCR Assay
Authors: Kessler Harald H. , Pierer Karen , Santner Brigitte I. , Vellimedu Srinivas K. , Stelzl Evelyn , Lackner Herwig , Moser Andrea , Marth Egon 
Published: October 2004

Abstract
The Amplicor™ HBV Monitor Test for quantitative detection of serum hepatitis B virus (HBV) DNA has recently been introduced. This assay is based on PCR and a non-radioactive hybridization and detection system on microwell plates. Evaluation in a routine diagnostic laboratory showed excellent sensitivity and adequate reproducibility; however, a more automated format would be desirable. The Amplicor™ HBV Monitor Test is useful for recognizing those patients who might benefit from antiviral treatment and for evaluation of the efficacy of anti-hepatitis B virus treatment.
Molecular Diagnostics for Cardiovascular Disease
Authors: Pang Chi-Pui 
Published: October 2004

Abstract
The etiology of cardiovascular diseases is known to be multi-factorial. Some forms of cardiovascular disease are influenced by unclear genetic factors but are predominantly affected by factors such as diet, obesity, cigarette smoking, diabetes mellitus and dyslipidaemia. Some are caused by specific gene defects, with environmental factors playing a precipitating role. Others result from complex gene-gene or gene-enviroment interactions. Advances in knowledge of the molecular genetics of lipidaemic and vascular disorders have identified gene aberrations that are associated with cardiovascular disease. Techniques in molecular biology have been applied for rapid and reliable detection of specific gene defects to provide unequivocal diagnosis beneficial for appropriate drug therapy and genetic counseling. Pre-symptomatic diagnosis is possible and carriers can be advised on effective preventive measures. However, prior to the provision of a molecular diagnostic service, all gene alterations associated with cardiovascular disease have to be identified and their prevalence established in a population. The number of mutations in so many causative genes is enormous. While more cost-effective laboratory methodologies will be developed in the future, it is also anticipated that more mutations with direct or indirect effects on cardiovascular disease will be discovered in different populations.
Association of Apolipoprotein E Polymorphism and Concentration with Serum Lipids and Apo-lipoprotein Level in the Chinese fromShanghai
Authors: Shen Xia , Xia Yongjing , Sass Catherine , Visvikis Sophie , Siest Gérard 
Published: October 2004

Abstract
The influence of apolipoprotein E polymorphism and apoE level on serum lipids and apolipoproteins was investigated in 71 healthy people and 43 patients with coronary artery disease from Shanghai. The frequency of apoE alleles was 0.06 for ε2, 0.86 for ε3, and 0.07 for ε4 in the healthy group, and 0.14 for ε2, 0.77 for ε3, and 0.09 for ε4 in the coronary artery disease group. There was no significant difference in the frequency of apoE alleles between these two groups. Serum levels of triglyceride and apo AI did not differ according to apoE genotypes, whereas serum level of apoB was significantly different according to apoE genotypes (p<0.05) both in healthy and coronary artery disease groups. However, in the healthy group, apo ε2 allele carriers had significantly higher level of apoE than apo ε3 and ε4 allele carriers (p<0.001) and apo ε4 allele carriers had significantly higher level of total cholesterol than apo ε3 and ε2 allele carriers. These were not observed in the coronary artery disease group. ApoE concentration was positively correlated with cholesterol, apoAI, and apoB levels in the control subjects and no significant correlation was observed with triglyceride level. In contrast, apoE level was positively related only to triglyceride level in the coronary artery disease group. In the control group, apoE genotypes and apoE level explained together 19.3 % and 26.6 % of the variability of apoB and cholesterol level, respectively, apoE polymorphism explained 23 % of the variability of apoE level and apoE level explained 13.2 % of the variability of apoAI level. In the coronary artery disease group, only apoE level explained 41.7 % of triglyceride variability. Finally we compared our results with those previously obtained in a French healthy population, the Stanislas cohort. Results suggested that there were some difference between the Chinese control and the French subjects.
Cholesteryl Ester Transfer Protein Mutations, Protein Activity and HDL-Cholesterol Concentration
Authors: Hill Stephen A. , Thomson Christopher , McQueen Matthew J. 
Published: October 2004

Abstract
We have examined a group of North American subjects, selected to include individuals with a wide variety of HDL-cholesterol concentrations for: 1) mutations in the genes coding for cholesteryl ester transfer protein and hepatic lipase, 2) apolipoprotein E genotype, 3) total cholesterol and triglycerides, 4) HDL-triglycerides. Cholesteryl ester transfer protein activity was also estimated, using a novel technique that does not require separation of substrate and product. Transfer activity was shown to have a monophasic distribution, with a mean activity of 21 pmol substrate transferred/3 h/μl plasma. The cholesterol ester transfer activity of the group with HDL-cholesterol >1.60 mmol/l was significantly less than those with HDL-cholesterol <1.60 mmol/l. The cholesteryl ester transfer protein G1533A mutation was detected at an overall allele frequency of 2.91 %. The mutation was more frequent in the group with HDL-cholesterol <1.60 mmol/l than in those >1.60 mmol/l. It was also more frequent in those with protein activity > 30 pmol/3h/μl plasma than in those with activity <30. These data suggest that this mutation in cholesteryl ester transfer protein is associated with increased transfer activity and reduced HDL-cholesterol concentrations. The cholesteryl ester transfer protein activity assay described here is simple and convenient. Subject to further evaluation and correlation with the present labour and time intensive assays, this commercially available assay offers the potential of rapid, simple analysis of large numbers of samples.
Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder
Authors: Whitfield John B. , Nightingale Brian N. , OBrien Martin E. , Heath Andrew C. , Birley Andrew J. , Martin Nicholas G. 
Published: October 2004

Abstract
Alcohol dependence, and the medical conditions which arise from prolonged excessive alcohol use, have no single cause. Like other complex diseases, they result from a combination of social, personal and genetic contributions; but within any society genetic variation has a substantial influence on individual risk. The genes presently known to affect alcohol dependence produce variation in alcohol metabolism; other genes which affect personality or susceptibility to intoxication are likely to be significant but so far reproducible evidence is scanty. Designs which include related subjects have advantages for the study of complex diseases, because any association effects can be placed in the context of overall heritability and because linkage analysis can also be included. Examples of our studies of alcohol metabolism, consumption and dependence are presented.
Screening for Tumour Suppressor p16(CDKN2A) Germline Mutations in Israeli Melanoma Families
Authors: Yakobson Emanuel A. , Zlotogorski Avraham , Shafir Rafael , Cohen Meir , Icekson Michael , Landau Marina , Brenner Sarah , Usher Sally , Peretz Hava 
Published: October 2004

Abstract
Approximately ten percent of patients with malignant melanoma have family histories of the disease, suggesting a genetic predisposition. Germline mutations in tumour suppressor p16 gene have been implicated as disease causing mutations in some of the melanoma families. The frequency of families with p16 germline mutations among melanoma prone families varies from eight to fifty percent. The range of the variability is influenced apparently by the number of melanoma affected individuals within the family, as well as by other, yet unidentified factors. Ethnic background is known to determine both the frequency and the nature of germline alterations. Recently, specific mutations in tumour suppressor genes involved in breast cancer and in colon cancer were found at elevated frequency among Ashkenazi Jews.
This report describes results of a screening for p16 germline alterations in a collection of Israeli melanoma families. We have analyzed genomic DNA from thirty one Ashkenazi and non-Ashkenazi Jewish melanoma families, as well as from thirty melanoma patients without an apparent family history of the disease. The entire coding region of the p16 gene was screened by single strand conformation polymorphism analysis and direct DNA sequencing.
We have detected a number of carriers with the Ala148 Thr polymorphism at the end of the second exon and several instances of 500(G⇒C) substitution at the 3′ untranslated portion of the gene.