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At least 541 records · Page 30Linked to original sources
PubMed2005

Inherited defects of coagulation Factor V: the thrombotic side.

DNA variations in the Factor V gene have played a major role in thrombosis research ever since the discovery of Factor V Leiden. Here, all relatively common DNA variations in the coding regions of the Factor V gene are discussed. Many of them have been associated with venous thrombosis or related diseases. However, most variations have been studied separately, without taking the presence of other variations in the same gene into account. This means that their association with disease should be interpreted with caution, as it may reflect linkage with another variation. An approach in which a haplotype-based analysis of the Factor V gene is combined with in vitro assays of recombinant proteins is advocated. Finally, a possible reason for the relatively polymorphic nature of the Factor V protein is discussed.

Blood Coagulation Disorders, Inherited↗
PubMed1991

Genetic studies of human apolipoproteins. XVIII. Apolipoprotein polymorphisms in Australian Aborigines.

A tribal aboriginal community, the Mowanjum, from the Kimberley region in Western Australia has been screened to determine the extent of genetic variation in the products of genes coding for apolipoproteins, which are intimately involved in lipid metabolism. Of the seven systems tested, APOE and APOH revealed common structural variations, but their distribution patterns are significantly different from those found in European populations. Australian Aborigines were found to be unique because they have no APOE*2 and APOH*3 alleles and have strikingly high frequencies of the APOE*4 (26%) and APOH*1 (13%) alleles. The contrast in variation observed at these apolipoprotein loci between Australian Aborigines and Europeans not only makes these loci useful genetic markers in biologic anthropology studies but also provides a unique opportunity to investigate the role of genetic-environment interaction in determining interpopulation differences in cardiovascular disease risk factors.

Apolipoproteins↗
PubMed2006

Optical density variations in CT films and their effect on image quality.

It was recently reported that optical density (OD) variations were observed in CT films printed with a laser camera, depending on the printing format and the frame position within the film. The purpose of the present study was to investigate if these variations are common to both laser and dry-film printers and if the different OD settings along with day-to-day and frame-to-frame variations may affect the image quality. Eight laser and five dry-film printers installed at 12 different CT facilities were tested. For each one, the SMPTE test pattern was printed on all frames of a film using the same printing format. The ODs of the 0%, 10%, 40% and 70% patches of the 11-step greyscale of the SMPTE patterns were measured with a densitometer in all frames, while all films were examined on a viewing box to assess subjectively the image quality by visual inspection of the test pattern. A wide range of OD settings and variations were recorded. Frame-to-frame variations in the same film of up to 0.19, 0.15 and 0.21 OD, were observed for contrast index (CI, the OD difference of patches 10% and 70%), speed index (SI, the OD of patch 40%) and maximum OD (OD(max), the OD of patch 0%), respectively. The variations were not always of the same magnitude, nor always followed the same pattern, even for printers of the same model. Considering all films and frames, the CI ranged from 1.26 to 1.74, the SI from 0.68 to 1.43 and the OD(max) from 2.5 to 3.11 OD, well beyond the proposed settings and tolerances of 1.55+/-0.15, 1.15+/-0.1 and 2.45+/-0.1 given in the literature for CI, SI and OD(max), respectively. Despite these large differences, the various problems that were identified in image quality from the visual inspection of the films could not be directly attributed to OD settings, as films with similar CI, SI and OD(max) presented quite different image quality levels. Therefore, for routine quality control, thorough visual inspection of the SMPTE test pattern provides all the necessary information about the imaging chain status.

Computer Peripherals↗
PubMed1990

HIV, trauma, and infection control: universal precautions are universally ignored.

The medical, legal, and ethical problems associated with routine HIV screening have led to the recommendation that all patients should be presumed to be seropositive and thus protective measures should be taken by all health care workers. This philosophy, termed "universal precautions," has been difficult to adhere to or enforce, however. Nevertheless, in some trauma population subsets, the prevalence of HIV seropositivity runs as high as 19%, and thus presents an occupational hazard to the trauma health care worker. The mainstays of universal precautions (UP) are barrier techniques against body fluid contact and protection from inadvertent needlestick. To judge compliance with a strict UP protocol, surgical residents engaged in trauma room resuscitations were observed on a random basis by trauma nurse coordinators. Previously, UP had been discussed in conferences and by memo. Over 2 months, 81 trauma rooms were observed, involving 18 house officers. Overall, there was only 16% compliance with strict UP. The most common protocol variations involved sharps technique. While glove use was nearly universal, protective eye wear, ankle and foot protection, and body protection such as gowns or aprons were commonly ignored. Even in the presence of invasive procedures such as endotracheal intubation or insertion of chest tubes, compliance was less than 40%. The reasons most commonly given by house officers for the lapse in UP were not knowing the protocol, forgetting the protocol, or not having time to implement the protocol. Even for the nine patients residents identified as suspected of being in a high-risk category, UP was strictly adhered to only once. Compliance with universal precautions is difficult to achieve under the best of circumstances. It cannot be assumed that passive informational measures can achieve this goal. Active infection control surveillance and ongoing housestaff inservice are required to minimize the risk of inadvertent injury or contamination.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity.

The SIR2/Sirt1 gene has been demonstrated as regulating lifespan in many model organisms, including yeast, Caenorhabditis elegans and rodents. These findings render the human homologue, SIRT1, a very plausible candidate as a modifier of human life expectancy. We therefore sought to investigate whether common allelic variation in the SIRT1 gene was associated with human longevity. Five single nucleotide polymorphisms (SNPs), distributed across the entire gene, including the promoter region, were genotyped in our extensive DNA collections of 1573 long-lived individuals (centenarians and nonagenarians) and matched younger controls. Four of the markers were haplotype-tagging SNPs (htSNPs) that defined five common haplotypes. No evidence for an association was detected between any of the tested SNPs and the longevity phenotype at the allele, genotype or haplotype levels. These findings, based on an htSNP approach, suggest that there is no noteworthy influence of SIRT1 sequence variation on exceptional human longevity in the German population. However, this does not rule out the possibility that allelic variants in direct regulators or downstream substrates of SIRT1 could play critical roles in extending lifespan in humans.

Aged↗
PubMed2024

A comparison of software for analysis of rare and common short tandem repeat (STR) variation using human genome sequences from clinical and population-based samples.

Short tandem repeat (STR) variation is an often overlooked source of variation between genomes. STRs comprise about 3% of the human genome and are highly polymorphic. Some cause Mendelian disease, and others affect gene expression. Their contribution to common disease is not well-understood, but recent software tools designed to genotype STRs using short read sequencing data will help address this. Here, we compare software that genotypes common STRs and rarer STR expansions genome-wide, with the aim of applying them to population-scale genomes. By using the Genome-In-A-Bottle (GIAB) consortium and 1000 Genomes Project short-read sequencing data, we compare performance in terms of sequence length, depth, computing resources needed, genotyping accuracy and number of STRs genotyped. To ensure broad applicability of our findings, we also measure genotyping performance against a set of genomes from clinical samples with known STR expansions, and a set of STRs commonly used for forensic identification. We find that HipSTR, ExpansionHunter and GangSTR perform well in genotyping common STRs, including the CODIS 13 core STRs used for forensic analysis. GangSTR and ExpansionHunter outperform HipSTR for genotyping call rate and memory usage. ExpansionHunter denovo (EHdn), STRling and GangSTR outperformed STRetch for detecting expanded STRs, and EHdn and STRling used considerably less processor time compared to GangSTR. Analysis on shared genomic sequence data provided by the GIAB consortium allows future performance comparisons of new software approaches on a common set of data, facilitating comparisons and allowing researchers to choose the best software that fulfils their needs.

Humans↗
PubMed1992

Accuracy of dental registrations in forensic odontology among dental students.

The registration of dental characteristics in forensic work is crucial to the identification procedure and because of this, standardised recordings of dental characteristics should be applied. In order to improve accuracy in identification it is important to evaluate the types of errors that are made during the different steps of the procedure. Attempting to identify the most common interindividual variations, twelve dental students made recordings on excised, macerated jaws at the Department of Forensic Medicine in Göteborg as a part of the course in Forensic Odontology. The most common error was incorrect judgement of the extent of single restorations. Furthermore, the students had difficulty in identifying premolars and molars, especially in the mandible, confusing the two groups of teeth. This study emphasises the importance of carefully re-examining the postmortem dental findings by an experienced forensic odontologist before comparing them with the antemortem data.

Dental Records↗
PubMed2000

Lipoprotein lipase gene variation is associated with adipose tissue lipoprotein lipase activity, and lipoprotein lipid and glucose concentrations in overweight postmenopausal women.

Adipose tissue lipoprotein lipase (LPL) activity is under strong genetic control in both mice and humans. This study determines whether common DNA variation in the LPL gene (PvuII and HindIII polymorphisms) is associated with adipose tissue LPL activity and metabolic risk factors in a homogeneous population of 75 overweight postmenopausal women (body mass index >25 kg/m2; age: 51-69 years old). The allele frequencies for the presence of the cut-sites for LPL HindIII and PvuII were 0.71 and 0.49, respectively. There were no associations between the HindIII polymorphism and any of the measured variables. Age, body mass index, percent body fat, waist-hip ratio, visceral and subcutaneous fat area, and gluteal (GLT) and abdominal (ABD) adipocyte size did not differ by LPL PvuII genotype. However, adipose tissue LPL activity at both GLT and ABD sites was higher in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous (+/-) or homozygous (+/+) for the cut-site (P<0.05). Total and LDL cholesterol were lower in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous or homozygous for the cut-site (P<0.05), whereas triglyceride and HDL levels were similar between LPL PvuII genotypes. Fasting glucose, but not insulin, was lower in women without the LPL PvuII cut-site (-/-). These data suggest that the LPL PvuII polymorphism is a possible marker for a functional mutation that is found in the LPL gene and that alters LPL activity in older overweight women.

Adipocytes↗
PubMed2005

Prospects and pitfalls in whole genome association studies.

Recent large-scale studies of common genetic variation throughout the human genome are making it feasible to conduct whole genome studies of genotype-phenotype associations. Such studies have the potential to uncover novel contributors to common complex traits and thus lead to insights into the aetiology of multifactorial phenotypes. Despite this promise, it is important to recognize that the availability of genetic markers and the ability to assay them at realistic cost does not guarantee success of this approach. There are a number of practical issues that require close attention, some forms of allelic architecture are not readily amenable to the association approach with even the most rigorous design, and doubtless new hurdles will emerge as the studies begin. Here we discuss the promise and current challenges of the whole genome approach, and raise some issues to consider in interpreting the results of the first whole genome studies.

Genetic Markers↗
PubMed2004

Systematic evaluation of genetic variation at the androgen receptor locus and risk of prostate cancer in a multiethnic cohort study.

Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen receptor (AR) gene has been associated with risk of prostate cancer in humans. This association has been the focus of >20 primary epidemiological publications and multiple review articles, but a consistent and reproducible association has yet to be confirmed. We systematically addressed possible causes of false-negative and false-positive association in >4,000 individuals from a multiethnic, prospective cohort study of prostate cancer, comprehensively studying genetic variation by microsatellite genotyping, direct resequencing of exons in advanced cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These data failed to confirm that common genetic variation in the AR gene locus influences risk of prostate cancer. A systematic approach that assesses both coding and noncoding genetic variation in large and diverse patient samples can help clarify hypotheses about association between genetic variants and disease.

Aged↗
PubMed2005

The role of school context in the increase in young people's health complaints in Finland.

According to biological indicators trends in young people's health appear favourable, but the psychosocial aspects suggest a different pattern. We studied the differences across schools in common health complaints and in three groups of factors behind them: pupils' individual characteristics, family related factors and school-related factors. Multilevel linear regression models were used to analyse repeated cross-sectional data from Finnish 8th and 9th graders (14- and 15-year-olds, n=60347) in 109 schools that were surveyed in 1996, 1998 and 2000. Common health complaints increased steadily during the follow-up for all schools and they varied across schools. Both individual and school-level factors contributed significantly to the variation in common health complaints. The study suggests that young people's psychosocial health involves a range of influences deriving from individual susceptibility and from the social and educational functioning of schools. However, none of these factors can account for the rapid decrease in young people's psychosocial health.

Adolescent↗
PubMed2006

Factor VII gene haplotypes and risk of ischemic stroke.

BACKGROUND: Coagulation factor VII (FVII) plays an important role in the activation of blood coagulation and clot formation. Recent studies have provided evidence for an association between common polymorphic markers in the FVII gene and plasma FVII concentrations. The 353R>Q sequence variation, and 3 common sequence variations in the promoter of the FVII gene-the 10-bp insertion/deletion at position -323 and the -401G>T and -402G>A sequence variations-are well-known determinants of circulating FVII concentrations. METHODS: To clarify the role of these sequence variations in the pathogenesis of ischemic stroke, we performed a case-control study with 242 patients with ischemic stroke before the age of 60 years and 239 healthy controls. RESULTS: The -323 insertion/deletion and the 353R>Q and -401G>T sequence variations were in strong linkage disequilibrium, and the resulting haplotypes occurred with equal frequencies in patients and controls. The variant form of FVII (-402G>A) occurred only in combination with the common (wild-type) sequences at all other loci. This haplotype was more frequent in patients than in healthy controls (28% vs 22%). The difference in the prevalence of carriers of this haplotype among patients and controls was statistically significant (P = 0.03; odds ratio = 1.6; 95% confidence interval, 1.1-2.6). CONCLUSION: According to our results, the FVII -402A allele seems to increase the risk of early ischemic cerebrovascular events, whereas the 353R>Q, G-401T, and -323ins/del sequence variations, which are in close linkage disequilibrium, apparently do not influence the risk of stroke.

Acute Disease↗
PubMed1992

Falsification of a single species hypothesis using the coefficient of variation: a simulation approach.

Dental variation remains an important criterion for assessing whether a morphologically homogeneous fossil primate sample includes more than one species. The Coefficient of Variation (CV) has commonly been used to compare variation in a fossil sample of unknown taxonomic composition with that of extant single-species samples, in order to determine whether more than one species might be present. However, statistical tests for differences between fossil and single species reference sample CVs often lack power, because fossil samples are usually small and confidence limits of the CV are consequently large. The present study presents a new methodology for using the CV to test the hypothesis that a sample represents only one species. Simulated sampling distributions of single-species and pooled-species CVs are generated based on variation observed in dental samples of extant Cercopithecus species. These simulated distributions are used to test a single-species hypothesis for 13 different combinations of two or three sympatric Cercopithecus species across four dental characteristics at different sample sizes. Two different ways to generate the reference value of the CV are used. Results show the proposed methodology has substantially greater power than previous methods for detecting multiple-species composition, while maintaining an acceptable Type I error rate. Results are also presented concerning the dependence of power on sample size and on the average difference between means in a pooled-species combination.

Animals↗
PubMed2003

Chemical defence in a sawfly: genetic components of variation in relevant life-history traits.

Larvae of several tenthredinid sawfly species readily release droplets of haemolymph through their integument when attacked by predators. This defence mechanism via 'bleeding' is characterised by a low integument resistance and a high haemolymph deterrence. Both traits are variable, and negatively correlated among species. We sought to determine if such differences in the propensity to bleed also occur intraspecifically by studying the heritability of traits potentially associated with the bleeding phenomenon in the turnip sawfly Athalia rosae ruficornis Jakovlev (Hymenoptera: Tenthredinidae, Allantinae). For three European populations, heritabilities were estimated in the laboratory in a parent-offspring and a full-sib design for haemolymph deterrence (measured as concentration of sequestered glucosinolate), integument resistance, body mass of eonymph and adult, and developmental time. Within A. rosae, no significant negative phenotypic correlation was found between the two traits directly related to the defence mechanism: integument resistance and haemolymph deterrence. However, the significant heritabilities found for these traits in the full-sib analysis (0.39 and 0.35, respectively, for males in the Swiss population) show that the variation has a genetic component. While full-sib analysis revealed highly significant heritabilities for most traits in all the three populations, parent-offspring regression revealed little or no evidence of heritable variation. Effects of common environment for siblings and variation in the host-plant quality between insect generations are likely to be the main factors explaining these differences. A consequence of such host-plant variation in the wild might be that genetic variation of such chemical defensive traits is largely invisible to natural selection.

Alleles↗
PubMed1996

Sources of covariation among Mini-Mental State Examination scores, education, and cognitive abilities.

An adoption/twin design was used to address issues concerning the relationship between education and Mini-Mental State Examination (MMSE) performance. Data on general cognitive abilities, education, and MMSE from 110 identical twin pairs and 177 fraternal pairs aged 50 through 88 were analyzed using multivariate quantitative genetic methods. Genetic influences account for 32% and 19% of the variation in MMSE for men and women, respectively. Furthermore, all of the genetic variation in MMSE is in common with genetic variation for cognitive abilities and education. Finally, correlations between education and MMSE (.21 and .16 for men and women, respectively), which were reduced to near zero when cognitive abilities were partialed out, are primarily attributable to genetic effects for cognitive abilities. These results support the hypothesis that the association between education and MMSE performance predominantly reflects genetically mediated cerebral capacity rather than test bias or health-endangering life styles in less educated individuals.

Cognition↗
PubMed2006

Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: the multiethnic cohort.

Collective evidence suggests that the insulin-like growth factor (IGF) system plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are the principal regulatory molecules that modulate IGF-I bioavailability in the circulation and tissues. To examine whether inherited differences in the IGFBP1 and IGFBP3 genes influence prostate and breast cancer susceptibility, we conducted two large population-based association studies of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3 exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure that we had identified all common missense variants and (b) characterized the linkage disequilibrium patterns and common haplotypes by genotyping 36 single nucleotide polymorphisms (SNP) spanning 71 kb across the loci ( approximately 20 kb upstream and approximately 40 kb downstream, respectively) in a panel of 349 control subjects of the five racial/ethnic groups. No new missense SNPs were found. We identified three regions of strong linkage disequilibrium and selected a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1 and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with prostate and breast cancer risk in two large case-control studies nested within the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases (largely postmenopausal)/controls = 1,615/1,962]. We observed no strong associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either prostate or breast cancer risk. Our results suggest that common genetic variation in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast cancer susceptibility.

Black or African American↗
PubMed2000

Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease.

Both the processes of atherosclerosis and plaque rupture are indicated to be influenced by matrix metalloproteinase (MMP) activity. We therefore searched for common functional variation in the matrix metalloelastase (MMP-12) gene locus that may be implicated in coronary artery disease. Single-strand conformation polymorphism analysis of DNA from healthy individuals detected a common polymorphism within the MMP-12 gene promoter (an A-to-G substitution at position -82). The frequency of the G allele was 0. 19. The polymorphism influences the binding of the transcription factor activator protein-1 (AP-1) in electromobility shift assay. A higher binding affinity of AP-1 to the A allele was associated with higher MMP-12 promoter activity in vitro in transient transfection studies in U937 and murine lung macrophage (MALU) cells. Phorbol 12-myristate 13-acetate (PMA) and insulin, 2 known activators of AP-1, increased the binding of AP-1 to the MMP-12 promoter, with higher affinity for the A allele. In transfection experiments, both the A and the G alleles responded to insulin and PMA, the A allele showing higher promoter activity than the G allele. Furthermore, Western blot analysis demonstrated that insulin increased MMP-12 protein production. To analyze whether the -82 A/G polymorphism is associated with coronary artery disease, 367 consecutive patients who underwent percutaneous transluminal coronary angiography with stent implantation were genotyped. In patients (n=71) with diabetes, the A allele was associated with a smaller luminal diameter. In conclusion, a common functional polymorphism within the MMP-12 promoter influences coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease.

Adult↗
PubMed2002

The tree Cedrela odorata (Meliaceae): a morphologically subdivided species in Costa Rica.

In Latin America. Cedrela odorata is a wide ranging species that occurs in several environments, where it shows significant morphological variation. A common garden experiment was established with seedlings from 63 families of ten populations from two habitat types (mesic and dry), distributed throughout Costa Rica, to examine the relationships between quantitative variation and site of population origin. Seedlings from dry areas tended to be distinct from those from mesic areas, with climatic grouping of provenance explaining a mean of 52% of the total variance and 80% of the genetic variance. Cluster analysis for seedling traits showed two natural groupings of families, which corresponded for the most part with the regional population groupings into mesic (Atlantic and South Pacific) and dry (North Pacific) groups. Cluster analysis based on seed weight and size also separated populations into mesic and dry climatic groups. Seeds from populations in dry areas were 43% heavier, and seedlings were 61% taller, 117% greater in diameter, and with leaflets 39% longer and 81% wider. These differences may be related to fast growth in the dry zone for taking advantage of early life cycle moisture availability. These findings may indicate incipient speciation in C. odorata in Costa Rica. Evaluation of reproductive isolating mechanisms between populations from the mesic and dry zones, and of clines at potential zones of hybridization would assist in testing a speciation hypothesis.

Analysis of Variance↗