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Genotype Analysis (genotype + analysis)
Selected AbstractsApoE Gene Polymorphisms, BMD, and Fracture Risk in Elderly Men and Women: The Rotterdam Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004Mariette WCJ Schoofs Abstract To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. Introduction: The E4 allele of the E2, E3, E4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. Materials and Methods: The study population consisted of 5857 subjects (2560 men; 3297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. Results and Conclusions: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures. [source] Radiation Response Genotype and Risk of Differentiated Thyroid Cancer: A Case-Control Analysis,THE LARYNGOSCOPE, Issue 6 2005Erich M. Sturgis MD Abstract Background: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC. Hypothesis: Germline variants of double-strand break repair genes are markers of DTC risk. Objective: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls. Study Design: Case-control study. Methods: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype. Results: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P = .006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9,4.9; P = .078). Conclusions: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies. [source] In vitro Epstein-Barr virus-immortalized lymphoma cell line carrying t(9;14)(p13;q32) chromosome abnormality, derived from splenic lymphoma with villous lymphocytesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Masanori Daibata Abstract We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350,400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo. © 2005 Wiley-Liss, Inc. [source] Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2009Chun-Shi Li Abstract Background and Aims:, The cytokine interleukin (IL)-27 is composed of two subunits, Epstein,Barr virus-induced gene 3 (EBI3) and p28, and IL-27 is a novel IL-12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL-27 gene and we suggested that the polymorphism of IL-27 is associated with the susceptibility to asthma. IL-27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL-27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL-27 polymorphisms were analyzed between the IBD patients and the healthy controls. Methods:, Genotype analysis of the IL-27 gene was performed by the single-base extension (SBE) method. The haplotype frequencies of IL-27 for multiple loci were estimated using the expectation maximization (EM) algorithm. Results:, The genotype frequencies of the g.-964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group (P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.-964A > G polymorphism were also significantly different from the frequencies of the healthy control group (P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group (P = 0.00004 and 0.021, respectively). Conclusion:, Our results suggest that the g.-964A > G polymorphism of the IL-27 gene located on the IBD1 locus might be associated with the susceptibility to IBD. [source] Virulence, phenotype and genotype characteristics of endodontic Enterococcus spp.MOLECULAR ORAL MICROBIOLOGY, Issue 1 2005C. M. Sedgley Background/aims:, Enterococci have been implicated in persistent root canal infections but their role in the infection process remains unclear. This study investigated the virulence, phenotype and genotype of 33 endodontic enterococcal isolates. Methods:, Phenotypic tests were conducted for antibiotic resistance, clumping response to pheromone, and production of gelatinase, hemolysin and bacteriocin. Genotype analysis involved polymerase chain reaction amplification of virulence determinants encoding aggregation substances asa and asa373, cytolysin activator cylA, gelatinase gelE, gelatinase-negative phenotype ef1841/fsrC, adherence factors esp and ace, and endocarditis antigen efaA. Physical DNA characterization involved pulsed-field gel electrophoresis of genomic DNA, and plasmid analysis. Results:, Potential virulence traits expressed included production of gelatinase by Enterococcus faecalis (n = 23), and response to pheromones in E. faecalis culture filtrate (n = 16). Fourteen strains produced bacteriocin. Five strains were resistant to tetracycline and one to gentamicin, whereas all were susceptible to ampicillin, benzylpenicillin, chloramphenicol, erythromycin, fusidic acid, kanamycin, rifampin, streptomycin and vancomycin. Polymerase chain reaction products encoding efaA, ace, and asa were detected in all isolates; esp was detected in 20 isolates, cylA in six isolates, but asa373 was never detected. The gelatinase gene (gelE) was detected in all isolates of E. faecalis (n = 31) but not in Enterococcus faecium (n = 2); a 23.9 kb deletion sequence corresponding to the gelatinase-negative phenotype was detected in six of the eight E. faecalis isolates that did not produce gelatinase. Pulsed-field gel electrophoresis and plasmid analyses revealed genetic polymorphism with clonal types evident. Plasmid DNA was detected in 25 strains, with up to four plasmids per strain and a similar (5.1 kb) plasmid occurring in 16 isolates. Conclusions:, Phenotypic and genotypic evidence of potential virulence factors were identified in endodontic Enterococcus spp., specifically production of gelatinase and response to pheromones. [source] Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigreeARTHRITIS & RHEUMATISM, Issue 6 2009Frank T. Saulsbury Pediatric granulomatous arthritis (PGA) has been associated with 12 different substitutions in the NOD2 gene thus far. We report a case of PGA in a 6-year-old girl with the NOD2 E383K gene substitution. Genotype analysis of the patient's family members revealed that her affected paternal aunt, as well as her asymptomatic father and 3 younger siblings, were heterozygous for the E383K substitution. The patient's mother did not have a NOD2 mutation. This is the first report of a pedigree in which 4 asymptomatic members carry the E383K substitution in NOD2, as well as the first observation of an asymptomatic carrier state for any of the NOD2 "Blau mutations." [source] Compound KIR - HLA genotype analyses in the Iranian population by a novel PCR,SSP assayINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010N. Tajik Summary Natural killer (NK) cells eliminate infected and transformed cells while still are self-tolerant. Interactions of the independently segregating Killer cell immunoglobulin-like receptors (KIR) and human leucocyte antigens (HLA) loci play a critical role in NK cell regulation. Different compound KIR-HLA genotypes can impart different thresholds of activation to the NK-cell repertoire and such genotypic variation has been found to confer altered risk in a number of human diseases including viral infections, autoimmune disorders, reproduction abnormalities and cancers. In this study, we presented a novel combined KIR-HLA polymerase chain reaction,sequence-specific primers genotyping assay for simultaneous determination of KIR genes and their three major HLA class I ligand groups (C1, C2, and Bw4). Moreover, known inhibitory and activating KIR + HLA (iKIR + HLA: 2DL2/3 + C1, 2DL1 + C2, 3DL1 + Bw4; and aKIR + HLA: 2DS2 + C1, 2DS1 + C2, 3DS1 + Bw4) combinations as well as co-inheritance of aKIR genes and iKIR + HLA pairs were analysed in a total of 200 unrelated healthy Iranian individuals. All tested subjects had at least one of the three iKIR + HLA pairs and the frequencies of various inhibitory combinations in the study group were: 31.5%, three iKIR + HLA pairs, 53.5%, two iKIR + HLA pairs, and 15%, 0ne iKIR + HLA pair. Furthermore, we revealed that majority of Iranians (69%) carry compound genotypes with greater number of inhibitory pairings than activating combinations (iKIR + HLA > aKIR + HLA). Conversely, iKIR + HLA < aKIR (45%) was dominant genotype in the study group. We conclude that selective evolutionary pressure has propensity to maintain KIR-HLA genotypes with more inhibitory combinations to guarantee self-tolerance. In contrast, existence of activating KIR genes without normal endogenous ligands, potentially arms the NK population for competent immunosurveillance and stronger defense against infections. [source] Implications of closed ecosystem conservation management: the decline of Rothschild's giraffe (Giraffa camelopardalis rothschildi) in Lake Nakuru National Park, KenyaAFRICAN JOURNAL OF ECOLOGY, Issue 4 2009Rick A. Brenneman Abstract Giraffe were historically free-ranging across most of sub-Saharan Africa but are now most often confined to national parks, conservation areas, or private ranches. Five viable populations of Rothschild's giraffe (Giraffa camelopardalis rothschildi) remain in protected areas in Kenya and Uganda. The viable population in Uganda is Murchison Falls National Park and the four populations in Kenya are Lake Nakuru National Park (LNNP), Ruma National Park, Giraffe Manor, and Mwea Natural Reserve. The Kenya Wildlife Service queried a rapid decline in LNNP giraffe numbers falling from 153 individuals (1995) to 62 individuals (2002) and the failure of that population to recruit young in those years. Significantly reduced browse options, inbreeding depression and preferential lion predation were considered as potential reasons for this trend. Population genetic parameter estimates derived from multilocus genotype analyses suggest that the LNNP population was in good genetic health with respect to the likelihood of inbreeding depression. The population decline coincided with the drought attributed to the 1994 El Niño. Possible dietary complications from highly concentrated tannin levels because of forced over consumption of the park's declining acacia trees may have compromised young giraffe, making them easy and opportunistic prey for the park's lion population. Résumé Dans le passé, des girafes évoluaient librement dans une grande partie de l'Afrique sub-saharienne, mais elles sont désormais confinées le plus souvent dans des parcs nationaux, des aires de conservation ou des ranches privés. Cinq populations viables de girafes de Rothschild (Giraffa camelopardalis rothschildi) subsistent dans des aires protégées au Kenya et en Ouganda. La population viable d'Ouganda est celle du Parc National des Murchison Falls, et les quatre populations du Kenya sont celles du Parc National du Lac Nakuru (LNNP), du Parc National de Ruma, du Giraffe Manor et de la Réserve Naturelle de Mwea. Le Kenya Wildlife Service s'est interrogé au sujet du déclin rapide du nombre de girafes au LNNP qui est passé de 153 individus en 1995 à 62 en 2002, et de l'échec de cette population pour recruter des jeunes ces années-là. Des possibilités alimentaires réduites, une dépression due à l'inbreeding, et une prédation préférentielle par les lions ont été envisagées comme raisons de cette tendance. Des estimations des paramètres génétiques de la population dérivées d'analyses de génotypes multilocus suggèrent que la population du LNNP est en bonne santé génétique en ce qui concerne la possibilité de dépression causée par l'inbreeding. Le déclin de la population a coïncidé avec la sécheresse attribuée à El Niño en 1994. Il est possible qu'elle ait souffert de complications alimentaires à cause de taux de tanins très concentrés, parce qu'elle a été forcée de consommer à l'excès les acacias du parc, qui sont en déclin, et que ces complications aient nui aux jeunes girafes et aient fait d'elles des proies faciles pour la population opportuniste des lions du parc. [source] Demographic genetics of the American beech (Fagus grandifolia Ehrh.) III.PLANT SPECIES BIOLOGY, Issue 1 2003Genetic substructuring of coastal plain population in Maryland Abstract Spatiotemporal genetic substructurings were investigated in the American beech population of the east-central coastal plain in Maryland. All trees including seedlings, various sizes of juveniles, and mature trees within the study site (10 × 100 m) were mapped, diameters measured, and leaves collected for allozyme analyses. Eleven polymorphic loci in eight enzyme systems were examined: 6Pgdh2, 6Pgdh3, Acp2, Adh1, Adh2, Fum, Got1, Got3, Lap, Pgi, and Pgm2. A total of 1945 trees were analyzed and 595 multilocus genotypes were detected. Six size-classes and 10 spatial blocks were discriminated for spatiotemporal analyses. Parameters for genetic variations (heterozygosity, Simpson's index, Shannon-Weaver's index, and inbreeding coefficient) decreased in larger size-classes. These genetic parameters fluctuated in spatial blocks of 10 m intervals, in which certain alleles were characteristic of specific blocks. The spatial autocorrelation by Moran's I and coancestry revealed the ranges of genetic relatedness to be only 20,30 m. Multilocus genotype analyses showed that higher genetic variations occur in larger size-classes and at gap openings where seed shadows for mother trees are overlapped. The relationships among reproductive trees, seedlings and juveniles suggested that the seed dispersal range of the American beech is normally in the range of 30,40 m. The mechanisms of a remarkably high genetic polymorphism maintained in this once artificially disturbed and grazed forest are discussed as related to conservation biology. [source] Aiming towards effective preventive medicine against Japanese cedar pollinosis: epidemiology, patient investigation and integrated research including genotype analysesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2 2005N. Terada Summary Environmental rather than genetic factors appear to play the major role in the recent increased prevalence of Japanese cedar pollinosis in Japan. However, investigating the genes that determine IgE levels and analysing gene polymorphisms may assist in finding new methods of treatment and establishing preventive medicine against this disease. Among a total of 219 asymptomatic individuals who were anti-Japanese cedar pollen IgE antibody positive as determined by radioallergosorbent test (RAST), only a handful subsequently developed symptoms of Japanese cedar pollinosis or secondary onset of Japanese cedar pollinosis over 5,14 years of follow-up. Among those who subsequently developed secondary onset of disease, >50% were found to have high initial RAST scores, suggesting that the incidence of Japanese cedar pollinosis is correlated with RAST score. Hence, it may be prudent to advise asymptomatic individuals with high RAST scores to avoid exposure to Japanese cedar pollen so as to delay onset of the disease. Analysis of sequence variants of the Fc,RI, gene revealed that patients with nasal allergy exhibit a single-nucleotide polymorphism in which the amino acid at 237 of the intracellular domain changes from glutamine to glycine more frequently than individuals without nasal allergy. Furthermore, Il homo polymorphism of the IL-4R, gene is associated with higher serum nonspecific IgE and Japanese cedar pollen-specific IgE levels than are seen in individuals showing Il,Val hetero and Val homo expression types. When the age of pollinosis onset was compared among these three genotypes, it was found to be significantly lower among Il homo type than the other two expression types, suggesting that Il homo type individuals seem characteristically pre-disposed to early onset of pollinosis. Studies comparing eosinophil-associated gene polymorphism in healthy and pollinosis phenotypes have revealed several relationships among the various genotypes and specific disease parameters and suggest that Eotaxin G (123G/A) and IL5 (,703C/T) genotypes can affect the timing of symptom onset after sensitization as well as nasal mucosal hyper-responsiveness. [source] Multiple displacement amplification to create a long-lasting source of DNA for genetic studies,HUMAN MUTATION, Issue 7 2006Lovisa Lovmar Abstract In many situations there may not be sufficient DNA collected from patient or population cohorts to meet the requirements of genome-wide analysis of SNPs, genomic copy number polymorphisms, or acquired copy number alternations. When the amount of available DNA for genotype analysis is limited, high performance whole-genome amplification (WGA) represents a new development in genetic analysis. It is especially useful for analysis of DNA extracted from stored histology slides, tissue samples, buccal swabs, or blood stains collected on filter paper. The multiple displacement amplification (MDA) method, which relies on isothermal amplification using the DNA polymerase of the bacteriophage ,29, is a recently developed technique for high performance WGA. This review addresses new trends in the technical performance of MDA and its applications to genetic analyses. The main challenge of WGA methods is to obtain balanced and faithful replication of all chromosomal regions without the loss of or preferential amplification of any genomic loci or allele. In multiple comparisons to other WGA methods, MDA appears to be most reliable for genotyping, with the most favorable call rates, best genomic coverage, and lowest amplification bias. Hum Mutat 27(7), 603,614, 2006. © 2006 Wiley-Liss, Inc. [source] Effects of base excision repair gene polymorphisms on pancreatic cancer survivalINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Donghui Li Abstract To explore the association between single nucleotide polymorphisms of DNA repair genes and overall survival of patients with pancreatic cancer, we conducted a study in 378 cases of pancreatic adenocarcinoma who were treated at The University of Texas M. D. Anderson Cancer Center between February 1999 and October 2004 and were followed up to April 2006. Genotypes were determined using genomic DNA and the MassCode method. Overall survival was analyzed using the Kaplan,Meier plot, log-rank test and Cox regression. We observed a strong effect of the POLB A165G and T2133C genotypes on overall survival. The median survival time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but significant effect on overall survival as demonstrated by either log rank test or multivariate COX regression after adjusting for other potential confounders. In combined genotype analysis, a predominant effect of the POLB homozygous variants on survival was observed. When POLB was not included in the model, a slightly better survival was observed among those carrying none of the adverse genotypes than those carrying at least one of the adverse genotypes. These observations suggest that polymorphisms of base excision repair genes significantly affect the clinical outcome of patients with pancreatic cancer. These observations need to be confirmed in a larger study of homogenous patient population. © 2007 Wiley-Liss, Inc. [source] Association between the TAP2 gene codon 665 polymorphism and Graves' DiseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Rong-Hsing Chen Abstract A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303,10.598 and 1.020,4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449,3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development. J. Clin. Lab. Anal. 20:93,97, 2006. © 2006 Wiley-Liss, Inc. [source] Heritability of platelet function in families with premature coronary artery diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007P. F. BRAY Summary.,Background:,Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.Methods:,Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.Results:,Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36,0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47,0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 ,M epinephrine, but the effect differed by race.Conclusions:,Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. [source] Cosegregation of a Factor VIII Microsatellite Marker with Mild Hemophilia A in Golden Retriever DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2005Marjory B. Brooks Mild hemophilia A (factor VIII deficiency) was diagnosed in Golden Retrievers and pedigree studies were undertaken to test the cosegregation of an intragenic factor VIII marker with the disease phenotype. The study population consisted of 30 client-owned dogs (22 males and 8 females). Hemophilic males (n = 12) typically demonstrated prolonged bleeding after trauma or surgery rather than spontaneous hemorrhagic events. The affected males had a proportionate reduction in factor VIII coagulant activity (mean FVIII:C = 4%) and factor VIII protein concentration (mean FVIII:Ag = 3%). Twenty-five dogs (10 affected males, 8 clear males, 2 obligate carrier dams, and 5 suspect carrier daughters) were genotyped for a factor VIII microsatellite marker, with allele size assigned by an automated capillary electrophoresis system. Five distinct marker alleles were present in the study pedigree and a 300-base pair allele was found to segregate with the hemophilia A phenotype. The inheritance of the hemophilia-associated allele defined carrier status for 5 suspect daughters of obligate carrier dams. The limitations inherent to linkage analyses (ie, lack of access to key family members and homozygosity at the marker locus) did not preclude carrier detection in this pedigree. We conclude that genotype analysis for the intragenic factor VIII marker can aid in control of canine hemophilia A through enhanced carrier detection. [source] Relationship between seed and clonal growth in the reproduction of Carex rugulosa Kük. in riverside meadowsPLANT SPECIES BIOLOGY, Issue 2 2008SATORU ARAKI Abstract Carex rugulosa Kük. develops riverside vegetation in brackish marshes along the lower parts of rivers. Because the rhizomatous ramets grow densely (590,950/m2) in its developed population, it is expected that seedlings cannot get enough light to grow if seeds germinate in crowded ramets. We studied the reproductive contribution of seed in a marshy meadow of the Ohashi River, Japan. The number of seeds produced was 6900,14 200/m2 in 2002. The number of buried seeds in the following germination season differed among sites from 1190 to 2690/m2. No seedlings were observed at plots where the ramets from rhizomes grew densely. In contrast, seedlings appeared in plots where all rhizomatous ramets were artificially cut. The number of seedlings corresponded to 17.5,39.5% of that of buried seeds. All these seedlings were submerged and died when it rained heavily. In the genotype analysis using allozyme detection, one of the phosphoglucoisomerase loci (Pgi-2) indicated a pair of alleles. Among eight plots (each plot was 50 or 60-cm square), four showed an excess of heterozygotes and two showed homozygote domination in the Pgi-2 genotype. These results suggest that: (i) seed germination is suppressed in crowded ramets; (ii) seedling survival is severely reduced by inundation; and (iii) the population is usually maintained by clonal growth. As germination is induced in open areas, it is hypothesized that the main role of seed is recovery after vegetation decline caused by environmental stresses or colonization to other areas without dense vegetation. [source] Matrix metalloproteinase-3 and intracranial arterial dolichoectasiaANNALS OF NEUROLOGY, Issue 4 2010Fernando Pico MD Objective Intracranial arterial dolichoectasia (IADE), also called dilatative arteriopathy of the brain, is defined as an increase in length and diameter of intracranial arteries. Abdominal aortic aneurysm and ectasia of coronary arteries have been reported in association with IADE. In both conditions, a dysfunction of matrix metalloproteinases (MMP)-2, -3, and -9 have been found. Our aim was to investigate these MMP pathways in stroke patients with IADE. Methods Five hundred ten Caucasians patients with brain infarction were consecutively recruited at 12 centers. The diagnosis of IADE was made by consensus between 2 neurologists based on magnetic resonance imaging scans. Determination of MMP-2, -3, and -9 plasma levels was centralized in 1 laboratory. Because we found a threshold effect of MMP-3 plasma levels with the risk of IADE, determination of the MMP-3 5A/6A polymorphism was carried out. Results IADE was identified in 12% of stroke patients. There was no association of IADE with mean MMP-2, -3, and -9 plasma levels. After categorization of MMP plasma levels into tertiles, we found a higher risk of IADE with the lowest MMP-3 tertile (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.17,5.23). In genotype analysis, there was a significant additive effect of the 5A allele on the risk of IADE, with an adjusted OR of 1.62 (95% CI, 1.03,2.55). Interpretation In this cohort of stroke patients of Caucasian ancestry, IADE was associated with low MMP-3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP-3. These results suggest that MMP-3 may play a role in IADE. ANN NEUROL 2010;67:508,515 [source] | |||||||||||||