Home  About us  Contact
 

Alleles

Distribution by Scientific Domains
Life Sciences54%
Medical Sciences41%
5 Other Domains5%
Distribution within Life Sciences
Evolution31%
Human Genetics7%
Genetics5%
Cell & Molecular Biology3%
35 Other Subdomains49%

Kinds of Alleles

  • alternative allele
  • ar allele
  • b allele
  • beneficial allele
  • bola-drb3 allele
  • bp allele
  • c allele
  • class i allele
  • class ii allele
  • common allele
  • complex allele
  • control allele
  • cyp2d6 allele
  • d allele
  • deficiency allele
  • deleterious allele
  • deletion allele
  • different allele
  • disease allele
  • disease susceptibility allele
  • dominant allele
    		•
  • dqb1 allele
  • dr allele
  • drb allele
  • drb1 allele
  • e allele
  • e4 allele
  • fmr1 allele
  • frequent allele
  • g allele
  • genetic allele
  • hla allele
  • hla class i allele
  • hla class ii allele
  • hla-b allele
  • hla-b27 allele
  • hla-drb1 allele
  • i allele
  • ii allele
  • insertion allele
  • knockout allele
  • long allele
    		•
  • loss-of-function allele
  • major allele
  • marker allele
  • maternal allele
  • mhc allele
  • mhc class i allele
  • microsatellite allele
  • minor allele
  • modifier allele
  • multiple allele
  • mutant allele
  • mutated allele
  • new allele
  • normal allele
  • novel allele
  • null allele
  • one allele
  • only one allele
  • other allele
  • parental allele
  • paternal allele
    		•
  • polymorphic allele
  • private allele
  • protective allele
  • qtl allele
  • rare allele
  • recessive allele
  • repeat allele
  • resistance allele
  • risk allele
  • same allele
  • short allele
  • single allele
  • specific allele
  • susceptibility allele
  • unique allele
  • val allele
  • variant allele
  • wild-type allele
  • wildtype allele

    • Terms modified by Alleles

  • allele b
  • allele c
  • allele carrier
  • allele combination
    		•
  • allele distribution
  • allele expression
  • allele frequency
  • allele frequency data
    		•
  • allele frequency difference
  • allele frequency distribution
  • allele number
  • allele sharing
    		•
  • allele size

    • Selected Abstracts

    THE APOLIPOPROTEIN 2 ALLELE IN ALZHEIMER'S DISEASE: SUGGESTIONS FOR A JUDICIOUS USE OF ANTIPLATELET AND ANTICOAGULANT MEDICATIONS

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2009
    Santosh B. Murthy MD
    No abstract is available for this article. [source]

    LIKELIHOOD-BASED INFERENCE IN ISOLATION-BY-DISTANCE MODELS USING THE SPATIAL DISTRIBUTION OF LOW-FREQUENCY ALLELES

    EVOLUTION, Issue 11 2009
    John Novembre
    Estimating dispersal distances from population genetic data provides an important alternative to logistically taxing methods for directly observing dispersal. Although methods for estimating dispersal rates between a modest number of discrete demes are well developed, methods of inference applicable to "isolation-by-distance" models are much less established. Here, we present a method for estimating ,,2, the product of population density (,) and the variance of the dispersal displacement distribution (,2). The method is based on the assumption that low-frequency alleles are identical by descent. Hence, the extent of geographic clustering of such alleles, relative to their frequency in the population, provides information about ,,2. We show that a novel likelihood-based method can infer this composite parameter with a modest bias in a lattice model of isolation-by-distance. For calculating the likelihood, we use an importance sampling approach to average over the unobserved intraallelic genealogies, where the intraallelic genealogies are modeled as a pure birth process. The approach also leads to a likelihood-ratio test of isotropy of dispersal, that is, whether dispersal distances on two axes are different. We test the performance of our methods using simulations of new mutations in a lattice model and illustrate its use with a dataset from Arabidopsis thaliana. [source]

    MATING DENSITY AND THE STRENGTH OF SEXUAL SELECTION AGAINST DELETERIOUS ALLELES IN DROSOPHILA MELANOGASTER

    EVOLUTION, Issue 4 2008
    Nathaniel P. Sharp
    Deleterious alleles constantly enter populations via mutation. Their presence reduces mean fitness and may threaten population persistence. It has been suggested that sexual selection may be an efficient way by which deleterious alleles are removed from populations but there is little direct experimental evidence. Because of its potential role in mutational meltdowns, there is particular interest in whether the strength of sexual selection changes with density. For each of eight visible markers in Drosophila melanogaster we have compared the strength of sexual selection at two densities. We find evidence of strong sexual selection against most but not all of these alleles. There is no evidence that sexual selection tends to be stronger (or weaker) at high density relative to low density. In addition, we also measure the effects of these mutations on two key parameters relevant to population productivity,juvenile viability and female fecundity. In most cases, sexual selection is as strong or stronger than these other forms of selection. [source]

    THE DIFFUSIVE SPREAD OF ALLELES IN HETEROGENEOUS POPULATIONS

    EVOLUTION, Issue 3 2004
    Garrick T. Skalski
    Abstract The spread of genes and individuals through space in populations is relevant in many biological contexts. I study, via systems of reaction-diffusion equations, the spatial spread of advantageous alleles through structured populations. The results show that the temporally asymptotic rate of spread of an advantageous allele, a kind of invasion speed, can be approximated for a class of linear partial differential equations via a relatively simple formula, c= 2,rD, that is reminiscent of a classic formula attributed to R. A. Fisher. The parameters r and D, represent an asymptotic growth rate and an average diffusion rate, respectively, and can be interpreted in terms of eigenvalues and eigenvectors that depend on the population's demographic structure. The results can be applied, under certain conditions, to a wide class of nonlinear partial differential equations that are relevant to a variety of ecological and evolutionary scenarios in population biology. I illustrate the approach for computing invasion speed with three examples that allow for heterogeneous dispersal rates among different classes of individuals within model populations. [source]

    FIXATION OF NEW ALLELES AND THE EXTINCTION OF SMALL POPULATIONS: DRIFT LOAD, BENEFICIAL ALLELES, AND SEXUAL SELECTION

    EVOLUTION, Issue 6 2000
    Michael C. Whitlock
    Abstract With a small effective population size, random genetic drift is more important than selection in determining the fate of new alleles. Small populations therefore accumulate deleterious mutations. Left unchecked, the effect of these fixed alleles is to reduce the reproductive capacity of a species, eventually to the point of extinction. New beneficial mutations, if fixed by selection, can restore some of this lost fitness. This paper derives the overall change in fitness due to fixation of new deleterious and beneficial alleles, as a function of the distribution of effects of new mutations and the effective population size. There is a critical effective size below which a population will on average decline in fitness, but above which beneficial mutations allow the population to persist. With reasonable estimates of the relevant parameters, this critical effective size is likely to be a few hundred. Furthermore, sexual selection can act to reduce the fixation probability of deleterious new mutations and increase the probability of fixing new beneficial mutations. Sexual selection can therefore reduce the risk of extinction of small populations. [source]

    A common variant in MTHFD1L is associated with neural tube defects and mRNA splicing efficiency,

    HUMAN MUTATION, Issue 12 2009
    Anne Parle-McDermott
    Abstract Polymorphisms in folate-related genes have emerged as important risk factors in a range of diseases including neural tube defects (NTDs), cancer, and coronary artery disease (CAD). Having previously identified a polymorphism within the cytoplasmic folate enzyme, MTHFD1, as a maternal risk factor for NTDs, we considered the more recently identified mitochondrial paralogue, MTHFD1L, as a candidate gene for NTD association. We identified a common deletion/insertion polymorphism, rs3832406, c.781-6823ATT(7,9), which influences splicing efficiency and is strongly associated with NTD risk. Three alleles of rs3832406 were detected in the Irish population with varying numbers of ATT repeats: Allele 1 consists of ATT7, whereas Alleles 2 and 3 consist of ATT8 and ATT9, respectively. Allele 2 of this triallelic polymorphism showed a decreased case risk as demonstrated by case,control logistic regression (P=0.002) and by transmission disequilibrium test (TDT) (P=0.001), whereas Allele 1 showed an increased case risk. Allele 3 showed no influence on NTD risk and represents the lowest frequency allele (0.15). Additional single nucleotide polymorphism (SNP) genotyping in the same genomic region provides additional supportive evidence of an association. We demonstrate that two of the three alleles of rs3832406 are functionally different and influence the splicing efficiency of the alternate MTHFD1L mRNA transcripts. Hum Mutat 30:1,7, 2009. © 2009 Wiley-Liss, Inc. [source]

    Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population

    INFLAMMATORY BOWEL DISEASES, Issue 12 2005
    T Takagawa MD
    Abstract Background: Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-, and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis. Methods: Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at ,607C/A and ,137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. Results: In UC, the ,137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The ,137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (,607A, ,137C), which had a lower promoter activity and IFN-, mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. Conclusions: IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC. [source]

    Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2003
    Cheng-Chan Lu
    Abstract NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (,40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2+B46+ individuals are at greater risk for NPC than A2,B46, individuals in both the population studied and the ,40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2+B38+ individuals were at higher risk than A2,B38, individuals in both the population studied and the ,40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus. © 2002 Wiley-Liss, Inc. [source]

    Molecular analysis of HumDN1 VNTR polymorphism of the human deoxyribonuclease I in systemic lupus erythematosus

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2010
    Suad AlFadhli
    Summary Deoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of systemic lupus erythematosus (SLE). The purpose of this study was to screen DNASE1 gene for mutations that may have an effect on susceptibility to develop SLE. DNA was extracted from 76 Kuwaiti SLE patients and 92 race-matched controls. PCR-direct sequencing was used to screen DNASE1 promoter, coding sequence and exon,intron boundaries for mutation. Association of genomic variations was assessed using a Chi-square test. Molecular analysis of the DNASE1 gene did not reveal any mutation. However, a 56-bp repeat was detected in intron4 which was previously reported and named HumDN1. The allelic and genotypic distributions of the HumDN1 VNTR were compared between SLE patients and healthy subjects. Alleles were denoted as 2, 3, 4, 5 and 6 corresponding to the number of repeats of the 56 bp unit. Alleles 4, 5, and 6 showed significant association with SLE. Allele 5 showed the highest association [,2 = 32.57; P , 0.001; OR = 4.16; 95% CI: (2.55,6.79)]. Association of allele 5 was also found at the genotypic level, where genotype 5/5 is more prevalent in SLE subjects as compared with controls (17% versus 9%). We report a significant association of HumDN1 VNTR polymorphism in DNASE1 gene with SLE. Further functional assays needed to assess the effect of this VNTR on DNASE1 activity and its association with SLE. [source]

    A search for cyclophilin-A gene (PPIA) variation and its contribution to the risk of atherosclerosis and myocardial infarction

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2008
    M. Palacín
    Summary Cyclophilin A is secreted by vascular smooth muscle cells in response to inflammatory stimuli, and could thus contribute to atherosclerosis. We hypothesized that the genetic variation at the cyclophilin A gene (PPIA) could affect the risk for developing atherosclerosis and myocardial infarction. This study included 250 myocardial infarction patients (all male and < 60 years; 95% are smokers). All these cases had at least one atherosclerotic diseased coronary vessel. DNA was obtained from patients and from 250 healthy controls. The variation at the PPIA gene was determined in the patients through single-strand conformation analysis and direct sequencing of seven polymerase chain reaction fragments. Allele and genotype frequencies were compared between patients and controls. The effect of a promoter polymorphism (,11 G/C) on gene expression was in vitro analysed with luciferase-reporter assays. We found two common polymorphisms in the PPIA promoter (,11 G/C) and the 5, non-translated (+36 G/A) regions. Cells transfected with luciferase-plasmids containing the ,11 G had significantly higher luciferase activity. Genotype frequencies for these polymorphisms did not differ between patients and controls. In conclusion, we reported a functional variant in the PPIA promoter. However, the PPIA variation did not significantly contribute to the risk of suffering from myocardial infarction among patients with atherosclerotic diseased vessels. [source]

    Promoter polymorphism of IL-18 gene in pulmonary tuberculosis in South Indian population

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2007
    M. Harishankar
    Summary Interleukin-18 (IL-18) plays a vital role in both innate and acquired immunity. We analysed polymorphisms at ,607(C/A) and ,137(G/A) in the promoter region of IL-18 gene by allele-specific polymerase chain reaction in normal healthy subjects (n = 173) and patients with pulmonary tuberculosis (n = 165). Allele, genotype and haplotype frequencies did not differ significantly between normal healthy subjects and patients. The results suggest that the IL-18 gene promoter polymorphisms are not associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population of Dravidian descent. [source]

    Genotyping for cytokine polymorphisms: allele frequencies in the Italian population

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2003
    M. Uboldi de Capei
    Summary It has been demonstrated that many cytokine genes [e.g. tumour necrosis factor , (TNF-,) and interleukin 10 (IL-10)] show polymorphisms which may affect gene transcription, causing individual variations in cytokine production. The majority of polymorphisms described are single nucleotide polymorphisms (SNPs). In 140 healthy Italian subjects, the allelic and genotype frequencies were determined for the cytokine genes IL-1, (T/C ,889), IL-1, (C/T ,511, T/C +3962), IL-12 (C/A ,1188), interferon (IFN)-, (A/T UTR 5644), transforming growth factor (TGF)-, (C/T codon 10, G/C codon 25), TNF-, (G/A ,308, G/A ,238), IL-2 (T/G ,330, G/T +166), IL-4 (T/G ,1098, T/C ,590, T/C ,33), IL-6 (G/C ,174, G/A nt565), IL-10 (G/A ,1082, C/T ,819, C/A ,592), IL-1R (C/T pst11970), IL-1RA (T/C mspa111100) and IL-4RA (G/A +1902). All typings were performed with PCR-SSP assays. Allele and genotype frequencies and linkage disequilibria were calculated and compared with those of other populations. [source]

    Low Dietary Riboflavin but Not Folate Predicts Increased Fracture Risk in Postmenopausal Women Homozygous for the MTHFR 677 T Allele,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2008
    Nahid Yazdanpanah
    Abstract The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ,55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4646 individuals (2692women). Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677- T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 ,M, p = 0. 01; trend, p = 0.02). Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. [source]

    A New Allele of the Short Tandem Repeat Locus D21S11 in a Venezuelan Population,

    JOURNAL OF FORENSIC SCIENCES, Issue 3 2006
    Noelia Lander B.S.
    POPULATION: Venezuelan, Caracas City, 255 individuals. [source]

    Risk factors of hepatitis C virus-related liver cirrhosis in young adults: Positive family history of liver disease and transporter associated with antigen processing 2 (TAP2) *0201 Allele

    JOURNAL OF MEDICAL VIROLOGY, Issue 2 2001
    Norio Akuta
    Abstract The aim of this study was to clinically characterize young patients with hepatitis-C-related cirrhosis. We compared 27 patients with liver cirrhosis (Group LC) who were anti-HCV positive, aged 40 years or less at the time of diagnosis, with 323 consecutive patients with HCV-related chronic hepatitis (Group CH) matched for age and gender. Furthermore, Group LC was divided into two arbitrary groups (29,35 years, n,=,8 /36,40 years, n,=,19), based on the age of patients at the time of diagnosis of liver cirrhosis. Patients' characteristics and family history were investigated, and the frequency of transporter associated with antigen processing 2 (TAP2) was determined. A family history of liver disease was present in 40.7% of Group LC but in 18.0% of Group CH (P,<,0.05). The younger the age of diagnosis of cirrhosis in Group LC, the higher the frequency of a positive family history (29,35 years, 87.5%; 36,40 years, 21.1%, P,<,0.05). The frequency of TAP2*0201 was significantly higher in young adult patients with HCV-related liver cirrhosis than in HCV carriers with normal ALT (P,<,0.05), and tended to be higher than in uninfected normal subjects (P,=,0.05). The cumulative survival rate of cirrhosis patients with family history of liver diseases was significantly lower than that of cirrhosis patients without such history (P,<,0.05). Our findings suggest that a positive family history of liver disease and TAP2*0201 polymorphism may be risk factors for HCV-related liver cirrhosis in young adults. J. Med. Virol. 64:109,116, 2001. © 2001 Wiley-Liss, Inc. [source]

    Naltrexone Selectively Elevates GABAergic Neuroactive Steroid Levels in Heavy Drinkers With the ASP40 Allele of the OPRM1 Gene: A Pilot Investigation

    ALCOHOLISM, Issue 8 2010
    Lara A. Ray
    Background:, Preclinical studies have implicated GABAergic neurosteroids in behavioral responses to alcohol. Naltrexone is thought to blunt the reinforcing effects of alcohol, and a few studies have found that the effects of naltrexone are moderated by the Asn40Asp polymorphisms of the OPRM1 gene. The present study seeks to integrate these lines of research by testing (i) the moderating role of the functional Asn40Asp polymorphism of the OPRM1 gene on naltrexone-induced alternations in GABAergic neurosteroid levels, namely (3,,5,)-3-hydroxypregnan-20-one (allopregnanolone, ALLO); and (ii) the combined effects of naltrexone or genotype with alcohol administration on neurosteroid levels in a sample of at-risk drinkers. Methods:, Participants were 32 (9 females) nontreatment-seeking heavy drinkers who completed a placebo-controlled laboratory study of naltrexone (50 mg/d for 3 days) and provided complete sets of serum samples for ALLO assays before and after alcohol administration under both naltrexone and placebo conditions. Results:, Naltrexone treatment raised ALLO levels among carriers of the Asp40 allele, but not homozygotes for the Asn40 allele. The Asn40Asp polymorphism did not moderate effects of naltrexone on cortisol levels. Ethanol infusion modestly reduced ALLO levels in all subjects, independent of genotype or naltrexone exposure. Conclusions:, Naltrexone increased ALLO levels among individuals with the Asn40Asp allele suggesting a potential neurosteroid contribution to the neuropharmacological effects of naltrexone among Asp40 carriers. [source]

    Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1*c2 Allele

    ALCOHOLISM, Issue 1 2010
    Elizabeth Gordillo-Bastidas
    Background:, Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out. Methods:, One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction,restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used. Results:, Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2, 51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype. Conclusions:, Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI. [source]

    Association of the ,2 Allele of Apoe Gene to Hypertriglyceridemia and to Early-Onset Alcoholic Cirrhosis

    ALCOHOLISM, Issue 4 2008
    Zamira H. Hernández-Nazará
    Background:, The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis. Methods:, In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non-hyperlipidemic (non-H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR-RFLP,s. Results:, A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein-cholesterol (HDL-c) was detected in young-aged patients (31.2 ± 6.2 years old vs. 46.3 ± 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non-H group. Conclusions:, This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process. [source]

    A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis

    ALLERGY, Issue 9 2009
    M. Benson
    Background:, Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective:, To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods:, CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results:, Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. Conclusion:, Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR. [source]

    Linkage analysis of schizophrenia to chromosome 15

    AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001
    Dr. Pablo V. Gejman
    Abstract We have mapped a sample of 68 families consisting of one or more affected sibling pairs with schizophrenia or schizoaffective disorder with 20 markers spanning all of chromosome 15 to investigate whether there is a locus on chromosome 15 that confers an increased susceptibility to schizophrenia using parametric and nonparametric linkage analyses. Allele sharing identical by descent and multipoint maximum likelihood score (MLS) statistics were employed. Results show excess allele sharing for multiple markers in 15q11.2,q25, a chromosomal region previously found linked to a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, a decrease associated with schizophrenia. Excess allele sharing was found for markers spanning about 48 cM in 15q11.2,q25 (D15S1002,D15S1023). The greatest single point allele sharing was found at D15S659 (62.6%). The multipoint MLS scores were greater than 1.0 in the 30,52 cM interval delimited by ACTC and D15S150, with a maximum value of 2.0 with GENEHUNTER PLUS near D15S1039. © 2001 Wiley-Liss, Inc. [source]

    LETTER TO THE EDITOR: Apolipoprotein E4 Allele and Recurrent Pregnancy Loss: Larger Samples Are Still Needed

    AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
    Hong-liang Zhang
    No abstract is available for this article. [source]

    Effects of GH gene polymorphism and sex on carcass traits and fatty acid compositions in Japanese Black cattle

    ANIMAL SCIENCE JOURNAL, Issue 1 2009
    Astrid ARDIYANTI
    ABSTRACT To investigate the effects of bovine growth hormone (bGH) gene polymorphism on carcass traits and fatty acid compositions in Japanese Black cattle caused by nucleotide substitution of CTG (allele A)/GTG (allele B) at codon 127 and of ACG (allele A and B)/ATG (allele C) at codon 172 of bGH, GH genotypes of 135 cattle were determined using allele specific-multiplex polymerase chain reaction (PCR). Allele A gave greater rib thickness and lower melting point of fat (MP) while allele B gave higher C18:1% (P < 0.05). Allele C gave higher C18:1, monounsaturated fatty acid (MUFA), unsaturated fatty acid (USFA) percentages (P < 0.05). It also gave lower saturated fatty acid (SFA) percentages, higher MUFA/SFA and USFA/SFA ratios, and lower MP (P < 0.05). Interactions of sex and GH alleles were analyzed. In heifers, allele A gave higher carcass weight, daily carcass gain, rib eye area, rib thickness, subcutaneous fat thickness, and BMS while allele B gave greater rib eye area and rib thickness (P < 0.05). Allele C gave higher C18:1 (P < 0.01), MUFA (P < 0.01), USFA percentages (P < 0.05) and MUFA/SFA and USFA/SFA ratios (P < 0.01), and lower C16:0 and SFA percentages (P < 0.05) and MP (P < 0.01). GH gene polymorphism affected carcass traits and fatty acid compositions although the effects were more pronounced in heifers. [source]

    Confirmation of an association between rs6822844 at the Il2,Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus

    ARTHRITIS & RHEUMATISM, Issue 2 2010
    Amit K. Maiti
    Objective Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2,IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies. Methods We evaluated case,control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies. Results We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (FST = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (Pmeta = 3.61 × 10,6), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (Pmeta = 3.48 × 10,12), type 1 DM (Pmeta = 5.33 × 10,5), and CD (Pmeta = 5.30 × 10,3). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; Pmeta = 2.61 × 10,25, odds ratio 0.73 [95% confidence interval 0.69,0.78]). Conclusion Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations. [source]

    Mutation screening of the macrophage migration inhibitory factor gene: Positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis

    ARTHRITIS & RHEUMATISM, Issue 9 2002
    Rachelle Donn
    Objective To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). Methods Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5,-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. Results A tetranucleotide repeat CATT(5,7) beginning at nucleotide position ,794 and 3 SNPs at positions ,173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4,2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type,specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). Conclusion The ,173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type,specific regulation of MIF, which may be central to understanding its role in inflammation. [source]

    Association of interferon-, +874A polymorphism with the risk of developing cervical cancer in north-Indian population

    BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2009
    R Gangwar
    Objective, Interferon gamma (IFN -,) is a pro-inflammatory cytokine playing a pivotal role in both innate and adaptive immune responses. A single nucleotide polymorphism located in the first intron of the human IFN-, gene can influence the secretion of cytokine. Therefore, we aimed to investigate the association of IFN-, T/A gene polymorphism with the risk of cervical cancer. Design, Case,control study. Setting, Uttar Pradesh State in India. Sample, Two hundred cases with histologically proven cancer of the cervix and healthy controls (n = 230), age and ethnicity matched were recruited in this study. Methods, Genotyping was performed for bi-allelic +874 (T/A) polymorphism of IFN-, by amplification refractory mutation system method. Main outcome measures, Low producer IFN-, +874 AA genotype was associated with high risk for cervical cancer, which further modulated the increased risk in tobacco users. Results,IFN-, AA genotype which is low producer of IFN-, was associated with increased risk of cervical cancer (OR = 2.43, P = 0.003). Allele A was at 1.54-fold increased risk of cervical cancer (OR=1.54, P = 0.002). The AA genotype showed statistically significant risk with high stage (III + IV) of cervical cancer (OR = 4.99, P = 0.001). In tobacco users, AA genotype showed significantly increased susceptibility to cervical cancer (OR = 5.08, P = 0.010). Conclusion, Variation in IFN-, +874 AA genotype because of ethnicity in north-Indian population may represent an important susceptibility biomarker for cervical cancer risk as well as other diseases and should be explored further. [source]

    Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ,786T>C gene polymorphisms and the risk of ischemic stroke

    ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010
    S. Saidi
    Saidi S, Mallat SG, Almawi WY, Mahjoub T. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ,786T>C gene polymorphisms and the risk of ischemic stroke Acta Neurol Scand: 2010: 121: 114,119. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose,,, Endothelial nitric oxide synthase (eNOS) gene polymorphisms were associated with reduced NO production, and were evaluated as risk factors for ischemic stroke (IS). We investigated the association between eNOS gene ,786T>C (promoter), 27-bp repeat 4b/4a (intron 4), and Glu298Asp (exon 7) polymorphisms with IS in 329 IS patients and 444 controls. Materials and methods,,, Glu298Asp and ,786T>C genotyping was done by PCR-RFLP, 4b/4a was assessed by PCR,ASA. The contribution of eNOS polymorphisms to IS was analyzed by haplotype and multivariate regression analysis. Results,,, Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 × 10,10), which remained independently associated with IS on multivariate analysis after controlling for traditional cerebrovascular risk factors. Allele and genotype distribution of 4b/4a and ,786T>C polymorphisms were comparable between patient and controls. Significantly higher prevalence of 298Asp/4b/,786T and 298Asp/4b/,786C haplotypes were seen in IS cases, thus conferring a disease susceptibility nature to these haplotypes. Multivariate regression analysis confirmed the association of 298Asp/4b/,786T and 298Asp/4b/,786C haplotypes, and in addition identified 298Asp/4a/,786T haplotype to be independently associated with IS, after controlling for traditional cerebrovascular risk factors. Conclusions,,, Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS. [source]

    Dopamine transporter gene (DAT1) VNTR polymorphism in major psychiatric disorders: family-based association study in the Bulgarian population

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002
    L. Georgieva
    Objective:,A 40-bp variable number tandem repeat in the 3,-UTR of dopamine transporter gene (DAT1) has been examined for association with major psychiatric disorders in several case,control studies. No significant results have been found. We used a new collection of parent,offspring trios to test for association with schizophrenia (SZ), bipolar 1 disorder (BPI) and schizoaffective (SA) disorder. Method:,We genotyped trios from Bulgarian origin where the proband had SZ (178 trios), BPI (77 trios) and SA (29 trios). Alleles ranging from 5 to 11 repeats were observed. The results were analysed with the extended TDT (ETDT). Results:,No preferential transmission of alleles was observed for any diagnostic group. The presence of allele DAT*10 was associated with the severity and frequency of auditory hallucinations, however, this result is not significant if corrected for multiple testing. Conclusion:,Our results are in agreement with previous reports of a lack of association between this polymorphism and major psychiatric disorders. [source]

    Common CX3CR1 Alleles Are Associated With a Reduced Risk of Headaches

    HEADACHE, Issue 7 2008
    Christophe Combadičre PhD
    Objectives., The aim of this study was to investigate the role of the chemokine receptor CX3CR1 in headaches and migraine. Methods., Distribution of 2 polymorphisms of the chemokine receptor CX3CR1 (V249I and T280M) was determined in a population-based sample of 1179 elderly individuals. Results., Heterozygotes for both CX3CR1 polymorphisms had a reduced risk of recurrent headaches, with an odds ratio (OR) of 0.64 (95% confidence interval [CI] = 0.46-0.90) for the I249 allele and 0.55 (95% CI = 0.38-0.81) for the M280 allele. Haplotype analysis showed that carriers of the rarer CX3CR1 I249-M280 haplotype had a reduced risk of recurrent headaches, with an OR of 0.57 (95% CI = 0.41-0.80, P = .001). This association was seen for both nonmigraine headaches (OR = 0.47, 95% CI = 0.28-0.79, P = .004) and migraine (OR = 0.65, 95% CI = 0.43-0.98, P = .041). Conclusions., These results need to be replicated but suggest that the chemokine receptor CX3CR1 may play a role in recurrent headaches. [source]

    A common variant in MTHFD1L is associated with neural tube defects and mRNA splicing efficiency,

    HUMAN MUTATION, Issue 12 2009
    Anne Parle-McDermott
    Abstract Polymorphisms in folate-related genes have emerged as important risk factors in a range of diseases including neural tube defects (NTDs), cancer, and coronary artery disease (CAD). Having previously identified a polymorphism within the cytoplasmic folate enzyme, MTHFD1, as a maternal risk factor for NTDs, we considered the more recently identified mitochondrial paralogue, MTHFD1L, as a candidate gene for NTD association. We identified a common deletion/insertion polymorphism, rs3832406, c.781-6823ATT(7,9), which influences splicing efficiency and is strongly associated with NTD risk. Three alleles of rs3832406 were detected in the Irish population with varying numbers of ATT repeats: Allele 1 consists of ATT7, whereas Alleles 2 and 3 consist of ATT8 and ATT9, respectively. Allele 2 of this triallelic polymorphism showed a decreased case risk as demonstrated by case,control logistic regression (P=0.002) and by transmission disequilibrium test (TDT) (P=0.001), whereas Allele 1 showed an increased case risk. Allele 3 showed no influence on NTD risk and represents the lowest frequency allele (0.15). Additional single nucleotide polymorphism (SNP) genotyping in the same genomic region provides additional supportive evidence of an association. We demonstrate that two of the three alleles of rs3832406 are functionally different and influence the splicing efficiency of the alternate MTHFD1L mRNA transcripts. Hum Mutat 30:1,7, 2009. © 2009 Wiley-Liss, Inc. [source]

    A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor ,-chain promoter

    IMMUNOLOGY, Issue 1 2006
    Ulrich J. H. Sachs
    Summary The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn-dependent transport across the placenta may influence antibody-mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1,VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7·5 and 92·0%, respectively). Real-time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1·66-fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0·003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG-binding capacities. [source]