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Sample records for harbors genetic polymorphisms

  1. Genetics Home Reference: Floating-Harbor syndrome

    MedlinePlus

    ... Arpin S, Afenjar A, Dubern B, Toutain A, Cabrol S, Héron D. Floating-Harbor Syndrome: report on a case ... G, Whiteford ML, Quaio CR, Gomy I, Bertola DR, Albrecht B, Platzer K, McGillivray G, Zou R, ...

  2. Pharmacogenetics and human genetic polymorphisms.

    PubMed

    Daly, Ann K

    2010-08-01

    The term pharmacogenetics was first used in the late 1950s and can be defined as the study of genetic factors affecting drug response. Prior to formal use of this term, there was already clinical data available in relation to variable patient responses to the drugs isoniazid, primaquine and succinylcholine. The subject area developed rapidly, particularly with regard to genetic factors affecting drug disposition. There is now comprehensive understanding of the molecular basis for variable drug metabolism by the cytochromes P450 and also for variable glucuronidation, acetylation and methylation of certain drugs. Some of this knowledge has already been translated to the clinic. The molecular basis of variation in drug targets, such as receptors and enzymes, is generally less well understood, although there is consistent evidence that polymorphisms in the genes encoding the beta-adrenergic receptors and the enzyme vitamin K epoxide reductase is of clinical importance. The genetic basis of rare idiosyncratic adverse drug reactions had also been examined. Susceptibility to reactions affecting skin and liver appears to be determined in part by the HLA (human leucocyte antigen) genotype, whereas reactions affecting the heart and muscle may be determined by polymorphisms in genes encoding ion channels and transporters respectively. Genome-wide association studies are increasingly being used to study drug response and susceptibility to adverse drug reactions, resulting in identification of some novel pharmacogenetic associations. PMID:20626352

  3. Genetic polymorphisms and idiopathic generalized epilepsies.

    PubMed

    Lucarini, Nazzareno; Verrotti, Alberto; Napolioni, Valerio; Bosco, Guido; Curatolo, Paolo

    2007-09-01

    In recent years, progress in understanding the genetic basis of idiopathic generalized epilepsies has proven challenging because of their complex inheritance patterns and genetic heterogeneity. Genetic polymorphisms offer a convenient avenue for a better understanding of the genetic basis of idiopathic generalized epilepsy by providing evidence for the involvement of a given gene in these disorders, and by clarifying its pathogenetic mechanisms. Many of these genes encode for some important central nervous system ion channels (KCNJ10, KCNJ3, KCNQ2/KCNQ3, CLCN2, GABRG2, GABRA1, SCN1B, and SCN1A), while many others encode for ubiquitary enzymes that play crucial roles in various metabolic pathways (HP, ACP1, ME2, LGI4, OPRM1, GRIK1, BRD2, EFHC1, and EFHC2). We review the main genetic polymorphisms reported in idiopathic generalized epilepsy, and discusses their possible functional significance in the pathogenesis of seizures. PMID:17765802

  4. 59. Cold Spring Harbor symposium on quantitative biology: Molecular genetics of cancer

    SciTech Connect

    1994-12-31

    Investigation of the mechanistic aspects of cancer has its roots in the studies on tumor viruses and their effects on cell proliferation, function, and growth. This outstanding progress was well documented in previous Cold Spring Harbor Symposia on Quantitative Biology. In the early to mid 1980s, progress on the development of chromosome mapping strategies and the accumulation of DNA probes that identified polymorphisms, encouraged by the international Human Genome Project, enabled the identification of other genes that contributed to familial inheritance of high susceptibility to specific cancers. This approach was very successful and led to a degree of optimism that one aspect of cancer, the multistep genetic process from early neoplasia to metastatic tumors, was beginning to be understood. It therefore seemed appropriate that the 59th Symposium on Quantitative Biology focus attention on the Molecular Genetics of Cancer. The concept was to combine the exciting progress on the identification of new genetic alterations in human tumor cells with studies on the function of the cancer gene products and how they go awry in tumor cells.

  5. Single nucleotide polymorphism in wheat chromosome region harboring Fhb1 for Fusarium head blight resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB) is a destructive disease that reduces wheat grain yield and quality. To date, the quantitative trait locus on 3BS (Fhb1) from Sumai 3 has shown the largest effect on FHB resistance. Single nucleotide polymorphism (SNP) is the most common form of genetic variation and suita...

  6. Genetic polymorphisms linked to susceptibility to malaria

    PubMed Central

    2011-01-01

    The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature. Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria. PMID:21929748

  7. Genetic polymorphisms associated with exertional rhabdomyolysis.

    PubMed

    Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval

    2013-08-01

    Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093

  8. Genetic polymorphisms and esophageal cancer risk.

    PubMed

    Hiyama, Toru; Yoshihara, Masaharu; Tanaka, Shinji; Chayama, Kazuaki

    2007-10-15

    The aim of this paper is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of esophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, in humans. All relevant studies available in MEDLINE and published before February 2007 were identified. Studies carried out in humans and that compared esophageal cancer patients with at least 1 standard control group were considered for analysis. One-hundred studies and 3 meta-analyses were identified. Eighty (80%) studies were conducted in Asian countries, particularly China including Taiwan (60 (60%) studies). The most intensively examined genes were those encoding carcinogen metabolic enzymes. The most widely studied gene was GSTM1 (15 studies), followed by ALDH2 (11 studies). ALDH2, MTHFR C677T, CYP1A1 Ile/Val, CYP1A1MspI, CYP2E1, GSTP1, GSTM1 and GSTT1 were examined by meta-analyses and significant relations were found between ALDH2*1*2 and the CYP1A1 Val allele and increased risk of esophageal cancer. In addition, increased risk of esophageal SCC was consistently associated with the ADH2*1*2 and the p53 codon 72 Pro/Pro genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in esophageal carcinogenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions. PMID:17674367

  9. Genetics Home Reference: catecholaminergic polymorphic ventricular tachycardia

    MedlinePlus

    ... for This Page Cerrone M, Napolitano C, Priori SG. Catecholaminergic polymorphic ventricular tachycardia: A paradigm to understand ... on PubMed Central Liu N, Ruan Y, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Prog Cardiovasc Dis. 2008 ...

  10. Impact of Candidate Genetic Polymorphisms in Prostate Cancer: An Overview.

    PubMed

    Salvi, S; Conteduca, V; Gurioli, G; Calistri, D; Casadio, V; De Giorgi, U

    2016-02-01

    In the last few years, the presence of single nucleotide polymorphisms (SNPs) has been investigated in many tumors as predictor of disease aggressiveness and clinical outcome. We searched for relevant articles from 1998 to 2015 about the impact of SNPs in prostate cancer. Particularly, in this article, we review the pathogenetic, prognostic and predictive significance of gene polymorphisms in prostate tumor, providing a brief overview of studies in which the possible role of genetic variants was investigated in clinical settings. Because conflicting results often emerge about the impact of gene polymorphisms in prostate cancer, further larger studies are warranted in order to introduce gene polymorphism into clinical practice as biomarkers. PMID:26518421

  11. Genetic Polymorphisms Influence Cognition in Patients Undergoing Carotid Interventions.

    PubMed

    Hitchner, Elizabeth; Morrison, Doug; Liao, Phoebe; Rosen, Allyson; Zhou, Wei

    2016-09-01

    While carotid interventions help decrease the risk of stroke, nearly 40% of patients experience cognitive deterioration. Genetic polymorphism in apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been implicated in cognitive impairment; however, it is unclear whether they may influence cognitive changes in patients undergoing carotid intervention. In this study, we seek to assess the role of genetic polymorphisms in carotid intervention-related cognitive change. Polymorphisms related to cognitive function were chosen for this preliminary analysis. Over 2 years, patients undergoing carotid interventions were prospectively recruited. Patients underwent neuropsychological testing 2 weeks prior to and at 1 month following their procedure. Saliva samples were collected for genetic analysis. Logistic regressions were used to identify associations between polymorphisms and cognitive measures. A total of 91 patients were included; all were male with an average age of 70 years. The majority of patients exhibited hypertension (95%) and a history of smoking (81%). Presence of ApoE 4 allele was associated with depression (p= 0.047). After correcting for age and genetic polymorphisms in BDNF and serotonin transporter (5-HTT), ApoE 4 allele was associated with depression (p= 0.044) and showed a trend with baseline cognitive impairment (p= 0.10). Age ≥ 70 years was associated with baseline cognitive impairment after adjusting for the three genetic polymorphisms (p= 0.03). Patients with ApoE 4 and BDNF A polymorphisms performed less well on the visual and verbal memory measures, respectively. Polymorphisms in ApoE and BDNF may provide insight on cognition in patients undergoing carotid interventions; however, the mechanism of this relationship remains unclear. PMID:27574384

  12. Turner syndrome and genetic polymorphism: a systematic review

    PubMed Central

    de Marqui, Alessandra Bernadete Trovó

    2015-01-01

    Objective: To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. Data sources: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. Data synthesis: The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Conclusions: Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome. PMID:25765448

  13. The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

    PubMed Central

    Han, Summer S.; Yeager, Meredith; Moore, Lee E.; Wei, Ming-Hui; Pfeiffer, Ruth; Toure, Ousmane; Purdue, Mark P.; Johansson, Mattias; Scelo, Ghislaine; Chung, Charles C.; Gaborieau, Valerie; Zaridze, David; Schwartz, Kendra; Szeszenia-Dabrowska, Neonilia; Davis, Faith; Bencko, Vladimir; Colt, Joanne S.; Janout, Vladimir; Matveev, Vsevolod; Foretova, Lenka; Mates, Dana; Navratilova, M.; Boffetta, Paolo; Berg, Christine D.; Grubb, Robert L.; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Burdett, Laurie; Brisuda, Antonin; McKay, James D.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Rosenberg, Philip S.; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Tucker, Margaret A.; Chanock, Stephen J.; Toro, Jorge R.

    2012-01-01

    In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10−8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17–1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10−14) and rs12617313 (P = 7.48 × 10−12), both highly correlated with rs9679290 (r2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10−9, per-allele OR = 1.28, 95% CI: 1.18–1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. PMID:22113997

  14. Genetic polymorphisms in Pakistani women with polycystic ovary syndrome.

    PubMed

    Liaqat, Irfana; Jahan, Nusrat; Krikun, Graciela; Taylor, Hugh S

    2015-03-01

    Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone β (fshrβ), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone β (lhβ), estrogen receptor α (esr1), and estrogen receptor β (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes. PMID:25100445

  15. New source of genetic polymorphisms in Lepidoptera?

    PubMed

    Hundsdoerfer, Anna K; Wink, Michael

    2005-01-01

    The variability level of the ISSR (inter-simple sequences repeat) primer (GACA)4 was examined in the three Lepidoptera families Pyralidae, Sphingidae and Pieridae. Our study shows that the tetra-repeat (GACA)n is evidently present in sufficient numbers in these butterflies to provide informative DNA fingerprints. The variability is mostly rather high, but within a comparable range to other ISSR studies. Although less polymorphisms may be encountered in some butterfly families, this study indicates that high variability of this marker may be a common characteristic of Lepidoptera genomes. An appeal for a minimal level of standardization of ISSR-PCR data analysis is formulated to enable an exact comparison between the groups of organisms studied with this fingerprint technique. PMID:16163839

  16. Harbor porpoise Phocoena phocoena strandings on the Dutch coast: No genetic structure, but evidence of inbreeding

    NASA Astrophysics Data System (ADS)

    van der Plas-Duivesteijn, Suzanne J.; Smit, Femmie J. L.; van Alphen, Jacques J. M.; Kraaijeveld, Ken

    2015-03-01

    Conservation management in the North Sea is often motivated by the population size of marine mammals, like harbor porpoises Phocoena phocoena. In the Dutch part of the North Sea, sighting and stranding data are used to estimate population sizes, but these data give little insight into genetic structuring of the population. In this study we investigated genetic structure among animals stranded at different locations and times of year. We also tested whether there is a link between stranding and necropsy data, and genetic diversity. We made use of both mitochondrial (mtDNA) and microsatellite DNA analysis of samples from dead stranded porpoises along the Dutch coast during 2007. mtDNA analysis showed 6 variable positions in the control region, defining 3 different haplotypes. mtDNA haplotypes were not randomly distributed along the Dutch coastline. However, microsatellite analysis showed that these mtDNA haplotypes did not represent separate groups on a nuclear level. Furthermore, microsatellite analysis revealed no genotypic differences between seasons, locations or genders. The results of this study indicate that the Dutch population is panmictic. In contrast, heterozygosity levels were low, indicating some level of inbreeding in this population. However, this was not corroborated by other indices of inbreeding. This research provided insight into genetic structuring of stranded porpoises in 2007, but data from multiple years should be included to be able to help estimate population sizes.

  17. [Intraspecific genetic polymorphism of Russian sturgeon Acipencer gueldenstaedtii].

    PubMed

    Timoshkina, N N; Barmintseva, A E; Usatov, A V; Miuge, N S

    2009-09-01

    Three populations (Azov, Caspian, and Black Sea) of Russian sturgeon Acipenser queldenstaedtii were tested for polymorphism at nuclear (RAPD and microsatellites) and mitochondrial (PCR identification of two mito-types) markers. In addition, morphometric analysis of he representatives of Azov population was carried out. According to the morphological characters, the Black Sea population occupied an intermediate position between the Caspian and Azov populations, reflecting the phylogeography of this species. In agreement with the morphometric data, genetic distances (the data of STR analysis) also placed the Black Sea population between the Caspian and Azov populations (FST = 0.058 and 0.043). The genetic distance between the Azov and Caspian population was somewhat higher (FST = 0.070). The highest allelic polymorphism at four microsatellite loci was found observed in Caspian population, while the lowest polymorphism was in the Sea of Azov. RAPD analysis distinguished high polymorphism within the populations, although it was not feasible for interpopulation analysis. Using the method differentiating the "baerii-like" and typical "gueldenstaedtii" mitotypes, the absence of the "baerii-like" marker in the Black Sea population was demonstrated. The frequency of this marker in Caspian and Azov populations constituted 31.1 and 1.8%, respectively. Possible evolutionary reasons for the interpopulation differences observed are discussed. PMID:19824546

  18. Evolutionary Insights from a Genetically Divergent Hantavirus Harbored by the European Common Mole (Talpa europaea)

    PubMed Central

    Kang, Hae Ji; Bennett, Shannon N.; Sumibcay, Laarni; Arai, Satoru; Hope, Andrew G.; Mocz, Gabor; Song, Jin-Won; Cook, Joseph A.; Yanagihara, Richard

    2009-01-01

    Background The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts. PMID:19582155

  19. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

    PubMed Central

    Ogata, Toru; Shibamura, Hidenori; Tromp, Gerard; Sinha, Moumita; Goddard, Katrina A. B.; Sakalihasan, Natzi; Limet, Raymond; MacKean, Gerald L.; Arthur, Claudette; Sueda, Taijiro; Land, Susan; Kuivaniemi, Helena

    2005-01-01

    findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt−1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual’s risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA. PMID:15944607

  20. Genetic polymorphisms as a risk factor for dyslipidemia in children

    PubMed Central

    Santos, Izabela R.; Fernandes, Ana Paula; Sousa, Marinez O.; Ferreira, Cláudia N.; Gomes, Karina B.

    2013-01-01

    Dyslipidemia is an important etiological factor for development of cardiovascular disease, which is the leading cause of deaths in adults. Given the growing global epidemic of dyslipidemia, lipoprotein metabolism disorders have become an important health problem not only in adulthood, but have also emerged as an increasingly risk factor in childhood. Although several genome-wide association studies in multiple large population-based cohorts of adults and meta-analyses have identified susceptibility genes or loci, especially in lipid-related traits, it is of great importance to evaluate genetic predisposition at an early age. Recent findings suggest that the identification of polymorphisms in the metabolism of lipids in childhood may help fight subclinical atherosclerosis and its progression to cardiovascular complications in adulthood. Therefore, the aim of this study was to review genetic polymorphisms as risk factors associated with dyslipidemia in children and adolescents.

  1. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  2. Chemokine genetic polymorphism in human health and disease.

    PubMed

    Qidwai, Tabish

    2016-08-01

    Chemokine receptor-ligand interaction regulates transmigration of lymphocytes and monocytes from circulation to the inflammatory sites. CC chemokine receptors, chemokine receptor 2(CCR2) and 5 (CCR5) are important in recruitment of immune cells as well as non-immune cells under pathological condition. CCR2, CCR5 and their ligands (CCL2 and CCL5) are major contributor to the autoimmune and inflammatory diseases and cancer. Currently studies are being done to explore genetic variations in chemokine genes and their involvement in diseases that could make clear disease severity and deaths. Conflicting results of studies in different populations and diseases promoted to investigate chemokines genetic polymorphisms in miscellaneous diseases. This study is aimed to evaluate the influence of chemokines genetic polymorphisms in pathogenesis and outcome of prevalent non infectious diseases. Present study demonstrates the likely role played by genetic variations in drug response and evolution. Moreover this study highlights chemokine as therapeutic target and diagnostic biomarker in pathological condition. PMID:27262929

  3. Genetic polymorphisms predicting the outcome of bone marrow transplants.

    PubMed

    Dickinson, Anne M; Middleton, Peter G; Rocha, Vanderson; Gluckman, Eliane; Holler, Ernst

    2004-12-01

    Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor alpha, interleukin-10, interferon gamma and interleukin (IL)-6, associate with more severe acute graft-versus-host disease (aGvHD). Donor genotype for IL-1 receptor antagonist (IL-1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL-1Ra, IL-6 and donor IL-1 alpha) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FC gamma receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and other post-transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA-matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non-HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT. PMID:15566351

  4. [Application of single nucleotide polymorphism in crop genetics and improvement].

    PubMed

    Du, Chun-Fang; Liu, Hui-Min; Li, Run-Zhi; Li, Peng-Bo; Ren, Zhi-Qiang

    2003-11-01

    Single nucleotide polymorphism(SNP) is the most common type of sequence difference between alleles, which can be used as a kind of high-throughput genetic marker. Several different routes have been developed to discover and identify SNP. These include the direct sequencing of PCR amplicons, electronic SNP(eSNP) and so on. SNP assays have been made in many crop species such as maize and soybean. The elite germplasm of some crops have been narrowed in genetic diversity, increasing the amount of linkage disequilibrium (LD) present and facilitating the association of SNP haplotypes at candidate gene loci with phenotypes. SNP analysis has been broadly used in the field of plant gene mapping, integration of genetic and physical maps, DNA marker-assisted breeding and functional genomics. PMID:15639972

  5. Latitude-correlated genetic polymorphisms: selection or gene flow?

    PubMed

    Ciminelli, B M; Jodice, C; Scozzari, R; Corbo, R M; Nahum, M; Pompei, F; Santachiara-Benerecetti, S A; Santolamazza, C; Morpurgo, G P; Modiano, G

    2000-08-01

    Latitude-correlated polymorphisms can be due to either selection-driven evolution or gene flow. To discriminate between them, we propose an approach that studies subpopulations springing from a single population that have lived for generations at different latitudes and have had a low genetic admixture. These requirements are fulfilled to a large extent by Ashkenazi and Sephardi Jews. The original population lived at a latitude of 35 degrees N, where the Sephardis still live. The Ashkenazis, however, moved to a latitude of 50 degrees N, starting about 10 centuries ago. The present study examines 3 latitude-correlated polymorphisms: PGP, PGM1, and AHSG. We found that PGP*2 and AHSG*2 alleles most likely underwent selection-driven evolution, but that PGM1*ts allele was not similarly affected. Since temperature might have been considered a reasonable selective factor, we also studied a population living at >800 m above sea level from Aosta Valley (Italy). PMID:11048786

  6. Genetic diversity and chemical polymorphism of some Thymus species.

    PubMed

    Rustaiee, Ali Reza; Yavari, Alireza; Nazeri, Vahideh; Shokrpour, Majid; Sefidkon, Fatemeh; Rasouli, Musa

    2013-06-01

    To ascertain whether there are chemical and genetic relationships among some Thymus species and also to determine correlation between these two sets of data, the essential-oil composition and genetic variability of six populations of Thymus including: T. daenensis ČELAK. (two populations), T. fallax FISCH. & C.A.MEY., T. fedtschenkoi RONNIGER, T. migricus KLOKOV & DES.-SHOST., and T. vulgaris L. were analyzed by GC and GC/MS, and also by randomly amplified polymorphic DNA (RAPD). Thus, 27 individuals were analyzed using 16 RAPD primers, which generated 264 polymorphic scorable bands and volatiles isolated by distillation extraction were subjected to GC and GC/MS analyses. The yields of oils ranged from 2.1 to 3.8% (v/w), and 34 components were identified, amounting to a total percentage of 97.8-99.9%. RAPD Markers allowed a perfect distinction between the different species based on their distinctive genetic background. However, they did not show identical clustering with the volatile-oil profiles. PMID:23776024

  7. Genetic Association Between PER3 Genetic Polymorphisms and Cancer Susceptibility

    PubMed Central

    Geng, Peiliang; Ou, Juanjuan; Li, Jianjun; Wang, Ning; Xie, Ganfeng; Sa, Rina; Liu, Chen; Xiang, Lisha; Liang, Houjie

    2015-01-01

    Abstract The genes along the circadian pathways control and modulate circadian rhythms essential for the maintenance of physiological homeostasis through self-sustained transcription-translation feedback loops. PER3 (period 3) is a circadian pathway gene and its variants (rs1012477, 4/5-repeat) have frequently been associated with human cancer. The mixed findings, however, make the role of the 2 variants in cancer susceptibility elusive. We aimed in this article to clarify the association of PER3 variants with cancer. We collected genetic data from 8 studies, providing 6149 individuals for rs1012477 and 5241 individuals for 4/5-repeat. Based on the genotype and allele frequency, we chose the fixed-effects model to estimate risk of cancer. Overall analysis did not suggest a global role of rs1012477 in cancer susceptibility. For PER3 4/5-repeat variant, we found a moderate increase in risk of cancer among individuals with the 5-allele compared to individuals with the 4-allele, although this association was not statistically significant (homozygous model: odds ratio [OR] 1.17, 95% confidence interval [CI] 0.81–1.67; recessive model: OR 1.17, 95% CI 0.82–1.67). No substantial heterogeneity was revealed in this analysis. Our meta-analysis provides no evidence supporting a global association of PER3 genetic variants with the incidence of cancer. PMID:25837749

  8. Potential for Incorporation of Genetic Polymorphism Data in Human Health Risk Assessment

    EPA Science Inventory

    This overview summarizes several EPA assessment publications evaluating the potential impact of genetic polymorphisms in ten metabolizing enzymes on the variability in enzyme function across ethnically diverse populations.

  9. Random amplified polymorphic DNA analysis of genetically modified organisms.

    PubMed

    Yoke-Kqueen, Cheah; Radu, Son

    2006-12-15

    Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45% similarity from the RAPD. RAPD analysis showed that the maize and soybean samples were clustered differently besides the GMO and non-GMO products. PMID:16860900

  10. Destabilizing Protein Polymorphisms in the Genetic Background Direct Phenotypic Expression of Mutant SOD1 Toxicity

    PubMed Central

    Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I.

    2009-01-01

    Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

  11. Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

    PubMed

    Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I

    2009-03-01

    Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

  12. Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture.

    PubMed

    Goddard, M E; Kemper, K E; MacLeod, I M; Chamberlain, A J; Hayes, B J

    2016-07-27

    Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement. PMID:27440663

  13. Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

    PubMed Central

    Goddard, M. E.; Kemper, K. E.; MacLeod, I. M.; Chamberlain, A. J.; Hayes, B. J.

    2016-01-01

    Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement. PMID:27440663

  14. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

    PubMed Central

    Okuyama Kishima, Marina; Brajão de Oliveira, Karen; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; de Almeida, Felipe Campos; Vitiello, Glauco Akelinghton Freire; Trugilo, Kleber Paiva; Guembarovski, Alda Fiorina Maria Losi; Jorge Sobrinho, Walter; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara

    2015-01-01

    CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337

  15. MMP-9 genetic polymorphism may confer susceptibility to COPD.

    PubMed

    Jiang, S; Yang, Z H; Chen, Y Y; He, Z; Zhou, Y; Gao, Y; Zhang, Q; Tan, M Q

    2016-01-01

    Correlations between genetic polymorphisms of three matrix metalloproteinase (MMP) genes and susceptibility to chronic obstructive pulmonary disease (COPD) were investigated. Relevant case-control studies were selected using rigorous inclusion and exclusion criteria. The comprehensive Meta-analysis 2.0 software was used to conduct the statistical analysis. An odds ratio with 95% confidence intervals was applied to assess the correlation between genetic polymorphisms of MMPs and susceptibility to COPD. Twelve high-quality studies were selected for inclusion in this meta-analysis. These studies included a combined total of 1533 COPD patients and 1530 healthy controls. The result of the meta-analysis showed that MMP-9 rs3918242 C > T was significantly correlated with increased susceptibility to COPD. However, MMP-1 rs1799750 1G > 2G and MMP-3 rs3025058 5A > 6A were not associated with COPD risk (all P > 0.05). Based on our meta-analysis, MMP-9 rs3918242 C > T is correlated with susceptibility to COPD, but MMP-1 rs1799750 1G > 2G and MMP-3 rs3025058 5A > 6A are not. These results should be further confirmed using a larger sample size. PMID:27173221

  16. The role of genetic polymorphisms in environmental health.

    PubMed Central

    Kelada, Samir N; Eaton, David L; Wang, Sophia S; Rothman, Nathaniel R; Khoury, Muin J

    2003-01-01

    Interest is increasing in the role of variations in the human genome (polymorphisms) in modifying the effect of exposures to environmental health hazards (often referred to as gene-environment interaction), which render some individuals or groups in the population more or less likely to develop disease after exposure. This review is intended for an audience of environmental health practitioners and students and is designed to raise awareness about this rapidly growing field of research by presenting established and novel examples of gene-environment interaction that illustrate the major theme of effect modification. Current data gaps are identified and discussed to illustrate limitations of past research and the need for the application of more robust methods in future research projects. Two primary benefits of incorporating genetics into the existing environmental health research framework are illustrated: a) the ability to detect different levels of risk within the population, and b) greater understanding of etiologic mechanisms. Both offer opportunities for developing new methods of disease prevention. Finally, we describe a basic framework for researchers interested in pursuing health effects research that incorporates genetic polymorphisms. PMID:12826477

  17. Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing cholangitis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Larson, Joseph J.; Ellinghaus, David; Franke, Andre; Lazaridis, Konstantinos N.

    2011-01-01

    Background The damaging cholestasis inherent to primary sclerosing cholangitis (PSC) results from bile duct stricturing because of progressive fibrosis. The matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and is expressed by activated liver stellate cells, and so is a candidate for involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene harbours polymorphisms associated with variation in its activity directly impacting clinical phenotypes. Aims We aimed to examine the influence of MMP3 polymorphisms on PSC risk and progression. Methods Nine single nucleotide polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed for PSC association by logistic regression and score tests. The effect of SNPs on survival to liver transplant or death was analysed using Cox regression, and Kaplan–Meier curves were constructed. Results No association of PSC with individual SNPs or haplotypes of MMP3 was detected. However, progression to death or liver transplant was significantly associated with homozygosity for minor alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with concurrent ulcerative colitis (UC) (strongest in redundant SNPs rs650108/rs683878, hazard ratio = 3.23, 95% confidence interval 1.45–7.25, P = 0.004). Conclusions Genetic variation in MMP3 influences PSC progression, possibly in the context of coexisting UC. While the functional variants and specific mechanisms remain unknown, this finding implicates the turnover of the extracellular matrix as an important and variable component of PSC pathogenesis. Efforts to understand this process could form the basis for developing effective treatments, which are currently lacking for PSC. PMID:21134112

  18. Single nucleotide polymorphism markers for genetic mapping in Drosophila melanogaster

    SciTech Connect

    Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.

    2001-04-16

    For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markers is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.

  19. Genetic Diversity among Clostridium botulinum Strains Harboring bont/A2 and bont/A3 Genes

    PubMed Central

    Raphael, Brian H.; Joseph, Lavin A.; Meno, Sarah R.; Fernández, Rafael A.; Maslanka, Susan E.

    2012-01-01

    Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE. PMID:23042179

  20. Genetic diversity among Clostridium botulinum strains harboring bont/A2 and bont/A3 genes.

    PubMed

    Lúquez, Carolina; Raphael, Brian H; Joseph, Lavin A; Meno, Sarah R; Fernández, Rafael A; Maslanka, Susan E

    2012-12-01

    Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE. PMID:23042179

  1. Candida milleri species reveals intraspecific genetic and metabolic polymorphisms.

    PubMed

    Vigentini, Ileana; Antoniani, Davide; Roscini, Luca; Comasio, Andrea; Galafassi, Silvia; Picozzi, Claudia; Corte, Laura; Compagno, Concetta; Dal Bello, Fabio; Cardinali, Gianluigi; Foschino, Roberto

    2014-09-01

    Candida milleri, together with Candida humilis, is the most representative yeast species found in type I sourdough ecosystems. In this work, comparison of the ITS region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping, mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5 microsatellite analyses, assimilation test of different carbohydrates, and metabolome assessment by FT-IR analysis, were investigated in seventeen strains isolated from four different companies as well as in type strains CBS6897(T) and CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong relatedness was confirmed with C. humilis as well, particularly for three strains. Genetic characterization showed a high degree of intraspecific polymorphism since 12 different genotypes were discriminated. The number of chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over 2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources assimilation. FT-IR spectra from yeast cells cultivated in different media and collected at different growth phases revealed a diversity of behaviour among strains in accordance with the results of PCR-based fingerprinting. A clear evidence of the polymorphic status of C. milleri species is provided thus representing an important feature for the development of technological applications in bakery industries. PMID:24929720

  2. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression

    PubMed Central

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2015-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  3. Lemierre's syndrome and genetic polymorphisms: a case report

    PubMed Central

    Constantin, Jean-Michel; Mira, Jean-Paul; Guerin, Renaud; Cayot-Constantin, Sophie; Lesens, Olivier; Gourdon, Florence; Romaszko, Jean-Pierre; Linval, Philippe; Laurichesse, Henri; Bazin, Jean-Etienne

    2006-01-01

    Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology. PMID:16846490

  4. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression.

    PubMed

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2016-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  5. [Genetic polymorphisms commonly influencing efficacy of diverse addictive substances].

    PubMed

    Nishizawa, Daisuke; Ikeda, Kazutaka

    2014-04-01

    Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. The authors have focused on G-protein-activated inwardly rectifying potassium (GIRK) channel subunits, GIRK2 and GIRK3, that are important molecules in opioid transmission, and found that the single-nucleotide polymorphisms (SNPs) within the GIRK2 and GIRK3 gene regions were significantly associated with postoperative requirements of analgesics including opioids in patients who underwent abdominal surgery and mRNA expression of these genes in postmortem specimens, one of which was also associated with vulnerability to methamphetamine (METH) dependence. Further, by conducting a multistage genome-wide association study (GWAS) in healthy subjects, the authors found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate SNP, rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. The results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. These outcomes provide valuable information for the

  6. Integrated genetic map of Anopheles gambiae: use of RAPD polymorphisms for genetic, cytogenetic and STS landmarks.

    PubMed

    Dimopoulos, G; Zheng, L; Kumar, V; della Torre, A; Kafatos, F C; Louis, C

    1996-06-01

    Randomly amplified polymorphic DNA (RAPD) markers have been integrated in the genetic and cytogenetic maps of the malaria vector mosquito, Anopheles gambiae. Fifteen of these markers were mapped by recombination, relative to microsatellite markers that had been mapped previously. Thirty-four gel-purified RAPD bands were cloned and sequenced, generating sequence tagged sites (STSs) that can be used as entry points to the A. gambiae genome. Thirty one of these STSs were localized on nurse cell polytene chromosomes through their unique hybridization signal in in situ hybridization experiments. Five STSs map close to the breakpoints of polymorphic inversions, which are notable features of the Anopheles genome. The usefulness and limitations of this integrated mosquito map are discussed. PMID:8725241

  7. Associations between heat shock protein 70 genetic polymorphisms and calving traits in crossbred Brahman cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stressors such as heat, cold, toxins, and oxygen deprivation are known to induce heat shock proteins. Genetic polymorphisms associated with heat shock protein genes have been associated with decreased male and female fertility. Our objectives were to 1) confirm single nucleotide polymorphisms (SNP) ...

  8. Genetic polymorphisms and non-small-cell lung cancer: future paradigms

    PubMed Central

    de Mello, Ramon Andrade Bezerra

    2014-01-01

    This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis. PMID:25628210

  9. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

    PubMed Central

    Haghvirdizadeh, Polin; Mohamed, Zahurin; Abdullah, Nor Azizan; Haghvirdizadeh, Pantea; Haerian, Monir Sadat; Haerian, Batoul Sadat

    2015-01-01

    Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM. PMID:26448950

  10. [A comparative study on genetic polymorphism and genetic relationship of 13 SNPs in three Chinese populations].

    PubMed

    Wang, Rui-Heng; Liu, Li-Min; Zhao, Jin-Ling

    2009-03-01

    Using the fluorescence labeled capillary electrophoresis of multi-PCR technique, the single nucleotide polymorphism (SNP) typing system of fragment length discrepant allele specific fluorescence labeled multi-PCR technique is established based on the principle of allele-specific PCR. The typing of the 13 SNP loci can be completed simultaneously according to the length of PCR products and the number of product peaks. It appears a single product peak when the SNP is homozygous, and two product peaks with 4 bp differences will appear when it is heterozygous. By using this system, we conducted population census about allele frequencies for 13 autosomal SNP loci in Southern Liaoning Han samples, Mongolian samples in Inner Mongolia and Zhuang samples in Guangxi area, and got the allele frequencies of the 13 SNP loci in the three populations, then preliminarily discussed their genetic relationship by comparing their differences in allelic polymorphism. The results indicate that the allelic distributions of the 13 SNP loci in the three populations are polymorphic, and the difference is significant in some SNP loci (P< or =0.01). The sampling survey shows that the result is consistent with Hardy-Weinberg equilibrium, and Han population in southern Liaoning has relatively closer relationship with Mongolian in Inner Mongolia than with Zhuang population in Guangxi by origin. PMID:19273440

  11. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn

    2016-01-01

    Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111

  12. Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines.

    PubMed

    Fukasawa, T; Suzuki, A; Otani, K

    2007-08-01

    Pharmacogenetic studies have shown that several cytochrome P450 (CYP) enzymes exhibit genetic polymorphisms. Several benzodiazepines (BZPs) are metabolized predominantly or partly by polymorphic CYP2C19 and CYP3A4/5. The pharmacokinetics of diazepam, etizolam, quazepam and desmethylclobazam have been shown to be affected by CYP2C19 polymorphism. The CYP3A5 polymorphism has been reported to affect the pharmacokinetics of alprazolam, but its effect on midazolam kinetics has been inconclusive. For etizolam and desmethylclobazam, some data suggest that CYP2C19 deficiency leads to side-effects or toxicity. For the remaining BZPs the clinical significance of the observed pharmacokinetic changes remains unclear. Further studies on the effects of genetic polymorphisms of CYP enzymes on the pharmacokinetics and pharmacodynamics of BZPs are necessary to guide treatment individualization and optimization. PMID:17635335

  13. The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

    PubMed Central

    Poggi, Chiara

    2014-01-01

    Abstract Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies. Antioxid. Redox Signal. 21, 1863–1880. PMID:24382101

  14. Reconfiguring phosphorylation signaling by genetic polymorphisms affects cancer susceptibility.

    PubMed

    Wang, Yongbo; Cheng, Han; Pan, Zhicheng; Ren, Jian; Liu, Zexian; Xue, Yu

    2015-06-01

    Large-scale sequencing has characterized an enormous number of genetic variations (GVs), and the functional analysis of GVs is fundamental to understanding differences in disease susceptibility and therapeutic response among and within populations. Using a combination of a sequence-based predictor with known phosphorylation and protein-protein interaction information, we computationally detected 9606 potential phosSNPs (phosphorylation-related single nucleotide polymorphisms), including 720 known, disease-associated SNPs that dramatically modify the human phosSNP-associated kinase-substrate network. Further analyses demonstrated that the proteins in the network are heavily associated in various signaling and cancer pathways, while cancer genes and drug targets are significantly enriched. We re-constructed four population-specific kinase-substrate networks and found that several inherited disease or cancer genes, such as IRS1, RAF1, and EGFR, were differentially regulated by phosSNPs. Thus, phosSNPs may influence disease susceptibility and be involved in cancer development by reconfiguring phosphorylation networks in different populations. Moreover, by systematically characterizing potential phosphorylation-related cancer mutations (phosCMs) in 12 types of cancers, we observed that both types of GVs preferentially occur in the known cancer genes, while a considerable number of phosphorylated proteins, especially those over-representing cancer genes, contain both phosSNPs and phosCMs. Furthermore, it was observed that phosSNPs were significantly enriched in amplification genes identified from breast cancers and tyrosine kinase circuits of lung cancers. Taken together, these results should prove helpful for further elucidation of the functional impacts of disease-associated SNPs. PMID:25722345

  15. Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

    SciTech Connect

    Suga, Tomo; Iwakawa, Mayumi; Tsuji, Hiroshi; Ishikawa, Hitoshi; Oda, Eisei; Noda, Shuhei; Otsuka, Yoshimi; Ishikawa, Atsuko; Ishikawa, Ken-Ichi; Shimazaki, Jun; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Imai, Takashi

    2008-11-01

    Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as 'risk genotypes.' Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor.

  16. RAGE Genetic Polymorphisms Are Associated with Risk, Chemotherapy Response and Prognosis in Patients with Advanced NSCLC

    PubMed Central

    Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren

    2012-01-01

    Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, −429T/C, −374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC. PMID:23071492

  17. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  18. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

    PubMed Central

    Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

    2016-01-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In

  19. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

    PubMed

    Sun, Wei; Kechris, Katerina; Jacobson, Sean; Drummond, M Bradley; Hawkins, Gregory A; Yang, Jenny; Chen, Ting-Huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R Graham; Basta, Patricia V; Bleecker, Eugene R; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H; Comellas, Alejandro; Crapo, James D; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A; Couper, David J; Curtis, Jeffrey L; Doerschuk, Claire M; Freeman, Christine M; Gouskova, Natalia A; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Hersh, Craig P; Hoffman, Eric A; Kaner, Robert J; Kanner, Richard E; Kleerup, Eric C; Lutz, Sharon; Martinez, Fernando J; Meyers, Deborah A; Peters, Stephen P; Regan, Elizabeth A; Rennard, Stephen I; Scholand, Mary Beth; Silverman, Edwin K; Woodruff, Prescott G; O'Neal, Wanda K; Bowler, Russell P

    2016-08-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In

  20. Ecosensitivity and genetic polymorphism of somatic traits in the perinatal development of twins.

    PubMed

    Waszak, Małgorzata; Cieślik, Krystyna; Skrzypczak-Zielińska, Marzena; Szalata, Marlena; Wielgus, Karolina; Kempiak, Joanna; Bręborowicz, Grzegorz; Słomski, Ryszard

    2016-04-01

    In view of criticism regarding the usefulness of heritability coefficients, the aim of this study was to analyze separately the information on genetic and environmental variability. Such an approach, based on the normalization of trait's variability for its value, is determined by the coefficients of genetic polymorphism (Pg) and ecosensitivity (De). The studied material included 1263 twin pairs of both sexes (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins) born between the 22nd and 41st week of gestation. Variability of six somatic traits was analyzed. The zygosity of same-sex twins was determined based on the polymorphism of DNA from lymphocytes of the umbilical cord blood, obtained at birth. The coefficients of genetic polymorphism and ecosensitivity for analyzed traits of male and female twins born at various months of gestation were calculated. Our study revealed that a contribution of the genetic component predominated over that of the environmental component in determining the phenotypic variability of somatic traits of newborns from twin pregnancies. The genetically determined phenotypic variability in male twins was greater than in the females. The genetic polymorphism and ecosensitivity of somatic traits were relatively stable during the period of fetal ontogeny analyzed in this study. Only in the case of body weight, a slight increase in the genetic contribution of polygenes to the phenotypic variance could be observed with gestational age, along with a slight decrease in the influence of environmental factors. PMID:26619791

  1. Survival and impact of genetically engineered Pseudomonas putida harboring mercury resistance gene in soil microcosms.

    PubMed

    Iwasaki, K; Uchiyama, H; Yagi, O

    1994-01-01

    The survival of genetically engineered and wild-type Pseudomonas putida PpY101, that contained a recombinant plasmid pSR134 conferring mercury resistance, were monitored in andosol and sand microcosms. The survival of genetically engineered and wild-type P. putida was not significantly different in andosol. The population change of the two strains was dissimilar in andosol and sand. The survival of genetically engineered and wild-type P. putida strains was affected by the water content of andosol, and increased with the increment of the water content. The impact of the addition of genetically engineered and wild-type P. putida strains on indigenous bacteria and fungi was examined. Inoculation of both strains had no apparent effect on the density of indigenous microorganisms. PMID:7764510

  2. Survival and impact of genetically engineered Pseudomonas putida harboring mercury resistance gene in aquatic microcosms.

    PubMed

    Iwasaki, K; Uchiyama, H; Yagi, O

    1993-08-01

    The survival of wild-type and genetically engineered Pseudomonas putida PpY101 that contained a recombinant plasmid pSR134 conferring mercury resistance were monitored in aquatic microcosms. We used lake, river, and spring water samples. The density of genetically engineered and wild-type P. putida decreased rapidly within 5 days (population change rate k -0.87 approximately -1.00 day-1), then moderately after 5 to 28 days (-0.10 approximately -0.14 day-1). The population change rates of genetically engineered and wild-type P. putida were not significantly different. We studied the important factors affecting the survival of genetically engineered and wild-type P. putida introduced in aquatic microcosms. Visible light exerted an adverse effect on the survival of the two strains. The densities of genetically engineered and wild-type P. putida were almost constant until 7 days after inoculation in natural water filtered with a 0.45-micron membrane filter, or treated with cycloheximide to inhibit the growth of protozoa. These results suggested that protozoan predation was one of the most important factors for the survival of two strains. We examined the impact of the addition of genetically engineered and wild-type P. putida on indigenous bacteria and protozoa. Inoculation of genetically engineered or wild-type P. putida had no apparent effect on the density of indigenous bacteria. The density of protozoa increased in microcosms inoculated with genetically engineered or wild-type P. putida at 3 days after inoculation, but after 5 to 21 days, the density of protozoa decreased to the same level as the control microcosms. PMID:7764012

  3. MTHFR genetic polymorphism increases the risk of preterm delivery

    PubMed Central

    Nan, Yanrong; Li, Hongmei

    2015-01-01

    Aims: This study aimed to investigate the association between the methylene tetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and premature delivery susceptibility. Methods: With matched age and gender, 108 premature delivery pregnant women as cases and 108 healthy pregnant women as controls were recruited in this case-control study. The cases and controls had same gestational weeks. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyze C677T and A1298C polymorphisms of the participants. Linkage disequilibrium (LD) and haplotype analysis were conducted by Haploview software. The differences for frequencies of gene type, allele and haplotypes in cases and controls were tested by chi-square test. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: TT gene type frequency of C677T polymorphsim was higher in cases than the controls (P=0.004, OR=3.077, 95% CI=1.469-6.447), so was allele T (P=0.002, OR=1.853, 95% CI=1.265-2.716). Whereas, CC gene type of A1298C polymorphism had a lower distribution in cases than the controls (P=0.008, OR=0.095, 95% CI=0.012-0.775), so was allele C (P=0.047, OR=0.610, 95% CI=0.384-0.970). Haplotype analysis and linkage disequilibrium test conducted on the alleles of two polymorphisms in MTHFR gene, we discovered that haplotype T-A had a higher distribution in cases, which indicated that susceptible haplotype T-A was the candidate factor for premature delivery. Conclusions: Gene type TT of MTHFR C677T polymorphism might make premature delivery risk rise while gene type CC of A1298C polymorphism might have protective influence on premature delivery. PMID:26261642

  4. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  5. [Genetically determined enzyme polymorphism in soy varieties (Glycine max) and in wild soy (Glycine soja)].

    PubMed

    Glazko, V I

    2000-01-01

    Analysis of 22 genetic-biochemical systems (42 loci) in 18 varieties of domestic soybean (G. max) and in 3 population of wild soybean (G. soja) was carried out. The part of polymorphous loci (P), intraspecies genetic differentiation (genetic distances--DN) were higher in domestic plants in comparison with wild ones (P = 45%, 17%: DN = 0.038-0.269, 0.059-0129). The preferable polymorphism of loci, coding the enzymes of glycolysis and Kreb's cycle was revealed in wild species. Domestic soybean had more polymorphous enzyme loci, which did not participate in glucose metabolism in comparison with wild species. The presence of the specific part of the gene pool in ancestor species, which was involved in soybean domestication and forming of varieties was discussed. PMID:10857206

  6. Protein Polymorphisms, Segregation in Genetic Crosses and Genetic Distances among Fishes of the Genus Xiphophorus (Poeciliidae)

    PubMed Central

    Morizot, Don C.; Siciliano, Michael J.

    1982-01-01

    The products of 49 protein-coding loci were examined by starch gel electrophoresis for populational variation in six species of Xiphophorus fishes and/or segregation in intra- and interspecific backcross and intercross hybrids. Electrophoretic variation was observed for 29 of the 35 locus products in a survey of 42 population samples. The highest frequency of polymorphic loci observed in noninbred populations was 0.143. After ten or more generations of inbreeding, all loci studied were monomorphic. Inbred strains generally exhibited the commonest electrophoretic alleles of the population from which they were derived. An assessment of genetic distances among Xiphophorus populations reflected classical systematic relationships and suggested incipient subspeciation between X. maculatus from different drainages as well as several species groups. Thirty-three loci were analyzed with respect to segregation in hybrids. The goodness of fit of segregations to Mendelian expectations at all loci analyzed (except loci in linkage group I) is interpreted as evidence for high genetic compatibility of the genomes of Xiphophorus species. It is anticipated that these data will result in a rapid expansion of the assignment of protein-coding loci to linkage groups in these lower vertebrate species. PMID:7173606

  7. Detection of genetic polymorphism in the populations of brinjal shoot and fruit borer, Leucinodes orbonalis (Guenee).

    PubMed

    Karthikeyan, K A M; Vijayakumar, I; Murali, P; Suresh, P; Janarthanan, S

    2005-06-01

    In the present study six different populations of L. orbonalis were collected and subjected to analysis of genetic variability in terms of carboxylesterase isozyme pattern and DNA polymorphism using RAPD-PCR. Pattern of carboxylesterase revealed a similar isozyme cluster in the populations namely, sivaganga (population-3), dindigal (population-4), virudhunagar (population-5) and coimbatore (population-6). Similarly, the populations of L. orbonalis recorded 3 distinct randomly amplified polymorphic DNA markers in all populations grouped above. This pattern of genetic variability in the populations was also supported by the analysis of the similarity indices and UPGMA dendrogram. PMID:15991581

  8. Genetic Diversity Revealed by Single Nucleotide Polymorphism Markers in a Worldwide Germplasm Collection of Durum Wheat

    PubMed Central

    Ren, Jing; Sun, Daokun; Chen, Liang; You, Frank M.; Wang, Jirui; Peng, Yunliang; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2013-01-01

    Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity. PMID:23538839

  9. Interferon-gamma Genetic Polymorphism and Expression in Kawasaki Disease

    PubMed Central

    Huang, Ying-Hsien; Hsu, Yu-Wen; Lu, Hsing-Fang; Wong, Henry Sung-Ching; Yu, Hong-Ren; Kuo, Hsing-Chun; Huang, Fu-Chen; Chang, Wei-Chiao; Kuo, Ho-Chang

    2016-01-01

    Abstract Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. IFNG gene encoding interferon (IFN)-γ, produced by natural killer cells and T cells, has been suggested to play an important role in the immunopathogenesis of Kawasaki disease. The aim of this study was to examin the correlation of gene polymorphisms of the IFNG gene and plasma levels of IFN-γ in KD patients and their outcomes. A total of 950 subjects (381 KD and 569 controls) were recruited. Three tagging single-nucleotide polymorphisms (rs2069718, rs1861493, rs2069705) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL), coronary artery aneurysms (CAA) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Plasma IFN-γ levels were also measured with an enzyme-linked immunosorbent assay. Polymorphisms of the IFNG gene were significantly different between the normal controls and KD patients. The G allele of rs1861493 conferred a better response to IVIG treatment in KD patients. AA allele frequencies of rs1861493 were also associated with a significantly higher risk of CAA in KD patients. Furthermore, the plasma IFN-γ level was lower in the AA allele than in the GG allele of rs1861493 both before and after IVIG treatment in KD patients. This study provides the first evidence supporting an association between IFNG gene polymorphisms, susceptibility of KD, IVIG responsiveness, and plasma IFN-γ levels in KD patients. PMID:27124053

  10. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    ERIC Educational Resources Information Center

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in…

  11. Association of polymorphism harbored by tumor necrosis factor alpha gene and sex of calf with lactation performance in cattle.

    PubMed

    Yudin, N S; Aitnazarov, R B; Voevoda, M I; Gerlinskaya, L A; Moshkin, M P

    2013-10-01

    In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of TNFα gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03). The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the TNFα -824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after birth of a

  12. Relationships of OPG Genetic Polymorphisms with Susceptibility to Cardiovascular Disease: A Meta-Analysis.

    PubMed

    Song, De-Hua; Zhou, Peng-Zhen; Xiu, Xiao-Lin; Zhou, Guang-Hui; Sun, Yu-Xia; Song, Chun

    2016-01-01

    BACKGROUND The aim of this meta-analysis was to determine whether genetic polymorphisms in the osteoprotegerin (OPG) gene contribute to increased risk of cardiovascular disease (CVD). MATERIAL AND METHODS Electronic databases were searched carefully without any language restriction. Analyses of data were conducted using STATA software. Odds ratios (OR) and 95% confidence intervals (95%CI) were also calculated. RESULTS Seven clinical case-control studies that enrolled 1170 CVD patients and 1194 healthy subjects were included. The results indicated that OPG gene polymorphism might be closely associated with susceptibility to CVD, especially for rs2073617 T>C and rs2073618 G>C polymorphisms. Ethnicity-stratified analysis indicated that genetic polymorphism in the OPG were closely related with the pathogenesis of CVD among Asians (all P<0.001), but no obvious relationship was found among Caucasians (all P>0.05). CONCLUSIONS Our meta-analysis provided quantitative evidence that OPG gene polymorphism may be closely related to an increased risk of CVD, especially for rs2073617 T>C and rs2073618 G>C polymorphisms. PMID:27068490

  13. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage--a meta-analysis.

    PubMed

    Medica, Igor; Ostojic, Sasa; Pereza, Nina; Kastrin, Andrej; Peterlin, Borut

    2009-09-01

    A meta-analysis of association studies was performed to assess whether the reported genetic polymorphisms in cytokine genes are risk factors for recurrent miscarriage (RM). The electronic PubMed database was searched for case-control studies on immunity-related genes in RM. Investigations of a single polymorphism/gene involvement in RM reported more than five times were selected. Aggregating data from seven case-control studies on -308/tumour necrosis factor-alpha polymorphism, the odds ratio (OR) for RM was 1.1 (0.87-1.39) if the polymorphism was considered under a dominant genetic model. In six studies on -1082/interleukin-10 (IL-10) polymorphism, the OR under a dominant model was 0.76 (0.58-0.99), and under a recessive model the OR was 0.90 (0.71-1.15). In five case-control studies on -174/IL-6 polymorphism, the OR for RM under a recessive model was 1.29 (0.69-2.40). The results show a statistically significant association with RM for the -1082/IL-10 genotype. PMID:19778488

  14. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival

    PubMed Central

    Kong, Jinyu; Xu, Fangxiu; Qu, Jinli; Wang, Yu; Gao, Ming; Yu, Herbert; Qian, Biyun

    2015-01-01

    Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. PMID:25544771

  15. Genetic polymorphism of the LW blood group system.

    PubMed

    Sistonen, P; Green, C A; Lomas, C G; Tippett, P

    1983-10-01

    Family studies of rare LW(a-b+) propositi confirm the recent finding based on frequency studies that the LW blood groups are polymorphic in Finland (Sistonen & Tippett, 1982); they are controlled by two alleles LWa (0.97) and LWb (0.03) independent from most other common blood group loci. Lod scores for LW and the loci for 27 markers are presented. PMID:6418057

  16. Double-stranded RNA viral infection of Trichomonas vaginalis and correlation with genetic polymorphism of isolates.

    PubMed

    Fraga, Jorge; Rojas, Lazara; Sariego, Idalia; Fernández-Calienes, Ayme

    2011-02-01

    Trichomonas vaginalis can be infected with double-stranded RNA (dsRNA) viruses known as T. vaginalis virus (TVV). This viral infection may have important implications for trichomonal virulence and disease pathogenesis. The objective of this study was to determine the possible correlation between the T. vaginalis genetic polymorphism and the isolate infection with TVV. The Random Amplified Polymorphic DNA (RAPD) technique was used to determine genetic differences among 37 isolates of T. vaginalis using a panel of 30 random primers and these genetic data were correlated with the infection of isolates with TVV. The trees drawn based on RAPD data showed significantly association with the presence of TVV (P = 0.028) demonstrating the existence of concordance between the genetic relatedness and the presence of TVV in T. vaginalis isolates. This result could point to a predisposition of T. vaginalis for the viral enters and/or survival. PMID:20875411

  17. Genetic Association Analysis of Dopamine DRD3 Ser9Gly Polymorphism and Schizophrenia in Malay Population

    PubMed Central

    Tee, SF; Tang, PY; Loh, HC

    2011-01-01

    Background: Molecular components of the dopamine receptor (DRD3) play an important role in the pathophysiology of schizophrenia (SCZ). Previous studies have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ but the results have been inconclusive. Method: In this study, we investigated this controversial association between the Ser9Gly (A/G) polymorphism and SCZ using Malay cases-control (261 cases/157 controls) samples. PCR-RFLP was performed to genotype the distribution of the DRD3 Ser9Gly polymorphism. Results: Both healthy control and SCHZ patient groups were in of Hardy-Weinberg equilibrium for the analyzed genetic variability. There was a significant association between the genotype distribution DRD3 polymorphisms and SCZ (χ2= 9.359; df = 2; P = 0.009). Conclusion: We believe that further studies are required to examine the association between others dopamine-related genes and the behavioral phenotypes of SCZ. PMID:23113067

  18. Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism

    SciTech Connect

    Nielsen, D.A.; Goldman, D. ); Dean, M. )

    1992-12-01

    The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformation polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. 37 refs., 2 figs., 1 tab.

  19. Dopaminergic Genetic Polymorphisms Predict Rule-based Category Learning.

    PubMed

    Byrne, Kaileigh A; Davis, Tyler; Worthy, Darrell A

    2016-07-01

    Dopaminergic genes play an important role in cognitive function. DRD2 and DARPP-32 dopamine receptor gene polymorphisms affect striatal dopamine binding potential, and the Val158Met single-nucleotide polymorphism of the COMT gene moderates dopamine availability in the pFC. Our study assesses the role of these gene polymorphisms on performance in two rule-based category learning tasks. Participants completed unidimensional and conjunctive rule-based tasks. In the unidimensional task, a rule along a single stimulus dimension can be used to distinguish category members. In contrast, a conjunctive rule utilizes a combination of two dimensions to distinguish category members. DRD2 C957T TT homozygotes outperformed C allele carriers on both tasks, and DARPP-32 AA homozygotes outperformed G allele carriers on both tasks. However, we found an interaction between COMT and task type where Met allele carriers outperformed Val homozygotes in the conjunctive rule task, but both groups performed equally well in the unidimensional task. Thus, striatal dopamine binding may play a critical role in both types of rule-based tasks, whereas prefrontal dopamine binding is important for learning more complex conjunctive rule tasks. Modeling results suggest that striatal dopaminergic genes influence selective attention processes whereas cortical genes mediate the ability to update complex rule representations. PMID:26918585

  20. Genetic diversity and relationship of chicory (Cichorium intybus L.) using sequence-related amplified polymorphism markers.

    PubMed

    Liang, X Y; Zhang, X Q; Bai, S Q; Huang, L K; Luo, X M; Ji, Y; Jiang, L F

    2014-01-01

    Chicory is a crop with economically important roles and is cultivated worldwide. The genetic diversity and relationship of 80 accessions of chicories and endives were evaluated by sequence-related amplified polymorphism (SRAP) markers to provide a theoretical basis for future breeding programs in China. The polymorphic rate was 96.83%, and the average polymorphic information content was 0.323, suggesting the rich genetic diversity of chicory. The genetic diversity degree of chicory was higher (GS = 0.677) than that of endive (GS = 0.701). The accessions with the highest genetic diversity (effective number of alleles, NE = 1.609; Nei's genetic diversity, H = 0.372; Shannon information index, I = 0.556) were from Italy. The richest genetic diversity was revealed in a chicory line (NE = 1.478, H = 0.289, I = 0.443) among the 3 types (line, wild, and cultivar). The chicory genetic structure of 8 geographical groups showed that the genetic differentiation coefficient (GST) was 14.20% and the number of immigrants per generation (Nm) was 3.020. A GST of 6.80% and an Nm of 6.853 were obtained from different types. This observation suggests that these chicory lines, especially those from the Mediterranean region, have potential for providing rich genetic resources for further breeding programs, that the chicory genetic structure among different countries obviously differs with a certain amount of gene flow, and that SRAP markers could be applied to analyze genetic relationships and classifications of Cichorium intybus and C. endivia. PMID:25299087

  1. Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus.

    PubMed

    Kasim, Nor Bahirah; Huri, Hasniza Zaman; Vethakkan, Shireene Ratna; Ibrahim, Luqman; Abdullah, Bashar Mudhaffar

    2016-01-01

    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM. PMID:26999420

  2. Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk

    PubMed Central

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2015-01-01

    Abstract Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis. Case–control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms. We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR = 1.44, 95% CI = 1.04–1.99, P values for heterogeneity test (Q-test) [PHet] = 0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile + Ile/Ile: OR = 1.41, 95% CI = 1.02–1.95, PHet = 0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR = 1.16, 95% CI = 1.00–1.36, PHet = 0.323; Val/Val + Ile/Val vs Ile/Ile: OR = 1.15, 95% CI = 0.99–1.34, PHet = 0.253). These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations. PMID:26376373

  3. Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk.

    PubMed

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2015-09-01

    Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis. Case-control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms. We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR = 1.44, 95% CI = 1.04-1.99, P values for heterogeneity test (Q-test) [P(Het)] = 0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile + Ile/Ile: OR = 1.41, 95% CI = 1.02-1.95, P(Het) = 0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR = 1.16, 95% CI = 1.00-1.36, P(Het) = 0.323; Val/Val + Ile/Val vs Ile/Ile: OR = 1.15, 95% CI = 0.99-1.34, P(Het) = 0.253). These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations. PMID:26376373

  4. Huangshan population of Chinese Zacco platypus (Teleostei, Cyprinidae) harbors diverse matrilines and high genetic diversity.

    PubMed

    Zheng, Xin; Zhou, Tian-Qi; Wan, Tao; Perdices, Anabel; Yang, Jin-Quan; Tang, Xin-Sheng; Wang, Zheng-Ping; Huang, Li-Qun; Huang, Song; He, Shun-Ping

    2016-03-18

    Six main mitochondrial DNA (mtDNA) lineages have been described in minnow (Zacco platypus) samples obtained from northern, western and southern China. Perdices et al. (2004) predicted that further sampling of other tributaries might discover more lineages of this species. In this study, we collected 26 Zacco platypus individuals in the Huangshan area of eastern China and determined the cytochrome b (cytb) sequence variations. Combined with reported data in GenBank, we identified ten matrilines (Zacco A-J) in a total of 169 samples, with relatively high molecular divergence found among them. The Huangshan population had the greatest genetic variation among all sampled regions and hosted six of the ten matrilines. Our results highlight the significance of the Huangshan area for the conservation of Zacco platypus. PMID:27029868

  5. Huangshan population of Chinese Zacco platypus (Teleostei, Cyprinidae) harbors diverse matrilines and high genetic diversity

    PubMed Central

    ZHENG, Xin; ZHOU, Tian-Qi; WAN, Tao; PERDICES, Anabel; YANG, Jin-Quan; TANG, Xin-Sheng; WANG, Zheng-Ping; HUANG, Li-Qun; HUANG, Song; HE, Shun-Ping

    2016-01-01

    Six main mitochondrial DNA (mtDNA) lineages have been described in minnow (Zacco platypus) samples obtained from northern, western and southern China. Perdices et al. (2004) predicted that further sampling of other tributaries might discover more lineages of this species. In this study, we collected 26 Zacco platypus individuals in the Huangshan area of eastern China and determined the cytochrome b (cytb) sequence variations. Combined with reported data in GenBank, we identified ten matrilines (Zacco A-J) in a total of 169 samples, with relatively high molecular divergence found among them. The Huangshan population had the greatest genetic variation among all sampled regions and hosted six of the ten matrilines. Our results highlight the significance of the Huangshan area for the conservation of Zacco platypus. PMID:27029868

  6. Genetic Variation Between Two Cucumber Genotypes Inferred from Genome-wide Microsatellite Polymorphism Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Variability at microsatellite loci has been used widely to infer the extent of genetic diversity among related plant taxa. However, typically, only the most polymorphic loci in the genome were analyzed that may result in a biased, and generally overestimated picture of genome-wide microsatellite div...

  7. Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral hemorrhage.

    PubMed

    Lee, Jiann-Der; Hsiao, Kuang-Ming; Lee, Tsong-Hai; Kuo, Ya-Wen; Huang, Yen-Chu; Hsu, Huan-Lin; Lin, Ya-Hui; Wu, Chih-Ying; Huang, Ying-Chih; Lee, Meng; Yang, Hsin-Ta; Hsu, Chia-Yu; Pan, Yi-Ting

    2014-02-01

    Intracranial hemorrhage is the third most common cause of cerebrovascular disease. Some polymorphisms that affect clotting factors increase the risk of thrombosis. However, few reports have analyzed the effect of polymorphisms on the hemostatic state in bleeding disorders. The low-density lipoprotein receptor (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the coagulation cascade. Patients with high levels of FVIII are at an increased risk of arterial and venous thrombosis. On the other hand, patients with insufficient FVIII tend to bleed excessively, such as in hemophilia A. In a previous study, analysis of the genetic LDLR variant rs688 provided evidence suggesting that genetic polymorphisms of rs688 are associated with thrombotic cardiovascular diseases. The current study aimed to investigate the potential role of rs688 in primary intracerebral hemorrhage (PICH). This genetic association study was conducted within an isolated Taiwanese population (447 PICH patients and 430 controls). Genotypes C/C and C/T were used as the reference genotypes, and the genotype T/T was found to be associated with a 73% decreased risk of PICH. The preliminary evidence suggests that genetic polymorphisms of LDLR are associated with PICH. PMID:24295502

  8. The application and performance of single nucleotide polymorphism markers for population genetic analyses of Lepidoptera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) are nucleotide substitution mutations that tend to be at high densities within eukaryotic genomes. The development of assays that detect allelic variation at SNP loci is attractive for genome mapping, population genetics, and phylogeographic applications. A p...

  9. VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts.

    PubMed

    Shimada, Makoto K; Matsumoto, Ryuzou; Hayakawa, Yosuke; Sanbonmatsu, Ryoko; Gough, Craig; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Imanishi, Tadashi; Gojobori, Takashi

    2009-01-01

    Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187,156 extensively annotated matured mRNA transcripts from 36,073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion-insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/. PMID:18953038

  10. Application of restriction site amplified polymorphism (RSAP) to genetic diversity in Saccharina japonica

    NASA Astrophysics Data System (ADS)

    Zhao, Cui; Liu, Cui; Li, Wei; Chi, Shan; Feng, Rongfang; Liu, Tao

    2013-07-01

    Restriction site amplified polymorphism (RSAP) was used, for the first time, to analyze the genetic structure and diversity of four, mainly cultivated, varieties of the brown alga, Saccharina japonica. Eighty-eight samples from varieties " Rongfu ", " Fujian ", " Ailunwan " and " Shengchanzhong " were used for the genetic analyses. One hundred and ninety-eight bands were obtained using eight combinations of primers. One hundred and ninety-one (96.46%) were polymorphic bands. Nei's genetic diversity was 0.360, and the coefficient of genetic differentiation was 0.357. No inbreeding-type recession was found in the four brown alga varieties and the results of the " Ailunwan " variety using samples from 2 years showed that the variety was becoming less diverse during the selection inherent in the breeding program. Genetic diversity and cluster analyses results were consistent with these genetic relationships. The results show the RSAP method is suitable for genetic analysis. Continuous inbreeding and selection could reduce the genetic diversity effectively; therefore periodical supervision is required.

  11. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

    PubMed Central

    Banerjee, Monisha; Saxena, Madhukar

    2014-01-01

    Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM. PMID:25126395

  12. Analysis of genetic diversity identified by amplified fragment length polymorphism marker in hybrid wheat.

    PubMed

    Ejaz, M; Qidi, Z; Gaisheng, Z; Na, N; Huiyan, Z; Qunzhu, W

    2015-01-01

    Amplified fragment length polymorphism markers were used to assess genetic diversity in 10 male sterile wheat crop lines (hetero-cytoplasm with the same nucleus) in relation to a restorer wheat line. These male sterile lines were evaluated using 64 amplified fragment length polymorphism primer combinations, and 13 primers produced polymorphic bands, generating a total 682 fragments. Of the 682 fragments, 113 were polymorphic. The polymorphic information content and marker index values demonstrated the utility of the primer combinations used in the present study. Unweighted pair group method with arithmetic mean and principal coordinate analysis of the genotypic data revealed clustering of accessions based on genetic relationships, and accessions were separated into 2 groups with their restorer line. Jaccard's similarity coefficient values suggested good variability among the male sterile lines, indicating their utility in breeding programs. The fallouts of analysis of molecular variance showed large within-group population variation, accounting for 77% of variation, while among-group comparison accounted for 23% of the total molecular variation, which was statistically significant. The molecular diversity observed in this study will be useful for selecting appropriate accessions for plant improvement and hybridization through molecular-breeding approaches and for developing suitable conservation strategies. PMID:26345825

  13. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species

    PubMed Central

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-01-01

    When long-lasting, balancing selection can lead to “trans-species” polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees—more generally, for pairs of species with low genetic diversity levels—these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  14. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species.

    PubMed

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-02-01

    When long-lasting, balancing selection can lead to "trans-species" polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees-more generally, for pairs of species with low genetic diversity levels-these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  15. Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers.

    PubMed

    Seo, Dongwon; Bhuiyan, Md Shamsul Alam; Sultana, Hasina; Heo, Jung Min; Lee, Jun Heon

    2016-04-01

    Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS) markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC) value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market. PMID:26949947

  16. Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers

    PubMed Central

    Seo, Dongwon; Bhuiyan, Md. Shamsul Alam; Sultana, Hasina; Heo, Jung Min; Lee, Jun Heon

    2016-01-01

    Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS) markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC) value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market. PMID:26949947

  17. Physical-capacity-related genetic polymorphisms in children with cystic fibrosis.

    PubMed

    Yvert, Thomas; Santiago, Catalina; Santana-Sosa, Elena; Verde, Zoraida; Gómez-Gallego, Felix; López-Mojares, Luis M; Pérez, Margarita; Garatachea, Nuria; Lucia, Alejandro

    2015-02-01

    In patients with cystic fibrosis (CF), physical capacity (PC) has been correlated with mortality risk. In turn, PC is dependent on genetic factors. This study examines several polymorphisms associated with PC and health-related phenotype traits (VO2peak, FEV1, FVC, PImax and muscular strength) in a group of children with CF (n = 66, primary purpose). The same analyses were also performed in a control group of healthy children (n = 113, secondary purpose). The polymorphisms determined were classified as muscle function polymorphisms (ACE rs1799752; AGT rs699; ACTN3 rs1815739; PTK2 rs7843014 and rs7460; MSTN rs1805086; TRHR rs7832552; NOS3 rs2070744) or energy metabolism polymorphisms (PPARGC1A rs8192678; NRF1 rs6949152; NRF2 rs12594956; TFAM rs1937; PPARD rs2267668; ACSL1 rs6552828). No significant polymorphism/phenotype correlations were detected in children with CF, with marginal associations being observed between NOS3 rs2070744 and VO2peak and FEV1, as well as between PPARGC1A rs8192678 and FEV1. Overall, similar findings were observed in the control group, i.e., no major associations. The PC-related polymorphisms examined seem to have no effects on the PC or health of children with CF. PMID:25051205

  18. [ROLE OF GENETIC POLYMORPHISM AND DIFFERENCES IN THE DETOXIFICATION OF CHEMICAL SUBSTANCES IN THE HUMAN BODY].

    PubMed

    Mogilenkova, L A; Rembovskiy V R

    2016-01-01

    There are given modern views on the role of genetic polymorphism on the detoxification of chemical substances and individual sensitivity in workers to the development of diseases associated with xenobiotics metabolism disorders. In the search for genetic markers of occupationally caused diseases it is promising to study allelomorphs of genes responsible for the polyfunctional response of the human body, including genes involved in xenobiotic biotransformation. There is substantiated the expediency of compilation and introduction of genetic passports for stuff occupied at hazardous chemical enterprises. PMID:27266025

  19. Insertion-deletion polymorphisms (indels) as genetic markers in natural populations

    PubMed Central

    Väli, Ülo; Brandström, Mikael; Johansson, Malin; Ellegren, Hans

    2008-01-01

    Background We introduce the use of short insertion-deletion polymorphisms (indels) for genetic analysis of natural populations. Results Sequence reads from light shot-gun sequencing efforts of different dog breeds were aligned to the dog genome reference sequence and gaps corresponding to indels were identified. One hundred candidate markers (4-bp indels) were selected and genotyped in unrelated dogs (n = 7) and wolves (n = 18). Eighty-one and 76 out of 94 could be validated as polymorphic loci in the respective sample. Mean indel heterozygosity in a diverse set of wolves was 19%, and 74% of the loci had a minor allele frequency of >10%. Indels found to be polymorphic in wolves were subsequently genotyped in a highly bottlenecked Scandinavian wolf population. Fifty-one loci turned out to be polymorphic, showing their utility even in a population with low genetic diversity. In this population, individual heterozygosity measured at indel and microsatellite loci were highly correlated. Conclusion With an increasing amount of sequence information gathered from non-model organisms, we suggest that indels will come to form an important source of genetic markers, easy and cheap to genotype, for studies of natural populations. PMID:18211670

  20. Functional genetic polymorphisms and female reproductive disorders: Part II—endometriosis

    PubMed Central

    Tempfer, C.B.; Simoni, M.; Destenaves, B.; Fauser, B.C.J.M.

    2009-01-01

    BACKGROUND Endometriosis has a strong genetic component, and numerous genetic studies have been reported. METHODS We have systematically reviewed these studies and included 114 in our final selection. RESULTS We found no consistent evidence linking endometriosis with specific polymorphisms in genes encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular function and tissue remodelling. Although a number of polymorphisms have been associated with endometriosis in selected populations, the associations have not been independently confirmed, either because only single studies were carried out on these markers/genes or because other studies reported no association. The most solid evidence linking specific polymorphisms to endometriosis came from studies investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of the GSTT1 null deletion variant showed consistent association with endometriosis with a 29% increased risk; however, it cannot be excluded that this result was due to publication bias, and this association should be independently confirmed in large-scale, well-designed case–control studies. CONCLUSIONS The evidence of an association between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1 null deletion may moderately increase the risk of this disease. We suggest that the methodology of association studies should be improved in order to identify and validate associations in endometriosis. PMID:18805939

  1. Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review.

    PubMed

    Longhi, Renata Maronna Praça; Zembrzuski, Verônica Marques; Basta, Paulo Cesar; Croda, Julio

    2013-01-01

    We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1- or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-α, IL-12p40 and IFN-γ production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease. PMID:23665009

  2. Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers.

    PubMed

    da Cunha Martins, Airton; Mazzaron Barcelos, Gustavo Rafael; Jacob Ferreira, Anna Laura Bechara; de Souza, Marilesia Ferreira; de Syllos Cólus, Ilce Mara; Antunes, Lusânia Maria Greggi; Bastos Paoliello, Monica Maria; Adeyemi, Joseph A; Barbosa, Fernando

    2015-01-01

    Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb. PMID:26275098

  3. Maize genetic diversity and association mapping using transposable element insertion polymorphisms.

    PubMed

    Zerjal, Tatiana; Rousselet, Agnès; Mhiri, Corinne; Combes, Valérie; Madur, Delphine; Grandbastien, Marie-Angèle; Charcosset, Alain; Tenaillon, Maud I

    2012-05-01

    Transposable elements are the major component of the maize genome and presumably highly polymorphic yet they have not been used in population genetics and association analyses. Using the Transposon Display method, we isolated and converted into PCR-based markers 33 Miniature Inverted Repeat Transposable Elements (MITE) polymorphic insertions. These polymorphisms were genotyped on a population-based sample of 26 American landraces for a total of 322 plants. Genetic diversity was high and partitioned within and among landraces. The genetic groups identified using Bayesian clustering were in agreement with published data based on SNPs and SSRs, indicating that MITE polymorphisms reflect maize genetic history. To explore the contribution of MITEs to phenotypic variation, we undertook an association mapping approach in a panel of 367 maize lines phenotyped for 26 traits. We found a highly significant association between the marker ZmV1-9, on chromosome 1, and male flowering time. The variance explained by this association is consistent with a flowering delay of +123 degree-days. This MITE insertion is located at only 289 nucleotides from the 3' end of a Cytochrome P450-like gene, a region that was never identified in previous association mapping or QTL surveys. Interestingly, we found (i) a non-synonymous mutation located in the exon 2 of the gene in strong linkage disequilibrium with the MITE polymorphism, and (ii) a perfect sequence homology between the MITE sequence and a maize siRNA that could therefore potentially interfere with the expression of the Cytochrome P450-like gene. Those two observations among others offer exciting perspectives to validate functionally the role of this region on phenotypic variation. PMID:22350086

  4. Genetic polymorphism of MMP family and coronary disease susceptibility: a meta-analysis.

    PubMed

    Li, Min; Shi, Jingpu; Fu, Lingyu; Wang, Hailong; Zhou, Bo; Wu, Xiaomei

    2012-03-01

    The issue that genetic polymorphism of matrix metalloproteinase (MMP) family is in association with coronary disease is controversial. So we did a meta-analysis to clarify it clearly. We made a literature search of PubMed, the Web of Science, and Cochrane Collaboration's database to identify eligible reports. The methodological quality of each included studies was assessed. We calculated the pooled ORs with their 95%CI for each genetic polymorphism in STATA 11 software. Separate analysis was performed to address the consistency of results across the subgroup with different continents. A total of 39 studies were included, with a sample of 42269 individuals. This meta-analysis provided evidence that genetic polymorphism of MMP1-1607 1G/2G, MMP3-Gly45lys, MMP3-376 G/C, MMP3-1171 5A/6A, MMP9-1562 C/T and MMP9-R279Q have a small to medium effect on incidence of coronary disease. There was no evidence that MMP1-519 A/G, MMP1-340 T/C and MMP2-1306 C/T polymorphism could increase risk of coronary disease. Results from subgroup analysis supported a relation between MMP3-1711 5A allele, MMP9-1562 C allele and coronary disease especially in Asian population. The results provide moderate association between the six common genetic polymorphism of matrix metalloproteinase family and coronary disease. However, the challenge for researcher is identifying separate effect on different races. PMID:22226810

  5. Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling

    PubMed Central

    de Albuquerque, Felipe Neves; Brandão, Andréa Araujo; da Silva, Dayse Aparecida; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; de Albuquerque, Denilson Campos

    2014-01-01

    Background The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. Objective To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Methods Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). Results The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0

  6. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    PubMed Central

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  7. Genetic Aberrations in Childhood Acute Lymphoblastic Leukaemia: Application of High-Density Single Nucleotide Polymorphism Array

    PubMed Central

    Sulong, Sarina

    2010-01-01

    Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip® Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia. PMID:22135543

  8. Genetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms.

    PubMed

    Frank, M J; Hutchison, K

    2009-11-24

    Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 function, respectively. Nevertheless, whereas the role for dopamine in positive learning is relatively well accepted, that in learning to avoid negative outcomes is more controversial. Here we further explore D2-receptor-related genetic contributions to probabilistic avoidance in humans, in light of recent data showing that particular DRD2 polymorphisms are associated with functional modulation of receptor expression [Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee M-LT, Xiao T, Papp A, Wang D, Sadée W (2007) Polymorphisms in human dopamine d2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A 104(51):20552-20557]. We find that a promoter polymorphism rs12364283 associated with transcription and D2 receptor density was strongly and selectively predictive of avoidance-based decisions. Two further polymorphisms (rs2283265 and rs1076560) associated with relatively reduced presynaptic relative to postsynaptic D2 receptor expression were predictive of relative impairments in negative compared to positive decisions. These previously undocumented effects of DRD2 polymorphisms were largely independent of those we reported previously for the C957T polymorphism (rs6277) associated with striatal D2 density. In contrast, effects of the commonly studied Taq1A polymorphism on reinforcement-based decisions were due to indirect association with C957T. Taken together these findings suggest multiple D2-dependent

  9. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

    PubMed Central

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). Conclusions VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  10. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population.

    PubMed

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    BACKGROUND VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1-1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. MATERIAL AND METHODS A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1-1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. RESULTS Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1-1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1-1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). CONCLUSIONS VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  11. Genetic polymorphisms associated with breast cancer in malaysian cohort.

    PubMed

    Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy

    2015-04-01

    Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ≤ 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction. PMID:25883419

  12. [Genetic polymorphisms commonly associated with sensitivity to various addictive substances].

    PubMed

    Nishizawa, Daisuke; Ikeda, Kazutaka

    2013-11-01

    Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. The authors have focused on G-protein-activated inwardly rectifying potassium (GIRK) channel subunits, GIRK2 and GIRK3, which are important molecules in opioid transmission, and found that the SNPs within the GIRK2 and GIRK3 gene region were significantly associated with postoperative analgesic requirements, one of which was also associated with vulnerability to methamphetamine (METH) dependence. Further, by conducting a multistage genome-wide association study (GWAS) in healthy subjects, the authors found that the rs2952768 single-nucleotide polymorphism (SNP) was strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery and consistent results were obtained in patients who underwent abdominal surgery. In addition, the SNP also showed significant association with vulnerability to severe drug dependence in patients with METH dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. These outcomes provide valuable information for the personalized treatment of pain and drug dependence. PMID:25069259

  13. Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma

    PubMed Central

    Sun, Yongjian; Wu, Yi; Li, Weicheng; Kong, Zhen; Zou, Xiaoming

    2015-01-01

    We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma. PMID:26339355

  14. Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma.

    PubMed

    Sun, Yongjian; Wu, Yi; Li, Weicheng; Kong, Zhen; Zou, Xiaoming

    2015-01-01

    We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma. PMID:26339355

  15. Genetic markers for detection of Escherichia coli K-12 harboring ampicillin-resistance plasmid from an industrial wastewater treatment effluent pond.

    PubMed

    Simões, G A R; Xavier, M A S; Oliveira, D A; Menezes, E V; Magalhães, S S G; Gandra, J A C D; Xavier, A R E O

    2016-01-01

    Biotechnology industries that use recombinant DNA technology are potential sources for release of genetically modified organisms to the environment. Antibiotic-resistance marker genes are commonly used for recombinant bacteria selection. One example is the marker gene coding for β-lactamase (bla) in plasmids found in Escherichia coli K-12. The aim of this study was to provide an approach to develop a molecular method for genetic marker detection in E. coli K-12 harboring bla genes from an industrial wastewater treatment effluent pond (IWTEP). For the detection of bla and Achromobacter lyticus protease I (api) genes in samples from IWTEP, we employed multiplex polymerase chain reaction (PCR) using E. coli K-12 genetic marker detection primers, previously described in the literature, and primers designed in our laboratory. The microbiological screening method resulted in 22 bacterial colony-forming units isolated from three different IWTEP harvesting points. The multiplex PCR amplicons showed that five isolates were positive for the bla gene marker and negative for the E. coli K-12 and api genes. The 16S rRNA regions of positive microorganisms carrying the bla gene were genotyped by the MicroSeq®500 system. The bacteria found were Escherichia spp (3/5), Chromobacterium spp (1/5), and Aeromonas spp (1/5). None of the 22 isolated microorganisms presented the molecular pattern of E. coli K-12 harboring the bla gene. The presence of microorganisms positive for the bla gene and negative for E. coli K-12 harboring bla genes at IWTEP suggests that the ampicillin resistance found in the isolated bacteria could be from microorganisms other than the E. coli K-12 strain harboring plasmid. PMID:27323199

  16. Genetic diversity in Capsicum germplasm based on microsatellite and random amplified microsatellite polymorphism markers.

    PubMed

    Rai, Ved Prakash; Kumar, Rajesh; Kumar, Sanjay; Rai, Ashutosh; Kumar, Sanjeet; Singh, Major; Singh, Sheo Pratap; Rai, Awadesh Bahadur; Paliwal, Rajneesh

    2013-10-01

    A sound knowledge of the genetic diversity among germplasm is vital for strategic germplasm collection, maintenance, conservation and utilisation. Genomic simple sequence repeats (SSRs) and random amplified microsatellite polymorphism (RAMPO) markers were used to analyse diversity and relationships among 48 pepper (Capsicum spp.) genotypes originating from nine countries. These genotypes covered 4 species including 13 germplasm accessions, 30 improved lines of 4 domesticated species and 5 landraces derived from natural interspecific crosses. Out of 106 SSR markers, 25 polymorphic SSR markers (24 %) detected a total of 76 alleles (average, 3.04; range, 2-5). The average polymorphic information content (PIC) was 0.69 (range, 0.29-0.92). Seventeen RAMPO markers produced 87 polymorphic fragments with average PIC of 0.63 (range, 0.44-0.81). Dendrograms based on SSRs and RAMPOs generated two clusters. All 38 Capsicum annuum genotypes and an interspecific landrace clustered together, whereas nine non-annuum (three Capsicum frutescens, one Capsicum chinense, one Capsicum baccatum and four interspecific landraces) genotypes clustered separately. Genetic variation within non-annuum genotypes was greater than the C. annuum genotypes. Distinctness of interspecific derivative landraces grown in northeast India was validated; natural crossing between sympatric Capsicum species has been proposed as the mechanism of their origin. PMID:24431527

  17. Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle

    PubMed Central

    Kim, B. S.; Kim, S. C.; Park, C. M.; Lee, S. H.; Cho, S. H.; Kim, N. K.; Jang, G. W.; Yoon, D. H.; Yang, B. S.; Hong, S. K.; Seong, H. H.; Choi, B. H.

    2013-01-01

    The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle. PMID:25049850

  18. [Genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population].

    PubMed

    Chen, Zhen-Bin; Zhu, Jin-Ling; Yan, Mei; Liang, Yan; Zhou, Yan; Tan, Shu-Zhen; Xiao, Bai; Liu, Jing-Zhong

    2004-07-01

    To elucidate the genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population and construct a preliminary database, EDTA-blood specimens were collected from unrelated individuals in Beijing. The DNAs were extracted with Chelex method and were amplified by PCR. The PCR products were analyzed by the PAG electrophoresis or by the approach of the automated fluorescent detection. The five STR loci consist of simple repeat motif and its distributions of genotypes are agreement with Hardy-Weinberg equation. Its polymorphism information content is all over 0.50. The obtained data can not only be used as evidences for genetic diagnosis of Down Syndrome, but also for calculating the probabilities in the paternity test and individual identification. PMID:15640034

  19. Polymorphism, Genetic Effect and Association with Egg Production Traits of Chicken Matrix Metalloproteinases 9 Promoter

    PubMed Central

    Zhu, Guiyu; Jiang, Yunliang

    2014-01-01

    Matrix metalloproteinases (MMP) are key enzymes involved in cell and tissue remodeling during ovarian follicle development and ovulation. The control of MMP9 transcription in ovarian follicles occurs through a core promoter region (−2,400 to −1,700 bp). The aim of this study was to screen genetic variations in the core promoter region and examine MMP9 transcription regulation and reproduction performance. A single cytosine deletion/insertion polymorphism was found at −1954 C+/C−. Genetic association analysis indicated significant correlation between the deletion genotype (C−) with total egg numbers at 28 weeks (p = 0.031). Furthermore, luciferase-reporter assay showed the deletion genotype (C−) had significantly lower promoter activity than the insertion genotype (C+) in primary granulosa cells (p<0.01). Therefore, the identified polymorphism could be used for marker-assisted selection to improve chicken laying performance. PMID:25358310

  20. Genetic Polymorphism Characteristics of Brucella canis Isolated in China

    PubMed Central

    Wang, Heng; Zhao, Hongyan; Piao, Dongri; Tian, Lili; Tian, Guozhong; Kang, Jingli; Mao, Xiang; Zhang, Xiaojun; Du, Pengfei; Zhu, Lin; Zhao, Zhuo; Mao, Lingling; Yao, Wenqing; Guan, Pingyuan; Fan, Weixing; Jiang, Hai

    2014-01-01

    In China, brucellosis is an endemic disease typically caused by Brucella melitensis infection (biovars 1 and 3). Brucella canis infection in dogs has not traditionally recognized as a major problem. In recent years however, brucellosis resulting from Brucella canis infection has also been reported, suggesting that infections from this species may be increasing. Data concerning the epidemiology of brucellosis resulting from Brucella canis infection is limited. Therefore, the purpose of this study was to assess the diversity among Chinese Brucella canis strains for epidemiological purposes. First, we employed a 16-marker VNTR assay (Brucella MLVA-16) to assess the diversity and epidemiological relationship of 29 Brucella canis isolates from diverse locations throughout China with 38 isolates from other countries. MLVA-16 analysis separated the 67 Brucella canis isolates into 57 genotypes that grouped into five clusters with genetic similarity coefficients ranging from 67.73 to 100%. Moreover, this analysis revealed a new genotype (2-3-9-11-3-1-5-1:118), which was present in two isolates recovered from Guangxi in 1986 and 1987. Second, multiplex PCR and sequencing analysis were used to determine whether the 29 Chinese Brucella canis isolates had the characteristic BMEI1435 gene deletion. Only two isolates had this deletion. Third, amplification of the omp25 gene revealed that 26 isolates from China had a T545C mutation. Collectively, this study reveals that considerable diversity exists among Brucella canis isolates in China and provides resources for studying the genetic variation and microevolution of Brucella. PMID:24465442

  1. Genetic relatedness of artichoke (Cynara scolymus L.) hybrids using random amplified polymorphic DNA (RAPD) fingerprinting.

    PubMed

    Sharaf-Eldin, M A; Al-Tamimi, A; Alam, P; Elkholy, S F; Jordan, J R

    2015-01-01

    The artichoke (Cynara scolymus L.) is an important food and medicinal crop that is cultivated in Mediterranean countries. Morphological characteristics, such as head shape and diameter, leaf shape, and bract shape, are mainly affected by environmental conditions. A molecular marker approach was used to analyze the degree of polymorphism between artichoke hybrid lines. The degree of genetic difference among three artichoke hybrids was evaluated using random amplified polymorphic DNA-PCR (RAPD-PCR). In this study, the DNA fingerprints of three artichoke lines (A13-010, A11-018, and A12-179) were generated, and a total of 10 decamer primers were applied for RAPD-PCR analyses. Polymorphism  (16.66 to 62.50%) was identified using eight arbitrary decamers and total genomic DNA extracted from the hybrids. Of the 59 loci detected, there were 25 polymorphic and 34 monomorphic loci. Jaccard's similarity index (JSI) ranged between 1.0 and 0.84. Based on the unweighted pair group method with arithmetic mean (UPGMA) similarity matrix and dendrogram, the results indicated that two hybrids (A13-010 and A11-018) were closely related to each other, and the A12-179 line showed more divergence. When identifying correct accessions, consideration of the genetic variation and genetic relationships among the genotypes are required. The RAPD-PCR fingerprinting of artichoke lines clearly showed that it is possible to analyze the RAPD patterns for correlation between genetic means and differences or resemblance between close accessions (A13-010 and A11- 018) at the genomic level. PMID:26782491

  2. 4P: fast computing of population genetics statistics from large DNA polymorphism panels.

    PubMed

    Benazzo, Andrea; Panziera, Alex; Bertorelle, Giorgio

    2015-01-01

    Massive DNA sequencing has significantly increased the amount of data available for population genetics and molecular ecology studies. However, the parallel computation of simple statistics within and between populations from large panels of polymorphic sites is not yet available, making the exploratory analyses of a set or subset of data a very laborious task. Here, we present 4P (parallel processing of polymorphism panels), a stand-alone software program for the rapid computation of genetic variation statistics (including the joint frequency spectrum) from millions of DNA variants in multiple individuals and multiple populations. It handles a standard input file format commonly used to store DNA variation from empirical or simulation experiments. The computational performance of 4P was evaluated using large SNP (single nucleotide polymorphism) datasets from human genomes or obtained by simulations. 4P was faster or much faster than other comparable programs, and the impact of parallel computing using multicore computers or servers was evident. 4P is a useful tool for biologists who need a simple and rapid computer program to run exploratory population genetics analyses in large panels of genomic data. It is also particularly suitable to analyze multiple data sets produced in simulation studies. Unix, Windows, and MacOs versions are provided, as well as the source code for easier pipeline implementations. PMID:25628874

  3. Recombination within a Subclass of Restriction Fragment Length Polymorphisms May Help Link Classical and Molecular Genetics

    PubMed Central

    Meagher, R. B.; McLean, M. D.; Arnold, J.

    1988-01-01

    Restriction fragment length polymorphisms (RFLPs) are being used to construct complete linkage maps for many eukaryotic genomes. These RFLP maps can be used to predict the inheritance of important phenotypic loci and will assist in the molecular cloning of linked gene(s) which affect phenotypes of scientific, medical and agronomic importance. However, genetic linkage implies very little about the actual physical distances between loci. An assay is described which uses genetic recombinants to measure physical distance from a DNA probe to linked phenotypic loci. We have defined the subset of all RFLPs which have polymorphic restriction sites at both ends as class II RFLPs. The frequency of class II RFLPs is computed as a function of sequence divergence and total RFLP frequency for highly divergent genomes. Useful frequencies exist between organisms which differ by more than 7% in DNA sequence. Recombination within class II RFLPs will produce fragments of novel sizes which can be assayed by pulsed field electrophoresis to estimate physical distance in kilobase pairs between linked RFLP and phenotypic loci. This proposed assay should have particular applications to crop plants where highly divergent and polymorphic species are often genetically compatible and thus, where class II RFLPs will be most frequent. PMID:2906304

  4. The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

    PubMed Central

    de Almeida, Elaine Regina Delicato; Reiche, Edna Maria Vissoci; Flauzino, Tamires; Watanabe, Maria Angelica Ehara

    2013-01-01

    Dyslipidemia has been frequently observed among individuals infected with human immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host, and antiretroviral therapy (ART) are involved in this phenomenon. This study reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary according to the HAART regimen, such as those with protease inhibitors (PIs). However, genetic factors may also be involved in dyslipidemia because not all patients receiving the same HAART regimen and with comparable demographic, virological, and immunological characteristics develop variations in the lipid profile. Polymorphisms in a large number of genes are involved in the synthesis of structural proteins, and enzymes related to lipid metabolism account for variations in the lipid profile of each individual. As some genetic polymorphisms may cause dyslipidemia, these allele variants should be investigated in HIV-1-infected patients to identify individuals with an increased risk of developing dyslipidemia during treatment with HAART, particularly during therapy with PIs. This knowledge may guide individualized treatment decisions and lead to the development of new therapeutic targets for the treatment of dyslipidemia in these patients. PMID:24319689

  5. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, Sandra; Palmer, A.G.; Sage, G.K.; Sonsthagen, Sarah A.; Swem, T.; Brimm, D.J.

    2014-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency.

  6. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, S.L.; Palmer, A.G.; Sage, G.K.; Sonsthagen, S.A.; Swem, T.; Brimm, D.J.; White, C.M.

    2011-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency. ?? 2011 The Authors.

  7. Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn’s disease

    PubMed Central

    Gao, Su-Jun; Zhang, Li; Lu, Wei; Wang, Lu; Chen, Lei; Zhu, Zhen; Zhu, Hai-Hang

    2015-01-01

    AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn’s disease (CD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st, 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated. RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual’s susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05). CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These

  8. Association between seven common OPG genetic polymorphisms and osteoporosis risk: a meta-analysis.

    PubMed

    Guo, Liang; Tang, Ke; Quan, Zhengxue; Zhao, Zenghui; Jiang, Dianming

    2014-01-01

    Functional polymorphisms of the osteoprotegerin (OPG) gene are known to be involved in bone mineral density and the development of osteoporosis; however, some conflicting results have been reported. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the relationship between seven common OPG genetic polymorphisms (T149C, A163G, G209A, T245G, T950C, G1181C, and C1217T) and osteoporosis risk. A literature search for eligible studies published before August 1st, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI (China National Knowledge Infrastructure) databases. Pooled odds ratios and their corresponding 95% confidence intervals were used to evaluate the strength of the association under fixed- or random-effect models according to a heterogeneity test. All analyses were performed using the STATA software, version 12.0. Fourteen case-control studies with a total of 2383 osteoporosis cases and 2280 healthy controls were included in this meta-analysis. Among the seven polymorphisms, A163G and G1181C revealed significant associations with osteoporosis risk. For A163G (rs3102735), the combined results showed that the G allele of the A163G polymorphism may be associated with an increased risk of osteoporosis. Stratified analyses showed that the magnitude of the effect was similar in Caucasian and postmenopausal woman subgroups. For G1181C (rs2073618), however, we found that individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asian and postmenopausal woman subgroups. In summary, this meta-analysis indicated that the G allele of the OPG A163G polymorphism might increase osteoporosis risk in Caucasians, whereas individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asians. Both of these effects were observed in postmenopausal women. These polymorphisms could probably be used with other genetic markers

  9. Identification of trends in scientific publications related to genetic polymorphisms in gestational diabetes mellitus.

    PubMed

    Gomes, J S; Minasi, L B; da Cruz, A D; Rodrigues, F M

    2016-01-01

    Gestational diabetes is a genetic multifactorial systemic disease that has been extensively studied. Consequently, there is a large volume of scientific literature pertaining to genes associated with gestational diabetes. The aim of this study was to characterize the main trends in scientific publications focusing on the associations between genetic polymorphisms and gestational diabetes mellitus (GDM). The related articles were extracted from Scopus using the key words "genetic polymorphism" and "gestational diabetes mellitus"; the collected data focused on various fields (medical, biochemical, etc.) and included papers published within December 2013. One hundred and eighty-three relevant articles published between 1987 and 2013 were identified; we observed a significantly increasing trend in the number of publications pertaining to GDM. A majority of the articles focused on the medical (59.9%), biochemical, and genetics and molecular biological (29.6%) aspects of the disease. The genes coding for transcription factor 7-like 2 and glucokinase (TCF7L2, 29% and GCK, 28%) were predominantly studied and reported. This study helped quantify the growth in research pertaining to GDM; researchers from the USA have published a majority of the publications related to GDM. Several candidate genes have been linked to diabetes; however, the specific gene locus responsible for GDM has not yet been identified. The results of this study could help determine the orientation of future research on genetic factors associated with GDM. PMID:27173344

  10. Polymorphic simple sequence repeat regions in chloroplast genomes: applications to the population genetics of pines.

    PubMed Central

    Powell, W; Morgante, M; McDevitt, R; Vendramin, G G; Rafalski, J A

    1995-01-01

    Simple sequence repeats (SSRs), consisting of tandemly repeated multiple copies of mono-, di-, tri-, or tetranucleotide motifs, are ubiquitous in eukaryotic genomes and are frequently used as genetic markers, taking advantage of their length polymorphism. We have examined the polymorphism of such sequences in the chloroplast genomes of plants, by using a PCR-based assay. GenBank searches identified the presence of several (dA)n.(dT)n mononucleotide stretches in chloroplast genomes. A chloroplast (cp) SSR was identified in three pine species (Pinus contorta, Pinus sylvestris, and Pinus thunbergii) 312 bp upstream of the psbA gene. DNA amplification of this repeated region from 11 pine species identified nine length variants. The polymorphic amplified fragments were isolated and the DNA sequence was determined, confirming that the length polymorphism was caused by variation in the length of the repeated region. In the pines, the chloroplast genome is transmitted through pollen and this PCR assay may be used to monitor gene flow in this genus. Analysis of 305 individuals from seven populations of Pinus leucodermis Ant. revealed the presence of four variants with intrapopulational diversities ranging from 0.000 to 0.629 and an average of 0.320. Restriction fragment length polymorphism analysis of cpDNA on the same populations previously failed to detect any variation. Population subdivision based on cpSSR was higher (Gst = 0.22, where Gst is coefficient of gene differentiation) than that revealed in a previous isozyme study (Gst = 0.05). We anticipate that SSR loci within the chloroplast genome should provide a highly informative assay for the analysis of the genetic structure of plant populations. Images Fig. 2 PMID:7644491

  11. Association between ABCB1 genetic polymorphism and the effect on epilepsy following phenytoin treatment

    PubMed Central

    Sun, Fei; Cao, Bo-Qiang; Wang, Bo; Wu, Shi-Qiang; Jiang, De-Hua

    2016-01-01

    The aim of the study was to analyze the effect of ABCB1 genetic polymorphisms on the efficacy of phenytoin (PHT) treatment in epilepsy patients. In total, 200 epilepsy patients who were administered PHT were divided into the responsive and pharmaco-resistance groups depending on the clinical data of PHT treatment in epilepsy patients. The serum concentration of PHT was detected by high-performance liquid chromatography (HPLC). ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction-fragment length polymorphism method. The C1236T, C3435T and G2677T/A haplotypes were reconstructed for the ABCB1 gene using SHEsis programs. One-way analysis of variance was used for data analysis. In ABCB1 C1236T, the rate of the CC genotype in pharmaco-resistance (17.5%) was higher than that of the responsive group (2.1%), while the rate of the TT genotype in pharmaco-resistance (41.6%) was lower than that of the responsive group (55.4%) (P<0.05). In ABCB1 G2677T/A, the rate of the GG genotype in pharmaco-resistance (29.6%) was higher than that of the responsive group (9.7%), while the rate of the TT genotype in pharmaco-resistance (4.6%) was lower than that of the responsive group (30.4%) (P<0.05). The rate of the TTC haploid in pharmaco-resistance (24.1%) was higher than that of the responsive group (8.8%) (P<0.05). The PHT serum concentration had no statistical significance in the patients with different genotypes. In conclusion, there was no association between ABCB1 genetic polymorphism and PHT serum concentration, although the polymorphisms affected the efficacy of PHT treatment in patients with epilepsy. PMID:27602091

  12. COMT val158met and 5-HTTLPR Genetic Polymorphisms Moderate Executive Control in Cannabis Users

    PubMed Central

    Verdejo-García, Antonio; Beatriz Fagundo, Ana; Cuenca, Aida; Rodriguez, Joan; Cuyás, Elisabet; Langohr, Klaus; de Sola Llopis, Susana; Civit, Ester; Farré, Magí; Peña-Casanova, Jordi; de la Torre, Rafael

    2013-01-01

    The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of Δ9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions. PMID:23449176

  13. Novel Polymorphic Microsatellite Markers Reveal Genetic Differentiation between Two Sympatric Types of Galaxea fascicularis

    PubMed Central

    Nakajima, Yuichi; Shinzato, Chuya; Satoh, Noriyuki; Mitarai, Satoshi

    2015-01-01

    The reef-building, scleractinian coral, Galaxea fascicularis, is classified into soft and hard types, based on nematocyst morphology. This character is correlated with the length of the mitochondrial non-coding region (mt-Long: soft colony type, and nematocysts with wide capsules and long shafts; mt-Short: hard colony type, and nematocysts with thin capsules and short shafts). We isolated and characterized novel polymorphic microsatellite markers for G. fascicularis using next-generation sequencing. Based upon the mitochondrial non-coding region, 53 of the 97 colonies collected were mt-Long (mt-L) and 44 were mt-Short (mt-S). Among the 53 mt-L colonies, 27 loci were identified as amplifiable, polymorphic microsatellite loci, devoid of somatic mutations and free of scoring errors. Eleven of those 27 loci were also amplifiable and polymorphic in the 44 mt-S colonies; these 11 are cross-type microsatellite loci. The other 16 loci were considered useful only for mt-L colonies. These 27 loci identified 10 multilocus lineages (MLLs) among the 53 mt-L colonies (NMLL/N = 0.189), and the 11 cross-type loci identified 7 MLLs in 44 mt-S colonies (NMLL/N = 0.159). Significant genetic differentiation between the two types was detected based on the genetic differentiation index (FST = 0.080, P = 0.001). Bayesian clustering also indicated that these two types are genetically isolated. While nuclear microsatellite genotypes also showed genetic differentiation between mitochondrial types, the mechanism of divergence is not yet clear. These markers will be useful to estimate genetic diversity, differentiation, and connectivity among populations, and to understand evolutionary processes, including divergence of types in G. fascicularis. PMID:26147677

  14. CYP2D6 Genetic Polymorphisms and Phenotypes in Different Ethnicities of Malaysian Breast Cancer Patients.

    PubMed

    Chin, Fee Wai; Chan, Soon Choy; Abdul Rahman, Sabariah; Noor Akmal, Sharifah; Rosli, Rozita

    2016-01-01

    The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the

  15. Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea.

    PubMed

    Dogru, Hatice Yilmaz; Ozsoy, Asker Zeki; Karakus, Nevin; Delibas, Ilhan Bahri; Isguder, Cigdem Kunt; Yigit, Serbulent

    2016-08-01

    Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF -173 and TNF -308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF -173G > C promoter polymorphism (rs755622) and TNF gene -308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position -173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position -308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene -173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of -308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α -308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea. PMID:27105877

  16. Genetic polymorphisms of TNFA and IL-1A and generalized aggressive periodontitis.

    PubMed

    Barnea, Teodora Virginia; Sava, Anca; Gentimir, Carmen; Goriuc, Ancuţa; Boişteanu, Otilia; Chelaru, Liliana; Iancu, Roxana Irina; Avram, Cătălina Anda; Acatrinei, Dragoş Daniel; Bogza, Elena Geanina; Răducanu, Oana Cristina; Cioloca, Daniel Petru; Vasincu, Decebal; Costuleanu, Marcel

    2015-01-01

    Virulent bacteria could cause gingival fibroblasts apoptosis through lipopolysaccharide release during generalized aggressive periodontitis (GAgP) development and evolution. We showed that treatment with lipopolysaccharide (LPS, 1 μg/mL) for 30 days induced the decrease in the number of cultured rat gingival fibroblasts as compared to control group, which received no treatment. GAgP is considered to have also a genetic etiology, so the aim of our study was to evaluate if some polymorphisms of tumor necrosis factor-alpha (TNFA) and interleukin 1A (IL-1A) genes are associated with GAgP in a sample of Romanian population. We selected a group of 32 subjects (22 cases and 10 controls) for studying the TNFA (-857) polymorphism and 97 subjects (66 cases and 31 controls) for IL-1A (-889) polymorphism. The single nucleotide polymorphisms were genotyped by real-time polymerase chain reaction for all subjects. The genotype and allelic distribution tended to be equally between the cases and the controls group. Similar results were obtained for the dominant and recessive model. The difference between the two groups did not reach statistic significance for neither of the two studied polymorphisms [p=0.76 for TNFA (-857) and p=0.84 for IL-1A (-889)]. The data suggest that TNFA (-857) C/T and IL-1A (-889) C/T polymorphisms are not associated with susceptibility to GAgP in this Romanian population, potentially because of the small sample size. This is the first such study for Romanian northeastern population. PMID:26193214

  17. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    PubMed Central

    Skjelbred, Camilla F; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M; Hoff, Geir; Kure, Elin H

    2007-01-01

    Background The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. Methods We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. Results A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Conclusion Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma. PMID:18093316

  18. Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.

    PubMed

    Kim, Dojung; Lee, Young-Joo; Ryu, Heui-Young; Lee, Jin-Hee; Kim, Hyun-Kyung; Kim, Eunhee; Moon, Jae-Dong; Chang, Dong Deuk; Yoon, Hae-Seong

    2013-01-01

    Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk. PMID:22131055

  19. [Does a genetic predisposition for infarction expansion exist? Evaluation of genetic polymorphisms of the renin-angiotensin system].

    PubMed

    Zedda, N; Onnis, E; Angius, A; Balata, F; Cherchi, P A; Sole, G; Olla, N; Poddie, D; Cao, A; Cherchi, A; Pirastu, M

    1997-03-01

    Aim of this study is to carry out a genetic analysis of polymorphisms of the renin-angiotensin system in a genetically homogeneous population, in patients with and without myocardial infarction (AMI) expansion and to evaluate the influence of non genetic, mechanical factors. The study was conducted on 299 patients with first AMI. Ecocardiography studies were performed on all patients on day 1 and 3 from the onset of AMI and before discharge. Eighty-four patients were excluded because of inadequate quality of echocardiograms and 215 (163 males, 52 females) were admitted. Of these, 157 had no evidence of AMI expansion (EXP-) while 58 had expansion (EXP+). DNA was extracted by standard methods from blood samples. Age and gender had no influence on AMI expansion. Anterior infarction (p < 0.000001) and Q-wave infarction (p < 0.00002) were found more frequently in EXP+. Peak of creatine phosphokinase was higher in EXP+ than in EXP- (p < 0.00001). The percent of patients treated with thrombolysis or with hypertension and/or left ventricular hypertrophy was not significantly different in the two groups. AGT MT235 polymorphism of angiotensinogen gene, I/D polymorphism of ACE gene and AT1 A1166C of AT1 receptor of angiotensin II were not significantly different in two groups. Stratified analysis showed that in patients with anterior AMI (n = 87), with a higher risk of AMI expansion, there is a significant difference (p < 0.02) in ACE genotype between EXP- and EXP+. Odds ratio assuming the dominant effect of I allele (II+ ID < DD) was 3.35 (confidence interval 1.41-7.56) with increased risk of expansion. More extension studies are need to verify if these results can contribute to early identification of patients at higher risk and to optimize therapeutic approach. PMID:9172934

  20. Mycoplasma hominis in Cuban Trichomonas vaginalis isolates: association with parasite genetic polymorphism.

    PubMed

    Fraga, Jorge; Rodríguez, Nadia; Fernández, Carmen; Mondeja, Brian; Sariego, Idalia; Fernández-Calienes, Aymé; Rojas, Lazara

    2012-07-01

    Trichomonas vaginalis can be naturally infected with intracellular Mycoplasma hominis. This bacterial infection may have implications for trichomonal virulence and disease pathogenesis. The objective of the study was to report the presence of M. hominis in Cuban T. vaginalis isolates and to describe the association between the phenotype M. hominis infected with RAPD genetic polymorphism of T. vaginalis. The Random Amplified Polymorphic DNA (RAPD) technique was used to determine genetic differences among 40 isolates of T. vaginalis using a panel of 30 random primers and these genetic data were correlated with the infection of isolates with M. hominis. The trees drawn based on RAPD data showed no relations with metronidazole susceptibility and significantly association with the presence of M. hominis (P=0.043), which demonstrates the existence of concordance between the genetic relatedness and the presence of M. hominis in T. vaginalis isolates. This result could point to a predisposition of T. vaginalis for the bacterial enters and/or survival. PMID:22584035

  1. Relationships of related genetic polymorphisms and individualized medication of tacrolimus in patients with renal transplantation

    PubMed Central

    Zhu, Lin; Zhang, Jing; Song, Hongtao; Wang, Qinghua; Tan, Jianming; Wu, Weizhen; Lin, Meiqin

    2015-01-01

    The aim of this study was to establish clinical and genetic factors-based individual administration model of tacrolimus for Chinese Han patients after renal transplantation (RT). The genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 in 216 RT patients were detected by PCR-RFLP, the genetic and clinical factors and blood concentration/dose × body weight (C/D) values of tacrolimus were performed the single factor correlation analysis, and established the dose prediction algorithm of tacrolimus by stepwise multiple regression analysis. CYP3A5*3, hematocrit and albumin were correlated with the C/D values of tacrolimus, the best regression model could explain 28.3% reason of individual dose differences of tacrolimus, among which CYP3A5*3 polymorphism could explain 23.5%. The genetic factors played an important role in the dose differences of tacrolimus, the patients should be checked CYP3A5*3 genotype before administration of tacrolimus to predict the tacrolimus doses, thus helping to improve the safety and effectiveness of tacrolimus application. PMID:26770526

  2. Random amplified polymorphic markers as indicator for genetic conservation program in Iranian pheasant (Phasianus colchicus).

    PubMed

    Elyasi Zarringhabaie, Ghorban; Javanmard, Arash; Pirahary, Ommolbanin

    2012-01-01

    The objective of present study was identification of genetic similarity between wild Iran and captive Azerbaijan Pheasant using PCR-RAPD markers. For this purpose, in overall, 28 birds were taken for DNA extraction and subsequently 15 arbitrary primers were applied for PCR-RAPD technique. After electrophoresis, five primers exhibited sufficient variability which yielded overall 65 distinct bands, 59 polymorphic bands, for detalis, range of number of bands per primer was 10 to 14, and produced size varied between 200 to 1500 bp. Highest and lowest polymorphic primers were OPC5, OPC16 (100%) and OPC15 (81%), respectively. Result of genetic variation between two groups was accounted as nonsignificant (8.12%) of the overall variation. According to our expectation the wild Iranian birds showed higher genetic diversity value than the Azerbaijan captive birds. As general conclusion, two pheasant populations have almost same genetic origin and probably are subpopulations of one population. The data reported herein could open the opportunity to search for suitable conservation strategy to improve richness of Iran biodiversity and present study here was the first report that might have significant impact on the breeding and conservation program of Iranian pheasant gene pool. Analyses using more regions, more birds, and more DNA markers will be useful to confirm or to reject these findings. PMID:23002388

  3. Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis

    PubMed Central

    Balduino Victorino, Daniella; de Godoy, Moacir Fernandes; Goloni-Bertollo, Eny Maria; Pavarino, Érika Cristina

    2014-01-01

    Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. PMID:25544792

  4. Association analysis between canine behavioural traits and genetic polymorphisms in the Shiba Inu breed.

    PubMed

    Takeuchi, Y; Kaneko, F; Hashizume, C; Masuda, K; Ogata, N; Maki, T; Inoue-Murayama, M; Hart, B L; Mori, Y

    2009-10-01

    The relationships between behavioural trait data and the genotype of 15 polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26-item questionnaire on the dog's behaviour, distributed to the dog's owners, through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis of the questionnaire items extracted eight factors accounting for 66.8% of the variance. An association analysis between these factors and genetic polymorphisms indicated that the polymorphism of c.471T>C in the solute carrier family 1 (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene was significantly associated with Factor 1, referred to as 'aggression to strangers'. This association remained stable in separate analyses of data from surveys obtained from the hospitals and those obtained from the magazine. The results suggest that the c.471T>C polymorphism is associated with some types of aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are necessary to extend these findings to dogs in general. PMID:19397510

  5. Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis.

    PubMed

    Balduino Victorino, Daniella; de Godoy, Moacir Fernandes; Goloni-Bertollo, Eny Maria; Pavarino, Érika Cristina

    2014-01-01

    Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I (2) statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. PMID:25544792

  6. Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil.

    PubMed

    Filho, Isaac Lima da Silva; Leite, Ana Claudia Celestino Bezerra; Moura, Patrícia Gomes; Ribeiro, Georgina Severo; Cavalcante, Andréa Cony; Azevedo, Flávia Carolina Marques de; Andrada-Serpa, Maria José de

    2011-06-01

    The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of β(S)-globin gene haplotypes and co-inheritance with α-thalassemia (-α(3.7kb)) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α(3.7kb) thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical β(S)-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95% 2.9-81.6) of CVD than the other β(S)-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population. PMID:21755116

  7. Hodgkin Lymphoma Risk: Role of Genetic Polymorphisms and Gene-Gene Interactions in DNA repair pathways

    PubMed Central

    Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa

    2011-01-01

    DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL. PMID:21374732

  8. Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Chen, Cheng; Wang, Lingyan; Liao, Qi; Xu, Leiting; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting

    2014-01-01

    Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC (p=0.03, odds ratio [OR]=1.18, 95% confidence interval [CI]=1.01–1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC (p=0.004, OR=1.498, 95% CI=1.139–1.970), and this significant association is specific in Caucasians (p=0.004, OR=1.603, 95% CI=1.165–2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC. PMID:24552298

  9. Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms

    PubMed Central

    Agusa, Tetsuro; Fujihara, Junko; Takeshita, Haruo; Iwata, Hisato

    2011-01-01

    Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways. PMID:21731446

  10. The Application and Performance of Single Nucleotide Polymorphism Markers for Population Genetic Analyses of Lepidoptera

    PubMed Central

    Coates, Brad Steven; Bayles, Darrell O.; Wanner, Kevin W.; Robertson, Hugh M.; Hellmich, Richard L.; Sappington, Thomas W.

    2011-01-01

    Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of “null” alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy–Weinberg equilibrium. Locus-by-locus FST, analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data. PMID:22303334

  11. Comparison of Randomly Amplified Polymorphic DNA with Amplified Fragment Length Polymorphism To Assess Genetic Diversity and Genetic Relatedness within Genospecies III of Pseudomonas syringae

    PubMed Central

    Clerc, Agathe; Manceau, Charles; Nesme, Xavier

    1998-01-01

    Recently, DNA pairing analyses showed that Pseudomonas syringae pv. tomato and related pathovars, including P. syringae pv. maculicola, form a genomic species (Pseudomonas tomato) (L. Gardan, H. L. Shafik, and P. A. D. Grimont, p. 445–448, in K. Rudolph, T. J. Burr, J. W. Mansfield, D. Stead, A. Vivian, and J. von Kietzell, ed., Pseudomonas syringae Pathovars and Related Pathogens, 1997). The genetic diversity of 23 strains belonging to this genomic species and 4 outgroup strains was analyzed with randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphic (AFLP) techniques. Simple boiling of P. syringae cells was suitable for subsequent DNA amplification to obtain reliable patterns in RAPD and AFLP analyses. In general, the grouping of P. syringae strains by both analysis techniques corresponded well with the classification obtained from an RFLP analysis of ribosomal DNA operons, DNA pairing studies, and an analysis of pathogenicity data. However, two strains of P. syringae pv. maculicola produced distinct DNA patterns compared to the DNA patterns of other P. syringae pv. maculicola strains; these patterns led us to assume that horizontal transfer of DNA could occur between bacterial populations. Both techniques used in this study have high discriminating power because strains of P. syringae pv. tomato and P. syringae pv. maculicola which were indistinguishable by other techniques, including pathogenicity tests on tomato, were separated into two groups by both RAPD and AFLP analyses. In addition, data analysis showed that the AFLP method was more efficient for assessing intrapathovar diversity than RAPD analysis and allowed clear delineation between intraspecific and interspecific genetic distances, suggesting that it could be an alternative to DNA pairing studies. However, it was not possible to distinguish the two races of P. syringae pv. tomato on the basis of an analysis of the data provided by either the AFLP or RAPD technique. PMID

  12. Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports.

    PubMed Central

    Guo, Z; Guilfoyle, R A; Thiel, A J; Wang, R; Smith, L M

    1994-01-01

    A simple and rapid method for the analysis of genetic polymorphisms has been developed using allele-specific oligonucleotide arrays bound to glass supports. Allele-specific oligonucleotides are covalently immobilized on glass slides in arrays of 3 mm spots. Genomic DNA is amplified by PCR using one fluorescently tagged primer oligonucleotide and one biotinylated primer oligonucleotide. The two complementary DNA strands are separated, the fluorescently tagged strand is hybridized to the support-bound oligonucleotide array, and the hybridization pattern is detected by fluorescence scanning. Multiple polymorphisms present in the PCR product may be detected in parallel. The effect of spacer length, surface density and hybridization conditions were evaluated, as was the relative efficacy of hybridization with single or double-stranded PCR products. The utility of the method was demonstrated in the parallel analysis of 5 point mutations from exon 4 of the human tyrosinase gene. Images PMID:7816638

  13. Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes.

    PubMed Central

    Jongeneel, C V; Briant, L; Udalova, I A; Sevin, A; Nedospasov, S A; Cambon-Thomsen, A

    1991-01-01

    We have identified three polymorphic microsatellites (which we call TNFa, TNFb, and TNFc) within a 12-kilobase region of the human major histocompatibility complex (MHC) that includes the tumor necrosis factor (TNF) locus. TNFc is located within the first intron of the TNF-beta gene and has only 2 alleles. TNFa and TNFb are 3.5 kilobases upstream (telomeric) of the TNF-beta gene and have at least 13 and 7 alleles, respectively. TNFa, -b, and -c alleles are in linkage disequilibrium with alleles at other loci within the MHC, including class I, class II, and class III. TNFa, -b, and -c alleles are also associated with extended HLA haplotypes. These TNF polymorphisms will allow a thorough genetic analysis of the involvement of TNF in MHC-linked pathologies. Images PMID:1946393

  14. A worldwide population study of the Ag-system haplotypes, a genetic polymorphism of human low-density lipoprotein.

    PubMed

    Breguet, G; Bütler, R; Bütler-Brunner, E; Sanchez-Mazas, A

    1990-03-01

    The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of

  15. A worldwide population study of the Ag-system haplotypes, a genetic polymorphism of human low-density lipoprotein.

    PubMed Central

    Breguet, G; Bütler, R; Bütler-Brunner, E; Sanchez-Mazas, A

    1990-01-01

    The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of

  16. Sequence-Related Amplified Polymorphism (SRAP) markers for assessing interrelationships and genetic diversity among members of the Saccharum complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Characterization of wild germplasm provides essential information on genetic diversity that breeders utilize for crop improvement. The potential of the sequence-related amplified polymorphism (SRAP) technique, which preferentially amplifies gene-rich regions, was evaluated to assess the genetic rela...

  17. Assessment of genetic diversity and relationships among wild and cultivated Tunisian plums (Prunus spp) using random amplified microsatellite polymorphism markers.

    PubMed

    Ben Tamarzizt, H; Ben Mustapha, S; Baraket, G; Abdallah, D; Salhi-Hannachi, A

    2015-01-01

    The usefulness of random amplified microsatellite polymorphism markers to study the genetic diversity and relationships among cultivars belonging to Prunus salicina and P. domestica and their wild relatives (P. insititia and P. spinosa) was investigated. A total of 226 of 234 bands were polymorphic (96.58%). The 226 random amplified microsatellite polymorphism markers were screened using 15 random amplified polymorphic DNA and inter-simple sequence repeat primers combinations for 54 Tunisian plum accessions. The percentage of polymorphic bands (96.58%), the resolving power of primers values (135.70), and the polymorphic information content demonstrated the efficiency of the primers used in this study. The genetic distances between accessions ranged from 0.18 to 0.79 with a mean of 0.24, suggesting a high level of genetic diversity at the intra- and interspecific levels. The unweighted pair group with arithmetic mean dendrogram and principal component analysis discriminated cultivars efficiently and illustrated relationships and divergence between spontaneous, locally cultivated, and introduced plum types. These procedures showed continuous variation that occurs independently of the status of the species and geographical origin of the plums. In this study, random amplified microsatellite polymorphism was found to be as a reliable molecular marker for fingerprinting and for examining the diversity study of the plum and its relatives. PMID:25867340

  18. MTHFR genetic polymorphism as a risk factor in Egyptian mothers with Down syndrome children.

    PubMed

    Meguid, Nagwa A; Dardir, Ahmed A; Khass, Mohamed; Hossieny, Lamia El; Ezzat, Afaf; El Awady, Mostafa K

    2008-01-01

    Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93-5.89) and 2.75 (95% CI 0.95-12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work. PMID:18057532

  19. Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

    PubMed Central

    Qu, Shimian; Long, Jirong; Cai, Qiuyin; Shu, Xiao-Ou; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2009-01-01

    Purpose Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of tumor metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. Experimental Design NME1 genotypes were analyzed in a cohort of 1134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. Results Single nucleotide polymorphisms (SNPs) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality (HR =1.4, 95% CI =1.1–1.9) as compared to those carrying the wild-type allele, and the association was more evident in patients with an early stage cancer (HR=1.7, 95% CI =1.2–2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR=1.3, 95% CI, 1.0–1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. Conclusion Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival. PMID:18676749

  20. Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer

    PubMed Central

    Lu, Yongchao; Gao, Kejian; Zhang, Miao; Zhou, Aiyan; Zhou, Xiaoming; Guan, Zhongan; Shi, Xuewen; Ge, Shujian

    2015-01-01

    Abstract Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer. Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all case–control studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the Mantel–Haenszel method (Ph > 0.05), and random-effects pooled ORs were estimated by the DerSimonian–Laird method (Ph < 0.05). Data on rs2066827 polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.86–0.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.74–0.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.85–0.98; model, TG vs. TT). These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular. PMID:26579796

  1. Genetic polymorphism of toll-like receptors 4 gene by polymerase chain reaction-restriction fragment length polymorphisms, polymerase chain reaction-single-strand conformational polymorphism to correlate with mastitic cows

    PubMed Central

    Gupta, Pooja H.; Patel, Nirmal A.; Rank, D. N.; Joshi, C. G.

    2015-01-01

    Aim: An attempt has been made to study the toll-like receptors 4 (TLR4) gene polymorphism from cattle DNA to correlate with mastitis cows. Materials and Methods: In present investigation, two fragments of TLR4 gene named T4CRBR1 and T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR), respectively from Kankrej (22) and Triple cross (24) cattle. The genetic polymorphisms in the two populations were detected by a single-strand conformational polymorphism in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results: Results showed that both alleles (A and B) of two loci were found in all the two populations and the value of polymorphism information content indicated that these were highly polymorphic. Statistical results of χ2 test indicated that two polymorphism sites in the two populations fit with Hardy–Weinberg equilibrium (p<0.05). Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score (SCS) indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of allele B (p<0.05). Thus, the allele A might play an important role in mastitis resistance in cows. Conclusion: The relationship between the bovine mastitis trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may play an important role in mastitis resistance. PMID:27047144

  2. The Significance of Genetic Polymorphisms within and between Founder Populations of Ceratitis capitata (Wied.) from Argentina

    PubMed Central

    Basso, Alicia; Martinez, Laura; Manso, Fanny

    2009-01-01

    Background The Mediterranean fruit fly Ceratitis Capitata (DIPTERA: Tephritidae) is a major agricultural pest in Argentina. One main cause for the success of non-contaminant control programs based on genetic strategies is compatibility between natural and laboratory germplasms. A comprehensive characterization of the fruit fly based on genetic studies and compatibility analysis was undertaken on two founder populations from the provinces of Buenos Aires and Mendoza, used in pioneering sterile male technique control programmes in our country. The locations are 1,000 km apart from each other. Methodology/Principal Findings We compared the genetic composition of both populations based on cytological, physiological and morphological characterization. Compatibility studies were performed in order to determine the presence of isolation barriers. Results indicate that the Buenos Aires germplasm described previously is partially different from that of the Mendoza population. Both laboratory colonies are a reservoir of mutational and cytological polymorphisms. Some sexual chromosome variants such as the XL and the YL resulting from attachment of a B-chromosome to the X-chromosome or Y-chromosome behave as a lethal sex-linked factor. Our results also show incompatibility between both germplasms and pre-zygotic isolation barriers between them. Our evidence is consistent with the fact that polymorphisms are responsible for the lack of compatibility. Conclusions The genetic control mechanism should be directly produced in the germplasm of the target population in order to favour mating conditions. This is an additional requirement for the biological as well as economic success of control programs based on genetic strategies such as the sterile insect technique. The analysis of representative samples also revealed natural auto-control mechanisms which could be used in modifying pest population dynamics. PMID:19252742

  3. Genetic diversity analysis of Capsicum spp germplasm bank accessions based on α/β-esterase polymorphism.

    PubMed

    Monteiro, E R; Bronzato, A R; Orasmo, G R; Lopes, A C A; Gomes, R L F; Mangolin, C A; Machado, M F P S

    2013-01-01

    Genetic diversity and structure were analyzed in 10 accessions belonging to Banco Ativo de Germoplasma de Capsicum located at Federal University of Piauí in northwestern Brazil that receives pepper samples grown in community gardens in various regions and Brazilian states. Selections were made from seeds of C. chinense (4 accessions), C. annuum (5 accessions), and C. baccatum (1 accession). Samples consisting of leaves were collected from 4-10 plants of each accession (a total of 85 plants). Native polyacrylamide gel electrophoresis was used to identify α- and β-esterase polymorphisms. Polymorphism was clearly detected in 5 loci. Sixteen alleles were found at 5 α/β-esterase loci of the three Capsicum species. In the C. chinense samples, the highest HO and HE values were 0.3625 and 0.4395, respectively, whereas in C. annuum samples, HO and HE values were 0.2980 and 0.3310, respectively; the estimated HO and HE values in C. chinense samples were higher than those detected in C. annuum samples. A deficit of homozygous individuals was found in C. chinense (FIS = -0.6978) and C. annuum (FIS = 0.7750). Genetic differentiation between C. chinense and C. annuum at these loci was high (FST = 0.1867) indicating that C. chinense and C. annuum are genetically structured species for α/β- esterase isozymes. The esterase analysis showed high genetic diversity among the C. chinense and C. annuum samples and very high genetic differentiation (FST = 0.6321) among the C. chinense and C. annuum samples and the C. baccatum accession. PMID:23661440

  4. Functional effects of endothelial nitric oxide synthase genetic polymorphisms on haemorheological parameters in healthy human individuals.

    PubMed

    Babaoglu, Melih O; Dikmenoglu, Neslihan; Ileri-Gurel, Esin; Seringec, Nurten; Zoto, Teuta; Yasar, Umit; Kayaalp, S Oguz; Bozkurt, Atilla

    2011-03-01

    The constitutive endothelial nitric oxide synthase (eNOS) plays a major role in circulatory homoeostasis and shows genetic polymorphism. eNOS is expressed and functional in blood cells, including erythrocytes. There is limited knowledge about the consequences of eNOS genetic variability in haemorheological parameters and erythrocyte functioning. The purpose of this study was to investigate the effects of three eNOS genetic polymorphisms, namely exonic G894T (Glu298Asp), intronic VNTR (27-bp repeat) and 5'-flanking T(-786)C polymorphisms on haemorheological variables, such as erythrocyte deformability and erythrocyte aggregation (rouleaux formation) in healthy non-smoking volunteers. Sixty subjects (19 women, 41 men) were examined for genotypes and haemorheological variables. Genotypes were determined by polymerase chain reaction and restriction analysis. Haemorheological variables were measured by means of a laser-assisted optical rotational cell analyser (LORCA). Erythrocyte aggregation was significantly decreased in individuals with 894TT genotype when compared to subjects with the (G) allele. Aggregation indices (AI) were 54.7±3.2% versus 61.0±0.9% (p=0.026), and the half-lives (t(1/2) ) for aggregation formation were 3.43±0.43 versus 2.55±0.12 sec. (p=0.024), respectively. Similarly, VNTR-bb genotype significantly altered erythrocyte aggregability. AI values were 58.7±1.1% in subjects with VNTR-a allele versus 63.7±1.2% in subjects with bb genotype (p=0.011); t(1/2) values were 2.86±0.16 versus 2.20±0.13 sec., respectively (p=0.016). T(-786)C polymorphism did not change any haemorheological parameters. These findings suggest that eNOS 894TT genotype is associated with decreased erythrocyte aggregation, while VNTR-bb genotype increases aggregability in healthy human individuals. eNOS genetic variants may contribute in the pathogenesis of microvascular disorders by altering erythrocyte functions in human beings. PMID:20977680

  5. Muju Virus, Harbored by Myodes regulus in Korea, Might Represent a Genetic Variant of Puumala Virus, the Prototype Arvicolid Rodent-Borne Hantavirus

    PubMed Central

    Lee, Jin Goo; Gu, Se Hun; Baek, Luck Ju; Shin, Ok Sarah; Park, Kwang Sook; Kim, Heung-Chul; Klein, Terry A.; Yanagihara, Richard; Song, Jin-Won

    2014-01-01

    The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red-backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544-nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S) segments of MUJV, as well as the amino acid sequences of their gene products, indicated that MUJV strains from different capture sites might represent genetic variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe. Distinct geographic-specific clustering of MUJV was found in different provinces in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common ancestry with PUUV. A better understanding of the taxonomic classification and pathogenic potential of MUJV must await its isolation in cell culture. PMID:24736214

  6. Single nucleotide polymorphisms for assessing genetic diversity in castor bean (Ricinus communis)

    PubMed Central

    2010-01-01

    Background Castor bean (Ricinus communis) is an agricultural crop and garden ornamental that is widely cultivated and has been introduced worldwide. Understanding population structure and the distribution of castor bean cultivars has been challenging because of limited genetic variability. We analyzed the population genetics of R. communis in a worldwide collection of plants from germplasm and from naturalized populations in Florida, U.S. To assess genetic diversity we conducted survey sequencing of the genomes of seven diverse cultivars and compared the data to a reference genome assembly of a widespread cultivar (Hale). We determined the population genetic structure of 676 samples using single nucleotide polymorphisms (SNPs) at 48 loci. Results Bayesian clustering indicated five main groups worldwide and a repeated pattern of mixed genotypes in most countries. High levels of population differentiation occurred between most populations but this structure was not geographically based. Most molecular variance occurred within populations (74%) followed by 22% among populations, and 4% among continents. Samples from naturalized populations in Florida indicated significant population structuring consistent with local demes. There was significant population differentiation for 56 of 78 comparisons in Florida (pairwise population ϕPT values, p < 0.01). Conclusion Low levels of genetic diversity and mixing of genotypes have led to minimal geographic structuring of castor bean populations worldwide. Relatively few lineages occur and these are widely distributed. Our approach of determining population genetic structure using SNPs from genome-wide comparisons constitutes a framework for high-throughput analyses of genetic diversity in plants, particularly in species with limited genetic diversity. PMID:20082707

  7. Optimal dosing of warfarin and other coumarin anticoagulants: the role of genetic polymorphisms.

    PubMed

    Daly, Ann K

    2013-03-01

    Coumarin anticoagulants, which include warfarin, acenocoumarol and phenprocoumon, are among the most widely prescribed drugs worldwide. There is now a large body of published data showing that genotype for certain common polymorphisms in the genes encoding the target vitamin K epoxide reductase (G-1639A/C1173T) and the main metabolizing enzyme CYP2C9 (CYP2C9*2 and *3 alleles) are important determinants of the individual coumarin anticoagulant dose requirement. Additional less common polymorphisms in these genes together with polymorphisms in other genes relevant to blood coagulation such as the cytochrome P450 CYP4F2, gamma-glutamyl carboxylase, calumenin and cytochrome P450 oxidoreductase may also be significant predictors of dose, especially in ethnic groups such as Africans where there have been fewer genetic studies compared with European populations. Using relevant genotypes to calculate starting dose may improve safety during the initiation period. Various algorithms for dose calculation, which also take patient age and other characteristics into consideration, have been developed for all three widely used coumarin anticoagulants and are now being tested in ongoing large randomised clinical trials. One recently completed study has provided encouraging results suggesting that calculation of warfarin dose on the basis of individual patient genotype leads to few adverse events and a higher proportion of time within the therapeutic coagulation rate window, but these findings still need confirmation. PMID:23376975

  8. Genetic effects of polymorphisms in myogenic regulatory factors on chicken muscle fiber traits.

    PubMed

    Yang, Zhi-Qin; Qing, Ying; Zhu, Qing; Zhao, Xiao-Ling; Wang, Yan; Li, Di-Yan; Liu, Yi-Ping; Yin, Hua-Dong

    2015-06-01

    The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TT-CT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens. PMID:25925055

  9. Genome-Wide Patterns of Genetic Polymorphism and Signatures of Selection in Plasmodium vivax

    PubMed Central

    Cornejo, Omar E.; Fisher, David; Escalante, Ananias A.

    2015-01-01

    Plasmodium vivax is the most prevalent human malaria parasite outside of Africa. Yet, studies aimed to identify genes with signatures consistent with natural selection are rare. Here, we present a comparative analysis of the pattern of genetic variation of five sequenced isolates of P. vivax and its divergence with two closely related species, Plasmodium cynomolgi and Plasmodium knowlesi, using a set of orthologous genes. In contrast to Plasmodium falciparum, the parasite that causes the most lethal form of human malaria, we did not find significant constraints on the evolution of synonymous sites genome wide in P. vivax. The comparative analysis of polymorphism and divergence across loci allowed us to identify 87 genes with patterns consistent with positive selection, including genes involved in the “exportome” of P. vivax, which are potentially involved in evasion of the host immune system. Nevertheless, we have found a pattern of polymorphism genome wide that is consistent with a significant amount of constraint on the replacement changes and prevalent negative selection. Our analyses also show that silent polymorphism tends to be larger toward the ends of the chromosomes, where many genes involved in antigenicity are located, suggesting that natural selection acts not only by shaping the patterns of variation within the genes but it also affects genome organization. PMID:25523904

  10. Genetic Effects of Polymorphisms in Myogenic Regulatory Factors on Chicken Muscle Fiber Traits

    PubMed Central

    Yang, Zhi-Qin; Qing, Ying; Zhu, Qing; Zhao, Xiao-Ling; Wang, Yan; Li, Di-Yan; Liu, Yi-Ping; Yin, Hua-Dong

    2015-01-01

    The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TT-CT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens. PMID:25925055

  11. MBL2 genetic polymorphisms and HIV-1 mother-to-child transmission in Zambia.

    PubMed

    Zupin, Luisa; Polesello, Vania; Segat, Ludovica; Kuhn, Louise; Crovella, Sergio

    2016-06-01

    Since antiretroviral drugs have been introduced to prevent mother-to-child transmission, the risk of HIV-1 infection in infants has decreased considerably worldwide. Nevertheless, many factors are involved in viral transmission and host susceptibility to infection. The immune system and its components, including mannose binding protein C (encoding by MBL2 gene), are already known to play an important role in this scenario. In the present study, 313 children and 98 of their mothers from Zambia were genotyped for the MBL2 promoter HL (rs11003125) and XY (rs7096206) polymorphisms and exon 1 D (rs5030737, at codon 52) B (rs1800450, at codon 54) and C (rs1800451, at codon 57) polymorphisms in order to investigate the potential role of these genetic variants in HIV-1 mother-to-child transmission. No statistical significant association was observed comparing transmitter and non-transmitter mothers and also confronting HIV-positive and HIV-negative children. The findings of the current study obtained on mother and children from Zambia evidence lack of association between MBL2 functional polymorphisms and HIV-1 mother-to-child transmission. PMID:26740328

  12. Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with the regulation of blood pressure

    PubMed Central

    Rondón, Fernando; Vargas, Clara Inés; Oróstegui, Myriam; Bautista, Leonelo; Serrano, Norma Cecilia; Páez, María c; Castillo, Adriana

    2012-01-01

    Introduction: In spite of nearly 40% of variability in blood pressure being explained by genetic factors, the identification of genes associated with essential high blood pressure is difficult to determine in populations where individuals have different genetic backgrounds. In these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease. Objective: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide. Methods: A sample of 552 unrelated individuals was studied through analysis of restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure. Results: Thirty-eight (38) Haplotypes were identified with GCCTG4b being the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and a genetic structure of populations was not evidenced (FST= 0.0038). Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium. This indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies. PMID:24893057

  13. Computer-aided identification of polymorphism sets diagnostic for groups of bacterial and viral genetic variants

    PubMed Central

    Price, Erin P; Inman-Bamber, John; Thiruvenkataswamy, Venugopal; Huygens, Flavia; Giffard, Philip M

    2007-01-01

    Background Single nucleotide polymorphisms (SNPs) and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species. Results The Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV) subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH) data for Campylobacter jejuni, Yersinia enterocolitica and Clostridium difficile. Conclusion Not-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data. PMID:17672919

  14. Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk.

    PubMed

    Galbiatti, Ana Lívia Silva; da Silva, Lidia Maria Rebolho Batista; Ruiz-Cintra, Mariangela Torreglosa; Raposo, Luis Sérgio; Maníglia, José Victor; Pavarino, Erika Cristina; Goloni-Bertollo, Eny Maria

    2012-07-01

    Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age ≥ 49 years (P<0.001), male gender (P=0.03), tobacco habit (P<0.001), MTHFR 1298AC/CC (P=0.028), MTR 2756AG/GG (P=0.010) and RFC1 80AG/GG (P=0.015) genotypes were associated with an increased risk of HNSCC. There were interactions between lower survival and CBS 844ins68 (P=0.005); age ≥ 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P=0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. PMID:22051736

  15. Gene-Based Single Nucleotide Polymorphism Markers for Genetic and Association Mapping in Common Bean

    PubMed Central

    2012-01-01

    Background In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. Results In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364 × G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93 × JALO EEP558 and DOR364 × BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041 cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. Conclusions In short, this study illustrates the power of intron

  16. [Pearl Harbor.

    ERIC Educational Resources Information Center

    Johnson, Jennifer, Ed.

    1992-01-01

    This issue of "Loblolly Magazine" was written in observance of the 50th anniversary of the U.S. entrance into World War II. The publication features interviews conducted by East Texas high school students with Clarence Otterman, one of the few survivors of the crew of the USS Arizona, which was bombed during the attack on Pearl Harbor, and with a…

  17. Human population genetic structure detected by pain-related mu opioid receptor gene polymorphisms

    PubMed Central

    López Soto, Eduardo Javier; Catanesi, Cecilia Inés

    2015-01-01

    Several single nucleotide polymorphisms (SNPs) in the Mu Opioid Receptor gene (OPRM1) have been identified and associated with a wide variety of clinical phenotypes related both to pain sensitivity and analgesic requirements. The A118G and other potentially functional OPRM1 SNPs show significant differences in their allele distributions among populations. However, they have not been properly addressed in a population genetic analysis. Population stratification could lead to erroneous conclusions when they are not taken into account in association studies. The aim of our study was to analyze OPRM1 SNP variability by comparing population samples of the International Hap Map database and to analyze a new population sample from the city of Corrientes, Argentina. The results confirm that OPRM1 SNP variability differs among human populations and displays a clear ancestry genetic structure, with three population clusters: Africa, Asia, and Europe-America. PMID:26273217

  18. Mapping quantitative trait loci for milk production and genetic polymorphisms of milk proteins in dairy sheep

    PubMed Central

    2005-01-01

    In this paper, we present recent advances in the molecular dissection of complex traits in dairy sheep and discuss their possible impact on breeding schemes. In the first step, we review the literature data on genetic polymorphisms and the effects of sheep αs1-casein and β-lactoglobulin loci. It is concluded that the results are rather inconsistent and cannot be used in dairy sheep selection. In a second step, we describe the strategy implemented in France, Italy and Spain taking advantage of the genetic maps for QTL detection. These studies were part of a European project, called "genesheepsafety", which investigated both milk production and functional traits. Preliminary QTL results are presented for production traits. PMID:15601591

  19. [Genetic polymorphism of flax Linum usitatissimum based on use of molecular cytogenetic markers].

    PubMed

    Rachinskaia, O A; Lemesh, V A; Muravenko, O V; Iurkevich, O Iu; Guzenko, E V; Bol'sheva, N L; Bogdanova, M V; Samatadze, T E; Popov, K V; Malyshev, S V; Shostak, N G; Heller, K; Khotyleva, L V; Zelenin, A V

    2011-01-01

    Using a set of approaches based on the use of molecular cytogenetic markers (DAPI/C-banding, estimation of the total area of DAPI-positive regions in prophase nuclei, FISH with 26S and 5S rDNA probes) and the microsatellite (SSR-PCR) assay, we studied genomic polymorphism in 15 flax (Linum usitatissimum L.) varieties from different geographic regions belonging to three directions of selection (oil, fiber, and intermediate flaxes) and in the k-37 x Viking hybrid. All individual chromosomes have been identified in the karyotypes of these varieties on the basis of the patterns of differential DAPI/C-banding and the distribution of 26S and 5S rDNA, and idiograms of the chromosomes have been generated. Unlike the oil flax varieties, the chromosomes in the karyotypes of the fiber flax varieties have, as a rule, pericentromeric and telomeric DAPI-positive bands of smaller size, but contain larger intercalary regions. Two chromosomal rearrangements (chromosome 3 inversions) were discovered in the variety Luna and in the k-37 x Viking hybrid. In both these forms, no colocalization of 26S rDNA and 5S rDNA on the satellite chromosome was detected. The SSR assay with the use of 20 polymorphic pairs of primers revealed 22 polymorphic loci. Based on the SSR data, we analyzed genetic similarity of the flax forms studied and constructed a genetic similarity dendrogram. The genotypes studied here form three clusters. The oil varieties comprise an independent cluster. The genetically related fiber flax varieties Vita and Luna, as well as the landrace Lipinska XIII belonging to the intermediate type, proved to be closer to the oil varieties than the remaining fiber flax varieties. The results of the molecular chromosomal analysis in the fiber and oil flaxes confirm their very close genetic similarity. In spite of this, the combined use of the chromosomal and molecular markers has opened up unique possibilities for describing the genotypes of flax varieties and creating their genetic

  20. Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

    PubMed

    Rai, Vandana

    2016-08-01

    Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism. PMID:26956130

  1. Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China

    PubMed Central

    He, Yongjun; Yang, Hua; Geng, Tingting; Feng, Tian; Yuan, Dongya; Kang, Longli; Luo, Manling; Jin, Tianbo

    2015-01-01

    Background: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. Methods: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ2 tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. Results: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. Conclusion: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities. PMID:26722533

  2. Genetic Polymorphism G894T and the Prognosis of Heart Failure Outpatients

    PubMed Central

    Tardin, Oziel Marcio Araujo; Pereira, Sabrina Bernardez; Velloso, Monica Wanderley Monçores; Balieiro, Henrique Miller; Costa, Bruno; Alves, Thiago Oliveira e; Giro, Camila; Pessoa, Leandro Pontes; Ribeiro, Georgina Severo; Mesquita, Evandro Tinoco

    2013-01-01

    Background Previous studies have analyzed the role of the genetic polymorphism of endothelial nitric oxide synthase on heart failure prognosis. However, there are no studies relating the G894T and heart failure in Brazil. Objective To evaluate the association between G894T GP and the prognosis of a sample of Brazilian outpatients with heart failure. Methods Cohort study included 145 patients with systolic heart failure, followed for up to 40 months (mean = 22), at two university hospitals, in the State of Rio de Janeiro. We evaluated the relationship between G894T and the following outcomes: reverse remodeling, improvement in functional class (NYHA), and mortality and hospitalization rates. The diameters of the left atrium and ventricle, as well as the ejection fraction of the left ventricle, were evaluated at baseline and at 6 months to assess reverse remodeling. The improvement in functional class was evaluated after 6 months, and mortality rate and hospitalization were evaluated during follow-up. Race was self-declared. G894T polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results The genotypic frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was guanine (64.1%) and thiamine (35.8%). There were no differences between the genotype or allelic frequencies according to self declared race, either as baseline characteristics. There was no relationship between genotype or allele frequency and the outcome measures. Conclusion No association was observed between the G894T polymorphism (Glu298Asp) and prognosis in this sample of Brazilian outpatients with systolic heart failure. PMID:23949326

  3. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    PubMed Central

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  4. [Genetic polymorphism of 9 STR loci in Chaoxian National Minority of China].

    PubMed

    Gao, Ya; Jin, Tian-bo; Lai, Jiang-hua; Chen, Teng; Zheng, Hai-bo; Zhu, Bo-feng; Hu, Song-nian; Wang, Jian; Li, Sheng-bin

    2002-11-01

    In order to enrich the Chinese genetic database,nine polymorphic loci of STR,such as D3S1358,vWA,FGA,TH01,TPOX,CSF1PO,D5S818,D13S317 and D7S820 were studied. Based on STR gene scan marked by fluorescence,91 unrelated Chinese Chaoxian individuals were observed.81 alleles and 196 genotypes were found. The corresponding gene frequency and genotype frequency were 0.0055-0.4615 and 0.0110-0.9890 respectively. The genogypes frequency of nine STR loci was good with the Hardy-Weinberg equilibrium (P approximately 0.05). The statistical analysis of nine STR loci showed the following: PIC (polymorphic information content) >or=0.6863, H (heterozygosity) >or=0.6919, DP (discrimination power) >or=0.8301, EPP (probability of paternity exclusion) >or=0.8590. The data studied can be used in Chinese population genetic studies and forensic medicine applications. PMID:15979957

  5. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

    PubMed Central

    Krueger, Sharon K.; Williams, David E.

    2005-01-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a “soft-nucleophile”, usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  6. [Genetic polymorphism of blood protein of six Passeriformes species in Zhalong National Nature Reserve].

    PubMed

    Xu, Xing-Jun; Lü, Jian-Wei; Xuan, Li-Fang; Zhang, Dong-Yue; Zhou, Shuang-Tao; Zhao, Kan; Wang, Bin; Shao, Shu-Li

    2009-06-01

    The polymorphism of hemoglobin (Hb), serum albumin (Alb), trandferring (Tf) and adenosin deaminase (Ada) in the blood of Emberiza elegans, Phylloscopus inornatus, E. aureola, Lanius tigrinus, Passer montanus, and E. spodocephala in Zhalong National Nature Reserve were studied by SDS-polyacrylamide-gel electrophoresis. All the protein loci of the six Passeriformes species exhibited polymorphism, and Ada locus had a relatively high heterozygosity. The analysis of average heterozygosity demonstrated that P. inornatus had a higher population genetic variance, while E. spodocephala was relatively stable. The six species could be classified into two clusters. E. elegans, E. aureola, E. spodocephala and P. inornatus were clustered into one group, while P. montanus and L. tigrinus were clustered into another group. This clustering was consistent with the actual taxonomic status of the six species. The higher thermoregulation index and predation pressure of the study area did not lead to the substantial variation of hereditary constitution of the six species, possibly due to the gene intercommunion between the six species and the outside of the study area, which decreased the variance and differentiation of the population genetics of the six species. PMID:19795660

  7. Characterization of polymorphic microsatellite markers and genetic diversity in wild bronze featherback, Notopterus notopterus (Pallas, 1769).

    PubMed

    Gupta, Arti; Lal, Kuldeep K; Punia, Peyush; Singh, Rajeev K; Mohindra, Vindhya; Sah, Rama S; Kumar, Rajesh; Luhariya, Rupesh K; Dwivedi, Arvind K; Masih, Prachi; Mishra, R M; Jena, J K

    2013-12-01

    Six polymorphic microsatellite DNA loci were identified in the primitive fish, bronze featherback, Notopterus notopterus for the first time and demonstrated significant population genetic structure. Out of the six primers, one primer (NN90) was specific to N. notopterus (microsatellite sequence within the RAG1 gene) and five primers were product of successful cross-species amplification. Sixty-four primers available from 3 fish species of order Osteoglossiformes and families Notopteridae and Osteoglossidae were tested to amplify homologous microsatellite loci in N. notopterus. Fifteen primer pairs exhibited successful cross-priming PCR product. However, polymorphism was detected only at five loci. To assess the significance of these six loci (including NN90) in population genetic study, 215 samples of N. notopterus from five rivers, viz Satluj, Gomti, Yamuna, Brahmaputra and Mahanadi were analyzed. The five sample sets displayed different diversity levels and observed heterozygosity ranged from 0.6036 to 0.7373. Significant genotype heterogeneity (P < 0.0001) and high FST (0.2205) over all loci indicated that the samples are not drawn from the same genepool. The identified microsatellite loci are promising for use in fine-scale population structure analysis of N. notopterus. PMID:24072656

  8. CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.

    PubMed

    Banin-Hirata, Bruna Karina; Losi-Guembarovski, Roberta; Oda, Julie Massayo Maeda; de Oliveira, Carlos Eduardo Coral; Campos, Clodoaldo Zago; Mazzuco, Tânia Longo; Borelli, Sueli Donizete; Ceribelli, Jesus Roberto; Watanabe, Maria Angelica Ehara

    2016-05-01

    Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation. PMID:25716470

  9. Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.

    PubMed

    Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J

    2013-11-01

    Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations. PMID:23872234

  10. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

    PubMed Central

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ2 test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association. PMID:26722563

  11. Construction of a Genetic Linkage Map Based on Amplified Fragment Length Polymorphism Markers and Development of Sequence-Tagged Site Markers for Marker-Assisted Selection of the Sporeless Trait in the Oyster Mushroom (Pleurotus eryngii)

    PubMed Central

    Ueda, Jun; Obatake, Yasushi; Murakami, Shigeyuki; Fukumasa, Yukitaka; Matsumoto, Teruyuki

    2012-01-01

    A large number of spores from fruiting bodies can lead to allergic reactions and other problems during the cultivation of edible mushrooms, including Pleurotus eryngii (DC.) Quél. A cultivar harboring a sporulation-deficient (sporeless) mutation would be useful for preventing these problems, but traditional breeding requires extensive time and labor. In this study, using a sporeless P. eryngii strain, we constructed a genetic linkage map to introduce a molecular breeding program like marker-assisted selection. Based on the segregation of 294 amplified fragment length polymorphism markers, two mating type factors, and the sporeless trait, the linkage map consisted of 11 linkage groups with a total length of 837.2 centimorgans (cM). The gene region responsible for the sporeless trait was located in linkage group IX with 32 amplified fragment length polymorphism markers and the B mating type factor. We also identified eight markers closely linked (within 1.2 cM) to the sporeless locus using bulked-segregant analysis-based amplified fragment length polymorphism. One such amplified fragment length polymorphism marker was converted into two sequence-tagged site markers, SD488-I and SD488-II. Using 14 wild isolates, sequence-tagged site analysis indicated the potential usefulness of the combination of two sequence-tagged site markers in cross-breeding of the sporeless strain. It also suggested that a map constructed for P. eryngii has adequate accuracy for marker-assisted selection. PMID:22210222

  12. Evaluation of genetic diversity in Chinese kale (Brassica oleracea L. var. alboglabra Bailey) by using rapid amplified polymorphic DNA and sequence-related amplified polymorphism markers.

    PubMed

    Zhang, J; Zhang, L G

    2014-01-01

    Chinese kale is an original Chinese vegetable of the Cruciferae family. To select suitable parents for hybrid breeding, we thoroughly analyzed the genetic diversity of Chinese kale. Random amplified polymorphic DNA (RAPD) and sequence-related amplified polymorphism (SRAP) molecular markers were used to evaluate the genetic diversity across 21 Chinese kale accessions from AVRDC and Guangzhou in China. A total of 104 bands were detected by 11 RAPD primers, of which 66 (63.5%) were polymorphic, and 229 polymorphic bands (68.4%) were observed in 335 bands amplified by 17 SRAP primer combinations. The dendrogram showed the grouping of the 21 accessions into 4 main clusters based on RAPD data, and into 6 clusters based on SRAP and combined data (RAPD + SRAP). The clustering of accessions based on SRAP data was consistent with petal colors. The Mantel test indicated a poor fit for the RAPD and SRAP data (r = 0.16). These results have an important implication for Chinese kale germplasm characterization and improvement. PMID:24615113

  13. Microsatellite polymorphism in the sexually transmitted human pathogen Trichomonas vaginalis indicates a genetically diverse parasite.

    PubMed

    Conrad, Melissa; Zubacova, Zuzana; Dunn, Linda A; Upcroft, Jacqui; Sullivan, Steven A; Tachezy, Jan; Carlton, Jane M

    2011-01-01

    Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven laboratory strains of diverse origin. We have (1) adapted our microsatellite typing method to incorporate affordable fluorescent labeling, (2) determined that the microsatellite loci remain stable in parasites continuously cultured for up to 17 months, and (3) evaluated microsatellite marker coverage of the six chromosomes that comprise the T. vaginalis genome, using fluorescent in situ hybridization (FISH). We have used the markers to show that T. vaginalis is a genetically diverse parasite in a population of commonly used laboratory strains. In addition, we have used phylogenetic methods to infer evolutionary relationships from our markers in order to validate their utility in future population analyses. Our panel is the first series of robust polymorphic genetic markers for T. vaginalis that can be used to classify and monitor lab strains, as well as provide a means to measure the genetic diversity and population structure of extant and future T. vaginalis isolates. PMID:20813140

  14. Polymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis.

    PubMed

    Chun, Matthew G H; Mao, Jian-Hua; Chiu, Christopher W; Balmain, Allan; Hanahan, Douglas

    2010-10-01

    Cancer is a disease subject to both genetic and environmental influences. In this study, we used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to identify a genetic locus that influences tumor progression to an invasive growth state. RT2 mice inbred into the C57BL/6 (B6) background develop both noninvasive pancreatic neuroendocrine tumors (PNET) and invasive carcinomas with varying degrees of aggressiveness. In contrast, RT2 mice inbred into the C3HeB/Fe (C3H) background are comparatively resistant to the development of invasive tumors, as are RT2 C3HB6(F1) hybrid mice. Using linkage analysis, we identified a 13-Mb locus on mouse chromosome 17 with significant linkage to the development of highly invasive PNETs. A gene residing in this locus, the anaplastic lymphoma kinase (Alk), was expressed at significantly lower levels in PNETs from invasion-resistant C3H mice compared with invasion-susceptible B6 mice, and pharmacological inhibition of Alk led to reduced tumor invasiveness in RT2 B6 mice. Collectively, our results demonstrate that tumor invasion is subject to polymorphic genetic control and identify Alk as a genetic modifier of invasive tumor growth. PMID:20855625

  15. Genetic Diversity of Eurycoma longifolia Inferred from Single Nucleotide Polymorphisms1[w

    PubMed Central

    Osman, Asiah; Jordan, Barbara; Lessard, Philip A.; Muhammad, Norwati; Haron, M. Rosli; Riffin, Norifiza Mat; Sinskey, Anthony J.; Rha, ChoKyun; Housman, David E.

    2003-01-01

    Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and breeding programs to support conservation of this species, although no such markers currently exist. To meet this need, we have applied a genome complexity reduction strategy to identify a series of single nucleotide polymorphisms (SNPs) within the genomes of several E. longifolia accessions. We have found that the occurrence of these SNPs reflects the geographic origins of individual plants and can distinguish different natural populations. This work demonstrates the rapid development of molecular genetic markers in species for which little or no genomic sequence information is available. The SNP markers that we have developed in this study will also be useful for identifying genetic fingerprints that correlate with other properties of E. longifolia, such as high regenerability or the appearance of bioactive metabolites. PMID:12644679

  16. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility

    PubMed Central

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-01-01

    There are several evidences supporting the role of 5–10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03–1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02–1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06–1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01–1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03–1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06–1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99–1.14; p = 0.05). PMID:26629412

  17. Genetic map of randomly amplified DNA polymorphisms closely linked to the mating type locus of tetrahymenta thermophila

    SciTech Connect

    Lynch, T.J.; Brickner, J.; Orias, E.; Nakano, K.J.

    1995-12-01

    We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosomes segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome. 39 refs., 5 figs., 4 tabs.

  18. Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms

    PubMed Central

    Arehart, Eric; Gleim, Scott; White, Bill; Hwa, John; Moore, Jason H

    2009-01-01

    Background The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs) constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation. Results We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR) approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194). We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI) database (n = 29967) and a control set of sequences (coding region) not associated with SNP sites randomly selected from the NCBI database (n = 29967). We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level of p ≤ 0.05. Significant models (p << 0.001) were detected for each SNP type examined in the larger NCBI dataset. Importantly, the flanking region models were elongated or truncated depending on the nucleotide change. Additionally, nucleotide distributions differed significantly at motif sites relative to the type of variation observed. The MDR approach effectively discerned specific sites within the flanking regions of observed SNPs and their respective identities, supporting the collective

  19. Analysis of multiple genetic polymorphisms in aggressive- and slow-growing abdominal aortic aneurysms

    PubMed Central

    Duellman, Tyler; Warren, Christopher L.; Matsumura, Jon; Yang, Jay

    2014-01-01

    Introduction The natural history of abdominal aortic aneurysm (AAA) suggests that some remain slow in growth rate while many develop a more accelerated growth rate reaching a threshold for intervention. We hypothesized that different mechanisms are responsible for AAA that remain slow-growth and never become actionable versus the aggressive-AAA that require intervention may be reflected by distinct associations with genetic polymorphisms. Methods 168 control and 141 AAA subjects all with ultrasound or CT imaging studies covering about 5 years were identified and the AAA growth rate determined from the serial imaging data. Genetic polymorphisms all previously reported as showing significant correlation with AAA: angiotensin 1 receptor (AT1R) (rs5186), interleukin-10 (IL-10) (rs1800896), methyl-tetrahydrofolate reductase (MTHFR) (rs1801133), low density lipoprotein receptor-related protein 1 (LRP1) (rs1466535), angiotensin converting enzyme (ACE) (rs1799752) and several MMP9 SNPs with functional effects on the expression or function were determined by analysis of the genomic DNA. Results AAA subjects were classified as slow-growth rate- (<3.25 mm /yr; n=81) vs. aggressive-AAA (growth rate >3.25 mm /yr, those presenting with a rupture, or those with maximal aortic diameter >5.5 cm (male) or >5.0 cm (female); n=60) and discriminating confounds between the groups identified by logistic regression. Analyses identified MMP9 p-2502 SNP (P=0.029, OR=0.54 (0.31-0.94)) as a significant confound discriminating between control- vs. slow-growth AAA, MMP-9 D165N (P=0.035) and LRP1 (P=0.034) between control vs. aggressive-AAA, and MTHFR (P=0.048, OR=2.99 (1.01-8.86)), MMP9 p-2502 (P=0.037, OR=2.19 (1.05-4.58), and LRP1 (P=0.046, OR= 4.96 (1.03-23.9)) as the statistically significant confounds distinguishing slow- vs. aggressive-AAA. Conclusion Logistic regression identified different genetic confounds for the slow-growth rate-and aggressive-AAA indicating a potential for different

  20. Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population

    PubMed Central

    Huang, Wen-Qing; Ye, Hui-Ming; Li, Fang-Fang; Yi, Ke-Hui; Zhang, Ya; Cai, Liang-Liang; Lin, Hui-Nuan; Lin, Qing; Tzeng, Chi-Meng

    2016-01-01

    Abstract Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ2 and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA

  1. Genetic polymorphism of microsatellite dna in two populations of northern sheatfish (Silurus soldatovi).

    PubMed

    Quan, Ying-Chun; Sun, Xiao-Wen; Liang, Li-Qun

    2006-10-01

    In this article, population variations and genetic structures of two populations of northern sheatfish (Silurus soldatovi) were analyzed using 24 microsatellite loci enriched from southern catfish (S. meriaionalis Chen) by magnetic beads. Gene frequency (P), observed heterozygosity (Ho), expected heterozygosity (He), polymorphism information contents (PIC), and number of effective alleles (Ne) were determined. One population was wild, ripe individuals collected from Heilongjiang River (HNS); the other was cultured fry collected from Songhuajiang River (SNS). The Hardy-Weinberg equilibrium (HWE) was tested by the genetic departure index (d). The coefficient of gene differentiation G(ST) and Phi(ST) by AMOVA (Analysis of Molecular Variety) was imputed using Arlequin software in this study. In addition, a phylogenetic tree was constructed by UPGMA method based on the pairwise Nei's standard distances using PHYLIP. A total of 1,357 fragments with sizes ranging between 102 bp and 385 bp were acquired by PCR amplifications. The average number of alleles of the two populations was 8.875. Results indicated that these microsatellite loci were highly polymorphic and could be used as genetic markers. The mean values of the parameters P, Ho, He, PIC, and Ne were 0.165, 0.435, 0.758, 0.742, and 5.019 for HNS and 0.147, 0.299, 0.847, 0.764, and 5.944 for SNS, respectively. Although there were differences, there were no significant differentiations except for the locus HLJcf37. These populations to a certain extent deviated from HWE, such as excessive and deficient heterozygote numbers. The value of G(ST) was 0.078 and above 98% of the variation were differences among individuals within the population, so the variation between populations was insignificant. Cluster analysis also showed that the relationships among individuals were very close. In conclusion, the microsatellite markers that were developed through this study are useful for genetic analysis and the genetic culture

  2. Common genetic polymorphisms affect the human requirement for the nutrient choline

    PubMed Central

    da Costa, Kerry-Ann; Kozyreva, Olga G.; Song, Jiannan; Galanko, Joseph A.; Fischer, Leslie M.; Zeisel, Steven H.

    2006-01-01

    Humans eating diets deficient in the essential nutrient choline can develop organ dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs) in genes involved in choline metabolism influence the dietary requirement of this nutrient. Fifty-seven humans were fed a low choline diet until they developed organ dysfunction or for up to 42 days. We tested DNA SNPs for allelic association with susceptibility to developing organ dysfunction associated with choline deficiency. We identified an SNP in the promoter region of the phosphatidylethanolamine N-methyltransferase gene (PEMT; −744 G→C; rs12325817) for which 18 of 23 carriers of the C allele (78%) developed organ dysfunction when fed a low choline diet (odds ratio 25, P=0.002). The first of two SNPs in the coding region of the choline dehydrogenase gene (CHDH; +318 A→C; rs9001) had a protective effect on susceptibility to choline deficiency, while a second CHDH variant (+432 G→T; rs12676) was associated with increased susceptibility to choline deficiency. A SNP in the PEMT coding region (+5465 G→A; rs7946) and a betaine:homocysteine methyl-transferase (BHMT) SNP (+742 G→A; rs3733890) were not associated with susceptibility to choline deficiency. Identification of common polymorphisms that affect dietary requirements for choline could enable us to identify individuals for whom we need to assure adequate dietary choline intake.—da Costa, K.-A., Kozyreva, O. G., Song, J., Galanko, J. A., Fischer, L. M., Zeisel, S. H. Common genetic polymorphisms affect the human requirement for the nutrient choline. PMID:16816108

  3. Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

    PubMed

    Huard, Richard C; Fabre, Michel; de Haas, Petra; Lazzarini, Luiz Claudio Oliveira; van Soolingen, Dick; Cousins, Debby; Ho, John L

    2006-06-01

    In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC. PMID:16740934

  4. Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

    PubMed Central

    2012-01-01

    Background The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91), as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12) when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91) in the population of interest. PMID:22702493

  5. Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.

    PubMed

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Zinbarg, Richard E; Adam, Emma K; Redei, Eva E; Hammen, Constance; Craske, Michelle G

    2015-11-01

    Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. PMID:26595467

  6. [Formation of genetic polymorphism in connection with phylogenesis and microevolution of the domestic dog Canis familiaris L].

    PubMed

    Kniazev, S P; Tikhonov, V N; Tanabe, Y; Morozov, P S

    1998-11-01

    The analysis of genetic relationships between numerous breeds and populations of domestic dogs of Asian and European origin was performed by studying their polymorphism for 14 loci of biochemical markers. Phylogenetic positions of different breed groups, related to one another and to ancestral forms from the center of domestication, were elucidated. Directions of gene flow in the formation of breed as well as dynamics and vectors of the forming genetic structure in microevolution of this extremely polytypic species, were established. PMID:10096028

  7. Genetic relationships among Aedes aegypti (Diptera: Culicidae) populations from Argentina using random amplified polymorphic DNA polymerase chain reaction markers.

    PubMed

    de Sousa, G B; Blanco, A; Gardenal, C N

    2001-05-01

    Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) polymorphism was analyzed in five Aedes aegypti (L.) populations from Argentina and one from Puerto Rico to estimate levels of intraspecific polymorphism and genetic relatedness. Allele frequencies were estimated assuming that RAPD products segregate as dominants and that genotype frequencies at those loci are in Hardy-Weinberg equilibrium. Mean expected heterozygosity (He) was 0.350; F(ST) values were significant at all loci except one, supporting the usefulness of the fragments used here to discriminate among populations. Rogers' genetic similarity between samples ranged from 0.806 to 0.621. The population from Puerto Rico was the most different from the Argentina populations. Considering that Ae. aegypti eggs, larvae, and pupae can be transported easily, relationships among the Argentinian populations may reflect the routes and intensity of commercial transit. PMID:11372960

  8. Investigation of the genetic diversity among native Turkish sheep breeds using mtDNA polymorphisms.

    PubMed

    Oner, Yasemin; Calvo, Jorge Hugo; Elmaci, Cengiz

    2013-04-01

    A total of 135 unrelated sheep from nine Turkish native sheep breeds (Daglıc, Kivircik, Imroz, Chios, Morkaraman, Ivesi, Hemsin, Karayaka and Akkaraman) were investigated to determinate the maternal genetic diversity using a sequence of a 531-bp segment of the mtDNA control region. Analysis of the mtDNA control region sequence revealed 63 haplotypes and 53 polymorphic sites. Haplotype diversity, nucleotide diversity and the average number of nucleotide differences were estimated to be 0.9496 ± 0.011, 0.01407 ± 0.00060 and 7.456, respectively. The sequence analysis also revealed high level of genetic diversity among the native Turkish breeds. These breeds were grouped into three major maternal haplogroups: A, B and C, with one animal belonging from the Akkaraman breed to the rare haplogroup E. Irregular shape of mismatch distribution of haplogroup C could be an indicator that haplogroup C may represent different haplogroups. Contrarily to previous studies carried out on Turkish native breeds, majority of animals grouped in haplogroup A in the present study. This result and the irregular shape of mismatch curve of haplogroup C indicate that genetic structure of Turkish native sheep breeds could be more complicated than it is thought. PMID:23135986

  9. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITIS) INDIGENOUS TO SITES ASSOCIATED WITH A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  10. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITUS) INDIGENOUS TO A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  11. DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients

    PubMed Central

    Wang, Chuan; Jia, Zhifang; Ma, Hongxi; Cao, Donghui; Wu, Xing; Wen, Simin; You, Lili; Cao, Xueyuan; Jiang, Jing

    2015-01-01

    DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients. PMID:26823816

  12. Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan

    PubMed Central

    Umemura, Takeji; Joshita, Satoru; Yamazaki, Tomoo; Komatsu, Michiharu; Katsuyama, Yoshihiko; Yoshizawa, Kaname; Tanaka, Eiji; Ota, Masao

    2016-01-01

    Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are liver-specific autoimmune conditions that are characterized by chronic hepatic damage and often lead to cirrhosis and hepatic failure. Specifically, the protein tyrosine phosphatase N22 (PTPN22) gene encodes the lymphoid protein tyrosine phosphatase, which acts as a negative regulator of T-cell receptor signaling. A missense single nucleotide polymorphism (SNP) (rs2476601) in PTPN22 has been linked to numerous autoimmune diseases in Caucasians. In the present series, nine SNPs in the PTPN22 gene were analyzed in 166 patients with AIH, 262 patients with PBC, and 322 healthy controls in the Japanese population using TaqMan assays. Although the functional rs3996649 and rs2476601 were non-polymorphic in all subject groups, the frequencies of the minor alleles at rs1217412, rs1217388, rs1217407, and rs2488458 were significantly decreased in AIH patients as compared with controls (all Pc < 0.05). There were no significant relationships with PTPN22 SNPs in PBC patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both AIH (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese. PMID:27406031

  13. The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis

    PubMed Central

    Malutan, Andrei M.; Drugan, Tudor; Ciortea, Razvan; Mihu, Dan

    2016-01-01

    Aim of the study Aim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis. Material and methods IL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored. Results Interleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ2 = 0.496, and χ2 = 0.928, OR = 1.3636, CI: 0.725-2.564). Conclusions The results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism. PMID:27536203

  14. Target region amplification polymorphism (TRAP) for assessing genetic diversity and marker-trait associations in chickpea (Cicer arietinum l.) germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilization of crop diversity held in genebanks is dependent on knowledge of useful traits including those identified genotypically. Target region amplification polymorphism (TRAP) markers were used to evaluate the genetic diversity and relationship among a sample of 263 chickpea landrace germplasm ...

  15. ASSOCIATIONS OF THE PORCINE IMMUNE RESPONSE AND GENETIC POLYMORPHISMS WITH THE SHEDDING OF SALMONELLA ENTERICA SEROVAR TYPHIMURIUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major focus of our collaborative research is to investigate the porcine response to infection with Salmonella to 1) identify porcine genes differentially regulated during infection and 2) identify and associate genetic polymorphisms within these genes with infection status across swine populations...

  16. Estimating Genetic Relationships Among Semi-Dormant and Nondormant Alfalfa Cultivars with Sequence Related Amplified Polymorphisms (SRAPs)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the present study was to assess the utility of molecular marker data generated by Sequence Related Amplified Polymorphisms (SRAPs) to assess genetic relationships among semi-dormant and non-dormant modern alfalfa cultivars using bulked DNAs. Marker data was also used to examine rel...

  17. A preliminary report on the genetic variation in pointed gourd (Trichosanthes dioica Roxb.) as assessed by random amplified polymorphic DNA.

    PubMed

    Adhikari, S; Biswas, A; Bandyopadhyay, T K; Ghosh, P D

    2014-06-01

    Pointed gourd (Trichosanthes dioica Roxb.) is an economically important cucurbit and is extensively propagated through vegetative means, viz vine and root cuttings. As the accessions are poorly characterized it is important at the beginning of a breeding programme to discriminate among available genotypes to establish the level of genetic diversity. The genetic diversity of 10 pointed gourd races, referred to as accessions was evaluated. DNA profiling was generated using 10 sequence independent RAPD markers. A total of 58 scorable loci were observed out of which 18 (31.03%) loci were considered polymorphic. Genetic diversity parameters [average and effective number of alleles, Shannon's index, percent polymorphism, Nei's gene diversity, polymorphic information content (PIC)] for RAPD along with UPGMA clustering based on Jaccard's coefficient were estimated. The UPGMA dendogram constructed based on RAPD analysis in 10 pointed gourd accessions were found to be grouped in a single cluster and may represent members of one heterotic group. RAPD analysis showed promise as an effective tool in estimating genetic polymorphism in different accessions of pointed gourd. PMID:24873909

  18. A high-density simple sequence repeat and single nucleotide polymorphism genetic map of the tetraploid cotton genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton genome complexity was investigated with a saturated molecular genetic map that combined several sets of microsatellites or simple sequence repeats (SSR) and the first major public set of single nucleotide polymorphism (SNP) markers in cotton genomes (Gossypium spp.), and that was constructed ...

  19. Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

    PubMed Central

    Kim, Mi-Jung; Han, Sae-Won; Lee, Dae-Won; Cha, Yongjun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Kim, Se Hyung; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

    2016-01-01

    Purpose Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. Materials and Methods Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. Results Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. Conclusion Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly. PMID:26790967

  20. Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A process to prepare high-density genotypic data for use in genomic prediction of genetic merit was developed. Marker genotypes from over 51,000 single nucleotide polymorphisms (SNP) were generated for 3,139 Holstein bulls on the Illumina Bovine SNP50™ chip. The SNP were categorized by minor allele ...

  1. Genetic variability in geographical populations of Culex quinquefasciatus Say (Diptera: Culicidae) from India based on random amplified polymorphic DNA analysis.

    PubMed

    Sharma, A K; Mendki, M J; Tikar, S N; Chandel, K; Sukumaran, D; Parashar, B D; Veer, Vijay; Agarwal, O P; Prakash, Shri

    2009-10-01

    Genetic variability and environmental factors may influence the refractiveness, propagation of pathogen and transmission of disease. Random amplified polymorphic DNA (RAPD) is one of the widely used molecular markers for population genetic diversity studies. In present study, RAPD is used to ascertain the genetic variability in Culex quinquefasciatus populations collected from various Indian geographical locations. Out of 50 RAPD primers screened, 14 primers exhibited clear, concrete and distinct banding pattern showing up to 100% polymorphism. Primer OPBD3 was tested with DNA of 14 geographical populations from India (including one laboratory population) showed 21 loci representing 14 populations with 100% polymorphism. The genetic diversity among the populations indicated the Shannon index (I) and gene diversity index (H(ST)), 0.48 and 0.31, respectively among the population, displaying rich genetic variation among the Cx. quinquefasciatus populations. Consensus tree showed two clusters indicating the genetic variation among the various geographical populations. The findings of this study may be useful to understand the population variation under different ecological conditions and development of effective vector management strategies. PMID:19577531

  2. Genetic polymorphisms and the development of invasive bacterial infections in children.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Orenti, Annalisa; Spena, Silvia; Montinaro, Valentina; Bianchini, Sonia; Zampiero, Alberto; Principi, Nicola

    2016-03-01

    To evaluate the associations between single nucleotide polymorphisms (SNPs) of factors involved in the development of invasive bacterial disease (IBD) in children, 47 SNPs of 18 candidate genes were analysed in 49 children with IBD and 100 controls. The G/T genotype of TLR2 rs2149356 and the C genotype of LTA rs2229094 were associated with significantly reduced risk of developing IBD (P=0.04 and P=0.05, respectively), whereas the C/T genotype of RFP175 rs1585110 was associated with a significantly higher risk of developing IBD (P=0.02). These results support the evidence that some genetic variants of factors involved in innate immunity may influence IBD risk in children. PMID:26684632

  3. Genetic polymorphism of 17 Y-STR loci in Han Chinese living in Lanzhou.

    PubMed

    Sun, Hong-bing; Yang, Xin; Ha, Fei; Zhang, Zi-long

    2013-12-01

    The genetic polymorphism across 17 Y-STR loci in a population of Han Chinese in Lanzhou was investigated. Haplotypes and allele frequencies for the 17 Y-chromosomal STRs loci DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448 were determined in 500 healthy unrelated autochthonous males from Lanzhou. The results showed that no shared haplotypes were observed. Gene diversity values ranged from 0.3987 (DYS391) to 0.9740 (DYS385a,b). It was concluded that these loci will be very useful for human identification in forensic cases and paternity tests within the Han Chinese population inhabiting Lanzhou. PMID:24337856

  4. A genetic variation map for chicken with 2.8 million single nucleotide polymorphisms

    SciTech Connect

    Wong, G K; Hillier, L; Brandstrom, M; Croojmans, R; Ovcharenko, I; Gordon, L; Stubbs, L; Lucas, S; Glavina, T; Kaiser, P; Gunnarsson, U; Webber, C; Overton, I

    2005-02-20

    We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines--contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb.

  5. Genetic polymorphism of IgG in mink. II. A genetic analysis of allotypes.

    PubMed

    Belyaev, D K; Fomicheva, I I; Taranin, A V; Baranov, O K

    1986-01-01

    Population distribution and inheritance pattern were analyzed in mink IgG allotypes: L1 (L chains), H2, H3, H4, H6, H7, and H8 (the constant region of the H chains, i.e. C gamma-allotypes) and conformational allotype 5 with unknown chain localization. Contrary to expectation, neither allelism, nor close linkage were demonstrated for these allotypes. The major feature of the inheritance of H2, H3, and H4 C gamma-allotypes, as well as allotype 5, was significant excess of negative (without these allotypes) progeny in the F1 generation from monohybrid cross. The explanation offered for this departure of the C gamma-allotypes from normal Mendelian genetics suggests widespread latencies of their expression in mink. PMID:3274048

  6. Genetic polymorphisms in obesity-related genes and endometrial cancer risk

    PubMed Central

    Chen, Xiaoli; Xiang, Yong-Bing; Long, Ji-Rong; Cai, Hui; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2011-01-01

    Background Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. Methods We selected 87 tagging SNPs to capture common genetic variants in these five genes. These SNPs were evaluated in 1,028 endometrial cancer cases and 1,932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI: 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became non-significant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, waist circumference, hip circumference, and BMI than controls with the major allele G (all P<0.05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR=0.70 (0.54-0.90)) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1, ADIPOR2, or LEPR genes were found to be associated with cancer risk. Conclusions Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ genes may play a role in endometrial cancer development. PMID:22038736

  7. Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

    PubMed

    Wu, Dapeng; Yu, Hongjie; Sun, Jielin; Qi, Jun; Liu, Qiang; Li, Ruipeng; Zheng, Siqun Lily; Xu, Jianfeng; Kang, Jian

    2015-07-01

    Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population. PMID:25738283

  8. Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms.

    PubMed

    NurWaliyuddin, Hanis Z A; Norazmi, Mohd N; Edinur, Hisham A; Chambers, Geoffrey K; Panneerchelvam, Sundararajulu; Zafarina, Zainuddin

    2015-01-01

    The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations. PMID:26565719

  9. The cumulative effect of genetic polymorphisms on depression and brain structural integrity.

    PubMed

    Kostic, Milutin; Canu, Elisa; Agosta, Federica; Munjiza, Ana; Novakovic, Ivana; Dobricic, Valerija; Maria Ferraro, Pilar; Miler Jerkovic, Vera; Pekmezovic, Tatjana; Lecic Tosevski, Dusica; Filippi, Massimo

    2016-06-01

    In major depressive disorder (MDD), the need to study multiple-gene effect on brain structure is emerging. Our aim was to assess the effect of accumulation of specific SERT, BDNF and COMT gene functional polymorphisms on brain structure in MDD patients. Seventy-seven MDD patients and 66 controls underwent a clinical assessment, genetic testing and MRI scan. Compared with controls, patients were more BDNF-Val homozygotes, COMT-Met carriers and SERT-L' carriers. Thus, subjects were split into three groups: 1. High-frequency susceptibility polymorphism group (hfSP, subjects with all three SPs); 2. Intermediate-frequency SP group (ifSP, two SPs); and 3. Low-frequency SP group (lfSP, one/none SP). Cortical thickness, volumetry of hippocampus, amygdala and subcortical structures, and white matter (WM) tract integrity were assessed. Compared to controls, hfSP patients showed thinning of the middle frontal cortex bilaterally, left frontal pole, and right lateral occipital cortex, and smaller hippocampal volume bilaterally; and both hfSP and lfSP patient groups showed thinning of the left inferior parietal cortex and reduced WM integrity of the corpus callosum. Compared to patients, hfSP controls showed greater integrity of the fronto-occipital cortices and corpus callosum. We showed that cortical prefrontal and occipital damage of MDD patients is modulated by the SP accumulation, while damage to the parietal cortex and corpus callosum seem to be independent of genetic accumulation. HfSP controls may experience protective mechanisms leading to a preserved integrity of critical cortical and WM regions. Investigating the effect of multiple genes is promising to understand the pathological mechanisms underlying MDD. Hum Brain Mapp 37:2173-2184, 2016. © 2016 Wiley Periodicals, Inc. PMID:26956059

  10. Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms

    PubMed Central

    NurWaliyuddin, Hanis Z. A.; Norazmi, Mohd N.; Edinur, Hisham A.; Chambers, Geoffrey K.; Panneerchelvam, Sundararajulu; Zafarina, Zainuddin

    2015-01-01

    The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations. PMID:26565719

  11. Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers

    PubMed Central

    Liu, Wei; Xiao, Zhidan; Bao, Xiuli; Yang, Xiaoyan; Fang, Jing; Xiang, Xu

    2015-01-01

    Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, ‘Heiye’ and ‘Wuye’, and ‘Chengtuo’ and ‘Baitangli 1’. A subset of 14 SNPs was sufficient to distinguish all the non-redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum

  12. Genetic study of eight AKT1 gene polymorphisms and their interaction with DRD2 gene polymorphisms in tardive dyskinesia.

    PubMed

    Zai, Clement C; Romano-Silva, Marco A; Hwang, Rudi; Zai, Gwyneth C; Deluca, Vincenzo; Müller, Daniel J; King, Nicole; Voineskos, Aristotle N; Meltzer, Herbert Y; Lieberman, Jeffrey A; Potkin, Steven G; Remington, Gary; Kennedy, James L

    2008-12-01

    Tardive dyskinesia (TD) is a motor adverse effect of chronic antipsychotic medication. It has been suggested to involve dopamine neurotransmission system changes. AKT1 acts downstream of the D(2) receptor that is blocked by all antipsychotics to some degree. The AKT1 gene has not been investigated in TD. We examined eight polymorphisms spanning the AKT1 gene and their association with TD in our schizophrenia sample of 193 Caucasians, 76 of which with TD. AKT1 polymorphisms and haplotypes were not significantly associated with TD. However, we detected a significant interaction between rs6275 of DRD2 and rs3730358 of AKT1 (p<1 x 10(-5)). PMID:18838251

  13. [Genetic polymorphism of FIBRA,DHFRP2 and ACTBP2 and their forensic application in Yunnan Han population].

    PubMed

    Jing, Qiang; Nie, Sheng-Jie

    2002-09-01

    To investigate the genetic polymorphism of FIBRA,DHFRP2 and ACTBP2 in Yunnan Han population as well as their application in forensic science, EDTA-blood specimens were collected from 200 healthy individuals. The DNA were extracted either by the Chloro form, phenol method or by the Chelex-100 method. The PCR products were analyzed by PAG vertical electrophoresis,following by silver staining. All gene frequencies, discrimination power (DP), exclusion of paternity probability (EPP), heterozygosity (H),polymorphisms information content (PIC),matching probability (PM) as well as the Hardy-Weinberg test were calculated. The obtained data are beneficial in the understanding of population genetics of the three STR loci in Yunnan Han population and the results suggest that these loci are valuable genetic markers for paternity testing and personal identification in forensic science practice. PMID:16135442

  14. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

    PubMed Central

    Kikuchi, Naoki; Nakazato, Koichi

    2015-01-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  15. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism.

    PubMed

    Kikuchi, Naoki; Nakazato, Koichi

    2015-09-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  16. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma.

    PubMed

    Giannitrapani, Lydia; Soresi, Maurizio; Balasus, Daniele; Licata, Anna; Montalto, Giuseppe

    2013-04-28

    Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC. PMID:23674845

  17. The influence of genetic drift on the formation and stability of polymorphisms arising from negative frequency-dependent selection.

    PubMed

    Zhao, Lei; Waxman, David

    2016-02-21

    We consider the simplest form of negative frequency-dependent selection in a biallelic haploid population, where the selection coefficient of a mutant allele is a linear function of the allele's frequency, and changes from positive to negative as the frequency is increased. In an effectively infinite population this behaviour leads to a stable polymorphism. We present a theoretical investigation of what occurs in a finite population, where a long-lived polymorphism may be formed, but which fluctuates and ultimately disappears due to random genetic drift. We model the dynamics as a branching process and explicitly take into account differences between the census population size and the effective population size, which play different roles in the dynamics. We characterise the behaviour of the population in terms of three distinct timescales associated with: (i) early loss of mutant alleles, (ii) achievement of the long-lived polymorphism, (iii) disappearance of the polymorphism. Timescales (i) and (iii) depend on the effective population size and are, as a consequence, affected by random genetic drift, while timescale (ii) depends primarily on the census size and is relatively insensitive to genetic drift. Analysis and simulations of the branching process clarify the different influences of the census and effective population sizes. One substantial quantitative difference, between populations where the effective and census population sizes coincide and where they differ, lies in the number of mutant alleles in the long-lived polymorphism. This number is approximately proportional to the census size. Thus assuming the census size equals a much smaller effective population size predicts a much smaller number of mutants in the long-lived polymorphism. PMID:26656188

  18. Start codon targeted (SCoT) and target region amplification polymorphism (TRAP) for evaluating the genetic relationship of Dendrobium species.

    PubMed

    Feng, Shangguo; He, Refeng; Yang, Sai; Chen, Zhe; Jiang, Mengying; Lu, Jiangjie; Wang, Huizhong

    2015-08-10

    Two molecular marker systems, start codon targeted (SCoT) and target region amplification polymorphism (TRAP), were used for genetic relationship analysis of 36 Dendrobium species collected from China. Twenty-two selected SCoT primers produced 337 loci, of which 324 (96%) were polymorphic, whereas 13 TRAP primer combinations produced a total of 510 loci, with 500 (97.8%) of them being polymorphic. An average polymorphism information content of 0.953 and 0.983 was detected using the SCoT and TRAP primers, respectively, showing that a high degree of genetic diversity exists among Chinese Dendrobium species. The partition of clusters in the unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis plot based on the SCoT and TRAP markers was similar and clustered the 36 Dendrobium species into four main groups. Our results will provide useful information for resource protection and will also be useful to improve the current Dendrobium breeding programs. Our results also demonstrate that SCoT and TRAP markers are informative and can be used to evaluate genetic relationships between Dendrobium species. PMID:25936992

  19. Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China

    PubMed Central

    Jin, Tianbo; Aikemu, Ainiwaer; Zhang, Mingxia; Geng, Tingting; Feng, Tian; Kang, Longli; Luo, Manlin

    2015-01-01

    Background Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. Material/Methods In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi’an Han Chinese. Results Using the χ2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). Conclusions Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population. PMID:26632549

  20. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes

    PubMed Central

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-01-01

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual’s viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. PMID:26912403

  1. Babesia canis: evidence for genetic diversity among isolates revealed by restriction fragment length polymorphism analysis.

    PubMed

    Citard, T; Mähl, P; Boulouis, H J; Chavigny, C; Druilhe, P

    1995-09-01

    The genetic diversity of B. canis was investigated by restriction fragment length polymorphism analysis. For this purpose, we identified a Babesia canis specific DNA probe named pS8. This 1.2 kbp probe can detect as low as 20 pg of B. canis DNA. Results suggest that the pS8 probe is distributed in multiple copies throughout the genome though is probably not itself internally repetitious, i.e. not structured into blocks of tandem units. This probe reveals discrete hybridizing fragments in B. canis enzyme-digested genomic DNA. RFLP patterns obtained with the pS8 probe revealed a large genetic diversity between various isolates and led us to distinguish several clones derived from a single isolate. Results suggest that for a single isolate, the fingerprints obtained reflect those of a few quantitatively dominant clones. This technique can now be routinely applied and provides a convenient tool for the characterization and the identification of B. canis isolates, strains and clones. PMID:8533020

  2. Genetic polymorphism of Hucul horse population based on 17 microsatellite loci.

    PubMed

    Fornal, Agnieszka; Radko, Anna; Piestrzyńska-Kajtoch, Agata

    2013-01-01

    Short tandem repeat (STR) loci, i.e. microsatellites are a class of genetic markers commonly used for population studies and parentage control. This study determined the usefulness of microsatellite markers recommended by International Society for Animal Genetics (ISAG) for identification and pedigree analysis in horses based on the example of Polish Hucul horse population (Equus caballus). The set of seventeen microsatellites loci was tested (AHT4, AHT5, ASB2, HMS2, HMS3, HMS6, HMS7, HTG10, HTG4, HTG6, HTG7, VHL20, ASB17, ASB23, CA425, HMS1, LEX3) for 216 individuals. All samples were genotyped and mean number of alleles per locus was estimated (7.00). Means of observed (Ho) and expected (He) heterozygosity were calculated 0.7288 and 0.7027, respectively. The observed heterozygosity was similar to the results of research on Hucul horse population in another area of Carpathians Mountains. The average polymorphism information content (PIC) for analyses of seventeen microsatellite markers indicates the usefulness of this set of markers for Hucul horse parentage testing. PMID:24432328

  3. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

    PubMed

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-03-01

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. PMID:26912403

  4. [Genetic aspects of endometriosis: features of the distribution of polymorphic gene frequencies].

    PubMed

    Spitsyn, V A; Andreeva, E N; Adamian, L V; Agapova, R K; Sandoval', Kh R

    1996-12-01

    In a group of patients with endometriosis and in a control group of healthy women, the polymorphism of the following systems were studied: ABO and RH blood-group systems; serum proteins haptoglobin (HP), transferrin (TF), vitamin D-transporting protein (GC), protease inhibitor (PI), and the third component of the complement (C3); serum enzymes-amylase of the loci 1 and 2 (AMY1 and AMY2), pseudocholinesterase (E2), and alkaline phosphatase (PP); erythrocytic enzymes-acid phosphatase (ACP1), phosphoglucomutase (PGM1), superoxide dismutase (SOD-A), esterase D (ESD), and glyoxalase (GLO1). Statistically significant differences between the groups compared were established for five genetic systems: ABO, E2, C3, TF, and PGM1. Among patient with endometriosis, the rare alleles of the locus ESD-ESD5 and ESD7-were found, along with ESD 5-5 homozygotes. Several genetic loci can be involved in the pathogenesis of endometriosis; their products can be specifically realized due to peculiarities of biochemical reactions in the organisms of people predisposed to this pathology. PMID:9102363

  5. Ecogenetics of mercury: from genetic polymorphisms and epigenetics to risk assessment and decision-making.

    PubMed

    Basu, Niladri; Goodrich, Jaclyn M; Head, Jessica

    2014-06-01

    The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex interactions between genetic ("nature") and environmental ("nurture") factors, most Hg studies thus far have focused solely on environmental factors. In recent years, ecogenetic-based studies have emerged and have started to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics of Hg. The present study reviews these studies and discusses their utility in terms of Hg risk assessment, management, and policy and offers perspectives on fruitful areas for future research. In brief, epidemiological studies on populations exposed to inorganic Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are showing that polymorphisms in a number of environmentally responsive genes can explain variations in Hg biomarker values and health outcomes. Studies on mammals (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings are beginning to increase understanding of the mechanisms of action of Hg, and in doing so they may help identify candidate biomarkers and pinpoint susceptible groups or life stages. Furthermore, they may help refine uncertainty factors and thus lead to more accurate risk assessments and improved decision-making. PMID:24038486

  6. Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

    PubMed Central

    Michalska, Kalina J.; Decety, Jean; Liu, Chunyu; Chen, Qi; Martz, Meghan E.; Jacob, Suma; Hipwell, Alison E.; Lee, Steve S.; Chronis-Tuscano, Andrea; Waldman, Irwin D.; Lahey, Benjamin B.

    2013-01-01

    Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4–6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. PMID:24550797

  7. Study of population genetic polymorphism and gene flow rate in Indian snow trout, Schizothorax richardsonii fish of Himalaya, India.

    PubMed

    Sivaraman, G K; Barat, A; Ali, S; Mahanta, P C

    2014-11-01

    The genetic polymorphism and gene flow rate among the Indian snow trout fish population S. richadsonii from three different locations viz., Chirapani stream of Champawat district, Kosi and Gola river of Nainital district, Uttarakhand State, India were assessed by employing twenty numbers of Randomly Amplified Polymorphic DNA (RAPD) markers. The overall percent polymorphisms among these three populations were 14.76 with 6.56, 4.92 and 3.28 in Chirapani, Kosi and Gola river population, respectively. Chirapani population had higher proportion of polymorphic loci as compared to the Kosi and Gola. The higher value of genetic distance (0.1565) was obtained between Chirapani and Gola population and the lower value of genetic distance was observed between Chirapani and Kosi (0.1058) river population. The cluster analysis revealed that in the formation of two clusters, one consisted of Chirapani and Kosi and the other was Gola fish population. Gst estimates among these populations showed some extent of homogeneity with lower genetic differentiation rate between populations and further suggested that higher tolerance to mutation, as expected that RAPD bands, arose from both coding and non-coding DNA regions. The findings revealed that the rate of gene flow in three populations seemed very low i.e. highly conserved its genetic diversity in their natural waterbodies and indicative of little migration among populations (geographically isolated and not the possibilities man made interventions/introduction of similar kind of fish species). It is further concluded that the Chirapani, Kosi and Gola river populations of S. richardsonii were being conserved naturally in their habitat and the species actual genetic potential were being maintained (adaptation to local climatic conditions, reproduction, production traits and disease resistance trait etc) in their natural habitat. PMID:25522514

  8. Genetic Diversity of Thottapalayam Virus, a Hantavirus Harbored by the Asian House Shrew (Suncus murinus) in Nepal

    PubMed Central

    Kang, Hae Ji; Kosoy, Michael Y.; Shrestha, Sanjaya K.; Shrestha, Mrigendra P.; Pavlin, Julie A.; Gibbons, Robert V.; Yanagihara, Richard

    2011-01-01

    Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus–host relationship. PMID:21896819

  9. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma

    PubMed Central

    Chen, Haitao; Lin, Xiaolin; Yu, Yang; Gou, Yuancheng; Hou, Jiangang; Jiang, Deke; Na, Rong; Wang, Xiang; Ding, Qiang; Xu, Jianfeng

    2016-01-01

    The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10−7). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10−10). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available. PMID:27229762

  10. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    PubMed Central

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227