Characterization of 10 new nuclear microsatellite markers in Acca sellowiana (Myrtaceae)1

PubMed Central

Klabunde, Gustavo H. F.; Olkoski, Denise; Vilperte, Vinicius; Zucchi, Maria I.; Nodari, Rubens O.

2014-01-01

• Premise of the study: Microsatellite primers were identified and characterized in Acca sellowiana in order to expand the limited number of pre-existing polymorphic markers for use in population genetic studies for conservation, phylogeography, breeding, and domestication. • Methods and Results: A total of 10 polymorphic microsatellite primers were designed from clones obtained from a simple sequence repeat (SSR)–enriched genomic library. The primers amplified di- and trinucleotide repeats with four to 27 alleles per locus. In all tested populations, the observed heterozygosity ranged from 0.269 to 1.0. • Conclusions: These new polymorphic SSR markers will allow future genetic studies to be denser, either for genetic structure characterization of natural populations or for studies involving genetic breeding and domestication process in A. sellowiana. PMID:25202632

Genetic diversity of the Arctic fox using SRAP markers.

PubMed

Zhang, M; Bai, X J

2013-12-04

Sequence-related amplified polymorphism (SRAP) is a recently developed molecular marker technique that is stable, simple, reliable, and achieves moderate to high numbers of codominant markers. This study is the first to apply SRAP markers in a mammal, namely the Arctic fox. In order to investigate the genetic diversity of the Arctic fox and to provide a reference for use of its germplasm, we analyzed 7 populations of Arctic fox by SRAP. The genetic similarity coefficient, genetic distance, proportion of polymorphic loci, total genetic diversity (Ht), genetic diversity within populations (Hs), and genetic differentiation (Gst) were calculated using the Popgene software package. The results indicated abundant genetic diversity among the different populations of Arctic fox studied in China. The genetic similarity coefficient ranged from 0.1694 to 0.0417, genetic distance ranged from 0.8442 to 0.9592, and the proportion of polymorphic loci was smallest in the TS group. Genetic diversity ranged from 0.2535 to 0.3791, Ht was 0.3770, Hs was 0.3158, Gst was 0.1624, and gene flow (Nm) was estimated at 2.5790. Thus, a high level of genetic diversity and many genetic relationships were found in the populations of Arctic fox evaluated in this study.

Genetic Polymorphism in Wine Yeasts: Mechanisms and Methods for Its Detection

PubMed Central

Guillamón, José M.; Barrio, Eladio

2017-01-01

The processes of yeast selection for using as wine fermentation starters have revealed a great phenotypic diversity both at interspecific and intraspecific level, which is explained by a corresponding genetic variation among different yeast isolates. Thus, the mechanisms involved in promoting these genetic changes are the main engine generating yeast biodiversity. Currently, an important task to understand biodiversity, population structure and evolutionary history of wine yeasts is the study of the molecular mechanisms involved in yeast adaptation to wine fermentation, and on remodeling the genomic features of wine yeast, unconsciously selected since the advent of winemaking. Moreover, the availability of rapid and simple molecular techniques that show genetic polymorphisms at species and strain levels have enabled the study of yeast diversity during wine fermentation. This review will summarize the mechanisms involved in generating genetic polymorphisms in yeasts, the molecular methods used to unveil genetic variation, and the utility of these polymorphisms to differentiate strains, populations, and species in order to infer the evolutionary history and the adaptive evolution of wine yeasts, and to identify their influence on their biotechnological and sensorial properties. PMID:28522998

Genetic association studies of obesity in Africa: a systematic review.

PubMed

Yako, Y Y; Echouffo-Tcheugui, J B; Balti, E V; Matsha, T E; Sobngwi, E; Erasmus, R T; Kengne, A P

2015-03-01

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies. © 2015 World Obesity.

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis

PubMed Central

Smith, J. Gustav; Almgren, Peter; Engström, Gunnar; Hedblad, Bo; Platonov, Pyotr G.; Newton-Cheh, Christopher; Melander, Olle

2013-01-01

Objectives Genome-wide association studies have recently identified genetic polymorphisms associated with common, etiologically complex diseases, for which direct-to-consumer genetic testing with provision of absolute genetic risk estimates is marketed by commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates but the robustness of such estimates across populations and study designs has not been studied. Design A systematic literature review with meta-analysis and assessment of between-study heterogeneity was performed for single nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. Results Data from 18 samples of European ancestry (n=12,100 cases; 115,702 controls) were identified for the SNP on chromosome 4q25 (rs220733), 16 samples (n=12,694 cases; 132,602 controls) for the SNP on 16q22 (rs2106261) and 4 samples (n=5,272 cases; 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the discovery studies were identified for SNPs on 1q21 and in GJA5 and IL6R, why no meta-analyses were performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs from genome-wide studies on 4q25 (OR 1.67, 95% CI=1.50–1.86, p=2×10−21) and 16q22 (OR 1.21, 95% CI=1.13–1.29, p=1×10−8), but not the SNP in KCNH2 from candidate gene studies (p=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I2=0.50–0.78, p<0.05), but not across prospective cohort studies (I2=0.39, p=0.15). Both polymorphisms were robustly associated with AF for each study design individually (p<0.05). Conclusions In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates. PMID:22690879

Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis.

PubMed

Gao, L; Tao, Y; Zhang, L; Jin, Q

2010-01-01

Host genetic susceptibility has been suggested as one of the most important explanations for inter-individual differences in tuberculosis (TB) risk. The vitamin D receptor (VDR) gene has been studied as a candidate locus due to genetic polymorphisms that affects the activity of the receptor and subsequent downstream vitamin D-mediated effects. We reviewed published studies on VDR polymorphisms and TB susceptibility up to 15 April 2009 and quantitatively summarised associations of the most widely studied polymorphisms (FokI, TaqI, ApaI and BsmI) using meta-analysis. A total of 23 eligible studies were included in this review. Heterogeneous results were observed, which may be partly explained by the differences between populations. Among Asians, the FokI ff genotype showed a pronounced positive association (OR 2.0, 95%CI 1.3-3.2), a significant inverse association was observed for the BsmI bb genotype (OR 0.5, 95%CI 0.4-0.8), and marginal significant associations were found for TaqI and ApaI polymorphisms. However, none of the polymorphisms was significantly related to TB among Africans or South Americans. The association of VDR polymorphisms with risk of TB observed in our analyses supports the hypothesis that vitamin D deficiency might play a role as risk factor during the development of TB.

[Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder].

PubMed

Ortega-Rojas, Jenny; Arboleda-Bustos, Carlos E; Morales, Luis; Benítez, Bruno A; Beltrán, Diana; Izquierdo, Álvaro; Arboleda, Humberto; Vásquez, Rafael

Attention deficit and hyperactive disorder (ADHD) is highly prevalent among children in Bogota City. Both genetic and environmental factors play a very important role in the etiology of ADHD. However, to date few studies have addressed the association of genetic variants and ADHD in the Colombian population. To test the genetic association between polymorphisms in the DAT1, HTTLPR, COMT and BDNF genes and ADHD in a sample from Bogota City. We genotyped the most common polymorphisms in DAT1, SERT, COMT and BDNF genes associated with ADHD using conventional PCR followed by restriction fragment length polymorphism (RFLP) in 97 trios recruited in a medical center in Bogota. The transmission disequilibrium test (TDT) was used to determine the association between such genetic variants and ADHD. The TDT analysis showed that no individual allele of any variant studied has a preferential transmission. Our results suggest that the etiology of the ADHD may be complex and involves several genetic factors. Further studies in other candidate polymorphisms in a larger sample size will improve our knowledge of the ADHD in Colombian population. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Assessment of genetic diversity among Indian potato (Solanum tuberosum L.) collection using microsatellite and retrotransposon based marker systems.

PubMed

Sharma, Vishakha; Nandineni, Madhusudan R

2014-04-01

Potato (Solanum tuberosum) is an important non-cereal crop throughout the world and is highly recommended for ensuring global food security. Owing to the complexities in genetics and inheritance pattern of potato, the conventional method of cross breeding for developing improved varieties has been difficult. Identification and tagging of desirable traits with informative molecular markers would aid in the development of improved varieties. Insertional polymorphism of copia-like and gypsy-like long terminal repeat retrotransposons (RTN) were investigated among 47 potato varieties from India using Inter-Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon Microsatellite Amplified Polymorphism (REMAP) marker techniques and were compared with the DNA profiles obtained with simple sequence repeats (SSRs). The genetic polymorphism, efficiency of polymorphism and effectiveness of marker systems were evaluated to assess the extent of genetic diversity among Indian potato varieties. A total of 139 polymorphic SSR alleles, 270 IRAP and 98 REMAP polymorphic bands, showing polymorphism of 100%, 87.9% and 68.5%, respectively, were used for detailed characterization of the genetic relationships among potato varieties by using cluster analysis and principal coordinate analysis (PCoA). IRAP analysis resulted in the highest number of polymorphic bands with an average of 15 polymorphic bands per assay unit when compared to the other two marker systems. Based on pair-wise comparison, the genetic similarity was calculated using Dice similarity coefficient. The SSRs showed a wide range in genetic similarity values (0.485-0.971) as compared to IRAP (0.69-0.911) and REMAP (0.713-0.947). A Mantel's matrix correspondence test showed a high positive correlation (r=0.6) between IRAP and REMAP, an intermediate value (r=0.58) for IRAP and SSR and the lowest value (r=0.17) for SSR and REMAP. Statistically significant cophenetic correlation coefficient values, of 0.961, 0.941 and 0.905 were observed for REMAP, IRAP and SSR, respectively. The widespread presence and distinct DNA profiles for copia-like and gypsy-like RTNs in the examined genotypes indicate that these elements are active in the genome and may have even contributed to the potato genome organization. Although the three marker systems were capable of distinguishing all the 47 varieties; high reproducibility, low cost and ease of DNA profiling data collection make IRAP and REMAP markers highly efficient whole-genome scanning molecular probes for population genetic studies. Information obtained from the present study regarding the genetic association and distinctiveness provides an useful guide for selection of germplasm for plant breeding and conservation efforts. Copyright © 2014. Published by Elsevier Inc.

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

PubMed

Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

2009-06-01

To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

Genetic diversity revealed by single nucleotide polymorphism markers in a worldwide germplasm collection of durum wheat.

PubMed

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

2013-03-28

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.

Association between vascular endothelial growth factor polymorphism and recurrent pregnancy loss: A systematic review and meta-analysis.

PubMed

Sun, Yaling; Chen, Min; Mao, Benyu; Cheng, Xianglin; Zhang, Xianping; Xu, Chuanxin

2017-04-01

Some studies have reported that vascular endothelial growth factor (VEGF) genetic polymorphisms are associated with recurrent pregnancy loss (RPL), but the results are controversial. This study is aimed to quantify the strength of this association. A systematic review of the published literature from Medline, Springer, and China National Knowledge Infra structure (CNKI) databases was conducted and investigations of VEGF genetic polymorphisms in RPL were selected. We estimated the pooled odds ratio (OR) to assess this possible association. Fifteen case-control studies comprising 2702 cases and 2667 controls and including five genetic polymorphisms (rs3025039, rs833061, rs15703060, rs2010963 and rs699947) were eligible for this meta-analysis. The overall analysis suggested that only two genetic polymorphisms (rs1570360, rs3025039) were associated with increased risk of RPL. A significant increased risk between VEGF rs1570360 polymorphism and RPL was only found under the dominant model in Caucasians (OR=1.70, 95% CI 1.02-2.82, P=0.04). Whereas, we found that VEGF rs3025039 polymorphism was significantly associated with RPL both under the dominant and recessive model in East Asians, and their summary odd ratios and 95% CIs were 1.26, 1.04-1.53, P=0.02 and 2.94, 1.80-4.83, P=0, respectively. This meta-analysis showed that only rs1570360 (especially in Caucasians) and rs3025039 (especially in East Asians) may be risk factors for RPL. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutral theory, microbial practice: challenges in bacterial population genetics.

PubMed

Rocha, Eduardo P C

2018-04-19

Kimura's outstanding contributions to population genetics included many elegant theoretical results on the vagaries of alleles in populations. Once polymorphism data showed extensive variation in natural populations, these results led naturally to the Neutral Theory. In this article, I'll depart from some of these results to focus on four major open problems in microbial population genetics with direct implications to the study of molecular evolution: the lack of neutral polymorphism, the modeling of genetic exchanges, the population genetics of ill-defined populations, and the difficulty of untangling selection and demography in the light of the previous issues. Whilst studies in population genetics usually focus on single nucleotide polymorphism and allelic recombination, ignoring even small indels, a large fraction of genetic diversification in Bacteria results from horizontal gene transfer. Ignoring this fact defeats the purpose of population genetics: to characterize the genetic variation in populations and their adaptive effects. I'll argue that, following on Kimura's life work, one may need to develop new approaches to study microbes that reproduce asexually but are able to engage in gene exchanges with very distantly related organisms in a context where random sampling is often unachievable, populations are ill-defined, genetic linkage is strong, and random drift is rare.

Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

PubMed

Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

2016-05-01

Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children <1-year old who underwent open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants <1-year old undergoing complex open heart surgery. © The Author(s) 2016.

Genetic Diversity of Toll-Like Receptors and Immunity to M. leprae Infection

PubMed Central

Hart, Bryan E.; Tapping, Richard I.

2012-01-01

Genetic association studies of leprosy cohorts across the world have identified numerous polymorphisms which alter susceptibility and outcome to infection with Mycobacterium leprae. As expected, many of the polymorphisms reside within genes that encode components of the innate and adaptive immune system. Despite the preponderance of these studies, our understanding of the mechanisms that underlie these genetic associations remains sparse. Toll-like receptors (TLRs) have emerged as an essential family of innate immune pattern recognition receptors which play a pivotal role in host defense against microbes, including pathogenic strains of mycobacteria. This paper will highlight studies which have uncovered the association of specific TLR gene polymorphisms with leprosy or tuberculosis: two important diseases resulting from mycobacterial infection. This analysis will focus on the potential influence these polymorphic variants have on TLR expression and function and how altered TLR recognition or signaling may contribute to successful antimycobacterial immunity. PMID:22529866

Genetic polymorphisms and the risk of stroke after cardiac surgery.

PubMed

Grocott, Hilary P; White, William D; Morris, Richard W; Podgoreanu, Mihai V; Mathew, Joseph P; Nielsen, Dahlia M; Schwinn, Debra A; Newman, Mark F

2005-09-01

Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery. Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies. A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3'UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (P=0.0020). We demonstrate that common genetic variants of CRP (3'UTR 1846C/T) and IL-6 (-174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post-cardiac surgery stroke.

PICALM gene rs3851179 polymorphism contributes to Alzheimer's disease in an Asian population.

PubMed

Liu, Guiyou; Zhang, Shuyan; Cai, Zhiyou; Ma, Guoda; Zhang, Liangcai; Jiang, Yongshuai; Feng, Rennan; Liao, Mingzhi; Chen, Zugen; Zhao, Bin; Li, Keshen

2013-06-01

PICALM gene rs3851179 polymorphism was reported to an Alzheimer's disease (AD) susceptibility locus in a Caucasian population. However, recent studies reported consistent and inconsistent results in an Asian population. Four studies indicated no association between rs3851179 and AD in a Chinese population and one study reported weak association in a Japanese population. We consider that the failure to replicate the significant association between rs3851179 and AD may be caused by at least two reasons. The first reason may be the genetic heterogeneity in AD among different populations, and the second may be the relatively small sample size compared with large-scale GWAS in Caucasian ancestry. In order to confirm this view, in this research, we first evaluated the genetic heterogeneity of rs3851179 polymorphism in Caucasian and Asian populations. We then investigated rs3851179 polymorphism in an Asian population by a pooled analysis method and a meta-analysis method. We did not observe significant genetic heterogeneity of rs3851179 in the Caucasian and Asian populations. Our results indicate that rs3851179 polymorphism is significantly associated with AD in the Asian population by both pooled analysis and meta-analysis methods. We believe that our findings will be very useful for future genetic studies in AD.

Functional analysis of regulatory single-nucleotide polymorphisms.

PubMed

Pampín, Sandra; Rodríguez-Rey, José C

2007-04-01

The identification of regulatory polymorphisms has become a key problem in human genetics. In the past few years there has been a conceptual change in the way in which regulatory single-nucleotide polymorphisms are studied. We revise the new approaches and discuss how gene expression studies can contribute to a better knowledge of the genetics of common diseases. New techniques for the association of single-nucleotide polymorphisms with changes in gene expression have been recently developed. This, together with a more comprehensive use of the old in-vitro methods, has produced a great amount of genetic information. When added to current databases, it will help to design better tools for the detection of regulatory single-nucleotide polymorphisms. The identification of functional regulatory single-nucleotide polymorphisms cannot be done by the simple inspection of DNA sequence. In-vivo techniques, based on primer-extension, and the more recently developed 'haploChIP' allow the association of gene variants to changes in gene expression. Gene expression analysis by conventional in-vitro techniques is the only way to identify the functional consequences of regulatory single-nucleotide polymorphisms. The amount of information produced in the last few years will help to refine the tools for the future analysis of regulatory gene variants.

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

Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review.

PubMed

Tan, Benjamin H L; Ross, James A; Kaasa, Stein; Skorpen, Frank; Fearon, Kenneth C H

2011-04-01

Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986-2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

Defining Genetic Risk for GVHD and Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Hansen, John A; Chien, Jason W; Warren, Edus H; Zhao, Lue Ping; Martin, Paul J

2011-01-01

Purpose of review To explore what is known about the genetics of hematopoietic stem cell transplantation (HCT) and how genetic polymorphism affects risk of graft-versus-host disease (GVHD) and mortality. Recent findings Genetic variation found across the human genome can impact HCT outcome by 1) causing genetic disparity between patient and donor, and 2) modifying gene function. Single nucleotide polymorphisms (SNP) and structural variation can result in mismatching for cellular peptides known as histocompatibility antigens (HA). At least 25 to 30 polymorphic genes are known to encode functional HA in mismatched individuals, but their individual contribution to clinical GVHD is unclear. HCT outcome may also be affected by polymorphism in donor or recipient. Association studies have implicated several genes with GVHD and mortality, however results have been inconsistent most likely due to limited sample size, and differences in racial diversity and clinical covariates. New technologies using DNA arrays genotyping for a million or more SNPs promise genome-wide discovery of HCT associated genes, however adequate statistical power requires study populations of several thousand patient-donor pairs. Summary Available data offers strong preliminary support for the impact that genetic variation has on risk of GVHD and mortality following HCT. Definitive results however await future genome-wide studies of large multi-center HCT cohorts. PMID:20827186

Development of microsatellite primers of the largest seagrass, Enhalus acoroides (Hydrocharitaceae).

PubMed

Gao, Hui; Jiang, Kai; Geng, Yan; Chen, Xiao-Yong

2012-03-01

Microsatellite primers were developed for the seagrass Enhalus acoroides to investigate genetic variation and identify clonal structure. Four polymorphic loci and 32 monomorphic loci were developed in E. acoroides. Two to four alleles per locus were observed at the polymorphic loci across 60 individuals of two E. acoroides populations. The observed and expected heterozygosities within populations ranged from 0.100 to 0.5667 and from 0.0977 to 0.5079, respectively. Our study revealed very low polymorphism in E. acoroides, even at the polymorphic loci. Nevertheless, these primers are a useful tool to study genetic variation, clonal structure, and mating system.

Patterns of genetic diversity in the polymorphic ground snake (Sonora semiannulata).

PubMed

Cox, Christian L; Chippindale, Paul T

2014-08-01

We evaluated the genetic diversity of a snake species with color polymorphism to understand the evolutionary processes that drive genetic structure across a large geographic region. Specifically, we analyzed genetic structure of the highly polymorphic ground snake, Sonora semiannulata, (1) among populations, (2) among color morphs (3) at regional and local spatial scales, using an amplified fragment length polymorphism dataset and multiple population genetic analyses, including FST-based and clustering analytical techniques. Based upon these methods, we found that there was moderate to low genetic structure among populations. However, this diversity was not associated with geographic locality at either spatial scale. Similarly, we found no evidence for genetic divergence among color morphs at either spatial scale. These results suggest that despite dramatic color polymorphism, this phenotypic diversity is not a major driver of genetic diversity within or among populations of ground snakes. We suggest that there are two mechanisms that could explain existing genetic diversity in ground snakes: recent range expansion from a genetically diverse founder population and current or recent gene flow among populations. Our findings have further implications for the types of color polymorphism that may generate genetic diversity in snakes.

Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

PubMed

Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

2006-06-01

Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

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. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

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. Copyright © 2011 Elsevier B.V. All rights reserved.

Polymorphisms of the lipoprotein lipase gene as genetic markers for stroke in colombian population: a case control study.

PubMed

Velásquez Pereira, Leydi Carolina; Vargas Castellanos, Clara Inés; Silva Sieger, Federico Arturo

2016-12-30

To analyze if there is an association between the presence of polymorphisms in the LPL gene (rs320, rs285 and rs328) with development of acute ischemic stroke in Colombian population. In a case control design, 133 acute ischemic stroke patients (clinical diagnosis and x-ray CT) and 269 subjects without stroke as controls were studied. PCR -RFLP technique was used to detect rs320, rs285 and rs328 polymorphisms in the LPL gene. In the present research was not found any association between any of the LPL gene polymorphism and acute ischemic stroke in the population studied; the allele and genotypic frequencies of the studied polymorphisms were similar in cases and controls and followed the Hardy-Weinberg equilibrium. The study was approved by the IRB and each subject signed the informed consent. LPL gene polymorphisms are not genetic markers for the development of stroke in the Colombian sample used.

Genetic characterization of three varieties of Astragalus lentiginosus (Fabaceae).

Treesearch

Brian J. Knaus; Rich C. Cronn; Aaron Liston

2005-01-01

Astragalus lentiginosus is a polymorphic species that occurs in geologically young habitats and whose varietal circumscription implies active morphological and genetic differentiation. In this preliminary study, we evaluate the potential of amplified fragment length polymorphism (AFLP) markers to resolve infraspecific taxa in three varieties of...

The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

PubMed Central

2013-01-01

Introduction Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study. Methods This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFα, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman's rank correlation coefficient or Spearman's rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission. Results Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (χ2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ = -0.19; P = 0.002), MMP-10 (ρ = 0.55; P <0.001), TNFα (ρ = 0.56; P <0.001), IL-10 (ρ = 0.48; P <0.001) and PAI-1 (ρ = 0.49; P <0.001). Conclusion The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance. PMID:23706069

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fahrenkrog, Annette M.; Neves, Leandro G.; Resende, Jr., Marcio F. R.

Genome-wide association studies (GWAS) have been used extensively to dissect the genetic regulation of complex traits in plants. These studies have focused largely on the analysis of common genetic variants despite the abundance of rare polymorphisms in several species, and their potential role in trait variation. Here, we conducted the first GWAS in Populus deltoides, a genetically diverse keystone forest species in North America and an important short rotation woody crop for the bioenergy industry. We searched for associations between eight growth and wood composition traits, and common and low-frequency single-nucleotide polymorphisms detected by targeted resequencing of 18 153 genesmore » in a population of 391 unrelated individuals. To increase power to detect associations with low-frequency variants, multiple-marker association tests were used in combination with single-marker association tests. Significant associations were discovered for all phenotypes and are indicative that low-frequency polymorphisms contribute to phenotypic variance of several bioenergy traits. Our results suggest that both common and low-frequency variants need to be considered for a comprehensive understanding of the genetic regulation of complex traits, particularly in species that carry large numbers of rare polymorphisms. Lastly, these polymorphisms may be critical for the development of specialized plant feedstocks for bioenergy.« less

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Genetic diversity analysis of Jatropha curcas L. (Euphorbiaceae) based on methylation-sensitive amplification polymorphism.

PubMed

Kanchanaketu, T; Sangduen, N; Toojinda, T; Hongtrakul, V

2012-04-13

Genetic analysis of 56 samples of Jatropha curcas L. collected from Thailand and other countries was performed using the methylation-sensitive amplification polymorphism (MSAP) technique. Nine primer combinations were used to generate MSAP fingerprints. When the data were interpreted as amplified fragment length polymorphism (AFLP) markers, 471 markers were scored. All 56 samples were classified into three major groups: γ-irradiated, non-toxic and toxic accessions. Genetic similarity among the samples was extremely high, ranging from 0.95 to 1.00, which indicated very low genetic diversity in this species. The MSAP fingerprint was further analyzed for DNA methylation polymorphisms. The results revealed differences in the DNA methylation level among the samples. However, the samples collected from saline areas and some species hybrids showed specific DNA methylation patterns. AFLP data were used, together with methylation-sensitive AFLP (MS-AFLP) data, to construct a phylogenetic tree, resulting in higher efficiency to distinguish the samples. This combined analysis separated samples previously grouped in the AFLP analysis. This analysis also distinguished some hybrids. Principal component analysis was also performed; the results confirmed the separation in the phylogenetic tree. Some polymorphic bands, involving both nucleotide and DNA methylation polymorphism, that differed between toxic and non-toxic samples were identified, cloned and sequenced. BLAST analysis of these fragments revealed differences in DNA methylation in some known genes and nucleotide polymorphism in chloroplast DNA. We conclude that MSAP is a powerful technique for the study of genetic diversity for organisms that have a narrow genetic base.

Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN International Studies.

PubMed

Cramer, S C; Procaccio, V

2012-05-01

Recovery after stroke occurs on the basis of specific molecular events. Genetic polymorphisms associated with impaired neural repair or plasticity might reduce recovery from stroke and might also account for some of the intersubject variability in stroke recovery. This study hypothesized that the ApoE ε4 polymorphism and the val(66) met polymorphism for brain-derived neurotrophic factor (BDNF) are each associated with poorer outcome after stroke. Associations with mitochondrial genotype were also explored. Genotypes were determined in 255 stroke patients who also received behavioral evaluations in the Glycine Antagonist In Neuroprotection (GAIN) clinical trials. The primary outcome measure was recovery during the first month post-stroke, as this is the time when neural repair is at a maximum and so when genetic influences might have their largest impact. Two secondary outcome measures at 3 months post-stroke were also examined.   Genotype groups were similar acutely post-stroke. Presence of the ApoE ε4 polymorphism was associated with significantly poorer recovery over the first month post-stroke (P = 0.023) and with a lower proportion of subjects with minimal or no disability (modified Rankin score 0-1, P = 0.01) at 3 months post-stroke. Indeed, those with this polymorphism were approximately half as likely to achieve minimal or no disability (18.2%) versus those with polymorphism absent (35.5%). Findings were confirmed in multivariate models. Results suggested possible effects from the val(66) met BDNF polymorphism and from the R0 mitochondrial DNA haplotype.   Genetic factors, particularly the ApoE ε4 polymorphism, might contribute to variability in outcomes after stroke. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Genome-wide association study reveals putative regulators of bioenergy traits in Populus deltoides

DOE PAGES

Fahrenkrog, Annette M.; Neves, Leandro G.; Resende, Jr., Marcio F. R.; ...

2016-09-06

Genome-wide association studies (GWAS) have been used extensively to dissect the genetic regulation of complex traits in plants. These studies have focused largely on the analysis of common genetic variants despite the abundance of rare polymorphisms in several species, and their potential role in trait variation. Here, we conducted the first GWAS in Populus deltoides, a genetically diverse keystone forest species in North America and an important short rotation woody crop for the bioenergy industry. We searched for associations between eight growth and wood composition traits, and common and low-frequency single-nucleotide polymorphisms detected by targeted resequencing of 18 153 genesmore » in a population of 391 unrelated individuals. To increase power to detect associations with low-frequency variants, multiple-marker association tests were used in combination with single-marker association tests. Significant associations were discovered for all phenotypes and are indicative that low-frequency polymorphisms contribute to phenotypic variance of several bioenergy traits. Our results suggest that both common and low-frequency variants need to be considered for a comprehensive understanding of the genetic regulation of complex traits, particularly in species that carry large numbers of rare polymorphisms. Lastly, these polymorphisms may be critical for the development of specialized plant feedstocks for bioenergy.« less

The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species.

PubMed

Bolton, Peri E; Rollins, Lee A; Griffith, Simon C

2015-06-01

Polymorphic species have been the focus of important work in evolutionary biology. It has been suggested that colour polymorphic species have specific evolutionary and population dynamics that enable them to persist through environmental changes better than less variable species. We suggest that recent empirical and theoretical work indicates that polymorphic species may be more vulnerable to extinction than previously thought. This vulnerability arises because these species often have a number of correlated sexual, behavioural, life history and ecological traits, which can have a simple genetic underpinning. When exacerbated by environmental change, these alternate strategies can lead to conflict between morphs at the genomic and population levels, which can directly or indirectly affect population and evolutionary dynamics. In this perspective, we identify a number of ways in which the nature of the correlated traits, their underpinning genetic architecture, and the inevitable interactions between colour morphs can result in a reduction in population fitness. The principles illustrated here apply to all kinds of discrete polymorphism (e.g. behavioural syndromes), but we focus primarily on colour polymorphism because they are well studied. We urge further empirical investigation of the genetic architecture and interactions in polymorphic species to elucidate the impact on population fitness. © 2015 John Wiley & Sons Ltd.

The dopamine-related polymorphisms BDNF, COMT, DRD2, DRD3, and DRD4 are not linked with changes in CSF dopamine levels and frequency of HIV infection.

PubMed

Horn, Anne; Scheller, C; du Plessis, S; Burger, R; Arendt, G; Joska, J; Sopper, S; Maschke, C M; Obermann, M; Husstedt, I W; Hain, J; Riederer, P; Koutsilieri, E

2017-04-01

We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4 + T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4 + T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3'UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.

PCR-based study of conserved and variable DNA sequences of Tritrichomonas foetus isolates from Saskatchewan, Canada.

PubMed Central

Riley, D E; Wagner, B; Polley, L; Krieger, J N

1995-01-01

The protozoan parasite Tritrichomonas foetus causes infertility and spontaneous abortion in cattle. In Saskatchewan, Canada, the culture prevalence of trichomonads was 65 of 1,048 (6%) among 1,048 bulls tested within a 1-year period ending in April 1994. Saskatchewan was previously thought to be free of the parasite. To confirm the culture results, possible T. foetus DNA presence was determined by the PCR. All of the 16 culture-positive isolates tested were PCR positive by a single-band test, but one PCR product was weak. DNA fingerprinting by both T17 PCR and randomly amplified polymorphic DNA PCR revealed genetic variation or polymorphism among the T. foetus isolates. T17 PCR also revealed conserved loci that distinguished these T. foetus isolates from Trichomonas vaginalis, from a variety of other protozoa, and from prokaryotes. TCO-1 PCR, a PCR test designed to sample DNA sequence homologous to the 5' flank of a highly conserved cell division control gene, detected genetic polymorphism at low stringency and a conserved, single locus at higher stringency. These findings suggested that T. foetus isolates exhibit both conserved genetic loci and polymorphic loci detectable by independent PCR methods. Both conserved and polymorphic genetic loci may prove useful for improved clinical diagnosis of T. foetus. The polymorphic loci detected by PCR suggested either a long history of infection or multiple lines of T. foetus infection in Saskatchewan. Polymorphic loci detected by PCR may provide data for epidemiologic studies of T. foetus. PMID:7615746

Genome-wide association study of fertility traits in dairy cattle using high-density single nucleotide polymorphism marker panels

USDA-ARS?s Scientific Manuscript database

Unfavorable genetic correlations between production and fertility traits are well documented. Genetic selection for fertility traits is slow, however, due to low heritabilities. Identification of single nucleotide polymorphisms (SNP) involved in reproduction could improve reliability of genomic esti...

SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.

PubMed

Sophie, Mariam; Hameed, Abdul; Muneer, Akhtar; Samdani, Azam J; Saleem, Saima; Azhar, Abid

2017-01-07

The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan. Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2  = 64); and rs17235409 and rs17235416 (r 2  = 78). This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.

Genetic variation within and among populations of Rhodiola alsia (Crassulaceae) native to the Tibetan Plateau as detected by ISSR markers.

PubMed

Xia, Tao; Chen, Shilong; Chen, Shengyun; Ge, Xuejun

2005-04-01

Genetic variation of 10 Rhodiola alsia (Crassulaceae) populations from the Qinghai-Tibet Plateau of China was investigated using intersimple sequence repeat (ISSR) markers. R. alsia is an endemic species of the Qinghai-Tibet Plateau. Of the 100 primers screened, 13 were highly polymorphic. Using these primers, 140 discernible DNA fragments were generated with 112 (80%) being polymorphic, indicating pronounced genetic variation at the species level. Also there were high levels of polymorphism at the population level with the percentage of polymorphic bands (PPB) ranging from 63.4 to 88.6%. Analysis of molecular variance (AMOVA) showed that the genetic variation was mainly found among populations (70.3%) and variance within populations was 29.7%. The main factors responsible for the high level of differentiation among populations are probably the isolation from other populations and clonal propagation of this species. Occasional sexual reproduction might occur in order to maintain high levels of variation within populations. Environmental conditions could also influence population genetic structure as they occur in severe habitats. The strong genetic differentiation among populations in our study indicates that the conservation of genetic variability in R. alsia requires maintenance of as many populations as possible.

Salivary protein polymorphisms and risk of dental caries: a systematic review.

PubMed

Lips, Andrea; Antunes, Leonardo Santos; Antunes, Lívia Azeredo; Pintor, Andrea Vaz Braga; Santos, Diana Amado Baptista Dos; Bachinski, Rober; Küchler, Erika Calvano; Alves, Gutemberg Gomes

2017-06-05

Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.

Association of "ADAM10" and "CAMK2A" Polymorphisms with Conduct Disorder: Evidence from Family-Based Studies

ERIC Educational Resources Information Center

Jian, Xue-Qiu; Wang, Ke-Sheng; Wu, Tie-Jian; Hillhouse, Joel J.; Mullersman, Jerald E.

2011-01-01

Twin and family studies have shown that genetic factors play a role in the development of conduct disorder (CD). The purpose of this study was to identify genetic variants associated with CD using a family-based association study. We used 4,720 single nucleotide polymorphisms (SNPs) from the Illumina Panel and 11,120 SNPs from the Affymetrix 10K…

Assessment of genetic diversity in lettuce (Lactuca sativa L.) germplasm using RAPD markers.

PubMed

Sharma, Shubhangi; Kumar, Pankaj; Gambhir, Geetika; Kumar, Ramesh; Srivastava, D K

2018-01-01

The importance of germplasm characterization is an important link between the conservation and utilization of plant genetic resources in various breeding programmes. In the present study, genetic variability and relationships among 25 Lactuca sativa L. genotypes were tested using random amplified polymorphic DNA (RAPD) molecular markers. A total of 45 random decamer oligonucleotide primers were examined to generate RAPD profiles, out of these reproducible patterns were obtained with 22 primers. A total of 87 amplicon were obtained, out of which all were polymorphic and 7 were unique bands. The level of polymorphism across genotypes was 100% as revealed by RAPD. Genetic similarity matrix, based on Jaccard's coefficients ranged from 13.7 to 84.10% indicating a wide genetic base. Dendrogram was constructed by unweighted pair group method with arithmetic averages method. RAPD technology could be useful for identification of different accessions as well as assessing the genetic similarity among different genotypes of lettuce. The study reveals the limited genetic base and the needs to diversify using new sources from the germplasm.

Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

PubMed

Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

2014-12-01

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and to develop their potential as susceptibility biomarkers of cachexia.

[Study on once sampling quantitation based on information entropy of ISSR amplified bands of Houttuynia cordata].

PubMed

Wang, Haiqin; Liu, Wenlong; He, Fuyuan; Chen, Zuohong; Zhang, Xili; Xie, Xianggui; Zeng, Jiaoli; Duan, Xiaopeng

2012-02-01

To explore the once sampling quantitation of Houttuynia cordata through its DNA polymorphic bands that carried information entropy, from other form that the expression of traditional Chinese medicine polymorphism, genetic polymorphism, of traditional Chinese medicine. The technique of inter simple sequence repeat (ISSR) was applied to analyze genetic polymorphism of H. cordata samples from the same GAP producing area, the DNA genetic bands were transformed its into the information entropy, and the minimum once sampling quantitation with the mathematical mode was measured. One hundred and thirty-four DNA bands were obtained by using 9 screened ISSR primers to amplify from 46 strains DNA samples of H. cordata from the same GAP, the information entropy was H=0.365 6-0.978 6, and RSD was 14.75%. The once sampling quantitation was W=11.22 kg (863 strains). The "once minimum sampling quantitation" were calculated from the angle of the genetic polymorphism of H. cordata, and a great differences between this volume and the amount from the angle of fingerprint were found.

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients.

PubMed

Chatzikyriakidou, Anthoula; Aidinidou, Louiza; Giannopoulos, Andreas; Papadopoulou-Legbelou, Kyriaki; Kalinderi, Kallirhoe; Fidani, Liana

2015-04-01

Kawasaki disease is an acute, febrile syndrome in infancy, characterised by vasculitis of medium-sized arteries, and affects predominantly young children. Family-based studies on Kawasaki disease supports the contribution of genetic factors in disorder manifestation. In a recent genome-wide association study, the polymorphism rs1801274 of FCGR2A [Fc fragment of immunoglobulin G, low-affinity IIa, receptor] gene has been implicated in disease pathogenesis. The aim of the present study was to explore the association of this variant, for the first time, in a group of Kawasaki-diseased patients of Greek origin. A total of 47 Kawasaki-diseased children and 50 control subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism assay was performed in rs1801274 genotyping. No association was observed between this polymorphism genotypes' or alleles' distribution between Kawasaki-diseased patients and controls. Furthermore, no association was revealed between this polymorphism and cardiovascular complications in Kawasaki-diseased patients. In the literature, the reported data over this polymorphism association with Kawasaki disease in Caucasian patients are contradictory. In addition, the disease shows low prevalence in the Caucasian populations. Therefore, the independent genetic association studies on rs1801274 with Kawasaki disease in various Caucasian groups increase the amount of genetic data, which could be used in a future meta-analysis, increasing the statistical power of the resultant conclusions.

Genetic diversity in intraspecific hybrid populations of Eucommia ulmoides Oliver evaluated from ISSR and SRAP molecular marker analysis.

PubMed

Yu, J; Wang, Y; Ru, M; Peng, L; Liang, Z S

2015-07-03

Eucommia ulmoides Oliver, the only extant species of Eucommiaceae, is a second-category state-protected endangered plant in China. Evaluation of genetic diversity among some intraspecific hybrid populations of E. ulmoides Oliver is vital for breeding programs and further conservation of this rare species. We studied the genetic diversity of 130 accessions from 13 E. ulmoides intraspecific hybrid populations using inter-simple sequence related (ISSR) and sequence-related amplified polymorphism (SRAP) markers. Of the 100 ISSR primers and 100 SRAP primer combinations screened, eight ISSRs and eight SRAPs were used to evaluate the level of polymorphism and discriminating capacity. A total number of 65 bands were amplified using eight ISSR primers, in which 50 bands (76.9%) were polymorphic, with an average of 8.1 polymorphic fragments per primer. Alternatively, another 244 bands were observed using eight SRAP primer combinations, and 163 (66.8%) of them were polymorphic, with an average of 30.5 polymorphic fragments per primer. The unweighted pair-group method (UPGMA) analysis showed that these 13 populations could be classified into three groups by the ISSR marker and two groups by the SRAP marker. Principal coordinate analysis using SRAP was completely identical to the UPGMA-based clustering, although this was partly confirmed by the results of UPGMA cluster analysis using the ISSR marker. This study provides insights into the genetic background of E. ulmoides intraspecific hybrids. The progenies of the variations "Huazhong-3", "big fruit", "Yanci", and "smooth bark" present high genetic diversity and offer great potential for E. ulmoides breeding and conservation.

Single nucleotide polymorphisms in candidate genes associated with fertilizing ability of sperm and subsequent embryonic development in cattle

USDA-ARS?s Scientific Manuscript database

Fertilization and development of the preimplantation embryo is under genetic control. The goal of the current study was to test 434 single nucleotide polymorphisms (SNPs) for association with genetic variation in fertilization and early embryonic development. The approach was to produce embryos from...

Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link?

PubMed Central

Margoob, Mushtaq A.; Mushtaq, Dhuha

2011-01-01

Though still in infancy, the field of psychiatric genetics holds great potential to contribute to the development of new diagnostic and therapeutic options to treat these disorders. Among a large number of existing neurotransmitter systems, the serotonin system dysfunction has been implicated in many psychiatric disorders and therapeutic efficacy of many drugs is also thought to be based on modulation of serotonin. Serotonin transporter gene polymorphism is one of the most extensively studied polymorphisms in psychiatric behavioral genetics. In this article, we review the status of evidence for association between the serotonin gene polymorphism and some common mental disorders like affective disorders, post-traumatic stress disorder, obsessive-compulsive disorder, suicide, autism, and other anxiety and personality disorders. Going beyond traditional association studies, gene-environment interaction, currently gaining momentum, is also discussed in the review. While the existing information of psychiatric genetics is inadequate for putting into practice genetic testing in the diagnostic work-up of the psychiatric patient, if consistent in future research attempts, such results can be of great help to improve the clinical care of a vast majority of patients suffering from such disorders. PMID:22303036

Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

PubMed

Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

2014-09-01

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

PubMed

Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

2015-07-01

The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic Map Construction in Cauliflower Using Specific-Locus Amplified Fragment Sequencing

PubMed Central

Zhao, Zhenqing; Gu, Honghui; Sheng, Xiaoguang; Yu, Huifang; Wang, Jiansheng; Huang, Long; Wang, Dan

2016-01-01

Molecular markers and genetic maps play an important role in plant genomics and breeding studies. Cauliflower is an important and distinctive vegetable; however, very few molecular resources have been reported for this species. In this study, a novel, specific-locus amplified fragment (SLAF) sequencing strategy was employed for large-scale single nucleotide polymorphism (SNP) discovery and high-density genetic map construction in a double-haploid, segregating population of cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were obtained after processing and 6815 polymorphic SLAFs between the two parents were detected. The average sequencing depths reached 52.66-fold for the female parent and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were used to genotype the population and further filtered based on several criteria to construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF markers, including 2741 SNPs, constituted the linkage map with average data integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference genome. The markers and genetic map developed in this study could provide an important foundation not only for comparative genomics studies within Brassica oleracea species but also for quantitative trait loci identification and molecular breeding of cauliflower. PMID:27047515

Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population.

PubMed

Nabi, Gowher; Akhter, Naseem; Wahid, Mohd; Bhatia, Kanchan; Mandal, Raju Kumar; Dar, Sajad Ahmad; Jawed, Arshad; Haque, Shafiul

2016-01-01

The PTPN22 1858C/T polymorphism is associated with rheumatoid arthritis (RA). However, reports from the Asian populations are conflicting in nature and lacks consensus. The aim of our study was to evaluate the association between the PTPN22 1858C/T polymorphism and RA in Asian and Caucasian subjects by carrying out a meta-analysis of Asian and Caucasian data. A total of 27 205 RA cases and 27 677 controls were considered in the present meta-analysis involving eight Asian and 35 Caucasian studies. The pooled odds ratios (ORs) were performed for the allele, dominant, and recessive genetic model. No statistically significant association was found between the PTPN22 1858C/T polymorphism and risk of RA in Asian population (allele genetic model: OR = 1.217, 95% confidence interval (CI) = 0.99-1.496, p value 0.061; dominant genetic model: OR = 1.238, 95% CI = 0.982-1.562, p value 0.071; recessive genetic model: OR = 1.964, 95% CI = 0.678-5.693, p value 0.213). A significant association with risk of RA in Caucasian population suggesting that T-- allele does confer susceptibility to RA in this subgroup was observed (allele genetic model: OR = 1.638, 95% CI = 1.574-1.705, p value < 0.0001; dominant genetic model: OR = 1.67, 95% CI = 1.598-1.745, p value < 0.0001; recessive genetic model: OR = 2.65, 95% CI = 2.273-3.089, p value < 0.0001). The PTPN22 1858C/T polymorphism is not associated with RA risk in Asian populations. However, our meta-analysis confirms that the PTPN22 1858C/T polymorphism is associated with RA susceptibility in Caucasians.

GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus.

PubMed

Wolkow, Pawel P; Kosiniak-Kamysz, Wladyslaw; Osmenda, Grzegorz; Wilk, Grzegorz; Bujak-Gizycka, Beata; Ignacak, Adam; Kanitkar, Mihir; Walus-Miarka, Malgorzata; Harrison, David G; Korbut, Ryszard; Malecki, Maciej T; Guzik, Tomasz J

2014-01-01

The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients. Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA). Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables. Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.

Development of SSR markers from Citrus clementina (Rutaceae) BAC end sequences and interspecific transferability in Citrus.

PubMed

Ollitrault, Frédérique; Terol, Javier; Pina, Jose Antonio; Navarro, Luis; Talon, Manuel; Ollitrault, Patrick

2010-11-01

Microsatellite primers were developed from bacterial artificial chromosome (BAC) end sequences of Citrus clementina and their transferability and polymorphism tested in the genus Citrus for future anchorage of physical and genetic maps and comparative interspecific genetic mapping. • Using PAGE and DNA silver staining, 79 primer pairs were selected for their transferability and polymorphism among 526 microsatellites mined in BES. A preliminary diversity study in Citrus was conducted with 18 of them, in C. reticulata, C. maxima, C. medica, C. sinensis, C. aurantium, C. paradisi, C. lemon, C. aurantifolia, and some papedas (wild citrus), using a capillary electrophoresis fragment analyzer. Intra- and interspecific polymorphism was observed, and heterozygous markers were identified for the different genotypes to be used for genetic mapping. • These results indicate the utility of the developed primers for comparative mapping studies and the integration of physical and genetic maps.

Failure of replicating the association between hippocampal volume and 3 single-nucleotide polymorphisms identified from the European genome-wide association study in Asian populations.

PubMed

Li, Ming; Ohi, Kazutaka; Chen, Chunhui; He, Qinghua; Liu, Jie-Wei; Chen, Chuansheng; Luo, Xiong-Jian; Dong, Qi; Hashimoto, Ryota; Su, Bing

2014-12-01

Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations. Copyright © 2014 Elsevier Inc. All rights reserved.

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 = 0.021, respectively). Conclusion The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters). PMID:24270863

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

PubMed

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

2014-01-01

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. To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. 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). 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 = 0.021, respectively). The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters).

Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia.

PubMed

Bae, Joon Seol; Kim, Jason Yongha; Park, Byung-Lae; Cheong, Hyun Sub; Kim, Jeong-Hyun; Namgoong, Suhg; Kim, Ji-On; Park, Chul Soo; Kim, Bong-Jo; Lee, Cheol-Soon; Lee, Migyung; Choi, Woo Hyuk; Shin, Tae-Min; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

2015-04-01

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran‑binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine‑5'‑triphosphate‑binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case‑control association analysis was performed. Using a TaqMan assay, five single‑nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

Identification and characterization of single nucleotide polymorphisms (SNPs) in Culex theileri (Diptera: Culicidae).

PubMed

Demirci, Berna; Lee, Yoosook; Lanzaro, Gregory C; Alten, Bulent

2012-05-01

Culex theileri Theobald (Diptera: Culicidae) is one of the most common mosquito species in northeastern Turkey and serves as a vector for various zoonotic diseases including West Nile virus. Although there have been some studies on the ecology of Cx. theileri, very little genetic data has been made available. We successfully sequenced 11 gene fragments from Cx. theileri specimens collected from the northeastern part of Turkey. On average, we found a Single nucleotide polymorphism every 45 bp. Transitions outnumbered transversions, at a ratio of 2:1. This is the first report of genetic polymorphisms in Cx. theileri and Single nucleotide polymorphism discovered from this study can be used to investigate population structure and gene-environmental interactions.

Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

PubMed

Borgonio-Cuadra, Verónica Marusa; González-Huerta, Norma Celia; Rojas-Toledo, Emma Xochitl; Morales-Hernández, Eugenio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Hernández-Díaz, Yazmín; López-Narváez, María Lilia; Miranda-Duarte, Antonio

2018-05-18

Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

Evaluation of Genetic Polymorphism of Leishmania (V.) braziliensis Isolates Obtained from the Same Patient before and after Therapeutic Failure or Reactivation of Cutaneous Lesions

PubMed Central

Baptista, Cibele; Schubach, Armando de Oliveira; Madeira, Maria de Fatima; de Freitas Campos Miranda, Luciana; Guimarães de Souza Pinto, Andressa; Helena da Silva Barros, Juliana; Conceição-Silva, Fatima; Fernandes Pimentel, Maria Ines; da Silva Pacheco, Raquel

2012-01-01

The aim of this study was to investigate genetic polymorphism in Leishmania braziliensis population previously typed through isoenzyme electrophoresis, isolated from the same patient in two different moments: (A) before the beginning of treatment and (B) after treatment failure to meglumine antimoniate or reactivation after successful initial treatment. Fifteen pairs of isolates were assessed using the polymorphic molecular marker LSSP-PCR and following the phenetic analysis. The genetic profiles of the 30 samples were grouped in four clusters. Only two patients presented total identity in the A and B isolates. Most isolates presented similarity coefficients varying from 0.63 to 0.91. In this group of patients genetic polymorphisms could be observed indicating low similarity between the pairs of isolates. The results demonstrate the existence of genetic polymorphism between the samples isolated before treatment and after reactivation or treatment failure, suggesting a possible differentiation of the structure of the original parasite population which could be involved in the mechanisms of resistance to treatment or reactivation of lesions in the ATL. This phenomenon is important, although other factors also could be involved in this context and are discussed in this paper. PMID:23304168

Genetic and epigenetic diversity and structure of Phragmites australis from local habitats of the Songnen Prairie using amplified fragment length polymorphism markers.

PubMed

Qiu, T; Jiang, L L; Yang, Y F

2016-08-19

The genetic and epigenetic diversity and structure of naturally occurring Phragmites australis populations occupying two different habitats on a small spatial scale in the Songnen Prairie in northeastern China were investigated by assessing amplified fragment length polymorphisms (AFLPs) and methylation-sensitive amplified polymorphisms (MSAPs) through fluorescent capillary detection. The two groups of P. australis were located in a seasonal waterlogged low-lying and alkalized meadow with a pH of 8-8.5 and in an alkaline patch without accumulated rainwater and with a pH greater than 10. These groups showed high levels of genetic diversity at the habitat level based on the percentage of polymorphic bands (90.32, 82.56%), Nei's gene diversity index (0.262, 0.248), and the Shannon diversity index (0.407, 0.383). Although little is known about the between-habitat genetic differentiation of P. australis on a small spatial scale, our results implied significant genetic differentiation between habitats. Extensive epigenetic diversity within habitats, along with clear differentiation, was found. Specifically, the former habitat (Habitat 1, designated H1) harbored higher levels of genetic and epigenetic diversity than the latter (Habitat 2, designated H2), and population-level diversity was also high. This study represents one of few attempts to predict habitat-based genetic differentiation of reeds on a small scale. These assessments of genetic and epigenetic variation are integral aspects of molecular ecological studies on P. australis. Possible causes for within- and between-habitat genetic and epigenetic variations are discussed.

Genetic analysis of Apuleia leiocarpa as revealed by random amplified polymorphic DNA markers: prospects for population genetic studies.

PubMed

Lencina, K H; Konzen, E R; Tsai, S M; Bisognin, D A

2016-12-19

Apuleia leiocarpa (Vogel) J.F. MacBride is a hardwood species native to South America, which is at serious risk of extinction. Therefore, it is of prime importance to examine the genetic diversity of this species, information required for developing conservation, sustainable management, and breeding strategies. Although scarcely used in recent years, random amplified polymorphic DNA markers are useful resources for the analysis of genetic diversity and structure of tree species. This study represents the first genetic analysis based on DNA markers in A. leiocarpa that aimed to investigate the levels of polymorphism and to select markers for the precise characterization of its genetic structure. We adapted the original DNA extraction protocol based on cetyltrimethyl ammonium bromide, and describe a simple procedure that can be used to obtain high-quality samples from leaf tissues of this tree. Eighteen primers were selected, revealing 92 bands, from which 75 were polymorphic and 61 were sufficient to represent the overall genetic structure of the population without compromising the precision of the analysis. Some fragments were conserved among individuals, which can be sequenced and used to analyze nucleotide diversity parameters through a wider set of A. leiocarpa individuals and populations. The individuals were separated into 11 distinct groups with variable levels of genetic diversity, which is important for selecting desirable genotypes and for the development of a conservation and sustainable management program. Our results are of prime importance for further investigations concerning the genetic characterization of this important, but vulnerable species.

Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L.

PubMed Central

Allegre, Mathilde; Argout, Xavier; Boccara, Michel; Fouet, Olivier; Roguet, Yolande; Bérard, Aurélie; Thévenin, Jean Marc; Chauveau, Aurélie; Rivallan, Ronan; Clement, Didier; Courtois, Brigitte; Gramacho, Karina; Boland-Augé, Anne; Tahi, Mathias; Umaharan, Pathmanathan; Brunel, Dominique; Lanaud, Claire

2012-01-01

Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr. PMID:22210604

[Prevalence of gene polymorphisms associated with immune-dependent diseases in the populations of North Eurasia].

PubMed

Cherednichenko, A A; Trifonova, E A; Vagaitseva, K V; Bocharova, A V; Varzari, A M; Radzhabov, M O; Stepanov, V A

2015-01-01

The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

Genomic and genotyping characterization of haplotype-based polymorphic microsatellites in Prunus

USDA-ARS?s Scientific Manuscript database

Efficient utilization of microsatellites in genetic studies remains impeded largely due to the unknown status of their primer reliability, chromosomal location, and allele polymorphism. Discovery and characterization of microsatellite polymorphisms in a taxon will disclose the unknowns and gain new ...

Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis.

PubMed

Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

2016-01-01

Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility.

Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis

PubMed Central

Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

2016-01-01

Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility. PMID:26816662

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

Human cancer xenografts in outbred nude mice can be confounded by polymorphisms in a modifier of tumorigenesis.

PubMed

Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R; Parelkar, Nikhil K; Jokar, Iman; Vielhauer, George A; Neufeld, Kristi L

2014-08-01

Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies. Copyright © 2014 by the Genetics Society of America.

Cacao single-nucleotide polymorphism (SNP) markers: A discovery strategy to identify SNPs for genotyping, genetic mapping and genome wide association studies (GWAS)

USDA-ARS?s Scientific Manuscript database

Single-nucleotide polymorphisms (SNPs) are the most common genetic markers in Theobroma cacao, occurring approximately once in every 200 nucleotides. SNPs, like microsatellites, are co-dominant and PCR-based, but they have several advantages over microsatellites. They are unambiguous, so that a SN...

[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.

Genetic polymorphisms associated with heart failure: A literature review.

PubMed

Guo, Mengqi; Guo, Guanlun; Ji, Xiaoping

2016-02-01

To review possible associations reported between genetic variants and the risk, therapeutic response and prognosis of heart failure. Electronic databases (PubMed, Web of Science and CNKI) were systematically searched for relevant papers, published between January 1995 and February 2015. Eighty-two articles covering 29 genes and 39 polymorphisms were identified. Genetic association studies of heart failure have been highly controversial. There may be interaction or synergism of several genetic variants that together result in the ultimate pathological phenotype for heart failure. © The Author(s) 2016.

TS Gene Polymorphisms Correlate with Susceptibility to Acute Lymphocytic Leukemia in Children.

PubMed

Zou, Runyin; He, Xiangling; Wu, Yanpeng; Tian, Xin; You, Yalan; Zheng, Mincui; Li, Wanli; Zou, Hui; Liu, Hua; Zhu, Xiujuan; Zhu, Chengguang

2017-06-24

BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups. Logistic regression analysis was used to determine genetic polymorphisms and ALL risk associations. RESULTS The results indicated that TS 3R allele frequency was significantly higher in the case group than in the control group (χ²=7.45, P<0.05). The MTHFR C677T and MTHFR A1298C polymorphisms were not associated with ALL risk. Compared to the TS 2R/2R genotype, subjects carrying TS 2R/3R were twice as likely to develop ALL, and the TS 3R/3R+3R/4R genotype carried a 4-fold higher risk of developing ALL (OR=1.96, CI: 1.14-3.36). CONCLUSIONS The TS genetic polymorphisms increase the ALL risk. The TS 3R allele was a risk factor for ALL. There were no associations between MTHFR C677T or MTHFR A1298C polymorphisms and ALL susceptibility.

Polymorphisms in the canine monoamine oxidase a (MAOA) gene: identification and variation among five broad dog breed groups.

PubMed

Sacco, James; Ruplin, Andrew; Skonieczny, Paul; Ohman, Michael

2017-01-01

In humans, reduced activity of the enzyme monoamine oxidase type A (MAOA) due to genetic polymorphisms within the MAOA gene leads to increased brain neurotransmitter levels associated with aggression. In order to study MAOA genetic diversity in dogs, we designed a preliminary study whose objectives were to identify novel alleles in functionally important regions of the canine MAOA gene, and to investigate whether the frequencies of these polymorphisms varied between five broad breed groups (ancient, herding, mastiff, modern European, and mountain). Fifty dogs representing these five breed groups were sequenced. A total of eleven polymorphisms were found. Seven were single nucleotide polymorphisms (SNPs; two exonic, two intronic and three in the promoter), while four were repeat intronic variations. The most polymorphic loci were repeat regions in introns 1, 2 (7 alleles) and 10 (3 alleles), while the exonic and the promoter regions were highly conserved. Comparison of the allele frequencies of certain microsatellite polymorphisms among the breed groups indicated a decreasing or increasing trend in the number of repeats at different microsatellite loci, as well as the highest genetic diversity for the ancient breeds and the lowest for the most recent mountain breeds, perhaps attributable to canine domestication and recent breed formation. While a specific promoter SNP (-212A > G) is rare in the dog, it is the major allele in wolves. Replacement of this ancestral allele in domestic dogs may lead to the deletion of heat shock factor binding sites on the MAOA promoter. Dogs exhibit significant variation in certain intronic regions of the MAOA gene, while the coding and promoter regions are well-conserved. Distinct genetic differences were observed between breed groups. Further studies are now required to establish whether such polymorphisms are associated in any way with MAOA level and canine behaviour including aggression.

An application of CART algorithm in genetics: IGFs and cGH polymorphisms in Japanese quail

NASA Astrophysics Data System (ADS)

Kaplan, Selçuk

2017-04-01

The avian insulin-like growth factor-1 (IGFs) and avian growth hormone (cGH) genes are the most important genes that can affect bird performance traits because of its important function in growth and metabolism. Understanding the molecular genetic basis of variation in growth-related traits is of importance for continued improvement and increased rates of genetic gain. The objective of the present study was to identify polymorphisms of cGH and IGFs genes in Japanese quail using conventional least square method (LSM) and CART algorithm. Therefore, this study was aimed to demonstrate at determining the polymorphisms of two genes related growth characteristics via CART algorithm. A simulated data set was generated to analyze by adhering the results of some poultry genetic studies which it includes live weights at 5 weeks of age, 3 alleles and 6 genotypes of cGH and 2 alleles and 3 genotypes of IGFs. As a result, it has been determined that the CART algorithm has some advantages as for that LSM.

The interplay between local ecology, divergent selection, and genetic drift in population divergence of a sexually antagonistic female trait.

PubMed

Green, Kristina Karlsson; Svensson, Erik I; Bergsten, Johannes; Härdling, Roger; Hansson, Bengt

2014-07-01

Genetically polymorphic species offer the possibility to study maintenance of genetic variation and the potential role for genetic drift in population divergence. Indirect inference of the selection regimes operating on polymorphic traits can be achieved by comparing population divergence in neutral genetic markers with population divergence in trait frequencies. Such an approach could further be combined with ecological data to better understand agents of selection. Here, we infer the selective regimes acting on a polymorphic mating trait in an insect group; the dorsal structures (either rough or smooth) of female diving beetles. Our recent work suggests that the rough structures have a sexually antagonistic function in reducing male mating attempts. For two species (Dytiscus lapponicus and Graphoderus zonatus), we could not reject genetic drift as an explanation for population divergence in morph frequencies, whereas for the third (Hygrotus impressopunctatus) we found that divergent selection pulls morph frequencies apart across populations. Furthermore, population morph frequencies in H. impressopunctatus were significantly related to local bioclimatic factors, providing an additional line of evidence for local adaptation in this species. These data, therefore, suggest that local ecological factors and sexual conflict interact over larger spatial scales to shape population divergence in the polymorphism. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Population genetics of the California National Primate Research Center’s (CNPRC) captive Callicebuscupreus colony

PubMed Central

Mendoza, Adrian; Ng, Jillian; Bales, Karen; Mendoza, Sally P.; George, Debra A.; Smith, David Glenn; Kanthaswamy, Sree

2014-01-01

The California National Primate Research Center (CNPRC) maintains a small colony of titi monkeys (Callicebuscupreus) for behavioral studies. While short tandem repeat (STR) markers are critical for the genetic management of the center’s rhesus macaque (Macacamulatta) breeding colony, STRs are not used for this purpose in the maintenance of the center’s titi monkey colony. Consequently, the genetic structure of this titi monkey population has not been characterized. A lack of highly informative genetic markers in titi monkeys has also resulted in scant knowledge of the species’ genetic variation in the wild. The purpose of this study was to develop a panel of highly polymorphic titi monkey STRs using a cross-species PCR amplification protocol that could be used for the genetic management of the titi monkey colony. We screened 16 STR primer pairs and selected those that generated robust and reproducible polymorphic amplicons. Loci that were found to be highly polymorphic, very likely to be useful for parentage verification, pedigree assessment, and for studying titi monkey population genetics, were validated using Hardy-Weinberg equilibrium and linkage disequilibrium analyses. The genetic data generated in this study were also used to directly assess the impact of a recent adenovirus outbreak on the colony’s genetic diversity. While the adenovirus epizootic disease caused significant mortality (19 deaths among the 65 colony animals), our results suggest that the disease exhibited little or no influence on the overall genetic diversity of the colony. PMID:25179309

Initial determination of DNA polymorphism of some Primula veris L. populations from Kosovo and Austria.

PubMed

Berisha, Naim; Millaku, Fadil; Gashi, Bekim; Krasniqi, Elez; Novak, Johannes

2015-01-01

Primula veris L. (Primulaceae) is a long lived perennial and well known pharmaceutical plant, widely collected for these reasons in almost all SE Europe and particularly in Kosovo. The aim of the study is to determine molecular polymorphism of cowslip (P. veris L.) populations from Kosovo. DNA extracted from leaves were  investigated in details for presence of polymorphism. RAPD analyses were conducted using 20 different short primers. Genomic DNA amplification profiles were analyzed and processed using data labelling. Comparison between cowslip populations in genetic composition revealed that samples from Bogaj were too distinct on their own. Molecular variation was observed to be more within populations (73 %) as compared to among populations (27 %). On the other hand, genetic distance of populations revealed that the highest genetic distance is between Leqinat and Maja e Madhe. Mean values of expected heterozygosity were highest in Bogaj population, while lowest in Maja e Madhe population. The obtained results indicated that Bogaj population are more polymorphic. From the obtained data it can be concluded that RAPD markers provided a useful technique to study genetic diversity in P. veris L. populations. This technology allows identification and assessment of the genetic similarities and differences among plant populations.

High temperatures reveal cryptic genetic variation in a polymorphic female sperm storage organ.

PubMed

Berger, David; Bauerfeind, Stephanie Sandra; Blanckenhorn, Wolf Ulrich; Schäfer, Martin Andreas

2011-10-01

Variation in female reproductive morphology may play a decisive role in reproductive isolation by affecting the relative fertilization success of alternative male phenotypes. Yet, knowledge of how environmental variation may influence the development of the female reproductive tract and thus alter the arena of postcopulatory sexual selection is limited. Yellow dung fly females possess either three or four sperm storage compartments, a polymorphism with documented influence on sperm precedence. We performed a quantitative genetics study including 12 populations reared at three developmental temperatures complemented by extensive field data to show that warm developmental temperatures increase the frequency of females with four compartments, revealing striking hidden genetic variation for the polymorphism. Systematic genetic differentiation in growth rate and spermathecal number along latitude, and phenotypic covariance between the traits across temperature treatments suggest that the genetic architecture underlying the polymorphism is shaped by selection on metabolic rate. Our findings illustrate how temperature can modulate the preconditions for sexual selection by differentially exposing novel variation in reproductive morphology. This implies that environmental change may substantially alter the dynamics of sexual selection. We further discuss how temperature-dependent developmental plasticity may have contributed to observed rapid evolutionary transitions in spermathecal morphology. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Fibroblast growth factor 20 (FGF20) polymorphism is a risk factor for Parkinson's disease in Chinese population.

PubMed

Pan, Jing; Li, Hui; Wang, Ying; Ma, Jian-Fang; Zhang, Jin; Wang, Gang; Liu, Jun; Wang, Xi-Jin; Xiao, Qin; Chen, Sheng-Di

2012-06-01

The etiology of Parkinson's disease (PD) is not well established. Genetic variation in fibroblast growth factor 20 (FGF20) might influence the risk of PD occurrence and development. In this study, Two DNA polymorphisms at genetic variation in FGF20, rs2720208 (C/T) and rs1721100 (C/G), were genotyped by direct sequencing in Han Chinese population, including 394 PD patients and 383 healthy controls. Statistical analyses revealed that for rs1721100 (C/G) polymorphism, there were significant differences in genotype distribution between PD and healthy-matched controls. For rs12720208 (C/T) polymorphism, there was no significant difference in genotype distribution and gender and age-related differences between PD and control group. Results in this study revealed that the rs1721100(C/G) polymorphism is a risk factor for PD in Han Chinese population, while rs12720208(C/T) polymorphism is not significantly associated with PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.

PubMed

Buono, R J; Ferraro, T N; O'Connor, M J; Sperling, M R; Abbey, M; Finanger, E; Lohoff, F; Mulholland, N; Berrettini, W H

2000-02-07

Genetic linkage studies in rodents and humans have identified specific chromosomal regions harboring seizure susceptibility genes. We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase (NaK-pump), a candidate gene for human temporal lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 12 base pairs upstream of the start of exon 2. We performed an association study between this polymorphism and TLE. Our study did not find a significant difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility factor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may yet be found to play a minor role in increased risk for seizure susceptibility. In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Americans and persons of European descent. This finding demonstrates the potential effect of population stratification on studies of this type and supports the growing use of parental and familial samples for controls in association studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-specific susceptibilities. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:79-83, 2000. Copyright 2000 Wiley-Liss, Inc.

Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

PubMed

Chatzidimitriou, M; Chatzidimitriou, D; Mavridou, M; Anetakis, C; Chatzopoulou, F; Lialiaris, T; Mitka, S

2017-12-01

Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455 G/A, FV HR2 + b-fibrinogen -455 G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL. © 2017 John Wiley & Sons Ltd.

Distribution of stromal cell-derived factor-1 genetic polymorphism in head and neck cancer patients of Indonesian population

NASA Astrophysics Data System (ADS)

Sabrina, H.; Midoen, Y. H.; Soedarsono, N.; Djamal, N. Z.; Suhartono, A. W.; Auerkari, E. I.

2018-05-01

Head and neck cancer (HNC), the fourth most common cancer in Indonesia, is associated with several risk factors, including genetic ones. The chemokine Stromal Cell-Derived Factor-1 (SDF-1) contributes to tumor growth, angiogenesis, and metastasis of cancer. Recent studies suggest the G801A genetic polymorphism of SDF-1 as a factor increasing susceptibility to HNC. The aim of this study was to investigate whether the G801A polymorphism of SDF-1 is associated with the susceptibility of HNC in the Indonesian population. Samples from 50 head and neck cancer patients and 50 healthy controls were genotyped by PCR-RFLP method. The distributions of genotypes and alleles were analyzed for the Hardy-Weinberg Equilibrium (HWE) and for the potential association with the head and neck cancer susceptibility by Fisher’s exact test. The study showed no statistically significant difference in the frequencies of SDF-1 G801A polymorphism between the control and case groups. The homozygous variant genotype occurred at low frequency in both cancer and control groups, while the wild type was not less common in the cancer group than in the control group. Unlike in some studies on other Asian populations, the polymorphism was not found to be significantly associated with HNC susceptibility in the Indonesian population.

Genetic diversity and geographic differentiation analysis of duckweed using inter-simple sequence repeat markers.

PubMed

Xue, Huiling; Xiao, Yao; Jin, Yanling; Li, Xinbo; Fang, Yang; Zhao, Hai; Zhao, Yun; Guan, Jiafa

2012-01-01

Duckweed, with rapid growth rate and high starch content, is a new alternate feedstock for bioethanol production. The genetic diversity among 27 duckweed populations of seven species in genus Lemna and Spirodela from China and Vietnam was analyzed by ISSR-PCR. Eight ISSR primers generating a reproducible amplification banding pattern had been screened. 89 polymorphic bands were scored out of the 92 banding patterns of 16 Lemna populations, accounting for 96.74% of the polymorphism. 98 polymorphic bands of 11 Spirodela populations were scored out of 99 banding patterns, and the polymorphism was 98.43%. The genetic distance of Lemna varied from 0.127 to 0.784, and from 0.138 to 0.902 for Spirodela, which indicated a high level of genetic variation among the populations studied. The unweighted pair group method with arithmetic average (UPGMA) cluster analysis corresponded well with the genetic distance. Populations from Sichuan China grouped together and so did the populations from Vietnam, which illuminated populations collected from the same region clustered into one group. Especially, the only one population from Tibet was included in subgroup A2 alone. Clustering analysis indicated that the geographic differentiation of collected sites correlated closely with the genetic differentiation of duckweeds. The results suggested that geographic differentiation had great influence on genetic diversity of duckweed in China and Vietnam at the regional scale. This study provided primary guidelines for collection, conservation, characterization of duckweed resources for bioethanol production etc.

A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels.

PubMed

Medici, Marco; van der Deure, Wendy M; Verbiest, Michael; Vermeulen, Sita H; Hansen, Pia S; Kiemeney, Lambertus A; Hermus, Ad R M M; Breteler, Monique M; Hofman, Albert; Hegedüs, Laszlo; Kyvik, Kirsten Ohm; den Heijer, Martin; Uitterlinden, André G; Visser, Theo J; Peeters, Robin P

2011-05-01

Minor variation in serum thyroid hormone (TH) levels can have important effects on various clinical endpoints. Although 45-65% of the inter-individual variation in serum TH levels is due to genetic factors, the causative genes are not well established. We therefore studied the effects of genetic variation in 68 TH pathway genes on serum TSH and free thyroxine (FT(4)) levels. Sixty-eight genes (1512 polymorphisms) were studied in relation to serum TSH and FT(4) levels in 1121 Caucasian subjects. Promising hits (P<0.01) were studied in three independent Caucasian populations (2656 subjects) for confirmation. A meta-analysis of all four studies was performed. For TSH, eight PDE8B polymorphisms (P=4×10(-17)) remained significant in the meta-analysis. For FT(4), two DIO1 (P=8×10(-12)) and one FOXE1 (P=0.0003) polymorphisms remained significant in the meta-analysis. Suggestive associations were detected for one FOXE1 (P=0.0028) and three THRB (P=0.0045) polymorphisms with TSH, and one SLC16A10 polymorphism (P=0.0110) with FT(4), but failed to reach the significant multiple-testing corrected P value (P<0.0022 and P<0.0033 respectively). Using a large-scale association analysis, we replicated previously reported associations with genetic variation in PDE8B, THRB, and DIO1. We demonstrate effects of genetic variation in FOXE1 on serum FT(4) levels, and borderline significant effects on serum TSH levels. A suggestive association of genetic variation in SLC16A10 with serum FT(4) levels was found. These data provide insight into the molecular basis of inter-individual variation in TH serum levels.

Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

PubMed

Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

2017-10-01

Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island

PubMed Central

Sousa, Ana Célia; Palma dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

2017-01-01

Abstract Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results. The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island. A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions. In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02). The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology. PMID:29049185

Association of I-FABP gene polymorphism and the risk of coronary heart disease.

PubMed

Yuan, Dong; Yu, Changqing; Zeng, Chunyu

2015-01-01

The study aimed to investigate the association between polymorphism of I-FABP gene and coronary heart disease (CHD). 225 patients with CHD were randomly recruited into the case group, and 196 healthy elderly volunteers were recruited from Medical Examination Center of our hospital as control. General clinical data were collected and plasma TC, TG, LDL-C, HDL-C levels were measured. Besides, polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technology were used to detect the polymorphism of Hha-I enzyme cleavage sites in I-FABP gene in the study population. Hha-I cleavage sites occurred at codon 54 in exon in the coding sequencing of I-FABP gene in all participants. After cleavage with Hha-I enzyme, the genotypes were identified as wild-type A/A, heterozygous mutant A/T and homozygous mutant T/T. In case group, A/T and T/T genetic carriers had significantly higher levels of TC, TG and LDL-C than A/A carriers (P<0.05). However, in control group, similar differences were not observed (P>0.05). BMI, dietary habits and I-FABP alleles were independent risk factors of CHD. The polymorphism of I-FABP gene existed in the study population. And this genetic variation had influence on lipid metabolism, which was associated with the risk of developing CHD. I-FABP gene polymorphism may contribute to the increased genetic susceptibility to CHD.

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

Evolution of genetic polymorphisms of Plasmodium falciparum merozoite surface protein (PfMSP) in Thailand.

PubMed

Kuesap, Jiraporn; Chaijaroenkul, Wanna; Ketprathum, Kanchanok; Tattiyapong, Puntanat; Na-Bangchang, Kesara

2014-02-01

Plasmodium falciparum malaria is a major public health problem in Thailand due to the emergence of multidrug resistance. The understanding of genetic diversity of malaria parasites is essential for developing effective drugs and vaccines. The genetic diversity of the merozoite surface protein-1 (PfMSP-1) and merozoite surface protein-2 (PfMSP-2) genes was investigated in a total of 145 P. falciparum isolates collected from Mae Sot District, Tak Province, Thailand during 3 different periods (1997-1999, 2005-2007, and 2009-2010). Analysis of genetic polymorphisms was performed to track the evolution of genetic change of P. falciparum using PCR. Both individual genes and their combination patterns showed marked genetic diversity during the 3 study periods. The results strongly support that P. falciparum isolates in Thailand are markedly diverse and patterns changed with time. These 2 polymorphic genes could be used as molecular markers to detect multiple clone infections and differentiate recrudescence from reinfection in P. falciparum isolates in Thailand.

Influence of A-21T and C-262T genetic polymorphisms at the promoter region of the catalase (CAT) on gene expression.

PubMed

Saify, Khyber; Saadat, Iraj; Saadat, Mostafa

2016-09-01

Catalase (CAT, OMIM: 115500) is one of the major antioxidant enzymes, which plays an important role in the clearance of reactive oxygen species. Three genetic polymorphisms of A-21T (rs7943316), C-262T (rs1001179), and C-844T (rs769214) in the promoter region of the CAT have been reported. It has been suggested that these polymorphisms may alter the recognition sites of transcriptional factors, therefore it might be concluded that these polymorphisms may alter the expression levels of the gene. The aim of the present study is to evaluate the associations between these genetic variations and the CAT mRNA levels in human peripheral blood cells. The present study consisted of 47 healthy students of Shiraz University (south-west Iran). Genotypes of the CAT polymorphisms were determined by PCR based method. The quantitative CAT mRNA expression levels were investigated using quantitative real-time PCR. Analysis of variance revealed significant differences between the study genotypes (For A-21T polymorphism: F = 7.45; df = 2, 44; P = 0.002; For C-262T polymorphism: F = 15.17; df = 2, 44; P < 0.001). The studied polymorphisms showed linkage disequilibrium (D' = 1.0, r 2  = 0.1813, χ 2  = 17.03, P < 0.0001). The mRNA levels of CAT in the AC/TT, TC/TC, TC/TT, and TC/TC diplotypes significantly were higher than the mRNA levels in AC/AC diplotype. There was a significant difference between the study genotypes (F = 9.24; df = 5, 41; P < 0.001). The TC/TC and TT/TT diplotypes showed about 2 and 4 folds CAT mRNA levels compared with the AC/AC diplotype. The present findings indicated that these polymorphisms were significantly associated with the gene expression.

Detection of Variation in Long-Term Micropropagated Mature Pistachio via DNA-Based Molecular Markers.

PubMed

Akdemir, Hülya; Suzerer, Veysel; Tilkat, Engin; Onay, Ahmet; Çiftçi, Yelda Ozden

2016-12-01

Determination of genetic stability of in vitro-grown plantlets is needed for safe and large-scale production of mature trees. In this study, genetic variation of long-term micropropagated mature pistachio developed through direct shoot bud regeneration using apical buds (protocol A) and in vitro-derived leaves (protocol B) was assessed via DNA-based molecular markers. Randomly amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), and amplified fragment length polymorphism (AFLP) were employed, and the obtained PIC values from RAPD (0.226), ISSR (0.220), and AFLP (0.241) showed that micropropagation of pistachio for different periods of time resulted in "reasonable polymorphism" among donor plant and its 18 clones. Mantel's test showed a consistence polymorphism level between marker systems based on similarity matrices. In conclusion, this is the first study on occurrence of genetic variability in long-term micropropagated mature pistachio plantlets. The obtained results clearly indicated that different marker approaches used in this study are reliable for assessing tissue culture-induced variations in long-term cultured pistachio plantlets.

Genetic diversity in longleaf pine (Pinus palustris): influence of historical and prehistorical events

Treesearch

Ronald C. Schmidtling; V. Hipkins

1998-01-01

Genetic diversity of allozymes at 24 loci was studied in 23 populations of longleaf pine (Pinus palustris Mill.), including three seed orchard populations and an old-growth stand. Overall, the mean number of alleles per polymorphic locus was 2.9, the percentage of polymorphic loci was 92 percent, and the mean expected heterozygosity was 0.105. These...

Genetic and epigenetic stability of cryopreserved and cold-stored hops (Humulus lupulus L.).

PubMed

Peredo, Elena L; Arroyo-García, Rosa; Reed, Barbara M; Revilla, M Angeles

2008-12-01

Conventional cold storage and cryopreservation methods for hops (Humulus lupulus L.) are available but, to our knowledge, the genetic and epigenetic stability of the recovered plants have not been tested. This study analyzed 51 accessions of hop using the molecular techniques, Random Amplified DNA Polymorphism (RAPD) and Amplified Fragment Length Polymorphism (AFLP), revealing no genetic variation among greenhouse-grown controls and cold stored or cryopreserved plants. Epigenetic stability was evaluated using Methylation Sensitive Amplified Polymorphism (MSAP). Over 36% of the loci were polymorphic when the cold and cryo-treated plants were compared to greenhouse plants. The main changes were demethylation events and they were common to the cryopreserved and cold stored plants indicating the possible effect of the in vitro establishment process, an essential step in both protocols. Protocol-specific methylation patterns were also detected indicating that both methods produced epigenetic changes in plants following cold storage and cryopreservation.

Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

PubMed

Revelas, Mary; Thalamuthu, Anbupalam; Oldmeadow, Christopher; Evans, Tiffany-Jane; Armstrong, Nicola J; Kwok, John B; Brodaty, Henry; Schofield, Peter R; Scott, Rodney J; Sachdev, Perminder S; Attia, John R; Mather, Karen A

2018-06-08

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. Copyright © 2018. Published by Elsevier B.V.

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

PubMed

Nikisch, Georg; Baumann, Pierre; Oneda, Beatrice; Kiessling, Bernhard; Weisser, Heike; Mathé, Aleksander A; Yoshitake, Takashi; Kehr, Jan; Wiedemann, Georg; Eap, Chin B

2011-07-01

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.

Evaluation of genetic variability in micropropagated propagules of ornamental pineapple [Ananas comosus var. bracteatus (Lindley) Coppens and Leal] using RAPD markers.

PubMed

Santos, M D M; Buso, G C S; Torres, A C

2008-10-21

The objective of the present study was to evaluate the genetic variability in micropropagated plantlets of ornamental pineapple, after the fourth period of subculture. The basal culture medium consisted of MS salts, vitamins, 3% sucrose, liquid formulation, supplemented with 6-benzylaminopurine (BAP) at concentrations of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L. The addition of BAP influenced the occurrence of genetic variation revealed using random amplified polymorphic DNA (RAPD) markers. Of a total of 520 primers tested, 44 were selected and amplified; 402 monomorphic bands (97.2%) and 18 polymorphic bands (2.8%) resulted among regenerated plantlets. The polymorphic fragments were produced by 12 primers (OPA-01, OPA-20, OPB-01, OPB-19, OPC-19, OPF-13, OPL-17, OPM-13, OPP-16, OPT-07, OPV-19, and OPX-03). Among the primers that identified polymorphism, OPA-01, OPA-20, OPB-19, OPC-19, OPL-17, OPP-16, and OPX-3 each showed, one polymorphic band and OPF-13 amplified a maximum of three bands. In this study, the RAPD technique was effective in showing the occurrence of somaclonal variations that occur during the micropropagation process of ornamental pineapple cultivation in BAP-supplemented medium, and it is possible to detect the presence of genetic variation in early stages of plant development.

Genetic diversity in populations of Isatis glauca Aucher ex Boiss. ssp. from Central Anatolia in Turkey, as revealed by AFLP analysis.

PubMed

Özbek, Özlem; Görgülü, Elçin; Yıldırımlı, Şinasi

2013-12-01

Isatidae L. is a complex and systematically difficult genus in Brassicaceae. The genus displays great morphological polymorphism, which makes the classification of species and subspecies difficult as it is observed in Isatis glauca Aucher ex Boiss. The aim of this study is characterization of the genetic diversity in subspecies of Isatis glauca Aucher ex Boiss. distributed widely in Central Anatolia, in Turkey by using Amplified Fragment Length Polymorphism (AFLP) technique. Eight different Eco RI-Mse I primer combinations produced 805 AFLP loci, 793 (98.5%) of which were polymorphic in 67 accessions representing nine different populations. The data obtained by AFLP was computed with using GDA (Genetic Data Analysis) and STRUCTURE (version 2.3.3) software programs for population genetics. The mean proportion of the polymorphic locus (P), the mean number of alleles (A), the number of unique alleles (U) and the mean value of gene diversity (He) were 0.59, 1.59, 20, and 0.23 respectively. The coancestry coefficient (ϴ) was 0.24. The optimal number of K was identified as seven. The principal component analysis (PCA) explained 85.61% of the total genetic variation. Isatis glauca ssp. populations showed a high level of genetic diversity, and the AFLP analysis revealed that high polymorphism and differentiated subspecies could be used conveniently for population genetic studies. The principal coordinate analysis (PCoA) based on the dissimilarity matrix, the dendrogram drawn with UPGMA method and STRUCTURE cluster analysis distinguished the accessions successfully. The accessions formed distinctive population structures for populations AA, AB, E, K, and S. Populations AG1 and AG2 seemed to have similar genetic content, in addition, in both populations several hybrid individuals were observed. The accessions did not formed distinctive population structures for both populations AI and ANP. Consequently, Ankara province might be the area, where species Isatis glauca Aucher ex Boiss. originated.

Genetic models of homosexuality: generating testable predictions

PubMed Central

Gavrilets, Sergey; Rice, William R

2006-01-01

Homosexuality is a common occurrence in humans and other species, yet its genetic and evolutionary basis is poorly understood. Here, we formulate and study a series of simple mathematical models for the purpose of predicting empirical patterns that can be used to determine the form of selection that leads to polymorphism of genes influencing homosexuality. Specifically, we develop theory to make contrasting predictions about the genetic characteristics of genes influencing homosexuality including: (i) chromosomal location, (ii) dominance among segregating alleles and (iii) effect sizes that distinguish between the two major models for their polymorphism: the overdominance and sexual antagonism models. We conclude that the measurement of the genetic characteristics of quantitative trait loci (QTLs) found in genomic screens for genes influencing homosexuality can be highly informative in resolving the form of natural selection maintaining their polymorphism. PMID:17015344

Comparative study on the use of specific and heterologous microsatellite primers in the stingless bees Melipona rufiventris and M. mondury (Hymenoptera, Apidae)

PubMed Central

2010-01-01

Due to their high degree of polymorphism, microsatellites are considered useful tools for studying population genetics. Nevertheless, studies of genetic diversity in stingless bees by means of these primers have revealed a low level of polymorphism, possibly the consequence of the heterologous primers used, since in most cases these were not specifically designed for the species under consideration. Herein we compared the number of polymorphic loci and alleles per locus, as well as observed heterozygosity in Melipona rufiventris and M. mondury populations, using specific and heterologous primers. The use of specific primers placed in evidence the greater frequency of polymorphic loci and alleles per locus, besides an expressive increase in observed heterozygosity in M. rufiventris and M. mondury, thereby reinforcing the idea that populational studies should be undertaken by preferably using species-specific microsatellite primers. PMID:21637499

Comparative study on the use of specific and heterologous microsatellite primers in the stingless bees Melipona rufiventris and M. mondury (Hymenoptera, Apidae).

PubMed

Lopes, Denilce Meneses; de Oliveira Campos, Lúcio Antônio; Salomão, Tânia Maria Fernandes; Tavares, Mara Garcia

2010-04-01

Due to their high degree of polymorphism, microsatellites are considered useful tools for studying population genetics. Nevertheless, studies of genetic diversity in stingless bees by means of these primers have revealed a low level of polymorphism, possibly the consequence of the heterologous primers used, since in most cases these were not specifically designed for the species under consideration. Herein we compared the number of polymorphic loci and alleles per locus, as well as observed heterozygosity in Melipona rufiventris and M. mondury populations, using specific and heterologous primers. The use of specific primers placed in evidence the greater frequency of polymorphic loci and alleles per locus, besides an expressive increase in observed heterozygosity in M. rufiventris and M. mondury, thereby reinforcing the idea that populational studies should be undertaken by preferably using species-specific microsatellite primers.

[Helgoland (Germany): hemogenetic study of an island population].

PubMed

Schmidt, H D; Scheil, H G; Winkelbauer, S

2001-03-01

24 haemogenetic markers (5 erythrocyte antigenes, 6 polymorphisms of serum proteins, 12 polymorphisms of red cell enzymes) had been studied in up to 80 individuals from the island of Helgoland (Germany). The cluster analysis separates clearly the Helgoland sample from the neighbouring populations as well as from European standard data. This special position is interpreted partly by genetic peculiarities developed in the course of time, partly as a consequence of genetic drift.

-383 A/C tumor necrosis factor receptor 1 polymorphism and ankylosing spondylitis in Mexicans: a preliminary study.

PubMed

Corona-Sanchez, Esther Guadalupe; Muñoz-Valle, José Francisco; Gonzalez-Lopez, Laura; Sanchez-Hernandez, Julia Dolores; Vazquez-Del Mercado, Monica; Ontiveros-Mercado, Heriberto; Huerta, Miguel; Trujillo, Xochitl; Rocha-Muñoz, Alberto Daniel; Celis, Alfredo; Ortega-Flores, Ricardo; Gamez-Nava, Jorge Ivan

2012-08-01

The objective of this study was to evaluate the differences in allele and genotype frequencies of -383 tumor necrosis factor receptor 1 (TNFR1) polymorphism between ankylosing spondylitis (AS) and controls. Mexican Mestizos with AS were matched by gender, age, and ethnicity with healthy controls and compared in allele and genotype frequencies of the -383 TNFR1 polymorphism. Polymorphisms were genotyped using PCR-RFLP. The AA genotype occurred at a higher frequency in the AS group (92%) compared with controls (79%, P = 0.03). A allele was increased in AS (96% vs. 88%, P = 0.015) and was associated with genetic susceptibility for AS (odds ratio = 3.48, 95% CI = 1.23-10.61). This preliminary study is the first assessing the association of the -383 A/C TNFR1 polymorphism with AS, although it has the limitation of a small sample size. These data are of interest for the genetic epidemiology of AS in the Mexican population, requiring further investigation in other countries.

CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients.

PubMed

Pelucchi, Sara; Mariani, Raffaella; Calza, Stefano; Fracanzani, Anna Ludovica; Modignani, Giulia Litta; Bertola, Francesca; Busti, Fabiana; Trombini, Paola; Fraquelli, Mirella; Forni, Gian Luca; Girelli, Domenico; Fargion, Silvia; Specchia, Claudia; Piperno, Alberto

2012-12-01

Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis.

CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients

PubMed Central

Pelucchi, Sara; Mariani, Raffaella; Calza, Stefano; Fracanzani, Anna Ludovica; Modignani, Giulia Litta; Bertola, Francesca; Busti, Fabiana; Trombini, Paola; Fraquelli, Mirella; Forni, Gian Luca; Girelli, Domenico; Fargion, Silvia; Specchia, Claudia; Piperno, Alberto

2012-01-01

Background Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. Design and Methods: In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. Results We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. Conclusions While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis. PMID:22773607

Cervical Cancer Genetic Susceptibility: A Systematic Review and Meta-Analyses of Recent Evidence

PubMed Central

Martínez-Nava, Gabriela A.; Fernández-Niño, Julián A.; Madrid-Marina, Vicente; Torres-Poveda, Kirvis

2016-01-01

Introduction Cervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies. Materials and Methods We conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the “PRISMA” statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies. Results We found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63–0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70–0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63–0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%). Conclusions Our results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations. PMID:27415837

GxG epistasis in growth and condition and the maintenance of genetic polymorphism in Gambusia holbrooki.

PubMed

Culumber, Zachary W; Kraft, Brittany; Lemakos, Valerie; Hoffner, Erika; Travis, Joseph; Hughes, Kimberly A

2018-05-01

Theory on indirect genetic effects (IGEs) indicates that variation in the genetic composition of social groups can generate GxG epistasis that may promote the evolution of stable polymorphisms. Using a livebearing fish with a genetic polymorphism in coloration and associated behavioral differences, we tested whether genotypes of social partners interacted with focal individual genotypes to influence growth and condition over 16 weeks of development. We found that IGEs had a significant influence on patterns of feeding, regardless of focal fish genotype. There was no influence of social environment on juvenile length, but there was significant GxG epistasis for body condition. Each focal juvenile was in better condition when its own genotype was not present in adult social partners. These data are consistent with negative frequency-dependent selection in which each morph performs better when it is rare. Neither variation in feeding nor activity-related behaviors explained variation in body condition, suggesting that GxG epistasis for condition was caused by physiological differences between the two genotypes. These findings indicate that GxG epistasis in a given polymorphism can generate fitness landscapes that contribute to the maintenance of that polymorphism and to maintenance of genetic variation for additional fitness-related traits. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

PubMed

Dissanayake, Vajira H W; Sirisena, Nirmala D; Weerasekera, Lakshini Y; Gammulla, Chumithri G; Seneviratne, Harshalal R; Jayasekara, Rohan W

2012-09-01

Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Endothelial Nitric Oxide Synthase Gene G894T Polymorphism and Myocardial Infarction: A Meta-Analysis of 34 Studies Involving 21068 Subjects

PubMed Central

Luo, Jian-Quan; Wen, Jia-Gen; Zhou, Hong-Hao; Chen, Xiao-Ping; Zhang, Wei

2014-01-01

Background Researches have revealed that the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting. Objective and Methods A meta-analysis was conducted to investigate the association between eNOS G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between eNOS G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model. Results A total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The eNOS G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08–1.84; P = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06–1.70; P = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04–1.34; P = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between eNOS G894T polymorphism and MI risk among non-Asians (P>0.05), but a positive significant association was found among Asians (P<0.05). Conclusions The eNOS G894T polymorphism is associated with increased MI risk in Asians. The results indicate that ethnicity plays important roles in the association between eNOS G894T polymorphism and MI. PMID:24498040

Comparative analyses of genetic/epigenetic diversities and structures in a wild barley species (Hordeum brevisubulatum) using MSAP, SSAP and AFLP.

PubMed

Shan, X H; Li, Y D; Liu, X M; Wu, Y; Zhang, M Z; Guo, W L; Liu, B; Yuan, Y P

2012-08-17

We analyzed genetic diversity and population genetic structure of four artificial populations of wild barley (Hordeum brevisubulatum); 96 plants collected from the Songnen Prairie in northeastern China were analyzed using amplified fragment length polymorphism (AFLP), specific-sequence amplified polymorphism (SSAP) and methylation-sensitive amplified polymorphism (MSAP) markers. Indices of (epi-)genetic diversity, (epi-)genetic distance, gene flow, genotype frequency, cluster analysis, PCA analysis and AMOVA analysis generated from MSAP, AFLP and SSAP markers had the same trend. We found a high level of correlation in the artificial populations between MSAP, SSAP and AFLP markers by the Mantel test (r > 0.8). This is incongruent with previous findings showing that there is virtually no correlation between DNA methylation polymorphism and classical genetic variation; the high level of genetic polymorphism could be a result of epigenetic regulation. We compared our results with data from natural populations. The population diversity of the artificial populations was lower. However, different from what was found using AFLP and SSAP, based on MSAP results the methylation polymorphism of the artificial populations was not significantly reduced. This leads us to suggest that the DNA methylation pattern change in H. brevisubulatum populations is not only related to DNA sequence variation, but is also regulated by other controlling systems.

Using specific length amplified fragment sequencing to construct the high-density genetic map for Vitis (Vitis vinifera L. × Vitis amurensis Rupr.).

PubMed

Guo, Yinshan; Shi, Guangli; Liu, Zhendong; Zhao, Yuhui; Yang, Xiaoxu; Zhu, Junchi; Li, Kun; Guo, Xiuwu

2015-01-01

In this study, 149 F1 plants from the interspecific cross between 'Red Globe' (Vitis vinifera L.) and 'Shuangyou' (Vitis amurensis Rupr.) and the parent were used to construct a molecular genetic linkage map by using the specific length amplified fragment sequencing technique. DNA sequencing generated 41.282 Gb data consisting of 206,411,693 paired-end reads. The average sequencing depths were 68.35 for 'Red Globe,' 63.65 for 'Shuangyou,' and 8.01 for each progeny. In all, 115,629 high-quality specific length amplified fragments were detected, of which 42,279 were polymorphic. The genetic map was constructed using 7,199 of these polymorphic markers. These polymorphic markers were assigned to 19 linkage groups; the total length of the map was 1929.13 cm, with an average distance of 0.28 cm between each maker. To our knowledge, the genetic maps constructed in this study contain the largest number of molecular markers. These high-density genetic maps might form the basis for the fine quantitative trait loci mapping and molecular-assisted breeding of grape.

Association between genetic polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT genes and radiosensitivity in breast cancer patients.

PubMed

Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

2011-09-01

Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR=53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR=38.26; 95% CI, 1.19-1232.52). To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic polymorphisms may be promising candidates for predicting acute radiosensitivity, but further studies are necessary to confirm our findings. Copyright © 2011 Elsevier Inc. All rights reserved.

Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

PubMed Central

Zetterberg, Henrik

2004-01-01

The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD) has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin) or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC) 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy. PMID:14969589

Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications.

PubMed

Zetterberg, Henrik

2004-02-17

The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD) has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin) or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC) 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update.

PubMed

de Lima, Suelen Cristina; Adelino, José Eduardo; Crovella, Sergio; de Azevedo Silva, Jaqueline; Sandrin-Garcia, Paula

2017-11-01

Studies performed in the past years showed PTNP22 1858 C > T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858 C > T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858 C > T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR = 1.54, 95% confidence interval (CI) = 1.38-1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR = 2.04, 95% CI = 1.09-3.82, p value = .030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR = 0.62, 95% CI = 0.54-0.72, p value = .000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR = 1.47, p value = .000) and Latin (OR = 2.41, p value = .000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR= 1.31; p value = .54) and African (OR = 2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858 C > T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858 C > T as a potential genetic marker in SLE susceptibility.

Environmental Adaptation Contributes to Gene Polymorphism across the Arabidopsis thaliana Genome

PubMed Central

Lee, Cheng-Ruei

2012-01-01

The level of within-species polymorphism differs greatly among genes in a genome. Many genomic studies have investigated the relationship between gene polymorphism and factors such as recombination rate or expression pattern. However, the polymorphism of a gene is affected not only by its physical properties or functional constraints but also by natural selection on organisms in their environments. Specifically, if functionally divergent alleles enable adaptation to different environments, locus-specific polymorphism may be maintained by spatially heterogeneous natural selection. To test this hypothesis and estimate the extent to which environmental selection shapes the pattern of genome-wide polymorphism, we define the "environmental relevance" of a gene as the proportion of genetic variation explained by environmental factors, after controlling for population structure. We found substantial effects of environmental relevance on patterns of polymorphism among genes. In addition, the correlation between environmental relevance and gene polymorphism is positive, consistent with the expectation that balancing selection among heterogeneous environments maintains genetic variation at ecologically important genes. Comparison of the gene ontology annotations shows that genes with high environmental relevance are enriched in unknown function categories. These results suggest an important role for environmental factors in shaping genome-wide patterns of polymorphism and indicate another direction of genomic study. PMID:22798389

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies.

PubMed

Zeng, Ling; Gu, Wei; Chen, Kehong; Jiang, Dongpo; Zhang, Lianyang; Du, Dingyuan; Hu, Ping; Liu, Qing; Huang, Suna; Jiang, Jianxin

2009-01-01

An excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS. A total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay. The -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores. Our results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.

Association study between the dopamine D4 receptor gene and schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petronis, A.; Macciardi, F.; Athanassiades, A.

The dopamine D4 receptor is of major interest in schizophrenia research due to its high affinity for the atypical neuroleptic clozapine and a high degree of variability in the receptor gene (DRD4). Although several genetic linkage analyses performed on schizophrenia multiplex families from different regions of the world have either excluded or failed to prove that DRD4 is a major genetic factor for the development of schizophrenia, analyses for moderate predisposing effects are still of significant interest. We performed a study examining differences in allele frequencies of 4 different DRD4 polymorphisms in schizophrenia patients and age, sex, and ethnic originmore » matched controls. None of these 4 polymorphisms showed evidence for genetic association with schizophrenia, although a trend towards excess of the allele with 7 repeats in the (48){sub n} bp exon III polymorphism was observed. Complexities in the DRD4 genetic investigation and further analytic approaches are discussed. 18 refs., 2 tabs.« less

Using information content and base frequencies to distinguish mutations from genetic polymorphisms in splice junction recognition sites.

PubMed

Rogan, P K; Schneider, T D

1995-01-01

Predicting the effects of nucleotide substitutions in human splice sites has been based on analysis of consensus sequences. We used a graphic representation of sequence conservation and base frequency, the sequence logo, to demonstrate that a change in a splice acceptor of hMSH2 (a gene associated with familial nonpolyposis colon cancer) probably does not reduce splicing efficiency. This confirms a population genetic study that suggested that this substitution is a genetic polymorphism. The information theory-based sequence logo is quantitative and more sensitive than the corresponding splice acceptor consensus sequence for detection of true mutations. Information analysis may potentially be used to distinguish polymorphisms from mutations in other types of transcriptional, translational, or protein-coding motifs.

Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children.

PubMed

Zaruma-Torres, Fausto; Lares-Asseff, Ismael; Lima, Aurea; Reyes-Espinoza, Aarón; Loera-Castañeda, Verónica; Sosa-Macías, Martha; Galaviz-Hernández, Carlos; Arias-Peláez, María C; Reyes-López, Miguel A; Quiñones, Luis A

2016-01-01

Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11-5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62-78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42-191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94-31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05-6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19-31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.

Correlation analysis of genetic diversity and population structure of Houttuynia cordata Thunb with regard to environment.

PubMed

Zhong, J; Wu, F-C; Qiu, P; Dai, L-J

2016-08-12

To study the levels of genetic diversity, and population structure, of Houttuynia cordata Thunb, the genetic background and relationships of populations were analyzed in terms of environmental factors. The genetic diversity and population structure of H. cordata were investigated using sequence-related amplified polymorphisms and correlation with environmental factors was analyzed using the SPSS software. Two thousand one hundred sixty-three sites were amplified from 41 pairs of primers, 1825 of which were polymorphic, and the percentage of polymorphic loci was 84.37%; the percentage of polymorphic sites was 72.14 and 67.77% at the species and population level, respectively. The observed number of alleles was 1.52 and 1.30 at species and population level, respectively. The effective number of alleles was 1.38 and 1.24 at species and population level, respectively. The Nei's diversity was 0.26 and 0.15 at species and population level, respectively. The Shannon's information index was 0.87 and 0.63 at species and population level, respectively. The genetic differentiation coefficient of populations was 0.51, and 12 populations were divided into three classes based on D = 0.20; the genetic diversities of different populations are correlated at different significance levels (P < 0.05) with environmental factors. Genetic differentiation existed among populations and the populations exhibited heteroplasmy.

Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

PubMed Central

Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.

2008-01-01

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211

The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations.

PubMed

Liu, Guiyou; Wang, Haiyang; Liu, Jiafeng; Li, Jingbo; Li, Hali; Ma, Guoda; Jiang, Yongshuai; Chen, Zugen; Zhao, Bin; Li, Keshen

2014-03-01

Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer's disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case-control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10(-4)) and the dominant model (P = 5.00 × 10(-3)). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10(-24)), dominant (P = 4.46 × 10(-17)), and recessive (P = 3.92 × 10(-12)) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys.

PubMed

Humblet, Olivier; Korrick, Susan A; Williams, Paige L; Sergeyev, Oleg; Emond, Claude; Birnbaum, Linda S; Burns, Jane S; Altshul, Larisa M; Patterson, Donald G; Turner, Wayman E; Lee, Mary M; Revich, Boris; Hauser, Russ

2013-01-01

Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism.

PubMed

Miyoshi, M; Mizuno, M; Ishiki, K; Nagahara, Y; Maga, T; Torigoe, T; Nasu, J; Okada, H; Yokota, K; Oguma, K; Tsuji, T

2001-07-01

The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [(13)C]-urea breath test at 1--2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56--75) and 62.4% (95% CI, 52--71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.

Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China.

PubMed

Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

2015-01-01

Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China.

Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China

PubMed Central

Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

2015-01-01

Purpose: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. Methods: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5’UTR, promoters, exons, introns, and 3’UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Results: Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. Conclusion: our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China. PMID:26261601

High efficiency and reliability of inter-simple sequence repeats (ISSR) markers for evaluation of genetic diversity in Brazilian cultivated Jatropha curcas L. accessions.

PubMed

Grativol, Clícia; da Fonseca Lira-Medeiros, Catarina; Hemerly, Adriana Silva; Ferreira, Paulo Cavalcanti Gomes

2011-10-01

Jatropha curcas L. is found in all tropical regions and has garnered lot of attention for its potential as a source of biodiesel. As J. curcas is a plant that is still in the process of being domesticated, interest in improving its agronomic traits has increased in an attempt to select more productive varieties, aiming at sustainable utilization of this plant for biodiesel production. Therefore, the study of genetic diversity in different accessions of J. curcas in Brazil constitutes a necessary first step in genetic programs designed to improve this species. In this study we have used ISSR markers to assess the genetic variability of 332 accessions from eight states in Brazil that produce J. curcas seeds for commercialization. Seven ISSR primers amplified a total of 21,253 bands, of which 19,472 bands (91%) showed polymorphism. Among the polymorphic bands 275 rare bands were identified (present in fewer than 15% of the accessions). Polymorphic information content (PIC), marker index (MI) and resolving power (RP) averaged 0.26, 17.86 and 19.87 per primer, respectively, showing the high efficiency and reliability of the markers used. ISSR markers analyses as number of polymorphic loci, genetic diversity and accession relationships through UPGMA-phenogram and MDS showed that Brazilian accessions are closely related but have a higher level of genetic diversity than accessions from other countries, and the accessions from Natal (RN) are the most diverse, having high value as a source of genetic diversity for breeding programs of J. curcas in the world.

Short Communication: Genetic linkage map of Cucurbita maxima with molecular and morphological markers.

PubMed

Ge, Y; Li, X; Yang, X X; Cui, C S; Qu, S P

2015-05-22

Cucurbita maxima is one of the most widely cultivated vegetables in China and exhibits distinct morphological characteristics. In this study, genetic linkage analysis with 57 simple-sequence repeats, 21 amplified fragment length polymorphisms, 3 random-amplified polymorphic DNA, and one morphological marker revealed 20 genetic linkage groups of C. maxima covering a genetic distance of 991.5 cM with an average of 12.1 cM between adjacent markers. Genetic linkage analysis identified the simple-sequence repeat marker 'PU078072' 5.9 cM away from the locus 'Rc', which controls rind color. The genetic map in the present study will be useful for better mapping, tagging, and cloning of quantitative trait loci/gene(s) affecting economically important traits and for breeding new varieties of C. maxima through marker-assisted selection.

Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene.

PubMed

Eskafi Sabet, E; Salehi, Z; Khodayari, S; Sabouhi Zarafshan, S; Zahiri, Z

2015-02-01

Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.

Genetic architecture of hybrid male sterility in Drosophila: analysis of intraspecies variation for interspecies isolation.

PubMed

Reed, Laura K; LaFlamme, Brooke A; Markow, Therese A

2008-08-27

The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Isofemale strains of D. mojavensis vary significantly in their production of sterile F(1) sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F(1) hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F(1) is complex, involving multiple QTL, epistasis, and cytoplasmic effects. The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation.

Pharmacogenetics of tacrolimus and sirolimus in renal transplant patients: from retrospective analyses to prospective studies.

PubMed

Anglicheau, D; Legendre, C; Thervet, E

2007-09-01

The promises of pharmacogenetics are to elucidate the inherited basis of differences between individual responses to drugs in order to identify the right drug and dose for each patient. The recent identification of genetic polymorphisms in drug-metabolizing enzymes and drug transporters led to the hypothesis that genetic factors may be implicated in the interindividual variability of the pharmacokinetic or pharmacodynamic characteristics of immunosuppressive drugs, major side effects, and efficacy. The purpose of this study was to provide a short overview of recent results obtained in the field of pharmacogenetics of tacrolimus and sirolimus, both substrates of the cytochrome P450 3A (CYP3A) enzymes and of the efflux pump P-glycoprotein, the product of the Multidrug Resistance-1 (MDR1) genes. A number of retrospective studies that demonstrated a link between the polymorphisms governing the CYP3A5 protein expression, with more conflicting results with the MDR1 gene polymorphisms, related to the daily dose necessary to achieve adequate blood tacrolimus levels. The CYP3A5 polymorphisms have also been associated with sirolimus pharmacokinetics. One challenge is to investigate the combined effect of a number of different polymorphisms in various genes to define genetic backgrounds with different pharmacokinetic profiles using high throughput technologies. Another challenge is to move toward prospective randomized studies to explore whether a pharmacogenetic approach, taking into account a limited number of polymorphisms prior to drug treatment, could be used on an individual basis to guide initial dosing of a given drug. The last challenge is based on "target" pharmacogenetics to investigate the role of the polymorphisms of other genes implicated in the efficacy and/or safety of the drug.

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

PubMed

Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

2014-01-01

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

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

2016-05-09

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.

Glutathion-S-Transferase P1 polymorphisms association with broncopulmonary dysplasia in preterm infants

PubMed Central

Karagianni, P; Rallis, D; Fidani, L; Porpodi, M; Kalinderi, K; Tsakalidis, C; Nikolaidis, N

2013-01-01

Background: Oxidative stress, characterized by the excretion of pre-oxidative and anti-oxidative proteases, has a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). One of the many host anti-oxidant enzymes is glutathione-S-transferase P1 (GSTP1), with three polymorphic alleles having been identified: homozygous ile, heterozygous ile/val and homozygous val isomorph. The aim of this study was to examine the genetic predisposition to BPD in the GSTP1 polymorphisms. Methods: A prospective case-control study was carried out in the 2nd Neonatal Intensive Care Unit of Aristotle University in Thessaloniki, Greece during 2008. The genetic polymorphisms of GSTP1 in 28 preterms <32 weeks gestational age (GA) with BPD compared to 74 controls (33 preterms without BPD and 41 healthy terms) were examined. Results: The homozygous ile isomorph was predominant in all groups (preterms with BPD: 82%, preterms without BPD: 70%, healthy terms: 78%), followed by the heterozygous ile/val (14%, 18% and 20% respectively) and the homozygous val isomorph (4%, 12% and 2% respectively). The homozygous ile isomorph was also identified in the majority of preterms with mild (80%), moderate (100%) and severe (73%) BPD. The GSTP1 genetic distribution did not differ between the groups and GSTP1 polymorphisms were not associated with the severity of BPD. Conclusions: This study could not confirm an association between GSTP1 polymorphisms and the development of BPD or the severity of the disease. PMID:25031518

Glutathion-S-Transferase P1 polymorphisms association with broncopulmonary dysplasia in preterm infants.

PubMed

Karagianni, P; Rallis, D; Fidani, L; Porpodi, M; Kalinderi, K; Tsakalidis, C; Nikolaidis, N

2013-10-01

Oxidative stress, characterized by the excretion of pre-oxidative and anti-oxidative proteases, has a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). One of the many host anti-oxidant enzymes is glutathione-S-transferase P1 (GSTP1), with three polymorphic alleles having been identified: homozygous ile, heterozygous ile/val and homozygous val isomorph. The aim of this study was to examine the genetic predisposition to BPD in the GSTP1 polymorphisms. A prospective case-control study was carried out in the 2nd Neonatal Intensive Care Unit of Aristotle University in Thessaloniki, Greece during 2008. The genetic polymorphisms of GSTP1 in 28 preterms <32 weeks gestational age (GA) with BPD compared to 74 controls (33 preterms without BPD and 41 healthy terms) were examined. The homozygous ile isomorph was predominant in all groups (preterms with BPD: 82%, preterms without BPD: 70%, healthy terms: 78%), followed by the heterozygous ile/val (14%, 18% and 20% respectively) and the homozygous val isomorph (4%, 12% and 2% respectively). The homozygous ile isomorph was also identified in the majority of preterms with mild (80%), moderate (100%) and severe (73%) BPD. The GSTP1 genetic distribution did not differ between the groups and GSTP1 polymorphisms were not associated with the severity of BPD. This study could not confirm an association between GSTP1 polymorphisms and the development of BPD or the severity of the disease.

Lack of association between genetic polymorphism of FTO, AKT1 and AKTIP in childhood overweight and obesity.

PubMed

Pereira, Patrícia de Araújo; Alvim-Soares, António Marcos; Sandrim, Valéria Cristina; Lanna, Carla Márcia Moreira; Souza-Costa, Débora Cristine; Belo, Vanessa de Almeida; de Paula, Jonas Jardim; Tanus-Santos, José Eduardo; Romano-Silva, Marco Aurélio; Miranda, Débora Marques de

2016-01-01

Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance. This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects. As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies. The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Assessment of genetic and epigenetic variation in hop plants regenerated from sequential subcultures of organogenic calli.

PubMed

Peredo, Elena L; Revilla, M Angeles; Arroyo-García, Rosa

2006-10-01

Organogenic calli induced from internodal segments were subcultured three times. Regenerated plants obtained from each subculture were analysed by molecular methods. No major genetic rearrangements were detected in the callus-derived plants since none of the amplified fragment-length polymorphism (AFLP) loci were found to be polymorphic. However, epigenetic changes due to a demethylation process were detected by methylation-sensitive amplified polymorphism (MSAP) technique. The results allowed inference of the possible relationship among the plants derived from different calli subcultures and the in vitro control. The plants recovered from the first and second callus subcultures clustered with the in vitro control pools in the phenogram while the regenerants from the third callus subculture showed the highest genetic distance with the controls. This is the first study reporting data about the genetic stability of callus-derived Humulus lupulus L. plants.

Genetic diversity of Brazilian natural populations of Anthonomus grandis Boheman (Coleoptera: Curculionidae), the major cotton pest in the New World.

PubMed

Martins, W F S; Ayres, C F J; Lucena, W A

2007-01-27

Twenty-five RAPD loci and 6 isozyme loci were studied to characterize the genetic variability of natural populations of Anthonomus grandis from two agroecosystems of Brazil. The random-amplified polymorphic DNA data disclosed a polymorphism that varied from 52 to 84% and a heterozygosity of 0.189 to 0.347. The index of genetic differentiation (GST) among the six populations was 0.258. The analysis of isozymes showed a polymorphism and a heterozygosity ranging from 25 to 100% and 0.174 to 0.277, respectively. The genetic differentiation (FST) among the populations obtained by isozyme data was 0.544. It was possible to observe rare alleles in the populations from the Northeast region. The markers examined allowed us to distinguish populations from large-scale, intensive farming region (cotton belts) versus populations from areas of small-scale farming

Genetic diversity analysis of Zingiber Officinale Roscoe by RAPD collected from subcontinent of India.

PubMed

Ashraf, Kamran; Ahmad, Altaf; Chaudhary, Anis; Mujeeb, Mohd; Ahmad, Sayeed; Amir, Mohd; Mallick, N

2014-04-01

The present investigation was undertaken for the assessment of 12 accessions of Zingiber officinale Rosc. collected from subcontinent of India by RAPD markers. DNA was isolated using CTAB method. Thirteen out of twenty primers screened were informative and produced 275 amplification products, among which 261 products (94.90%) were found to be polymorphic. The percentage polymorphism of all 12 accessions ranged from 88.23% to 100%. Most of the RAPD markers studied showed different levels of genetic polymorphism. The data of 275 RAPD bands were used to generate Jaccard's similarity coefficients and to construct a dendrogram by means of UPGMA. Results showed that ginger undergoes genetic variation due to a wide range of ecological conditions. This investigation was an understanding of genetic variation within the accessions. It will also provide an important input into determining resourceful management strategies and help to breeders for ginger improvement program.

Genetic diversity analysis of Zingiber Officinale Roscoe by RAPD collected from subcontinent of India

PubMed Central

Ashraf, Kamran; Ahmad, Altaf; Chaudhary, Anis; Mujeeb, Mohd.; Ahmad, Sayeed; Amir, Mohd.; Mallick, N.

2013-01-01

The present investigation was undertaken for the assessment of 12 accessions of Zingiber officinale Rosc. collected from subcontinent of India by RAPD markers. DNA was isolated using CTAB method. Thirteen out of twenty primers screened were informative and produced 275 amplification products, among which 261 products (94.90%) were found to be polymorphic. The percentage polymorphism of all 12 accessions ranged from 88.23% to 100%. Most of the RAPD markers studied showed different levels of genetic polymorphism. The data of 275 RAPD bands were used to generate Jaccard’s similarity coefficients and to construct a dendrogram by means of UPGMA. Results showed that ginger undergoes genetic variation due to a wide range of ecological conditions. This investigation was an understanding of genetic variation within the accessions. It will also provide an important input into determining resourceful management strategies and help to breeders for ginger improvement program. PMID:24600309

Isolation and Characterization of Polymorphic Microsatellite Loci from Metapenaeopsis barbata Using PCR-Based Isolation of Microsatellite Arrays (PIMA)

PubMed Central

Chiang, Tzen-Yuh; Tzeng, Tzong-Der; Lin, Hung-Du; Cho, Ching-Ju; Lin, Feng-Jiau

2012-01-01

The red-spot prawn, Metapenaeopsis barbata, is a commercially important, widely distributed demersal species in the Indo-West Pacific Ocean. Overfishing has made its populations decline in the past decade. To study conservation genetics, eight polymorphic microsatellite loci were isolated. Genetic characteristics of the SSR (simple sequence repeat) fingerprints were estimated in 61 individuals from adjacent seas of Taiwan and China. The number of alleles, ranging from 2 to 4, as well as observed and expected heterozygosities in populations, ranging from 0.048 to 0.538, and 0.048 and 0.654, respectively, were detected. No deviation from Hardy–Weinberg expectations was detected at either locus. No significant linkage disequilibrium was detected in locus pairs. The polymorphic microsatellite loci will be useful for investigations of the genetic variation, population structure, and conservation genetics of this species. PMID:22489123

[Genetic polymorphism of Tulipa gesneriana L. evaluated on the basis of the ISSR marking data].

PubMed

Kashin, A S; Kritskaya, T A; Schanzer, I A

2016-10-01

Using the method of ISSR analysis, the genetic diversity of 18 natural populations of Tulipa gesneriana L. from the north of the Lower Volga region was examined. The ten ISSR primers used in the study provided identification of 102 PCR fragments, of which 50 were polymorphic (49.0%). According to the proportion of polymorphic markers, two population groups were distinguished: (1) the populations in which the proportion of polymorphic markers ranged from 0.35 to 0.41; (2) the populations in which the proportion of polymorphic markers ranged from 0.64 to 0.85. UPGMA clustering analysis provided subdivision of the sample into two large clusters. The unrooted tree constructed using the Neighbor Joining algorithm had similar topology. The first cluster included slightly variable populations and the second cluster included highly variable populations. The AMOVA analysis showed statistically significant differences (F CT = 0.430; p = 0.000) between the two groups. Local populations are considerably genetically differentiated from each other (F ST = 0.632) and have almost no links via modern gene flow, as evidenced by the results of the Mantel test (r =–0.118; p = 0.819). It is suggested that the degree of genetic similarities and differences between the populations depends on the time and the species dispersal patterns on these territories.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

PubMed

Li, Yongning; Song, Dongjing; Jiang, Yongshuai; Wang, Jingwei; Feng, Rennan; Zhang, Liangcai; Wang, Guangyu; Chen, Zugen; Wang, Renzhi; Jiang, Qinghua; Liu, Guiyou

2016-08-01

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association. Here, we reinvestigated the association using all the samples from three independent studies in Chinese population (N = 4047, 1244 AD cases and 2803 controls). We also selected three independent studies in European ancestry population (N = 11787, 3939 AD cases and 7848 controls) to evaluate the effect of rs3818361 polymorphism on AD risk in different ethnic backgrounds. In Chinese population, we did not identified significant heterogeneity using additive, recessive, and dominant genetic models. Meta-analysis showed significant association between rs3818361 and AD with P = 6.00E-03 and P = 5.00E-03. We further identified no heterogeneity of rs3818361 polymorphism between Chinese and European populations. We found that rs3818361 polymorphism contributed to AD with similar genetic risk in Chinese and European populations. In summary, this is the first study to show significant association between rs3818361 polymorphism and AD in Chinese population by a meta-analysis method. Our findings indicate that the effect of CR1 rs3818361 polymorphism on AD risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts.

Meta-analysis of human leukocyte antigen genetic polymorphisms and susceptibility to chronic myelogenous leukemia in Chinese population.

PubMed

Zhang, Min-Yue; Chen, Fang-Yuan; Zhong, Hua

2011-12-01

Human leukocyte antigen (HLA) genetic polymorphisms are assumed to be correlated to the risk of chronic myelogenous leukemia (CML) in various ethnicities. Up to now, no clear consensus has been reached. Our goal is to address this issue in Chinese population. By searching the data in PubMed, Embase and four Chinese databases (prior to July 2010), the association of HLA genetic polymorphisms with CML has been fixed as the research objective. We studied a totality of 12 studies, comprising 2281 CML cases and 41000 health controls. The data demonstrated that HLA-A*11, A*74, HLA-B*40, B*47, B*55 and B*81 alleles were correlated with the increasing risk of CML. Nevertheless, HLA-DRB1*13 allele seemed to contribute to the genetic protection to CML. Conclusively we suggested that certain HLA alleles might be in association with the pathogenesis of CML in Chinese population. Due to little statistical scale, larger studies and particularly in a mono-people background, our hypothesis need to be further investigated in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

PubMed

Bunyavanich, Supinda; Shargorodsky, Josef; Celedón, Juan C

2011-06-01

There is a significant genetic contribution to allergic rhinitis (AR). Genetic association studies for AR have been performed, but varying results make it challenging to decipher the overall potential effect of specific variants. The Th2 pathway plays an important role in the immunological development of AR. We performed meta-analyses of genetic association studies of variants in Th2 pathway genes and AR. PubMed and Phenopedia were searched by double extraction for original studies on Th2 pathway-related genetic polymorphisms and their associations with AR. A meta-analysis was conducted on each genetic polymorphism with data meeting our predetermined selection criteria. Analyses were performed using both fixed and random effects models, with stratification by age group, ethnicity, and AR definition where appropriate. Heterogeneity and publication bias were assessed. Six independent studies analyzing three candidate polymorphisms and involving a total of 1596 cases and 2892 controls met our inclusion criteria. Overall, the A allele of IL13 single nucleotide polymorphism (SNP) rs20541 was associated with increased odds of AR (estimated OR=1.2; 95% CI 1.1-1.3, p-value 0.004 in fixed effects model, 95% CI 1.0-1.5, p-value 0.056 in random effects model). The A allele of rs20541 was associated with increased odds of AR in mixed age groups using both fixed effects and random effects modeling. IL13 SNP rs1800925 and IL4R SNP 1801275 did not demonstrate overall associations with AR. We conclude that there is evidence for an overall association between IL13 SNP rs20541 and increased risk of AR, especially in mixed-age populations. © 2011 John Wiley & Sons A/S.

Studying Genome Heterogeneity within the Arbuscular Mycorrhizal Fungal Cytoplasm

PubMed Central

Halary, Sébastien; Bapteste, Eric; Hijri, Mohamed

2015-01-01

Although heterokaryons have been reported in nature, multicellular organisms are generally assumed genetically homogeneous. Here, we investigate the case of arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The growth advantages they confer to their hosts are of great potential benefit to sustainable agricultural practices. However, measuring genetic diversity for these coenocytes is a major challenge: Within the same cytoplasm, AMF contain thousands of nuclei and show extremely high levels of genetic variation for some loci. The extent and physical location of polymorphism within and between AMF genomes is unclear. We used two complementary strategies to estimate genetic diversity in AMF, investigating polymorphism both on a genome scale and in putative single copy loci. First, we used data from whole-genome pyrosequencing of four AMF isolates to describe genetic diversity, based on a conservative network-based clustering approach. AMF isolates showed marked differences in genome-wide diversity patterns in comparison to a panel of control fungal genomes. This clustering approach further allowed us to provide conservative estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative single copy genomic markers, which we investigated by massive parallel amplicon sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most loci showed high polymorphism, with up to 103 alleles per marker. This polymorphism could be distributed within or between nuclei. However, we argue that the Rhizophagus isolates under study might be heterokaryotic, at least for the putative single copy markers we studied. Considering that genetic information is the main resource for identification of AMF, we suggest that special attention is warranted for the study of these ecologically important organisms. PMID:25573960

Studying genome heterogeneity within the arbuscular mycorrhizal fungal cytoplasm.

PubMed

Boon, Eva; Halary, Sébastien; Bapteste, Eric; Hijri, Mohamed

2015-01-07

Although heterokaryons have been reported in nature, multicellular organisms are generally assumed genetically homogeneous. Here, we investigate the case of arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The growth advantages they confer to their hosts are of great potential benefit to sustainable agricultural practices. However, measuring genetic diversity for these coenocytes is a major challenge: Within the same cytoplasm, AMF contain thousands of nuclei and show extremely high levels of genetic variation for some loci. The extent and physical location of polymorphism within and between AMF genomes is unclear. We used two complementary strategies to estimate genetic diversity in AMF, investigating polymorphism both on a genome scale and in putative single copy loci. First, we used data from whole-genome pyrosequencing of four AMF isolates to describe genetic diversity, based on a conservative network-based clustering approach. AMF isolates showed marked differences in genome-wide diversity patterns in comparison to a panel of control fungal genomes. This clustering approach further allowed us to provide conservative estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative single copy genomic markers, which we investigated by massive parallel amplicon sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most loci showed high polymorphism, with up to 103 alleles per marker. This polymorphism could be distributed within or between nuclei. However, we argue that the Rhizophagus isolates under study might be heterokaryotic, at least for the putative single copy markers we studied. Considering that genetic information is the main resource for identification of AMF, we suggest that special attention is warranted for the study of these ecologically important organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Application of next-generation sequencing technology to study genetic diversity and identify unique SNP markers in bread wheat from Kazakhstan.

PubMed

Shavrukov, Yuri; Suchecki, Radoslaw; Eliby, Serik; Abugalieva, Aigul; Kenebayev, Serik; Langridge, Peter

2014-09-28

New SNP marker platforms offer the opportunity to investigate the relationships between wheat cultivars from different regions and assess the mechanism and processes that have led to adaptation to particular production environments. Wheat breeding has a long history in Kazakhstan and the aim of this study was to explore the relationship between key varieties from Kazakhstan and germplasm from breeding programs for other regions. The study revealed 5,898 polymorphic markers amongst ten cultivars, of which 2,730 were mapped in the consensus genetic map. Mapped SNP markers were distributed almost equally across the A and B genomes, with between 279 and 484 markers assigned to each chromosome. Marker coverage was approximately 10-fold lower in the D genome. There were 863 SNP markers identified as unique to specific cultivars, and clusters of these markers (regions containing more than three closely mapped unique SNPs) showed specific patterns on the consensus genetic map for each cultivar. Significant intra-varietal genetic polymorphism was identified in three cultivars (Tzelinnaya 3C, Kazakhstanskaya rannespelaya and Kazakhstanskaya 15). Phylogenetic analysis based on inter-varietal polymorphism showed that the very old cultivar Erythrospermum 841 was the most genetically distinct from the other nine cultivars from Kazakhstan, falling in a clade together with the American cultivar Sonora and genotypes from Central and South Asia. The modern cultivar Kazakhstanskaya 19 also fell into a separate clade, together with the American cultivar Thatcher. The remaining eight cultivars shared a single sub-clade but were categorised into four clusters. The accumulated data for SNP marker polymorphisms amongst bread wheat genotypes from Kazakhstan may be used for studying genetic diversity in bread wheat, with potential application for marker-assisted selection and the preparation of a set of genotype-specific markers.

The Genomic Architecture of Sporadic Heart Failure

PubMed Central

Dorn, Gerald W

2011-01-01

Common or sporadic systolic heart failure (heart failure) is the clinical syndrome of insufficient forward cardiac output resulting from myocardial disease. Most heart failure is the consequence of ischemic or idiopathic cardiomyopathy. There is a clear familial predisposition to heart failure, with a genetic component estimated to confer between 20 and 30% of overall risk. The multifactorial etiology of this syndrome has complicated identification of its genetic underpinnings. Until recently, almost all genetic studies of heart failure were designed and deployed according to the common disease-common variant hypothesis, in which individual risk alleles impart a small positive or negative effect and overall genetic risk is the cumulative impact of all functional genetic variations. Early studies employed a candidate gene approach, focused mainly on factors within adrenergic and renin-angiotensin pathways that affect heart failure progression and are targeted by standard pharmacotherapeutics. Many of these reported allelic associations with heart failure have not been replicated. However, the preponderance of data support risk-modifier effects for the Arg389Gly polymorphism of β1-adrenergic receptors and the intron 16 in/del polymorphism of angiotensin converting enzyme. Recent unbiased studies using genome-wide single nucleotide polymorphism (SNP) microarrays have shown fewer positive results than when these platforms were applied to hypertension, myocardial infarction, or diabetes, possibly reflecting the complex etiology of heart failure. A new cardiovascular gene-centric sub-genome SNP array identified a common heat failure risk allele at 1p36 in multiple independent cohorts, but the biological mechanism for this association is still uncertain. It is likely that common gene polymorphisms account for only a fraction of individual genetic heart failure risk, and future studies using deep resequencing are likely to identify rare gene variants with larger biological effects. PMID:21566223

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments.

PubMed

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person's perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual's genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations.

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments

PubMed Central

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Introduction Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. Methods and results We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. Conclusion This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person’s perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual’s genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations. PMID:25061327

Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis

PubMed Central

Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

2015-01-01

The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025–1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

PPARγ2Pro12Ala Polymorphism and Human Health

PubMed Central

He, Weimin

2009-01-01

The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies. PMID:19390629

The rs4846049 polymorphism in the 3'UTR region of the MTHFR gene increases the migraine susceptibility in an Iranian population.

PubMed

Salehi, Mohaddeseh; Amin-Beidokhti, Mona; Safarpour Lima, Behnam; Gholami, Milad; Javadi, Gholam-Reza; Mirfakhraie, Reza

2018-01-01

Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model ( P =0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups ( P =0.009; OR =2.48; 95% CI, 1.25-4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations.

Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence.

PubMed

Wojnar, Marcin; Brower, Kirk J; Strobbe, Stephen; Ilgen, Mark; Matsumoto, Halina; Nowosad, Izabela; Sliwerska, Elzbieta; Burmeister, Margit

2009-04-01

The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger. The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

Association between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

PubMed Central

Wojnar, Marcin; Brower, Kirk J.; Strobbe, Stephen; Ilgen, Mark; Matsumoto, Halina; Nowosad, Izabela; Sliwerska, Elzbieta; Burmeister, Margit

2009-01-01

Background The purpose of this study was to examine relationships between genetic markers of central serotonin and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. Methods The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately one year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. Results Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse (OR = 2.62; p = 0.019), and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (HR = 4.93, p = 0.001) were even stronger. Conclusions The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies. PMID:19170664

Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers.

PubMed

Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

2015-09-01

To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype "MS F" (in both markers) was highly diverse and genotypes "Q104 F" (SCoT) and "82-18 F" (CBDP) were least diverse among the female genotype populations. Among male genotypes, "32 M" (CBDP) and "MS M" (SCoT) revealed highest h and I values while "58-5 M" (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups, one group consisting of all female genotypes and another group comprising of all male genotypes. During the present investigation, CBDP markers proved more informative in studying genetic diversity among Jojoba. Such genetically diverse genotypes would thus be of great significance for breeding, management and conservation of elite (high yielding) Jojoba germplasm.

[Using IRAP markers for analysis of genetic variability in populations of resource and rare species of plants].

PubMed

Boronnikova, S V; Kalendar', R N

2010-01-01

Species-specific LTR retrotransposons were first cloned in five rare relic species of drug plants located in the Perm' region. Sequences of LTR retrotransposons were used for PCR analysis based on amplification of repeated sequences from LTR or other sites of retrotransposons (IRAP). Genetic diversity was studied in six populations of rare relic species of plants Adonis vernalis L. by means of the IRAP method; 125 polymorphic IRAP-markers were analyzed. Parameters for DNA polymorphism and genetic diversity of A. vernalis populations were determined.

Chloroplast microsatellite primers for cacao (Theobroma cacao) and other Malvaceae.

PubMed

Yang, Ji Y; Motilal, Lambert A; Dempewolf, Hannes; Maharaj, Kamaldeo; Cronk, Q C B

2011-12-01

Chloroplast microsatellites were developed in Theobroma cacao to examine the genetic diversity of cacao cultivars in Trinidad and Tobago. Nine polymorphic microsatellites were designed from the chloroplast genomes of two T. cacao accessions. These microsatellites were tested in 95 hybrid accessions from Trinidad and Tobago. An average of 2.9 alleles per locus was found. These chloroplast microsatellites, particularly the highly polymorphic pentameric repeat, were useful in assessing genetic variation in T. cacao. In addition, these markers should also prove to be useful for population genetic studies in other species of Malvaceae.

Analysis of genetic diversity in pigeon pea germplasm using retrotransposon-based molecular markers.

PubMed

Maneesha; Upadhyaya, Kailash C

2017-09-01

Pigeon pea (Cajanus cajan), an important legume crop is predominantly cultivated in tropical and subtropical regions of Asia and Africa. It is normally considered to have a low degree of genetic diversity, an impediment in undertaking crop improvement programmes.We have analysed genetic polymorphism of domesticated pigeon pea germplasm (47 accessions) across the world using earlier characterized panzee retrotransposon-based molecularmarkers. Itwas conjectured that since retrotransposons are interspersed throughout the genome, retroelements-based markers would be able to uncover polymorphism possibly inherent in the diversity of retroelement sequences. Two PCR-based techniques, sequence-specific amplified polymorphism (SSAP) and retrotransposon microsatellite amplified polymorphism (REMAP) were utilized for the analyses.We show that a considerable degree of polymorphism could be detected using these techniques. Three primer combinations in SSAP generated 297 amplified products across 47 accessions with an average of 99 amplicons per assay. Degree of polymorphism varied from 84-95%. In the REMAP assays, the number of amplicons was much less but up to 73% polymorphism could be detected. On the basis of similarity coefficients, dendrograms were constructed. The results demonstrate that the retrotransposon-based markers could serve as a better alternative for the assessment of genetic diversity in crops with apparent low genetic base.

Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria.

PubMed

Oshodi, Y; Ojewunmi, O; Oshodi, T A; Ijarogbe, G T; Ogun, O C; Aina, O F; Lesi, Fea

2017-09-01

The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

PubMed Central

Sanhueza, Jorge A.; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A.

2016-01-01

Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders. Key points Genetic factors influencing sports performance in the Chilean population are unknown. Differential outcomes from athletes who completed a triathlon competition were associated with five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11). We show that genetic variants within stress- and anxiety-related genes affect athletic performance. PMID:27928199

Phylogenetic information in polymorphic L1 and Alu insertions from East Asians and Native American populations.

PubMed

Mateus Pereira, L H; Socorro, A; Fernandez, I; Masleh, M; Vidal, D; Bianchi, N O; Bonatto, S L; Salzano, F M; Herrera, R J

2005-09-01

This study attempts to ascertain genetic affinities between Native American and East Asian populations by analyzing four polymorphic Alu insertions (PAIs) and three L1 polymorphic loci. These two genetic systems demonstrated strong congruence when levels of diversity and genetic distances were considered. Overall, genetic relatedness within Native American groups does not correlate with geographical and linguistic structure, although strong grouping for Native Americans with East Asians was demonstrated, with clear discrimination from African and European groups. Most of the variation was assigned to differences occurring within groups, but the interpopulation variation found for South Amerindians was recognizably higher in comparison to the other sampled groups of populations. Our data suggest that bottleneck events followed by strong influence of genetic drift in the process of the peopling of the Americas may have been determinant factors in delineating the genetic background of present-day South Amerindians. Since no clear subgroups were detected within Native Americans and East Asians, there is no indication of multiple waves in the early colonization of the New World. (c) 2005 Wiley-Liss, Inc.

How and how much does RAD-seq bias genetic diversity estimates?

PubMed

Cariou, Marie; Duret, Laurent; Charlat, Sylvain

2016-11-08

RAD-seq is a powerful tool, increasingly used in population genomics. However, earlier studies have raised red flags regarding possible biases associated with this technique. In particular, polymorphism on restriction sites results in preferential sampling of closely related haplotypes, so that RAD data tends to underestimate genetic diversity. Here we (1) clarify the theoretical basis of this bias, highlighting the potential confounding effects of population structure and selection, (2) confront predictions to real data from in silico digestion of full genomes and (3) provide a proof of concept toward an ABC-based correction of the RAD-seq bias. Under a neutral and panmictic model, we confirm the previously established relationship between the true polymorphism and its RAD-based estimation, showing a more pronounced bias when polymorphism is high. Using more elaborate models, we show that selection, resulting in heterogeneous levels of polymorphism along the genome, exacerbates the bias and leads to a more pronounced underestimation. On the contrary, spatial genetic structure tends to reduce the bias. We confront the neutral and panmictic model to "ideal" empirical data (in silico RAD-sequencing) using full genomes from natural populations of the fruit fly Drosophila melanogaster and the fungus Shizophyllum commune, harbouring respectively moderate and high genetic diversity. In D. melanogaster, predictions fit the model, but the small difference between the true and RAD polymorphism makes this comparison insensitive to deviations from the model. In the highly polymorphic fungus, the model captures a large part of the bias but makes inaccurate predictions. Accordingly, ABC corrections based on this model improve the estimations, albeit with some imprecisions. The RAD-seq underestimation of genetic diversity associated with polymorphism in restriction sites becomes more pronounced when polymorphism is high. In practice, this means that in many systems where polymorphism does not exceed 2 %, the bias is of minor importance in the face of other sources of uncertainty, such as heterogeneous bases composition or technical artefacts. The neutral panmictic model provides a practical mean to correct the bias through ABC, albeit with some imprecisions. More elaborate ABC methods might integrate additional parameters, such as population structure and selection, but their opposite effects could hinder accurate corrections.

Generalization of Associations of Kidney-Related Genetic Loci to American Indians

PubMed Central

Haack, Karin; Almasy, Laura; Laston, Sandra; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard R.; MacCluer, Jean W.; Howard, Barbara V.; Umans, Jason G.; Cole, Shelley A.

2014-01-01

Summary Background and objectives CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. Design, setting, participants, & measurements This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. Results This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10-3 to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. Conclusion This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries. PMID:24311711

Prevalence of factor V leiden, MTHFR C677T and MTHFR A1298C polymorphisms in patients with deep vein thrombosis in Central Iran.

PubMed

Ehsani, Majid; Imani, Aida; Moravveji, Alireza

2018-05-31

Deep vein thrombosis (DVT) is a common disease, especially among elderly patients, which is associated with high costs of treatment and high rates of recurrence. The risk factors for venous thrombosis are primarily related to hypercoagulability, which can be genetic or acquired, or because of immobilization and venous stasis. Among relevant genetic markers are a number of common polymorphisms and mutations in the genes coding for Factor V leiden and methylenetetrahydrofolate reductase. Differential associations of these polymorphisms have been reported in different populations with DVT due to ethnic variations. However, no study has been reported with respect to these polymorphisms in DVT in Iran. Thus, the aim of the present study is to determine the prevalence of FVL, MTHFR C677T and MTHFR A1298C gene polymorphisms in patients with DVT in central Iran. In the present cross-sectional study, a total of 100 patients with first and recurrent episodes of DVT and age less than 70 years were recruited during 2016-2017. Blood sample was collected from the recruited patients and FVL mutation was screened using ARMS-PCR method, MTHFR C677T and MTHFR A1298C mutations were screened using PCR-RFLP method. The results revealed that MTHFR A1298C gene polymorphism in both homozygote and heterozygote form was found to be most frequent i.e. 77% among cases, followed by MTHFR C677T (67%) and FVL (17%). The study highlights the importance of screening of these genetic markers among patients with DVT in this region.

[Antipsychotic-induced weight gain--pharmacogenetic studies].

PubMed

Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy

2006-01-01

Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.

Genetic differentiation in natural populations of Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae) with different phenotypic spot patterns on tergites in males.

PubMed

Silva, M H; Nascimento, M D S B; Leonardo, F S; Rebêlo, J M M; Pereira, S R F

2011-01-01

Entomological surveys in the state of Maranhão have recorded morphologically distinct populations of Lutzomyia longipalpis (Lutz & Neiva). Some populations have one pair of spots (1S) on the fourth tergite, while others have two pairs (2S) on the third and fourth tergites of males. In the present study we investigated the degree of genetic polymorphism among four populations in the municipalities of Caxias, Codó and Raposa, in the state of Maranhão, Brazil, by using RAPD (Random Amplified Polymorphic DNA) markers. A total of 35 loci were identified, of which 30 were polymorphic. The highest polymorphism was observed with primer OPA 4, which produced 11 different profiles. Genetic diversity was assessed using grouping methods that produced a dendrogram in which the genotypes could be clearly separated into two main clades according to the number of spots on the male abdominal tergites. One cluster contained the populations from Caxias and Codó, and the other was formed by the populations from Raposa and Codó. The results of our RAPD analysis showed a clear separation between the populations with one and two pairs of spots. The epidemiologic significance of this genetic differentiation should be investigated in future studies.

Genetic Diversity of Blumeria graminis f. sp. hordei in Central Europe and Its Comparison with Australian Population

PubMed Central

Komínková, Eva; Dreiseitl, Antonín; Malečková, Eva; Doležel, Jaroslav

2016-01-01

Population surveys of Blumeria graminis f. sp. hordei (Bgh), a causal agent of more than 50% of barley fungal infections in the Czech Republic, have been traditionally based on virulence tests, at times supplemented with non-specific Restriction fragment length polymorphism or Random amplified polymorphic DNA markers. A genomic sequence of Bgh, which has become available recently, enables identification of potential markers suitable for population genetics studies. Two major strategies relying on transposable elements and microsatellites were employed in this work to develop a set of Repeat junction markers, Single sequence repeat and Single nucleotide polymorphism markers. A resolution power of the new panel of markers comprising 33 polymorphisms was demonstrated by a phylogenetic analysis of 158 Bgh isolates. A core set of 97 Czech isolates was compared to a set 50 Australian isolates on the background of 11 diverse isolates collected throughout the world. 73.2% of Czech isolates were found to be genetically unique. An extreme diversity of this collection was in strong contrast with the uniformity of the Australian one. This work paves the way for studies of population structure and dynamics based on genetic variability among different Bgh isolates originating from geographically limited regions. PMID:27875588

Analysis of polymorphisms in milk proteins from cloned and sexually reproduced goats.

PubMed

Xing, H; Shao, B; Gu, Y Y; Yuan, Y G; Zhang, T; Zang, J; Cheng, Y

2015-12-08

This study evaluates the relationship between the genotype and milk protein components in goats. Milk samples were collected from cloned goats and normal white goats during different postpartum (or abortion) phases. Two cloned goats, originated from the same somatic line of goat mammary gland epithelial cells, and three sexually reproduced normal white goats with no genetic relationships were used as the control. The goats were phylogenetically analyzed by polymerase chain reaction-restriction fragment length polymorphism. The milk protein components were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicated that despite the genetic fingerprints being identical, the milk protein composition differed between the two cloned goats. The casein content of cloned goat C-50 was significantly higher than that of cloned goat C-4. Conversely, although the genetic fingerprints of the normal white goats N-1, N-2, and N-3 were not identical, the milk protein profiles did not differ significantly in their milk samples (obtained on postpartum day 15, 20, 25, 30, and 150). These results indicated an association between milk protein phenotypes and genetic polymorphisms, epigenetic regulation, and/or non-chromosomal factors. This study extends the knowledge of goat milk protein polymorphisms, and provides new strategies for the breeding of high milk-yielding goats.

CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations.

PubMed

Zhang, Shuyan; Zhang, Donghui; Jiang, Yongshuai; Wu, Lina; Shang, Hong; Liu, Jiafeng; Feng, Rennan; Liao, Mingzhi; Zhang, Liangcai; Liu, Yong; Liu, Guiyou; Li, Keshen

2015-03-01

It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer's disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E-04 and P = 2.00E-04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD.

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study1234

PubMed Central

Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

2015-01-01

Background: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. Objective: The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. Design: We conducted a genomewide association study with 1.1 million genetic markers in 815 children. Results: We found serum uric acid to be significantly heritable [h2 ± SD = 0.45 ± 0.08, P = 5.8 × 10−11] and associated with SLC2A9 variants (P values between 10−16 and 10−7). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001). Conclusions: Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. PMID:25833971

In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

PubMed Central

Clara Bicho, Maria; Areias, Maria José; Rebelo, Irene

2014-01-01

Preeclampsia (PE) may affect the risk for future cardiovascular disease. Haptoglobin (Hp), an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35 ± 5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP), myeloperoxidase (MPO), and nitric oxide metabolites (total and nitrites), and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B). Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT), whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women. PMID:25101128

A 3'UTR polymorphism of IL-6R is associated with Chinese pediatric tuberculosis.

PubMed

Shen, Chen; Qi, Hui; Sun, Lin; Xiao, Jing; Yin, Qing-qin; Jiao, Wei-wei; Wu, Xi-rong; Tian, Jian-ling; Han, Rui; Shen, A-dong

2014-01-01

IL-6 is a proinflammatory cytokine that plays a critical role in host defense against tuberculosis (TB). Genetic polymorphisms of IL-6 and its receptor IL-6R had been discussed in adult TB recently. However, their role in pediatric TB is still unclear. Due to the obvious differences in TB pathophysiology in children, which may also reflect differences in genetic background, further association studies in pediatric populations are needed. A case-control study was carried out in a Chinese pediatric population including 353 TB patients and 400 healthy controls. Tag-SNPs of IL-6 and IL-6R genes were selected by Haploview software, genotyped using MassArray, and analyzed statistically. One polymorphism, rs2229238, in the 3'UTR region of IL-6R was observed to be associated with increased resistance to TB (adjusted P = 0.03). The rs2229238 T allele contributed to a reduced risk to TB in recessive heritable model (OR, 0.53; 95% CI, 0.35-0.78). By tag-SNP genotyping based case-control study, we identified a genetic polymorphism in the IL-6R 3'UTR that regulates host resistance to pediatric TB in a Chinese population.

Genetic structure and inter-generic relationship of closed colony of laboratory rodents based on RAPD markers.

PubMed

Kumar, Mahadeo; Kumar, Sharad

2014-11-01

Molecular genetic analysis was performed using random amplified polymorphic DNA (RAPD) on three commonly used laboratory bred rodent genera viz. mouse (Mus musculus), rat (Rattus norvegicus) and guinea pig (Cavia porcellus) as sampled from the breeding colony maintained at the Animal Facility, CSIR-Indian Institute of Toxicology Research, Lucknow. In this study, 60 samples, 20 from each genus, were analyzed for evaluation of genetic structure of rodent stocks based on polymorphic bands using RAPD markers. Thirty five random primers were assessed for RAPD analysis. Out of 35, only 20 primers generated a total of 56.88% polymorphic bands among mice, rats and guinea pigs. The results revealed significantly variant and distinct fingerprint patterns specific to each of the genus. Within-genera analysis, the highest (89.0%) amount of genetic homogeneity was observed in mice samples and the least (79.3%) were observed in guinea pig samples. The amount of genetic homogeneity was observed very high within all genera. The average genetic diversity index observed was low (0.045) for mice and high (0.094) for guinea pigs. The inter-generic distances were maximum (0.8775) between mice and guinea pigs; and the minimum (0.5143) between rats and mice. The study proved that the RAPD markers are useful as genetic markers for assessment of genetic structure as well as inter-generic variability assessments.

The study of relatedness and genetic diversity in cranes

USGS Publications Warehouse

Gee, G.F.; Dessauer, H.C.; Longmire, J.; Briles, W.E.; Simon, R.C.; Wood, Don A.

1992-01-01

The U.S. Fish and Wildlife Service (Service) is responsible for recovery of endangered species in the wild and, when necessary, maintenance in captivity. These programs provide an immediate measure of insurance against extinction. A prerequisite inherent in all of these programs is the preservation of enough genetic diversity to maintain a viable population and to maintain the capacity of the population to respond to change. Measures of genetic diversity examine polymorphic genes that are not influenced by selection pressures. Examples of these techniques and those used to determine relatedness are discussed. Studies of genetic diversity, electrophoresis of blood proteins, relatedness, blood typing, and restriction fragment length polymorphisms which are being used by the Patuxent Wildlife Research Center are discussed in detail.

The Integration of Genetic Propensities into Social-Control Models of Delinquency and Violence among Male Youths

ERIC Educational Resources Information Center

Guo, Guang; Roettger, Michael E.; Cai, Tianji

2008-01-01

This study, drawing on approximately 1,100 males from the National Longitudinal Study of Adolescent Health, demonstrates the importance of genetics, and genetic-environmental interactions, for understanding adolescent delinquency and violence. Our analyses show that three genetic polymorphisms--specifically, the 30-bp promoter-region variable…

Transferability of STS markers in studying genetic relationships of marvel grass (Dichanthium annulatum).

PubMed

Saxena, Raghvendra; Chandra, Amaresh

2011-11-01

Transferability of sequence-tagged-sites (STS) markers was assessed for genetic relationships study among accessions of marvel grass (Dichanthium annulatum Forsk.). In total, 17 STS primers of Stylosanthes origin were tested for their reactivity with thirty accessions of Dichanthium annulatum. Of these, 14 (82.4%) reacted and a total 106 (84 polymorphic) bands were scored. The number of bands generated by individual primer pairs ranged from 4 to 11 with an average of 7.57 bands, whereas polymorphic bands ranged from 4 to 9 with an average of 6.0 bands accounts to an average polymorphism of 80.1%. Polymorphic information content (PIC) ranged from 0.222 to 0.499 and marker index (MI) from 1.33 to 4.49. Utilizing Dice coefficient of genetic similarity dendrogram was generated through un-weighted pairgroup method with arithmetic mean (UPGMA) algorithm. Further, clustering through sequential agglomerative hierarchical and nested (SAHN) method resulted three main clusters constituted all accessions except IGBANG-D-2. Though there was intermixing of few accessions of one agro-climatic region to another, largely groupings of accessions were with their regions of collections. Bootstrap analysis at 1000 scale also showed large number of nodes (11 to 17) having strong clustering (> 50). Thus, results demonstrate the utility of STS markers of Stylosanthes in studying the genetic relationships among accessions of Dichanthium.

[Studies on the adverse effects of fluvoxamine treatment in children with autistic disorder: correlation with genetic polymorphism in serotonin related genes].

PubMed

Sugie, Yoko; Sugie, Hideo; Fukuda, Tokiko; Ito, Masataka; Ohzeki, Takehiko

2003-05-01

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.

PubMed

Kim, Sang-Heon; Kim, Yoon-Keun; Park, Heung-Woo; Jee, Young-Koo; Kim, Sang-Hoon; Bahn, Joon-Woo; Chang, Yoon-Seok; Kim, Seung-Hyun; Ye, Young-Min; Shin, Eun-Soon; Lee, Jong-Eun; Park, Hae-Sim; Min, Kyung-Up

2007-04-01

Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype. We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls). Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015). These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma.

Association Studies of Specific Cholesterol Related Genes (APOE, LPL, and CETP) with Lipid Profile and Memory Function: A Correlative Study Among Rural and Tribal Population of Dharmapuri District, India.

PubMed

Periyasamy, Sabapathy; Sathya, Mohan; Karthick, Chennakesavan; Kandasamy, Mahesh; Shanmugaapriya, Sellathamby; Tamilselvan, Jeyavelu; Jayachandran, Kesavan Swaminathan; Anusuyadevi, Muthuswamy

2017-01-01

 Epidemiological studies state that dementia has multiple etiologies including genetic mutation, genetic variation, and environmental factors. Accumulating evidence suggests that dysregulation of cholesterol homeostasis is the major etiological factor in initiating neurodegeneration. Apolipoprotein E (APOE) polymorphic alleles and associated polymorphism of lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) that are important components in regulating cholesterol metabolism are implicated in neurodegenerative diseases. Therefore, the current study focused on identifying the association between several common polymorphism (viz., APOE, CETP, and LPL) to that of change in serum lipid levels and memory symptoms. Volunteer subjects aged 50 and above from rural and tribal areas of the Dharmapuri district, Tamilnadu, India were chosen for the current study and polymorphism was analyzed using PCR-RFLP. Fasting lipid profile and memory function using simplified version of Global Clinical Dementia rating were assessed. Significant difference in the major lipid profile parameters were observed (TC, TGL, LDL, VLDL) among rural and tribal populations that were associated with significant genotypic variation of APOE, CETP, and LPL. Regression analysis revealed significant risk for memory loss that are dependent on age and genetic variants like CETP. These data predict positive correlation between cholesterol-associated genes and their relationship to altered lipid profile and memory symptoms, which possibly link gene-polymorphism and susceptibility ratio for aging and dementia.

AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

PubMed

Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

2014-07-01

Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves’ disease and Hashimoto's thyroiditis)

PubMed Central

Pastuszak-Lewandoska, Dorota; Sewerynek, Ewa; Domańska, Daria; Gładyś, Aleksandra; Skrzypczak, Renata

2012-01-01

Introduction Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis, HT and Graves' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients. Material and methods Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). Results Statistical analysis (χ2 test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups. Conclusions CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients. PMID:22851994

CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis).

PubMed

Pastuszak-Lewandoska, Dorota; Sewerynek, Ewa; Domańska, Daria; Gładyś, Aleksandra; Skrzypczak, Renata; Brzeziańska, Ewa

2012-07-04

Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis, HT and Graves' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients. Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). Statistical analysis (χ(2) test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups. CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients.

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

PubMed

Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p < 0.05). Corresponding relative ln (concentration-dose ratios) values for SCN1A IVS5-91 variants differed by the genotypic order GG > GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.

PubMed

Dissanayake, Vajira H W; Weerasekera, Lakshini Y; Gammulla, C Gayani; Jayasekara, Rohan W

2009-10-01

We investigated the prevalence of genotypes/alleles of single nucleotide polymorphisms (SNP) and haplotypes defined by them in three genes in which variations are associated with venous thromboembolism in 80 Sinhalese, 80 Sri Lankan Tamils and 80 Moors in the Sri Lankan population and compared the SNP data with that of other populations in Southern India and haplotype data with that of HapMap populations. The genes and polymorphisms investigated were Methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133), 1298A>C (rs1801131), 1317T>C, 1793G>A (rs2274976); Factor V (F5) - 1691G>A (rs6025) and 4070A>G (rs1800595); and prothrombin (F2) - 20210G>A (rs1799963). The polymorphisms were genotyped using PCR/RFLP methods. The prevalence of the variant alleles of each polymorphism in the Sinhalese, Tamils, and Moors was MTHFR 677T: Sinhalese - 13%, Tamils - 9%, Moors - 9%. 1317T>C: Sinhalese - 0%; Tamils - 0%; Moors - 0%. 1793A: Sinhalese - 19%, Tamils - 19%, Moors - 19%. F5 1691A: Sinhalese - 2%, Tamils - 3%, Moors - 2%. 4070G: Sinhalese - 6%, Tamils - 5%, Moors - 8%. F2 20210A: Sinhalese - 0%, Tamils - 0%, Moors - 0%. The frequencies observed were similar to data from other South Indian populations; the haplotype data showed haplotypes unique to the Sri Lankan population when compared to HapMap populations. rs9651118 was identified as a SNP that splits the haplotypes harbouring the functionally significant 677T allele in the MTHFR gene. This data would be useful in planning genetic association studies in the Sri Lankan population and in deciding on which genetic variants should be tested in a clinical genetic testing service.

Genetic diversity of Plasmodium Vivax revealed by the merozoite surface protein-1 icb5-6 fragment.

PubMed

Ruan, Wei; Zhang, Ling-Ling; Feng, Yan; Zhang, Xuan; Chen, Hua-Liang; Lu, Qiao-Yi; Yao, Li-Nong; Hu, Wei

2017-06-05

Plasmodium vivax remains a potential cause of morbidity and mortality for people living in its endemic areas. Understanding the genetic diversity of P. vivax from different regions is valuable for studying population dynamics and tracing the origins of parasites. The PvMSP-1 gene is highly polymorphic and has been used as a marker in many P. vivax population studies. The aim of this study was to investigate the genetic diversity of the PvMSP-1 gene icb5-6 fragment and to provide more genetic polymorphism data for further studies on P. vivax population structure and tracking of the origin of clinical cases. Nested PCR and sequencing of the PvMSP-1 icb5-6 marker were performed to obtain the nucleotide sequences of 95 P. vivax isolates collected from Zhejiang province, China. To investigate the genetic diversity of PvMSP-1, the 95 nucleotide sequences of the PvMSP-1 icb5-6 fragment were genotyped and analyzed using DnaSP v5, MEGA software. The 95 P. vivax isolates collected from Zhejiang province were either indigenous cases or imported cases from different regions around the world. A total of 95 sequences ranging from 390 to 460 bp were obtained. The 95 sequences were genotyped into four allele-types (Sal I, Belem, R-III and R-IV) and 17 unique haplotypes. R-III and Sal I were the predominant allele-types. The haplotype diversity (Hd) and nucleotide diversity (Pi) were estimated to be 0.729 and 0.062, indicating that the PvMSP-1 icb5-6 fragment had the highest level of polymorphism due to frequent recombination processes and single nucleotide polymorphism. The values of dN/dS and Tajima's D both suggested neutral selection for the PvMSP-1icb5-6 fragment. In addition, a rare recombinant style of R-IV type was identified. This study presented high genetic diversity in the PvMSP-1 marker among P. vivax strains from around the world. The genetic data is valuable for expanding the polymorphism information on P. vivax, which could be helpful for further study on population dynamics and tracking the origin of P. vivax.

Genetic determination of the vascular reactions in humans in response to the diving reflex.

PubMed

Baranova, Tatiana I; Berlov, Dmitrii N; Glotov, Oleg S; Korf, Ekaterina A; Minigalin, Alexey D; Mitrofanova, Alla V; Ahmetov, Ildus I; Glotov, Andrey S

2017-03-01

The purpose of this study was to investigate the genetic mechanisms of the defense vascular reactions in response to the diving reflex in humans with polymorphisms in the genes ADBR2, ACE, AGTR1, BDKRB2 , and REN We hypothesized that protective vascular reactions, in response to the diving reflex, are genetically determined and are distinguished in humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin system. A total of 80 subjects (19 ± 1.4 yr) participated in the study. The intensity of the vascular response was estimated using photoplethysmogram. The I/D polymorphism (rs4340) of ACE was analyzed by PCR. REN (G/A, rs2368564), AGTR1 (A/C, rs5186), BDKRB2 (T/C, rs1799722), and ADBR2 (A/G, rs1042713) polymorphisms were examined using the two-step multiplex PCR followed by carrying allele hybridization on the biochip. Subjects with the BDKRB2 (C/C), ACE (D/D), and ADBR2 (G/G, G/A) genotypes exhibited the strongest peripheral vasoconstriction in response to diving. In subjects with a combination of the BDKRB2 (C/C) plus ACE (D/D) genotypes, we observed the lowest pulse wave amplitude and pulse transit time values and the highest arterial blood pressure during face immersion compared with the heterozygous individuals, suggesting that these subjects are more susceptible to diving hypoxia. This study observed that humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin systems demonstrate various expressions of protective vascular reactions in response to the diving reflex. The obtained results might be used in estimation of resistance to hypoxia of any origin in human beings or in a medical practice. NEW & NOTEWORTHY Our study demonstrates that the vascular reactions in response to the diving reflex are genetically determined and depend on gene polymorphisms of the kinin-bradykinin and the renin-angiotensin systems. Copyright © 2017 the American Physiological Society.

Association between environmental tobacco smoke exposure and lung cancer susceptibility: modification by antioxidant enzyme genetic polymorphisms.

PubMed

Fathy, Mona; Hamed, Mai; Youssif, Omnia; Fawzy, Nahla; Ashour, Wafa

2014-02-01

Environmental tobacco smoke (ETS) is the primary etiologic factor responsible for lung cancer. However, only 10-15 % of smokers develop lung cancer, suggesting a genetic role in modifying individual susceptibility to lung cancer. Antioxidant enzymes and genetic polymorphisms should be considered. The present study aimed to evaluate the role of antioxidant enzyme activity and genetic polymorphisms in modifying the susceptibility to lung cancer among individuals exposed to ETS. A total of 150 male subjects were divided into three groups: 50 lung cancer patients, 50 chronic smokers, and 50 passive smokers. Genotyping of microsomal epoxide hydrolase (mEH) exon 3 (Tyr(113)Hist) and exon 4 (Hist(139)Arg) polymorphisms were done by the polymerase chain reaction-restriction fragment length polymorphism technique. MnSOD (Val(16)Ala) polymorphism was detected by the real time-TaqMan assay. Erythrocyte MnSOD activity was measured spectrophotometrically. ETS-exposed individuals (both active and passive smokers) who carried the His allele of mEH exon3 have a 2.9-fold increased risk of lung cancer (odds ratio [OR] 2.9, P < 0.001). In addition, ETS-exposed carriers of the Arg allele of mEH exon 4 have a 2.1-fold increased risk of lung cancer (OR 2.1, P = 0.024). However, no association between the MnSOD Val(16)Ala polymorphism and lung cancer was detected among ETS-exposed individuals (OR 1.6, P = 0.147), although the lung cancer group had significantly lower MnSOD activity than the chronic or passive smoker groups (P = 0.03). Exons 3 and 4 polymorphisms of the mEH gene may contribute to lung cancer susceptibility through disturbed antioxidant balance. However, this was not the case with the MnSOD Val(16)Ala single-nucleotid polymorphism. Antioxidant enzymes may modulate the influence of ETS exposure on lung cancer risk.

[Genetic differentiation of Isaria farinosa populations in Anhui Province of East China].

PubMed

Sun, Zhao-Hong; Luan, Feng-Gang; Zhang, Da-Min; Chen, Ming-Jun; Wang, Bin; Li, Zeng-Zhi

2011-11-01

Isaria farinosa is an important entomopathogenic fungus. By using ISSR, this paper studied the genetic heterogeneity of six I. farinosa populations at different localities of Anhui Province, East China. A total of 98.5% polymorphic loci were amplified with ten polymorphic primers, but the polymorphism at population level varied greatly, within the range of 59.6%-93.2%. The genetic differentiation index (G(st)) between the populations based on Nei's genetic heterogenesis analysis was 0.3365, and the gene flow (N(m)) was 0.4931. The genetic differentiation between the populations was lower than that within the populations, suggesting that the genetic variation of I. farinosa mainly come from the interior of the populations. The UPGMA clustering based on the genetic similarities between the isolates revealed that the Xishan population was monophylectic, while the other five populations were polyphylectic, with the Yaoluoping population being the most heterogenic and the Langyashan population being the least heterogenic. No correlations were observed between the geographic distance and the genetic distance of the populations. According to the UPGMA clustering based on the genetic distance between the populations, the six populations were classified into three groups, and this classification was accorded with the clustering based on geographic environment, suggesting the effects of environmental heterogeneity on the population heterogeneity.

[Analysis on genetic polymorphism of 5 STR loci selected from X chromosome].

PubMed

Liu, Qi-ji; Gong, Yao-qin; Zhang, Xi-yu; Gao, Gui-min; Li, Jiang-xia; Guo, Yi-shou

2005-02-01

To select short tandem repeats(STR) from X chromosome. STR is a universal genetic marker that has changeable polymorphism and stable heredity in human genome. It is a specific DNA segment composed of 2-6 base pairs as its core sequence. It is an ideal DNA marker used in linkage analysis and gene mapping. In this study, 8 short tandem repeats were selected from two genomic clones on X chromosome by using BCM Search Launcher. Primers amplifying the STR loci were designed by using Primer 3.0 according to the unique sequence flanking the STRs. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five of these STRs were polymorphic. Chi-square test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium (P>0.05). Five polymorphic short tandem repeats have been identified on chromosome X and will be useful for linkage analysis and gene mapping.

Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

PubMed

Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

2014-01-01

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

PubMed Central

Durieux, Gillian; Burke, Terry; Dugdale, Hannah L.

2015-01-01

Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes. PMID:26473495

Genome skimming identifies polymorphism in tern populations and species

PubMed Central

2012-01-01

Background Terns (Charadriiformes: Sterninae) are a lineage of cosmopolitan shorebirds with a disputed evolutionary history that comprises several species of conservation concern. As a non-model system in genetics, previous study has left most of the nuclear genome unexplored, and population-level studies are limited to only 15% of the world's species of terns and noddies. Screening of polymorphic nuclear sequence markers is needed to enhance genetic resolution because of supposed low mitochondrial mutation rate, documentation of nuclear insertion of hypervariable mitochondrial regions, and limited success of microsatellite enrichment in terns. Here, we investigated the phylogenetic and population genetic utility for terns and relatives of a variety of nuclear markers previously developed for other birds and spanning the nuclear genome. Markers displaying a variety of mutation rates from both the nuclear and mitochondrial genome were tested and prioritized according to optimal cross-species amplification and extent of genetic polymorphism between (1) the main tern clades and (2) individual Royal Terns (Thalasseus maxima) breeding on the US East Coast. Results Results from this genome skimming effort yielded four new nuclear sequence-based markers for tern phylogenetics and 11 intra-specific polymorphic markers. Further, comparison between the two genomes indicated a phylogenetic conflict at the base of terns, involving the inclusion (mitochondrial) or exclusion (nuclear) of the Angel Tern (Gygis alba). Although limited mitochondrial variation was confirmed, both nuclear markers and a short tandem repeat in the mitochondrial control region indicated the presence of considerable genetic variation in Royal Terns at a regional scale. Conclusions These data document the value of intronic markers to the study of terns and allies. We expect that these and additional markers attained through next-generation sequencing methods will accurately map the genetic origin and species history of this group of birds. PMID:22333071

XPG genetic polymorphisms and clinical outcome of patients with advanced non-small cell lung cancer under platinum-based treatment: a meta-analysis of 12 studies.

PubMed

Xiang, Tianxin; Kang, Xiuhua; Gong, Zhenghua; Bai, Wei; Chen, Chuanhui; Zhang, Wei

2017-04-01

A number of studies on the relationship between xeroderma pigmentosum group G (XPG) polymorphisms and clinical outcomes in non-small cell cancer (NSCLC) have led to inconclusive results. This meta-analysis evaluates the predictive value of XPG polymorphisms on the treatment response rate and overall survival of patients with NSCLC. To measure the correlative strength of the relationship between XPG polymorphisms and outcomes of patients with NSCLC, we searched electronic databases, including PubMed and China National Knowledge Infrastructure, to retrieve studies up to August 2016. We also employed pooled odds ratios (ORs) and hazard ratios (HRs) corresponding to 95% confidence intervals (95% CIs). Twelve studies involving 2877 patients with NSCLC were included: 8 studies involving 1473 patients examined the correlation between XPG polymorphisms and tumor response rate and 7 studies involving 2329 patients reported on the correlation of XPG polymorphisms with overall survival. None of the XPG His1104Asp(C>G)/His46His(C>T) polymorphisms exhibited a correlation with treatment response rate or overall survival. However, in a further stratified analysis by ethnicity, carriers of the 1104G allele were associated with good response among Asians in the homozygote model (GG vs. CC: OR = 1.57, 95% CI: 1.05-2.34, P = 0.027). Meanwhile, further stratified by ethnicity, His46His polymorphism was not associated with RR and OS in any genetic models. No strong evidence was found to support the use of XPG polymorphisms as tumor response and prognostic factors of patients with NSCLC receiving a platinum-based treatment regimen, which is attributed to marginal association. Studies with large-scale and multiple ethnicities need to be conducted to verify the conclusion.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca

Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individualmore » genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic polymorphisms may be promising candidates for predicting acute radiosensitivity, but further studies are necessary to confirm our findings.« less

Effects of interleukin-1 receptor antagonist (IL-1Ra) gene 86 bp VNTR polymorphism on recurrent pregnancy loss: a case-control study.

PubMed

Hajizadeh, Yasamin Sayed; Emami, Elina; Nottagh, Marina; Amini, Zahra; Maroufi, Nazila Fathi; Azimian, Saba Haj; Isazadeh, Alireza

2017-05-26

Objective Recurrent pregnancy loss (RPL) is a heterogeneous disease which is defined as two or more consecutive fetal losses during early pregnancy. Interleukin-1 receptor antagonist (IL-1Ra) is a anti-inflammatory cytokine, which inhibits IL-1 activity by binding to its receptors. The aim of this study was to investigate the association between RPL and IL-1Ra intron 2 polymorphism (86 bp VNTR) in Iranian women. Materials and methods In this case control study, genetic polymorphism was studied in 140 RPL patients and 140 healthy women as controls. Genomic DNA was extracted from the blood samples and polymorphism analysis was performed using the polymerase chain reaction (PCR) method. Finally, the data obtained were analyzed by statistical software. Results We found an increased frequency of the IL-1Ra 1/1 genotype in the case group compared to the control group. Whereas, the frequency of IL-1Ra genotype 1/2 was higher in control group than in the case group. However, we did not observe an association between IL-1Ra 86 bp VNTR polymorphism in intron 2 and RPL patients (p > 0.05). Conclusion IL-1Ra VNTR polymorphism may not be a genetic factor for RPL. However, investigation of IL-1Ra polymorphism was recommended in other populations and patients with recurrent pregnancy loss.

[Research progress of molecular genetic analysis in Schistosoma variation].

PubMed

Zheng, Su-Yue; Li, Fei

2014-02-01

The development of molecular biology techniques makes important contributions to the researches of heritable variation of Schistosoma. In recent years, the molecular genetic analysis in the Schistosoma variation researches mainly includes the restriction fragment length polymorphism (RFLP), random amplified polymorphism technology (RAPD), microsatellite anchored PCR (SSR-PCR), and polymerase reaction single-strand conformation polymorphism (PCR-SSCP). This article reviews the research progress of molecular genetic analysis in Schistosoma variation in recent years.

Thelytokous parthenogenesis, male clonality and genetic caste determination in the little fire ant: new evidence and insights from the lab.

PubMed

Foucaud, J; Estoup, A; Loiseau, A; Rey, O; Orivel, J

2010-08-01

Previous studies indicate that some populations of the little fire ant, Wasmannia auropunctata, display an unusual reproduction system polymorphism. Although some populations have a classical haplodiploid reproduction system, in other populations queens are produced by thelytokous parthenogenesis, males are produced by a male clonality system and workers are produced sexually. An atypical genetic caste determination system was also suggested. However, these conclusions were indirectly inferred from genetic studies on field population samples. Here we set up experimental laboratory nests that allow the control of the parental relationships between individuals. The queens heading those nests originated from either putatively clonal or sexual populations. We characterized the male, queen and worker offspring they produced at 12 microsatellite loci. Our results unambiguously confirm the unique reproduction system polymorphism mentioned above and that male clonality is strictly associated with thelytokous parthenogenesis. We also observed direct evidence of the rare production of sexual gynes and arrhenotokous males in clonal populations. Finally, we obtained evidence of a genetic basis for caste determination. The evolutionary significance of the reproduction system polymorphism and genetic caste determination as well as future research opportunities are discussed.

Using specific length amplified fragment sequencing to construct the high-density genetic map for Vitis (Vitis vinifera L. × Vitis amurensis Rupr.)

PubMed Central

Guo, Yinshan; Shi, Guangli; Liu, Zhendong; Zhao, Yuhui; Yang, Xiaoxu; Zhu, Junchi; Li, Kun; Guo, Xiuwu

2015-01-01

In this study, 149 F1 plants from the interspecific cross between ‘Red Globe’ (Vitis vinifera L.) and ‘Shuangyou’ (Vitis amurensis Rupr.) and the parent were used to construct a molecular genetic linkage map by using the specific length amplified fragment sequencing technique. DNA sequencing generated 41.282 Gb data consisting of 206,411,693 paired-end reads. The average sequencing depths were 68.35 for ‘Red Globe,’ 63.65 for ‘Shuangyou,’ and 8.01 for each progeny. In all, 115,629 high-quality specific length amplified fragments were detected, of which 42,279 were polymorphic. The genetic map was constructed using 7,199 of these polymorphic markers. These polymorphic markers were assigned to 19 linkage groups; the total length of the map was 1929.13 cm, with an average distance of 0.28 cm between each maker. To our knowledge, the genetic maps constructed in this study contain the largest number of molecular markers. These high-density genetic maps might form the basis for the fine quantitative trait loci mapping and molecular-assisted breeding of grape. PMID:26089826

Role of gene polymorphisms in gastric cancer and its precursor lesions: Current knowledge and perspectives in Latin American countries

PubMed Central

Chiurillo, Miguel Angel

2014-01-01

Latin America shows one of the highest incidence rates of gastric cancer in the world, with variations in mortality rates among nations or even within countries belonging to this region. Gastric cancer is the result of a multifactorial complex process, for which a multistep model of carcinogenesis is currently accepted. Additionally to the infection with Helicobacter pylori, that plays a major role, environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process. The differences in population origin, demographic structure, socio-economic development, and the impact of globalization lifestyles experienced in Latin America in the last decades, all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer. The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world. A total of 40 genes or genomic regions and 69 genetic variants, 58% representing markers involved in inflammatory response, have been used in a number of studies in which predominates a low number of individuals (cases and controls) included. Polymorphisms of IL-1B (-511 C/T, 14 studies; -31 T/C, 10 studies) and IL-1RN (variable number of tandem repeats, 17 studies) are the most represented ones in the reviewed studies. Other genetic variants recently evaluated in large meta-analyses and associated with gastric cancer risk were also analyzed in a few studies [e.g., prostate stem cell antigen (PSCA), CDH1, Survivin]. Further and better analysis centered in gene polymorphisms linked to other covariates, epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to develop appropriate health programs in Latin America. PMID:24782603

Is There a Genetic Predisposition to Anterior Cruciate Ligament Tear? A Systematic Review.

PubMed

John, Rakesh; Dhillon, Mandeep Singh; Sharma, Siddhartha; Prabhakar, Sharad; Bhandari, Mohit

2016-12-01

Injuries to the anterior cruciate ligament (ACL) are among the most common knee ligament injuries and frequently warrant reconstruction. The etiopathogenesis of these injuries has focused mainly on mechanism of trauma, patient sex, and anatomic factors as predisposing causes. Several genetic factors that could predispose to an ACL tear have recently been reported. This systematic review summarizes the current evidence for a genetic predisposition to ACL tears. The principal research question was to identify genetic factors, based on the available literature, that could predispose an individual to an ACL tear. Systematic review. The PubMed, EMBASE, Cochrane, and HuGE databases were searched; the search was run from the period of inception until June 21, 2015. A secondary search was performed by screening the references of full-text articles obtained and by manually searching selected journals. Articles were screened with prespecified inclusion criteria. The quality of studies included in the review was assessed for risk of bias by 2 reviewers using the Newcastle-Ottawa Scale. A total of 994 records were identified by the search, out of which 17 studies (16 case-control studies and 1 cross-sectional study) were included in the final review. Two studies observed a familial predisposition to an ACL tear. Fourteen studies looked at specific gene polymorphisms in 20 genes, from which different polymorphisms in 10 genes were positively associated with an ACL tear. In addition to these polymorphisms, 8 haplotypes were associated with ACL tear. One study looked at gene expression analysis. Although specific gene polymorphisms and haplotypes have been identified, it is difficult to come to a conclusion on the basis of the existing literature. Several sources of bias have been identified in these studies, and the results cannot be extrapolated to the general population. More studies are needed in larger populations of different ethnicities. Gene-gene interactions and gene expression studies in the future may delineate the exact role of these gene polymorphisms in ACL tears. © 2016 The Author(s).

Effects of BDNF polymorphisms on antidepressant action.

PubMed

Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic effects on specific depressive symptom-clusters.

Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (review).

PubMed

Kobayashi, Hiroshi; Imanaka, Shogo; Nakamura, Haruki; Tsuji, Ayumi

2014-05-01

Endometriosis is a complex disease influenced by genetic, epigenetic and environmental factors. The aim of the present study was to describe genomic instability, genetic polymorphisms and their haplotype, epigenetic alterations associated with predisposition to endometriosis, and the key factors associated with endometriosis-related ovarian neoplasms. Focus has been given on the developing paradigm that epigenetic alterations or genetic mutations in endometriosis may start in utero or in adolescent and young adults. A search was conducted between 1966 and 2010 through the English language literature (online Medline PubMed database) using the keywords endometriosis combined with epigenetic, genetic and environment. Genetic/epigenetic alterations include single‑nucleotide polymorphisms (SNPs), copy number variation, loss of heterozygosity (LOH), and promoter methylation. Several genes with genetic polymorphisms analyzed in the present study tended to overlap previously reported endometriosis susceptibility genes. Retrograde menstruation leads to iron overload, which facilitates the accumulation of somatic mutations through Fenton reaction-mediated oxidative stress. The epigenetic disruption of gene expression plays an important role in the development of endometriosis through interaction with environmental changes. There seems to be at least three spatiotemporally distinct phases of the development of endometriosis: the initial phase of genetic background inherited from parents; followed by epigenetic modifications in the female offspring; and iron overload, which is subject to dynamic modulation later in life. In conclusion, the marked regulation of endometriosis susceptibility genes may stem from a mechanism responsible for epigenetic and genetic mutations based on the microenvironmental changes.

Study of the S427G polymorphism and of MYBL2 variants in patients with acute myeloid leukemia.

PubMed

Dolz, Sandra; García, Paloma; Llop, Marta; Fuster, Óscar; Luna, Irene; Ibáñez, Mariam; Gómez, Inés; López, María; Such, Esperanza; Cervera, José; Sanz, Miguel A; De Juan, Inmaculada; Palanca, Sarai; Murria, Rosa; Bolufer, Pascual; Barragán, Eva

2015-06-19

Dysregulation of MYBL2 has been associated to tumorigenesis and the S427G polymorphism could induce partial inactivation of MYBL2, associating it with cancer risk. It has previously been shown that MYBL2 was over-expressed in some acute myeloid leukemias (AML), portending poor prognosis. However, to date no studies have investigated the S427G or other genetic variants of MYBL2 in AML. This study analyzed the S427G in 197 AML patients and 179 controls and screened the MYBL2 sequence in patients. In contrast to other studies in solid tumors, the S427G was not associated with the incidence of AML. This study detected four unannotated genetic alterations, of which the Q67X could be involved in MYBL2 dysfunction. Eight polymorphisms were identified, among which the rs73116571, located in a splicing region, was associated with higher incidence in AML and weaker MYBL2 expression, suggesting pre-disposition to AML. Additional functional studies should be performed to verify these genetic variations as possible targets in AML.

[Genetic diversity and genetic structure of endangered wild Sinopodophyllum emodi by start codon targeted polymorphism].

PubMed

Chen, Da-Xia; Zhao, Ji-Feng; Liu, Xiang; Wang, Chang-Hua; Zhang, Zhi-Wei; Qin, Song-Yun; Zhong, Guo-Yue

2013-01-01

Revealed the genetic diversity level and genetic structure characteristics in Sinopodophyllum emodi, a rare and endangered species in China. We detected the genetic polymorphism within and among six wild populations (45 individuals) by the approach of Start Codon Targeted (SCoT) Polymorphism. The associated genetic parameters were calculated by POP-GENE1.31 and the relationship was constructed based on UPGMA method. A total of 350 bands were scored by 27 primers and 284 bands of them were polymorphic. The average polymorphic bands of each primer were 10.52. At species level, there was a high level of genetic diversity among six populations (PPB = 79.27%, N(e) = 1.332 7, H = 0.210 9 and H(sp) = 0.328 6). At population level, the genetic diversity level was low (PPB = 10.48% (4.00% -23.71%), N(e) = 1.048 7 (1.020 7-1.103 7), H = 0.029 7 (0.012 9-0.063 1), H(pop) = 0.046 2 (0.019 9-0.098 6). The Nei's coefficient of genetic differentiation was 0.841 1, which was consistent with the Shannon's coefficient of genetic differentiation (0.849 4). Two calculated methods all showed that most of the genetic variation existed among populations. The gene flow (N(m) = 0.094 4) was less among populations, indicating that the degree of genetic differentiation was higher. Genetic similarity coefficient were changed from 0.570 8 to 0.978 7. By clustering analysis, the tested populations were divided into two classes and had a tendency that the same geographical origin or material of similar habitats clustered into one group. The genetic diversity of samples of S. emodi is high,which laid a certain foundation for effective protection and improvement of germplasm resources.

Genetic and environmental factors in human osteoporosis.

PubMed

Özbaş, Halil; Tutgun Onrat, Serap; Özdamar, Kazım

2012-12-01

Osteoporosis is a common disorder, with prolongation of the average life span it has become a major public health problem. On the formation of osteoporosis genetic factors and environmental influences could play a role then it is considered as multi-factorial. Because a variety of functions to affect susceptibility to the formation of osteoporosis VDR-F, VDR-B, COL1A1, ESR1X, ESR1P and CTR are thought to be candidate genes. In this study, the aim is to investigate the relationship between these genes polymorphism and bone mineral density (BMD) values of lumbar vertebra and femoral neck in 188 Turkish people. Lumbar spine and femoral neck BMD of the individuals included in the study were measured by the dual X-ray absorptiometry method. The genotyped polymorphisms by simultaneous amplification of five regions of the genome, containing six SNPs of interest and detecting the amplified product, using the kit MetaBone Clinical Arrays(®). Statistical analyses indicated that; VDR-B gene polymorphisms major (P = 0.013), VDR-F polymorphisms have minor (P = 0.082) effect on femur BMD. None of the other genes has any significant effect on spinal BMD. Patient age, body mass index and diet has significant effect on femoral and spinal BMD. Osteoporosis is a multi-factorial disease and many genetic and non-genetic risk factors contribute to the development of osteoporosis. Early detection of a genetic predisposition to osteoporosis should allow delay and/or limit unfavorable changes in the bone tissue.

Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis

PubMed Central

Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R.; Parelkar, Nikhil K.; Jokar, Iman; Vielhauer, George A.; Neufeld, Kristi L.

2014-01-01

Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies. PMID:24913681

Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder

PubMed Central

Kitzlerová, Eva; Lelková, Petra; Jirák, Roman; Zvěřová, Martina; Hroudová, Jana; Manukyan, Ada; Martásek, Pavel; Raboch, Jiří

2018-01-01

Background Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer’s disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and high-risk groups. We tested for the contribution of interactions between multiple functional polymorphisms in the risk of MDD or AD. Material/Methods A genetic association case-control study was performed in 68 MDD cases, 84 AD cases (35 of them with comorbid depression), and 90 controls. The contribution of 7 polymorphisms from 5 genes (APOE, HSPA1A, SLC6A4, HTR2A, and BDNF) related to risk of MDD or AD development was analyzed. Results Significant associations were found between MDD and interactions among polymorphisms in HSPA1A, SLC6A4, and BDNF or HSPA1A, BDNF, and APOE genes. For polymorphisms in the APOE gene in AD, significant differences were confirmed on the distributions of alleles and genotype rates compared to the control or MDD. Increased probability of comorbid depression was found in patients with AD who do not carry the ɛ4 allele of APOE. Conclusions Assessment of the interactions among polymorphisms of susceptibility loci in both MDD and AD confirmed a synergistic effect of genetic factors influencing inflammatory, serotonergic, and neurotrophic pathways at these heterogenous complex diseases. The effect of interactions was greater in MDD than in AD. A presence of the ɛ4 allele was confirmed as a genetic susceptibility factor in AD. Our findings indicate a role of APOE genotype in onset of comorbid depression in a subgroup of patients with AD who are not carriers of the APOE ɛ4 allele. PMID:29703883

Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

PubMed

Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

2017-10-01

The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Detecting a hierarchical genetic population structure via Multi-InDel markers on the X chromosome

PubMed Central

Fan, Guang Yao; Ye, Yi; Hou, Yi Ping

2016-01-01

Detecting population structure and estimating individual biogeographical ancestry are very important in population genetics studies, biomedical research and forensics. Single-nucleotide polymorphism (SNP) has long been considered to be a primary ancestry-informative marker (AIM), but it is constrained by complex and time-consuming genotyping protocols. Following up on our previous study, we propose that a multi-insertion-deletion polymorphism (Multi-InDel) with multiple haplotypes can be useful in ancestry inference and hierarchical genetic population structures. A validation study for the X chromosome Multi-InDel marker (X-Multi-InDel) as a novel AIM was conducted. Genetic polymorphisms and genetic distances among three Chinese populations and 14 worldwide populations obtained from the 1000 Genomes database were analyzed. A Bayesian clustering method (STRUCTURE) was used to discern the continental origins of Europe, East Asia, and Africa. A minimal panel of ten X-Multi-InDels was verified to be sufficient to distinguish human ancestries from three major continental regions with nearly the same efficiency of the earlier panel with 21 insertion-deletion AIMs. Along with the development of more X-Multi-InDels, an approach using this novel marker has the potential for broad applicability as a cost-effective tool toward more accurate determinations of individual biogeographical ancestry and population stratification. PMID:27535707

Genetic diversity, linkage disequilibrium, and association mapping analyses of gossypium barbadense l. germplasm and cultivars

USDA-ARS?s Scientific Manuscript database

Limited polymorphism and narrow genetic base, due to genetic bottleneck through historic domestication, highlight a need for comprehensive characterization and utilization of existing genetic diversity in cotton germplasm collections. In this study, 288 worldwide Gossypium barbadense L. cotton germ...

Evaluation of genetic diversity in jackfruit (Artocarpus heterophyllus Lam.) based on amplified fragment length polymorphism markers.

PubMed

Shyamalamma, S; Chandra, S B C; Hegde, M; Naryanswamy, P

2008-07-22

Artocarpus heterophyllus Lam., commonly called jackfruit, is a medium-sized evergreen tree that bears high yields of the largest known edible fruit. Yet, it has been little explored commercially due to wide variation in fruit quality. The genetic diversity and genetic relatedness of 50 jackfruit accessions were studied using amplified fragment length polymorphism markers. Of 16 primer pairs evaluated, eight were selected for screening of genotypes based on the number and quality of polymorphic fragments produced. These primer combinations produced 5976 bands, 1267 (22%) of which were polymorphic. Among the jackfruit accessions, the similarity coefficient ranged from 0.137 to 0.978; the accessions also shared a large number of monomorphic fragments (78%). Cluster analysis and principal component analysis grouped all jackfruit genotypes into three major clusters. Cluster I included the genotypes grown in a jackfruit region of Karnataka, called Tamaka, with very dry conditions; cluster II contained the genotypes collected from locations having medium to heavy rainfall in Karnataka; cluster III grouped the genotypes in distant locations with different environmental conditions. Strong coincidence of these amplified fragment length polymorphism-based groupings with geographical localities as well as morphological characters was observed. We found moderate genetic diversity in these jackfruit accessions. This information should be useful for tree breeding programs, as part of our effort to popularize jackfruit as a commercial crop.

IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

PubMed Central

Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

2016-01-01

Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers. PMID:27019828

Vision Issues and Space Flight: Evaluation of One-Carbon Metabolism Polymorphisms

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Gregory, Jesse F.; Zeisel, Steven; Ueland, Per; Gibson, C. R.; Mader, Thomas; Kinchen, Jason; Ploutz-Snyder, Robert; Zwart, Sara R.

2015-01-01

Intermediates of the one-carbon metabolic pathway are altered in astronauts who experience vision-related issues during and after space flight. Serum concentrations of homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were higher in astronauts with ophthalmic changes than in those without (Zwart et al., J Nutr, 2012). These differences existed before, during, and after flight. Potential confounding factors did not explain the differences. Genetic polymorphisms could contribute to these differences, and could help explain why crewmembers on the same mission do not all have ophthalmic issues, despite the same environmental factors (e.g., microgravity, exercise, diet). A follow-up study was conducted to evaluate 5 polymorphisms of enzymes in the one-carbon pathway, and to evaluate how these relate to vision and other ophthalmic changes after flight. Preliminary evaluations of the genetic data indicate that all of the crewmembers with the MTRR GG genotype had vision issues to one degree or another. However, not everyone who had vision issues had this genetic polymorphism, so the situation is more complex than the involvement of this single polymorphism. Metabolomic and further data analyses are underway to clarify these findings, but the preliminary assessments are promising.

Using Massive Parallel Sequencing for the Development, Validation, and Application of Population Genetics Markers in the Invasive Bivalve Zebra Mussel (Dreissena polymorpha)

PubMed Central

Peñarrubia, Luis; Sanz, Nuria; Pla, Carles; Vidal, Oriol; Viñas, Jordi

2015-01-01

The zebra mussel (Dreissena polymorpha, Pallas, 1771) is one of the most invasive species of freshwater bivalves, due to a combination of biological and anthropogenic factors. Once this species has been introduced to a new area, individuals form dense aggregations that are very difficult to remove, leading to many adverse socioeconomic and ecological consequences. In this study, we identified, tested, and validated a new set of polymorphic microsatellite loci (also known as SSRs, Single Sequence Repeats) using a Massive Parallel Sequencing (MPS) platform. After several pruning steps, 93 SSRs could potentially be amplified. Out of these SSRs, 14 were polymorphic, producing a polymorphic yield of 15.05%. These 14 polymorphic microsatellites were fully validated in a first approximation of the genetic population structure of D. polymorpha in the Iberian Peninsula. Based on this polymorphic yield, we propose a criterion for establishing the number of SSRs that require validation in similar species, depending on the final use of the markers. These results could be used to optimize MPS approaches in the development of microsatellites as genetic markers, which would reduce the cost of this process. PMID:25780924

The influence of PRNP polymorphisms on human prion disease susceptibility: an update.

PubMed

Kobayashi, Atsushi; Teruya, Kenta; Matsuura, Yuichi; Shirai, Tsuyoshi; Nakamura, Yoshikazu; Yamada, Masahito; Mizusawa, Hidehiro; Mohri, Shirou; Kitamoto, Tetsuyuki

2015-08-01

Two normally occurring polymorphisms of the human PRNP gene, methionine (M)/valine (V) at codon 129 and glutamic acid (E)/lysine (K) at codon 219, can affect the susceptibility to prion diseases. It has long been recognized that 129M/M homozygotes are overrepresented in sporadic Creutzfeldt-Jakob disease (CJD) patients and variant CJD patients, whereas 219E/K heterozygotes are absent in sporadic CJD patients. In addition to these pioneering findings, recent progress in experimental transmission studies and worldwide surveillance of prion diseases have identified novel relationships between the PRNP polymorphisms and the prion disease susceptibility. For example, although 219E/K heterozygosity confers resistance against the development of sporadic CJD, this genotype is not entirely protective against acquired forms (iatrogenic CJD and variant CJD) or genetic forms (genetic CJD and Gerstmann-Sträussler-Scheinker syndrome) of prion diseases. In addition, 129M/V heterozygotes predispose to genetic CJD caused by a pathogenic PRNP mutation at codon 180. These findings show that the effects of the PRNP polymorphisms may be more complicated than previously thought. This review aims to summarize recent advances in our knowledge about the influence of the PRNP polymorphisms on the prion disease susceptibility.

Genetic Architecture of Hybrid Male Sterility in Drosophila: Analysis of Intraspecies Variation for Interspecies Isolation

PubMed Central

Reed, Laura K.; LaFlamme, Brooke A.; Markow, Therese A.

2008-01-01

Background The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. Methodology/Principal Findings Isofemale strains of D. mojavensis vary significantly in their production of sterile F1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL) mapping analyses directly on F1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS) in the F1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. Conclusions/Significance The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation. PMID:18728782

Population genetic structure of rare and endangered plants using molecular markers

USGS Publications Warehouse

Raji, Jennifer; Atkinson, Carter T.

2013-01-01

This study was initiated to assess the levels of genetic diversity and differentiation in the remaining populations of Phyllostegia stachyoides and Melicope zahlbruckneri in Hawai`i Volcanoes National Park and determine the extent of gene flow to identify genetically distinct individuals or groups for conservation purposes. Thirty-six Amplified Fragment Length Polymorphic (AFLP) primer combinations generated a total of 3,242 polymorphic deoxyribonucleic acid (DNA) fragments in the P. stachyoides population with a percentage of polymorphic bands (PPB) ranging from 39.3 to 65.7% and 2,780 for the M. zahlbruckneri population with a PPB of 18.8 to 64.6%. Population differentiation (Fst) of AFLP loci between subpopulations of P. stachyoides was low (0.043) across populations. Analysis of molecular variance of P. stachyoides showed that 4% of the observed genetic differentiation occurred between populations in different kīpuka and 96% when individuals were pooled from all kīpuka. Moderate genetic diversity was detected within the M. zahlbruckneri population. Bayesian and multivariate analyses both classified the P. stachyoides and M. zahlbruckneri populations into genetic groups with considerable sub-structuring detected in the P. stachyoides population. The proportion of genetic differentiation among populations explained by geographical distance was estimated by Mantel tests. No spatial correlation was found between genetic and geographic distances in both populations. Finally, a moderate but significant gene flow that could be attributed to insect or bird-mediated dispersal of pollen across the different kīpuka was observed. The results of this study highlight the utility of a multi-allelic DNA-based marker in screening a large number of polymorphic loci in small and closely related endangered populations and revealed the presence of genetically unique groups of individuals in both M. zahlbruckneri and P. stachyoides populations. Based on these findings, approaches that can assist conservation efforts of these species are proposed. 

Determination of genetic diversity among Saccharina germplasm using ISSR and RAPD markers.

PubMed

Cui, Cuiju; Li, Yan; Liu, Yanling; Li, Xiaojie; Luo, Shiju; Zhang, Zhuangzhi; Wu, Ruina; Liang, Guangjin; Sun, Juan; Peng, Jie; Tian, Pingping

2017-02-01

Various species of genus Saccharina are economically important brown macroalgae cultivated in China. The genetic background of the conserved Saccharina germplasm was not clear. In this report, DNA-based molecular markers such as inter simple sequence repeats (ISSR) and random amplified polymorphic DNA (RAPD) were used to assess the genetic diversity and phylogenetic relationships among 48 Saccharina germplasms. A total of 50 ISSR and 50 RAPD primers were tested, of which only 33 polymorphic primers (17 ISSR and 16 RAPD) had an amplified clear and reproducible profile, and could be used. Seventeen ISSR primers yielded a total of 262 bands, of which 256 were polymorphic, and 15.06 polymorphic bands per primer were amplified from 48 kelp gametophytes. Sixteen RAPD primers produced 355 bands, of which 352 were polymorphic, and 22 polymorphic bands per primer were observed across 48 individuals. The simple matching coefficient of ISSR, RAPD and pooled ISSR and RAPD dendrograms ranged from 0.568 to 0.885, 0.670 to 0.873, and 0.667 to 0.862, revealing high genetic diversity. Based on the unweighted pair group method with the arithmetic averaging algorithm (UPGMA) cluster analysis and the principal components analysis (PCA) of ISSR data, the 48 gametophytes were divided into three main groups. The Mantel test revealed a similar polymorphism distribution pattern between ISSR and RAPD markers, the correlation coefficient r was 0.62, and the results indicated that both ISSR and RAPD markers were effective to assess the selected gametophytes, while matrix correlation of the ISSR marker system (r=0.78) was better than that of the RAPD marker system (r=0.64). Genetic analysis data from this study were helpful in understanding the genetic relationships among the selected 17 kelp varieties (or lines) and provided guidance for molecular-assisted selection for parental gametophytes of hybrid kelp breeding. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes.

PubMed

Henkhaus, Rebecca S; Bittel, Douglas C; Butler, Merlin G

2010-09-01

Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process.

5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.

PubMed

Kim, Dai-Jin; Park, Byung Lae; Yoon, Sujung; Lee, Hae-Kook; Joe, Keun-Ho; Cheon, Young-Hoon; Gwon, Do-Hoon; Cho, Sung-Nam; Lee, Hye Won; NamGung, Suk; Shin, Hyoung Doo

2007-06-15

Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.

Molecular identification and genetic variation of varieties of Styphnolobium japonicum (Fabaceae) using SRAP markers.

PubMed

Sun, R X; Zhang, C H; Zheng, Y Q; Zong, Y C; Yu, X D; Huang, P

2016-05-06

Thirty-four Styphnolobium japonicum varieties were analyzed using sequence-related amplified polymorphism (SRAP) markers, to investigate genetic variation and test the effectiveness of SRAP markers in DNA fingerprint establishment. Twelve primer pairs were selected from 120 primer combinations for their reproducibility and high polymorphism. We found a total of 430 amplified fragments, of which 415 fragments were considered polymorphic with an average of 34.58 polymorphic fragments for each primer combination. The percentage of polymorphic fragments was 96.60%, and four primer pairs showed 100% polymorphism. Moreover, simple matched coefficients ranged between 0.68 and 0.89, with an average of 0.785, indicating that the genetic variation among varieties was relatively low. This could be because of the narrow genetic basis of the selected breeding material. Based on the similarity coefficient value of 0.76, the varieties were divided into four major groups. In addition, abundant and clear SRAP fingerprints were obtained and could be used to establish DNA fingerprints. In the DNA fingerprints, each variety had its unique pattern that could be easily distinguished from others. The results demonstrated that 34 varieties of S. japonicum had a relatively narrow genetic variation. Hence, a broadening of the genetic basis of breeding material is necessary. We conclude that establishment of DNA fingerprint is feasible by means of SRAP markers.

Phytomonas: analysis of polymorphism and genetic relatedness between isolates from plants and phytophagous insects from different geographic regions by RAPD fingerprints and synapomorphic markers.

PubMed

Serrano, M G; Camargo, E P; Teixeira, M M

1999-01-01

The random amplification of polymorphic DNA was used for easy, quick and sensitive assessment of genetic polymorphism within Phytomonas to discriminate isolates and determine genetic relationships within the genus. We examined 48 Phytomonas spp., 31 isolates from plants and 17 from insects, from different geographic regions. Topology of the dendrogram based on randomly amplified polymorphic DNA fingerprints segregated the Phytomonas spp. into 5 main clusters, despite the high genetic variability within this genus. Similar clustering could also be obtained by both visual and cross-hybridization analysis of randomly amplified synapomorphic DNA fragments. There was some concordance between the genetic relationship of isolates and their plant tissue tropism. Moreover, Phytomonas spp. from plants and insects were grouped according to geographic origin, thus revealing a complex structure of this taxon comprising several clusters of very closely related organisms.

Effect of genetic polymorphisms on development of gout.

PubMed

Urano, Wako; Taniguchi, Atsuo; Inoue, Eisuke; Sekita, Chieko; Ichikawa, Naomi; Koseki, Yumi; Kamatani, Naoyuki; Yamanaka, Hisashi

2013-08-01

To validate the association between genetic polymorphisms and gout in Japanese patients, and to investigate the cumulative effects of multiple genetic factors on the development of gout. Subjects were 153 Japanese male patients with gout and 532 male controls. The genotypes of 11 polymorphisms in the 10 genes that have been indicated to be associated with serum uric acid levels or gout were determined. The cumulative effects of the genetic polymorphisms were investigated using a weighted genotype risk score (wGRS) based on the number of risk alleles and the OR for gout. A model to discriminate between patients with gout and controls was constructed by incorporating the wGRS and clinical factors. C statistics method was applied to evaluate the capability of the model to discriminate gout patients from controls. Seven polymorphisms were shown to be associated with gout. The mean wGRS was significantly higher in patients with gout (15.2 ± 2.01) compared to controls (13.4 ± 2.10; p < 0.0001). The C statistic for the model using genetic information alone was 0.72, while the C statistic was 0.81 for the full model that incorporated all genetic and clinical factors. Accumulation of multiple genetic factors is associated with the development of gout. A prediction model for gout that incorporates genetic and clinical factors may be useful for identifying individuals who are at risk of gout.

Genetic variants in oxytocin receptor gene (OXTR) and childhood physical abuse collaborate to modify the risk of aggression in chinese adolescents.

PubMed

Zhang, Yanmei; Wu, Chunxia; Chang, Hongjuan; Yan, Qiuge; Wu, Linguo; Yuan, Shanshan; Xiang, Jingjing; Hao, Wen; Yu, Yizhen

2018-03-15

Accumulating evidence suggests that genetic and environmental factors may influence aggression susceptibility. However, the etiology of aggressive behavior remains unknown. Compared to some extensively studied candidate genes of aggression, very little is known about the OXTR gene. The objective of this study was to determine whether OXTR genetic variants were associated with aggression risk and whether these polymorphisms showed interactive effects with childhood maltreatment on aggression in Chinese adolescents. A total of 996 participants including 488 cases and 488 controls were selected in our study. Aggression, childhood maltreatment were measured by self-reported questionnaire. Buccal cells were collected. Genotyping was performed using SNPscan. Logistic regressions were used to estimate both main effects of OXTR polymorphisms and the interactive effects with childhood maltreatment on aggressive behavior. Participants who carried the rs237885 TT genotypes in OXTR had a higher risk of aggression compared to those who carried GG or GT genotypes under the recessive model (OR=1.40, 95% CI, 1.04-1.89) after controlling for potential confounders. In addition, we also found that the polymorphism had a synergic additive interaction with childhood physical abuse on the aggression risk. The subjects in the present study were only males, thus our findings and conclusions could not be generalized to females. The present study provides evidence that OXTR genetic variants may contribute to aggression susceptibility. Moreover, this is the first study reporting significant interactive effects of OXTR polymorphism and childhood physical abuse on aggressive behavior in Chinese adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Higher risk of progressing breast cancer in Kurdish population associated to CDH1 -160 C/A polymorphism

PubMed Central

Zarei, Farzaneh; Menbari, Mohammad Nazir; Ghaderi, Bayazid; Abdi, Mohammad; Vahabzadeh, Zakaria

2017-01-01

There is an increasing interest about studying possible effects of genetic polymorphisms and risk of cancer progression. E-cadherin (CDH1) involves in many important cellular processes including cell-cell interactions, cell development and genetic changes of this molecule has been associated with greater tumor metastasis. The present study was aimed to evaluate the possible role of CDH1 -160 C/A polymorphism as a potential risk factor for breast cancer in Kurdish population. This case-control study consisted of 100 breast cancer patients and 200 healthy controls. Clinicopathological findings of all individuals were reported and immunohistochemistry staining was carried out on tissue samples. The CDH1 -160 C/A genotype was determined by polymerase chain reaction- restriction fragment length polymorphism method (PCR-RFLP). CDH1 -160 C/A polymorphism was differently distributed between patient and control groups. The A allele of CDH1 -160 C/A polymorphism significantly increased in patients compared to controls. In addition we found that the A allele of this polymorphism might be a potential risk factor for progression of breast cancer in our studied population. Patients with A allele of CDH1 -160 C/A was in higher risk to progress invasive ductal carcinoma. The A allele was also correlated with high grade and stage IV and also with metastatic tumors in studied subjects. The CDH1 -160 C/A polymorphism is correlated with clinicopathologial findings of breast cancer patients. The A allele of CDH1 -160 C/A may be a risk factor for progression of breast cancer in Kurdish patients. PMID:29285016

Higher risk of progressing breast cancer in Kurdish population associated to CDH1 -160 C/A polymorphism.

PubMed

Zarei, Farzaneh; Menbari, Mohammad Nazir; Ghaderi, Bayazid; Abdi, Mohammad; Vahabzadeh, Zakaria

2017-01-01

There is an increasing interest about studying possible effects of genetic polymorphisms and risk of cancer progression. E-cadherin (CDH1) involves in many important cellular processes including cell-cell interactions, cell development and genetic changes of this molecule has been associated with greater tumor metastasis. The present study was aimed to evaluate the possible role of CDH1 -160 C/A polymorphism as a potential risk factor for breast cancer in Kurdish population. This case-control study consisted of 100 breast cancer patients and 200 healthy controls. Clinicopathological findings of all individuals were reported and immunohistochemistry staining was carried out on tissue samples. The CDH1 -160 C/A genotype was determined by polymerase chain reaction- restriction fragment length polymorphism method (PCR-RFLP). CDH1 -160 C/A polymorphism was differently distributed between patient and control groups. The A allele of CDH1 -160 C/A polymorphism significantly increased in patients compared to controls. In addition we found that the A allele of this polymorphism might be a potential risk factor for progression of breast cancer in our studied population. Patients with A allele of CDH1 -160 C/A was in higher risk to progress invasive ductal carcinoma. The A allele was also correlated with high grade and stage IV and also with metastatic tumors in studied subjects. The CDH1 -160 C/A polymorphism is correlated with clinicopathologial findings of breast cancer patients. The A allele of CDH1 -160 C/A may be a risk factor for progression of breast cancer in Kurdish patients.

[Genetic polymorphism of Gentiana lutea L. (Gentianaceae) populations from Chornohora Ridge of Ukrainian Carpathians].

PubMed

Mosula, M Z; Konvaliuk, I I; Mel'nyk, V M; Drobyk, N M; Tsaryk, I V; Nesteruk, Iu I; Kunakh, V A

2014-01-01

The features of genetic structure and level of diversity were investigated for G. lutea populations from Chornohora Ridge of Ukrainian Carpathians using RAPD- and ISSR-PCR. We have shown a high level of genetic diversity for investigated populations. The differences between populations account for 59-72% of the total genetic variation, whereas intrapopulation polymorphism makes up 28-41%. The relationships among genetic variability level and ecological-geographical conditions as well as biological features of the species were assumed to be possible. The obtained results indicate the genetic isolation of G. lutea Chornohora populations from Ukrainian Carpathians. Pozhyzhevska agropopulation was characterized by a high level of polymorphism that means the possibility to use artificial plantings of the investigated species for its conservation.

Analysis of genetic diversity of Chinese dairy goats via microsatellite markers.

PubMed

Wang, G Z; Chen, S S; Chao, T L; Ji, Z B; Hou, L; Qin, Z J; Wang, J M

2017-05-01

In this study, 15 polymorphic microsatellite markers were used to analyze the genetic structure and phylogenetic relationships of 6 dairy goat breeds in China, including 4 native developed breeds and 2 introduced breeds. The results showed that a total of 172 alleles were detected in 347 samples of the dairy goat breeds included in this study. The mean number of effective alleles per locus was 4.92. Except for BMS0812, all of the remaining microsatellite loci were highly polymorphic (polymorphism information content [PIC] > 0.5). The analysis of genetic diversity parameters, including the number of effective alleles, PIC, and heterozygosity, revealed that the native developed dairy goat breeds in China harbored a rich genetic diversity. However, these breeds showed a low breeding degree and a high population intermix degree, with a certain degree of inbreeding and within-subpopulation inbreeding coefficient ( > 0). The analysis of population genetic differentiation and phylogenetic tree topologies showed a moderate state of genetic differentiation among subpopulations of native developed breed dairy goats in China (0.05 < gene fixation coefficient [] < 0.15). The native developed breeds shared a common ancestor, namely, the Saanen dairy goat, originating from Europe. The results showed that there was a close genetic relationship between Wendeng and Laoshan dairy goats while the Guanzhong dairy goat and the Xinong Saanen dairy goat were also found to have a close genetic relationship, which were both in agreement with the formation history and geographical distribution of the breeds. This study revealed that adopting genetic management strategies, such as expanding pedigree source and strengthening multi-trait selection, is useful in maintaining the genetic diversity of native developed breeds and improving the population uniformity of dairy goats.

Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma

PubMed Central

Han, Xuesong; Zheng, Tongzhang; Lan, Qing; Zhang, Yaqun; Kilfoy, Briseis A.; Qin, Qin; Rothman, Nathaniel; Zahm, Shelia H.; Holford, Theodore R.; Leaderer, Brian; Zhang, Yawei

2010-01-01

Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histological subtype in Connecticut women including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma (DLBCL) and Follicular lymphoma (FL). Two single nucleotide polymorphisms (SNPs) in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma (FL). When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruit were examined separately, strong interaction effects were narrowed to vegetable intake among DLBCL patients. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the nitric oxide synthase genes, modify the association between vegetable and fruit intake and risk of NHL. PMID:19423521

Spatial and temporal drivers of phenotypic diversity in polymorphic snakes.

PubMed

Cox, Christian L; Davis Rabosky, Alison R

2013-08-01

Color polymorphism in natural populations presents an ideal opportunity to study the evolutionary drivers of phenotypic diversity. Systems with striking spatial, temporal, and qualitative variation in color can be leveraged to study the mechanisms promoting the distribution of different types of variation in nature. We used the highly polymorphic ground snake (Sonora semiannulata), a putative coral snake mimic with both cryptic and conspicuous morphs, to compare patterns of neutral genetic variation and variation over space and time in color polymorphism to investigate the mechanistic drivers of phenotypic variation across scales. We found that strong selection promotes color polymorphism across spatial and temporal scales, with morph frequencies differing markedly between juvenile and adult age classes within a single population, oscillating over time within multiple populations, and varying drastically over the landscape despite minimal population genetic structure. However, we found no evidence that conspicuousness of morphs was related to which color pattern was favored by selection or to any geographic factors, including sympatry with coral snakes. We suggest that complex patterns of phenotypic variation in polymorphic systems may be a fundamental outcome of the conspicuousness of morphs and that explicit tests of temporal and geographic variation are critical to the interpretation of conspicuousness and mimicry.

Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan

PubMed Central

Ting, Ke-Hsin; Ueng, Kwo-Chang; Chiang, Whei-Ling; Chou, Ying-Erh; Yang, Shun-Fa; Wang, Po-Hui

2015-01-01

The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD) in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p = 0.012). Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.176–2.921, p = 0.008). In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event. PMID:26688689

Genetic selection pressure in TLR9 gene may enforce risk for SLE in Indian Tamils.

PubMed

Yusuf, J H; Kaliyaperumal, D; Jayaraman, M; Ramanathan, G; Devaraju, P

2017-03-01

Objectives Lupus is a classical systemic autoimmune disease with genetics as one of the well known causative factors for the disease pathogenesis. Toll-like receptors are the major pattern recognition receptors associated with innate immunity and also act as an interface with the adaptive immunity. Genetic polymorphisms in genes encoding TLRs were implicated in the development of infections, malignancies and autoimmune diseases. TLR9 is a member of TLR family, and recognizes the CpG DNA motifs of pathogens. Though the incidence rate of lupus in Asians was reported to be low (30 - 50/100,000 population), poor disease prognosis due to higher incidence of renal complications and aggressive disease worsens the scenario. The ability of TLR9 to detect and elicit an immune response against double-stranded DNA makes TLR9 a relevant factor to be tested for its association with the clinical and serological phenotypes of lupus. However, lack of relevant genetic data on normative frequencies of the TLR9 (rs187084) polymorphism may serve as a constraint to derive the sample size to conduct case control association studies. Hence this study was conducted to establish the normative frequency of TLR9 (rs187084) polymorphism in Indian Tamils. Materials and methods The TLR9 (rs187084) polymorphism was screened in South Indian Tamils ( n = 208) by PCR-RFLP. Results and discussion We observed a higher occurrence of the mutant allele (65%) in South Indian Tamils. No gender disparity with respect to the mutant allele frequency was observed. The higher incidence of mutant allele in both genders suggests that this population had undergone a genetic selection pressure as an evolutionary genetic measure to withstand the prevailing endemic infections like TB and malaria. Though the enhanced expression of TLR9 was protective against infections, it may also influence the development of autoimmune diseases. Conclusion The higher incidence of theTLR9 (rs187084) over-expression mutation in Indian Tamils is suggestive of a genetic adaptation or selection pressure to withstand the prevailing endemic infectious and parasitic diseases. However, this genetic adaptation poses a greater risk to develop autoimmune diseases like SLE etc through complex gene environment interactions. The normative frequency of the TLR9 (rs187084) polymorphism established in our population could now be used to define the sample size for future case control studies.

Polygenic influences on dyslipidemias.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2018-04-01

Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants - single nucleotide polymorphisms (SNPs) - have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20-30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20-50% of susceptibility can be accounted for by this assortment of genetic variants. Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

Migraine and genetic polymorphisms: an overview.

PubMed

Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

2012-01-01

The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), β-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine.

Migraine and Genetic Polymorphisms: An Overview

PubMed Central

Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

2012-01-01

The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), β-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine. PMID:22962564

Plasminogen Activator Inhibitor-2 Polymorphism Associates with Recurrent Coronary Event Risk in Patients with High HDL and C-Reactive Protein Levels

PubMed Central

Corsetti, James P.; Salzman, Peter; Ryan, Dan; Moss, Arthur J.; Zareba, Wojciech; Sparks, Charles E.

2013-01-01

The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key actions involved in the fibrinolytic process. PMID:23874812

Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women.

PubMed

Chávez, Bertha; Vilchis, Felipe; Rojano-Mejía, David; Coral Vázquez, Ramón Mauricio; Aguirre-García, María Del Carmen; Canto, Patricia

2017-08-01

Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy-Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r 2 ). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p = 0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.

Population and allelic variation of A-to-I RNA editing in human transcriptomes.

PubMed

Park, Eddie; Guo, Jiguang; Shen, Shihao; Demirdjian, Levon; Wu, Ying Nian; Lin, Lan; Xing, Yi

2017-07-28

A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing. In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure. Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.

Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome

PubMed Central

Leppert, Tami; Anex, Deon S.; Hilmer, Jonathan K.; Matsunami, Nori; Baird, Lisa; Stevens, Jeffery; Parsawar, Krishna; Durbin-Johnson, Blythe P.; Rocke, David M.; Nelson, Chad; Fairbanks, Daniel J.; Wilson, Andrew S.; Rice, Robert H.; Woodward, Scott R.; Bothner, Brian; Hart, Bradley R.; Leppert, Mark

2016-01-01

Human identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts. PMID:27603779

RAPD and SSR Polymorphisms in Mutant Lines of Transgenic Wheat Mediated by Low Energy Ion Beam

NASA Astrophysics Data System (ADS)

Wang, Tiegu; Huang, Qunce; Feng, Weisen

2007-10-01

Two types of markers-random amplified polymorphic DNA (RAPD) and simple sequence repeat DNA (SSR)-have been used to characterize the genetic diversity among nine mutant lines of transgenic wheat intermediated by low energy ion beam and their four receptor cultivars. The objectives of this study were to analyze RAPD-based and SSR-based genetic variance among transgenic wheat lines and with their receptors, and to find specific genetic markers of special traits of transgenic wheat lines. 170 RAPD primers were amplified to 733 fragments in all the experimental materials. There were 121 polymorphic fragments out of the 733 fragments with a ratio of polymorphic fragments of 16.5%. 29 SSR primer pairs were amplified to 83 fragments in all the experiment materials. There were 57 polymorphic fragments out of the 83 fragments with a ratio of polymorphic fragments of 68.7%. The dendrograms were prepared based on a genetic distance matrix using the UPGMA (Unweighted Pair-group Method with Arithmetic averaging) algorithm, which corresponded well to the results of the wheat pedigree analysis and separated the 13 genotypes into four groups. Association analysis between RAPD and SSR markers with the special traits of transgenic wheat mutant lines discovered that three RAPD markers, s1, opt-16, and f14, were significantly associated with the muticate trait, while three SSR markers, Rht8 (Xgwm261), Rht-B1b, and Rht-D1b, highly associated with the dwarf trait. These markers will be useful for marker-assistant breeding and can be used as candidate markers for further gene mapping and cloning.

Microsatellite markers for Leucobryum boninense (Leucobryaceae), endemic to the Bonin Islands, Japan1

PubMed Central

Oguri, Emiko; Yamaguchi, Tomio; Kajita, Tadashi; Murakami, Noriaki

2013-01-01

• Premise of the study: Microsatellite primers were developed for Leucobryum boninense, endemic to the Bonin Islands, Japan, to investigate its level of genetic diversity and population genetic structure. • Methods and Results: Using next-generation sequencing, 21 primer sets were developed, among which nine loci were polymorphic in the populations of the Bonin Islands. Among these polymorphic loci, the number of alleles per locus ranged from two to 10 (mean = 3.444) and the expected heterozygosity ranged from 0.066 to 0.801 (mean = 0.338). • Conclusions: These results indicate the utility of the nine microsatellite markers that we developed for population genetic studies of L. boninense. PMID:25202543

Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8 and the Risk of Respiratory Infections and Acute Otitis Media in Children.

PubMed

Toivonen, Laura; Vuononvirta, Juho; Mertsola, Jussi; Waris, Matti; He, Qiushui; Peltola, Ville

2017-05-01

Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu. Children were followed up for respiratory infections until 24 months of age with daily diaries. Polymerase chain reaction and antigen tests were used for detection of respiratory viruses from nasal swabs. Children with MBL variant genotype had a mean of 59 days with symptoms of respiratory infection per year, compared with 49 days in those with wild-type (P = 0.01). TLR8 polymorphisms were associated with an increased risk and TLR7 polymorphisms with a decreased risk of recurrent rhinovirus infections (P = 0.02 for both). TLR2 polymorphisms were associated with recurrent acute otitis media (P = 0.02). MBL polymorphisms were associated with an increased and TLR7 polymorphisms with a decreased risk of rhinovirus-associated acute otitis media (P = 0.03 and P = 0.006, respectively). Genetic polymorphisms in MBL and TLRs promote susceptibility to or protection against respiratory infections. In addition to environmental factors, genetic variations may explain why some children are more prone to respiratory infections.

Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

PubMed

Bae, Joon Seol; Kim, Jason Yongha; Park, Byung-Lae; Kim, Jeong-Hyun; Kim, Bomi; Park, Chul Soo; Kim, Bong-Jo; Lee, Cheol-Soon; Lee, Migyung; Choi, Woo Hyuk; Shin, Tae-Min; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

2014-10-01

Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

Genetic polymorphism of inosine-triphosphate-pyrophosphatase influences mercaptopurine metabolism and toxicity during treatment of acute lymphoblastic leukemia individualized for thiopurine-S-methyl-transferase status.

PubMed

Stocco, Gabriele; Crews, Kristine R; Evans, William E

2010-01-01

Although genetic polymorphisms in the gene encoding human thiopurine methyltransferase (TPMT) are known to have a marked effect on mercaptopurine metabolism and toxicity, there are many patients with wild-type TPMT who develop toxicity. Furthermore, when mercaptopurine dosages are adjusted in patients who are heterozygous at the TPMT locus, there are still some patients who develop toxicity for reasons that are not fully understood. Therefore, we recently studied the effects of a common polymorphism in another gene encoding an enzyme involved in mercaptopurine metabolism (SNP rs1127354 in inosine-triphospate-pyrophosphatase, ITPA), showing that genetic polymorphism of ITPA is a significant determinant of mercaptopurine metabolism and of febrile neutropenia following combination chemotherapy of acute lymphoblastic leukemia (ALL) in which mercaptopurine doses are individualized based on TPMT genotype. In this review, we summarize the knowledge available about the effect and clinical relevance of TPMT and ITPA on mercaptopurine pharmacogenomics, with a particular focus on the use of this medication in pediatric patients with ALL. Reader will gain insights into: i) the effects of pharmacogenomic traits on mercaptopurine toxicity and efficacy for the treatment of ALL and ii) individualization strategies that can be used to mitigate toxicity without compromising efficacy in pediatric patients with ALL. Mercaptopurine dose can be adjusted on the basis of TPMT genotype to mitigate toxicity in pediatric patients with ALL. As treatment is individualized in this way for the most relevant genetic determinant of drug response (i.e., for mercaptopurine, TPMT), the importance of other genetic polymorphisms emerges (e.g., ITPA).

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

2015-12-28

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.

Genetic predisposition toward suicidal ideation in patients with acute coronary syndrome.

PubMed

Kang, Hee-Ju; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Hong, Young Joon; Ahn, Youngkeun; Jeong, Myung Ho; Yoon, Jin-Sang; Kim, Jae-Min

2017-11-07

The genetic predisposition toward suicidal ideation has been explored to identify subgroups at high risk and to prevent suicide. Acute coronary syndrome (ACS) is associated with an increased risk of suicide, but few studies have explored the genetic predisposition toward suicide in ACS populations. Therefore, this longitudinal study explored the genetic predisposition toward suicidal ideation in ACS patients. In total, of 969 patients within 2 weeks after ACS, 711 were followed at 1 year after ACS. Suicidal ideation was evaluated with the relevant items on the Montgomery-Åsberg Depression Rating Scale. Ten genetic polymorphisms associated with serotonergic systems, neurotrophic factors, carbon metabolism, and inflammatory cytokines were examined. Associations between genetic polymorphisms and suicidal ideation within 2 weeks and 1 year of ACS were investigated using logistic regression models. The 5-HTTLPR s allele was significantly associated with suicidal ideation within 2 weeks of ACS after adjusting for covariates and after the Bonferroni correction. TNF-α -308 G/A , IL-1β -511 C/T , and IL-1β + 3953C/T were significantly associated with suicidal ideation within 2 weeks after ACS, but these associations did not reach significance after the Bonferroni correction in unadjusted analyses and after adjusting for covariance. However, no significant association between genetic polymorphisms and suicidal ideation was found at 1 year. Genetic predisposition, 5-HTTLPR s allele in particular, may confer susceptibility to suicidal ideation in ACS patients during the acute phase of ACS.

A Population Genetics Study of Anopheles Darlingi (Diptera: Culicidae) from Colombia Based on Random Amplified Polymorphic DNA-Polymerase Chain Reaction and Amplified Fragment Length Polymorphism Markers

DTIC Science & Technology

2007-06-01

Biology of Disease Vectors, University Press of Colorado. Niwot, co. p. 417-437. Tadei WI’, Santos JMN, Rabbani MG 1982. Biologia de anofelinos amazonicos...wR 4𔃼.0 Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 102(3): 255-262, June 2007 255 A population genetics study ofAnopheles darlingi (Diptera... de Ciencias y rdcullad de Salud. Universidad del Valle, (’.ali, Colombia *Depanment of Entomology, Walter Reed Army Institute of Research. Silver

Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan.

PubMed

Kühne, Annett; Kaiser, Rolf; Schirmer, Markus; Heider, Ulrike; Muhlke, Sabine; Niere, Wiebke; Overbeck, Tobias; Hohloch, Karin; Trümper, Lorenz; Sezer, Orhan; Brockmöller, Jürgen

2007-07-01

Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.

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

PubMed Central

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

Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis

PubMed Central

Wang, Jiantao; Fan, Niannian; Deng, Yili; Zhu, Jie; Mei, Jing; Chen, Yao; Yang, Heng

2016-01-01

Interleukins (ILs) are the most typical inflammatory and immunoregulatory cytokines. Evidences have shown that polymorphisms in ILs are associated with cerebral infarction risk. However, the results remain inconclusive. The present study was to evaluate the role of ILs polymorphisms in cerebral infarction susceptibility. Relevant case-control studies published between January 2000 and December 2015 were searched and retrieved from the electronic databases of Web of Science, PubMed, Embase and the Chinese Biomedical Database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. A total of 55 articles including 12619 cerebral infarction patients and 14436 controls were screened out. Four ILs (IL-1, IL-6, IL-10 and IL-18) contained nine single nucleotide polymorphisms (SNPs; IL-1α −899C/T, IL-1β −511C/T and IL-1β +3953C/T; IL-6 −174G/C and −572C/G; IL-10 −819C/T and −1082A/G; IL-18 −607C/A and −137G/C). Our result showed that IL-1α −899C/T and IL-18 −607C/A (under all the genetic models), and IL-6 −572C/G (under the allelic model, heterogeneity model and dominant model) were associated with increased the risk of cerebral infarction (P<0.05). Subgroup analysis by ethnicity showed that IL-6 −174G/C polymorphism (under all the five models) and IL-10 −1082A/G polymorphism (under the allelic model and heterologous model) were significantly associated with increased the cerebral infarction risk in Asians. Other genetic polymorphisms were not related with cerebral infarction susceptibility under any genetic models. In conclusion, IL-1α −899C/T, IL-6 −572C/G and IL-18 −607C/A might be risk factors for cerebral infarction development. Further studies with well-designed and large sample size are still required. PMID:27679860

Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers

PubMed Central

Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

2015-01-01

To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype “MS F” (in both markers) was highly diverse and genotypes “Q104 F” (SCoT) and “82–18 F” (CBDP) were least diverse among the female genotype populations. Among male genotypes, “32 M” (CBDP) and “MS M” (SCoT) revealed highest h and I values while “58-5 M” (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups, one group consisting of all female genotypes and another group comprising of all male genotypes. During the present investigation, CBDP markers proved more informative in studying genetic diversity among Jojoba. Such genetically diverse genotypes would thus be of great significance for breeding, management and conservation of elite (high yielding) Jojoba germplasm. PMID:26110116

Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.

2014-05-01

Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives ofmore » research on genetic susceptibility in HNSCC are discussed.« less

Genetic differentiation of Octopus minor (Mollusca, Cephalopoda) off the northern coast of China as revealed by amplified fragment length polymorphisms.

PubMed

Yang, J M; Sun, G H; Zheng, X D; Ren, L H; Wang, W J; Li, G R; Sun, B C

2015-12-02

Octopus minor (Sasaki, 1920) is an economically important cephalopod that is found in the northern coastal waters of China. In this study, we investigated genetic differentiation in fishery populations using amplified fragment length polymorphisms (AFLPs). A total of 150 individuals were collected from five locations: Dalian (DL), Yan-tai (YT), Qingdao (QD), Lianyungang (LY), and Zhoushan (ZS), and 243 reproducible bands were amplified using five AFLP primer combinations. The percentage of polymorphic bands ranged from 53.33 to 76.08%. Nei's genetic identity ranged from 0.9139 to 0.9713, and the genetic distance ranged from 0.0291 to 0.0900. A phylogenetic tree was constructed using the unweighted pair group method with arithmetic mean, based on the genetic distance. The DL and YT populations originated from one clade, while the QD, LY, and ZS populations originated from another. The results indicate that the O. minor stock consisted of two genetic populations with an overall significantly analogous FST value (0.1088, P < 0.05). Most of the variance was within populations. These findings will be important for more sustainable octopus fisheries, so that this marine resource can be conserved for its long-term utilization.

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster.

PubMed

Bangham, Jenny; Knott, Sara A; Kim, Kang-Wook; Young, Robert S; Jiggins, Francis M

2008-09-01

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen--the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.

Investigating the genetic basis of theory of mind (ToM): the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

PubMed

Xia, Haiwei; Wu, Nan; Su, Yanjie

2012-01-01

The ability to deduce other persons' mental states and emotions which has been termed 'theory of mind (ToM)' is highly heritable. First molecular genetic studies focused on some dopamine-related genes, while the genetic basis underlying different components of ToM (affective ToM and cognitive ToM) remain unknown. The current study tested 7 candidate polymorphisms (rs4680, rs4633, rs2020917, rs2239393, rs737865, rs174699 and rs59938883) on the catechol-O-methyltransferase (COMT) gene. We investigated how these polymorphisms relate to different components of ToM. 101 adults participated in our study; all were genetically unrelated, non-clinical and healthy Chinese subjects. Different ToM tasks were applied to detect their theory of mind ability. The results showed that the COMT gene rs2020917 and rs737865 SNPs were associated with cognitive ToM performance, while the COMT gene rs5993883 SNP was related to affective ToM, in which a significant gender-genotype interaction was found (p = 0.039). Our results highlighted the contribution of DA-related COMT gene on ToM performance. Moreover, we found out that the different SNP at the same gene relates to the discriminative aspect of ToM. Our research provides some preliminary evidence to the genetic basis of theory of mind which still awaits further studies.

Susceptibility to breast cancer and three polymorphisms of GSTZ1.

PubMed

Saadat, Iraj; Khalili, Maryam; Nafissi, Samane; Omidvari, Shahpour; Saadat, Mostafa

2012-03-01

Glutathione S-transferases class zeta (GSTζ) is involved in the detoxification of xenobiotic compounds and catalyzes the biotransformation of a variety of α-haloacids including dichloroacetic acid and chlorofluoroacetic acid. It has been reported that, in mice, deficiency of Gstz1 (a member of GSTζ) resulted in the generation of a constant level of oxidative stress. The present study was carried out to investigate the association between genetic polymorphisms of GSTZ1 (in promoter site G-1002A and in coding sites Glu32Lys and Gly42Arg) and risk of breast cancer. We included 106 females with breast cancer and 106 healthy females frequency matched for age. The study polymorphisms were not associated with risk of breast cancer (p>0.05). The polymorphisms of GSTZ1 showed strong linkage disequilibrium among cancer patients and control subjects (p<0.0001). There was no significant difference between cancer patients and controls for frequencies of the GSTZ1 haplotypes (p>0.05). It seems there is no meaningful relationship between the genetic polymorphisms of GSTZ1 and risk of breast cancer.

Using microarray analysis to evaluate genetic polymorphisms involved in the metabolism of environmental chemicals.

PubMed

Ban, Susumu; Kondo, Tomoko; Ishizuka, Mayumi; Sasaki, Seiko; Konishi, Kanae; Washino, Noriaki; Fujita, Syoichi; Kishi, Reiko

2007-05-01

The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphisms (SNPs). SNPs in human genes are generally considered to be very useful in determining inherited genetic disorders, susceptibility to certain diseases, and cancer predisposition. Quick and accurate discrimination of SNPs is the key characteristic of technology used in DNA diagnostics. For this study, we first developed a DNA microarray and then evaluated its efficacy by determining the detection ability and validity of this method. Using DNA obtained from 380 pregnant Japanese women, we examined 13 polymorphisms of 9 genes, which are associated with the metabolism of environmental chemical compounds found in high frequency among Japanese populations. The ability to detect CYP1A1 I462V, CYP1B1 L432V, GSTP1 I105V and AhR R554K gene polymorphisms was above 98%, and agreement rates when compared with real time PCR analysis methods (kappa values) showed high validity: 0.98 (0.96), 0.97 (0.93), 0.90 (0.81), 0.90 (0.91), respectively. While this DNA microarray analysis should prove important as a method for initial screening, it is still necessary that we find better methods for improving the detection of other gene polymorphisms not part of this study.

Development of cleaved amplified polymorphic sequence markers and a CAPS-based genetic linkage map in watermelon (Citrullus lanatus [Thunb.] Matsum. and Nakai) constructed using whole-genome re-sequencing data

PubMed Central

Liu, Shi; Gao, Peng; Zhu, Qianglong; Luan, Feishi; Davis, Angela R.; Wang, Xiaolu

2016-01-01

Cleaved amplified polymorphic sequence (CAPS) markers are useful tools for detecting single nucleotide polymorphisms (SNPs). This study detected and converted SNP sites into CAPS markers based on high-throughput re-sequencing data in watermelon, for linkage map construction and quantitative trait locus (QTL) analysis. Two inbred lines, Cream of Saskatchewan (COS) and LSW-177 had been re-sequenced and analyzed by Perl self-compiled script for CAPS marker development. 88.7% and 78.5% of the assembled sequences of the two parental materials could map to the reference watermelon genome, respectively. Comparative assembled genome data analysis provided 225,693 and 19,268 SNPs and indels between the two materials. 532 pairs of CAPS markers were designed with 16 restriction enzymes, among which 271 pairs of primers gave distinct bands of the expected length and polymorphic bands, via PCR and enzyme digestion, with a polymorphic rate of 50.94%. Using the new CAPS markers, an initial CAPS-based genetic linkage map was constructed with the F2 population, spanning 1836.51 cM with 11 linkage groups and 301 markers. 12 QTLs were detected related to fruit flesh color, length, width, shape index, and brix content. These newly CAPS markers will be a valuable resource for breeding programs and genetic studies of watermelon. PMID:27162496

High throughput SNP discovery and genotyping in grapevine (Vitis vinifera L.) by combining a re-sequencing approach and SNPlex technology

PubMed Central

Lijavetzky, Diego; Cabezas, José Antonio; Ibáñez, Ana; Rodríguez, Virginia; Martínez-Zapater, José M

2007-01-01

Background Single-nucleotide polymorphisms (SNPs) are the most abundant type of DNA sequence polymorphisms. Their higher availability and stability when compared to simple sequence repeats (SSRs) provide enhanced possibilities for genetic and breeding applications such as cultivar identification, construction of genetic maps, the assessment of genetic diversity, the detection of genotype/phenotype associations, or marker-assisted breeding. In addition, the efficiency of these activities can be improved thanks to the ease with which SNP genotyping can be automated. Expressed sequence tags (EST) sequencing projects in grapevine are allowing for the in silico detection of multiple putative sequence polymorphisms within and among a reduced number of cultivars. In parallel, the sequence of the grapevine cultivar Pinot Noir is also providing thousands of polymorphisms present in this highly heterozygous genome. Still the general application of those SNPs requires further validation since their use could be restricted to those specific genotypes. Results In order to develop a large SNP set of wide application in grapevine we followed a systematic re-sequencing approach in a group of 11 grape genotypes corresponding to ancient unrelated cultivars as well as wild plants. Using this approach, we have sequenced 230 gene fragments, what represents the analysis of over 1 Mb of grape DNA sequence. This analysis has allowed the discovery of 1573 SNPs with an average of one SNP every 64 bp (one SNP every 47 bp in non-coding regions and every 69 bp in coding regions). Nucleotide diversity in grape (π = 0.0051) was found to be similar to values observed in highly polymorphic plant species such as maize. The average number of haplotypes per gene sequence was estimated as six, with three haplotypes representing over 83% of the analyzed sequences. Short-range linkage disequilibrium (LD) studies within the analyzed sequences indicate the existence of a rapid decay of LD within the selected grapevine genotypes. To validate the use of the detected polymorphisms in genetic mapping, cultivar identification and genetic diversity studies we have used the SNPlex™ genotyping technology in a sample of grapevine genotypes and segregating progenies. Conclusion These results provide accurate values for nucleotide diversity in coding sequences and a first estimate of short-range LD in grapevine. Using SNPlex™ genotyping we have shown the application of a set of discovered SNPs as molecular markers for cultivar identification, linkage mapping and genetic diversity studies. Thus, the combination a highly efficient re-sequencing approach and the SNPlex™ high throughput genotyping technology provide a powerful tool for grapevine genetic analysis. PMID:18021442

Genetic Association Study of KCNQ5 Polymorphisms with High Myopia.

PubMed

Liao, Xuan; Yap, Maurice K H; Leung, Kim Hung; Kao, Patrick Y P; Liu, Long Qian; Yip, Shea Ping

2017-01-01

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give P asym values, and multiple comparisons were corrected by permutation test to give P emp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63-0.90; P emp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64-0.89; P emp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study.

PubMed

Han, Ae Ra; Choi, Young Min; Hong, Min A; Kim, Jin Ju; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan

2018-05-20

Aberrant apoptosis at the trophoblast-maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy-Weinberg equilibrium. Fas -670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas -1377 G/A and FasL -844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.

Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

PubMed

Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong

2012-02-01

Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.

Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review.

PubMed

Hoofwijk, D M N; van Reij, R R I; Rutten, B P; Kenis, G; Buhre, W F; Joosten, E A

2016-12-01

Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. A systematic review of the literature was performed, and additional literature was obtained by reference tracking. The primary outcome was CPSP, defined as pain at least 2 months after the surgery. Studies performed exclusively in animals were excluded. Out of the 1001 identified studies, 14 studies were selected for inclusion. These studies described 5269 participants in 17 cohorts. A meta-analysis was not possible because of heterogeneity of data and data analysis. Associations with the prevalence or severity of CPSP were reported for genetic variants in the COMT gene, OPRM1, potassium channel genes, GCH1, CACNG, CHRNA6, P2X7R, cytokine-associated genes, human leucocyte antigens, DRD2, and ATXN1 CONCLUSIONS: Research on the topic of genetic variants associated with CPSP is still in its initial phase. Hypothesis-free, genome-wide association studies on large cohorts are needed in this field. In addition, future studies may also integrate genetic risk factors and patient characteristic, clinical, and psychological predictors for CPSP. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Epistatic interaction between FCRL3 and NFκB1 genes in Spanish patients with rheumatoid arthritis

PubMed Central

Martínez, A; Sánchez, E; Valdivia, A; Orozco, G; López‐Nevot, M A; Pascual‐Salcedo, D; Balsa, A; Fernández‐Gutiérrez, B; de la Concha, E G; García‐Sánchez, A; Koeleman, B P C; Urcelay, E; Martín, J

2006-01-01

Background A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor‐like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21–23. Objectives To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor κB (NFκB), a functional polymorphism located in the NFκB1 gene was included. Methods 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The −94ins/delATTG NFκB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3×2 contingency tables and χ2 values. Results No overall differences were found in any of the FCRL3 polymorphisms and in the NFκB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFκB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFκB1 (pc = 0.003). Conclusions The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFκB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations. PMID:16476711

No association of apolipoprotein B gene polymorphism and blood lipids in obese Egyptian subjects.

PubMed

Bogari, Neda M; Abdel-Latif, Azza M; Hassan, Maha A; Ramadan, Abeer; Fawzy, Ahmed

2015-03-18

Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations. Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism. This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

PubMed Central

Imboden, M; Nieters, A; Bircher, AJ; Brutsche, M; Becker, N; Wjst, M; Ackermann-Liebrich, U; Berger, W; Probst-Hensch, NM

2006-01-01

Background Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. Methods Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. Results We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. Conclusion Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes. PMID:16759385

Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population

PubMed Central

Mahjoubi, Imen; Kallel, Amani; Sbaï, Mohamed Hédi; Ftouhi, Bochra; ben Halima, Meriam; Jemaa, Zeineb; Feki, Moncef; Slimane, Hedia; Jemaa, Riadh; Kaabachi, Naziha

2016-01-01

Background & objectives: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population. Methods: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577). Interpretation & conclusions: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population. PMID:27834325

Single nucleotide polymorphisms associated with coronary heart disease predict incident ischemic stroke in the atherosclerosis risk in communities study.

PubMed

Morrison, Alanna C; Bare, Lance A; Luke, May M; Pankow, James S; Mosley, Thomas H; Devlin, James J; Willerson, James T; Boerwinkle, Eric

2008-01-01

Ischemic stroke and coronary heart disease (CHD) may share genetic factors contributing to a common etiology. This study investigates whether 51 single nucleotide polymorphisms (SNPs) associated with CHD in multiple antecedent studies are associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. From the multiethnic ARIC cohort of 14,215 individuals, 495 validated ischemic strokes were identified. Cox proportional hazards models, adjusted for age and gender, identified three SNPs in Whites and two SNPs in Blacks associated with incident stroke (p

A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait

PubMed Central

Geroldinger, Ludwig; Bürger, Reinhard

2014-01-01

The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. PMID:24726489

A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait.

PubMed

Geroldinger, Ludwig; Bürger, Reinhard

2014-06-01

The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sequence-related amplified polymorphism (SRAP) marker as a new method for identification of endophytic fungi from Taxus.

PubMed

Ren, Na; Liu, Jiajia; Yang, Dongliang; Chen, Jianhua; Luan, Mingbao; Hong, Juan

2012-01-01

A total of 20 endophytic fungi stains were classified into four groups using traditional morphological identification method, and were studied for genetic diversity by sequence-related amplified polymorphism (SRAP) technique. Genomic DNA (deoxyribonucleic acid) of these strains was extracted with CTAB method. SRAP analysis was done with 24 pairs of primers. All strains could be uniquely distinguished with 584 bands and 446 polymorphism bands which generated 76.4% of polymorphic ratio. Unweighted pair-group method with arithmetical averages cluster analysis enabled construction of a dendrogram for estimating genetic distances between different strains. All strains, which were just divided into four groups by traditional morphology identification, were clustered into four major groups at GS = 0.603 and further separated into eight sub-groups at GS = 0.921. Dendrogram also revealed a large genetic variation in 20 strains; different primer combinations allowed them distinctly distinguished one from others with relatively low genetic similarity. The results show that the SRAP technology is more efficient than traditional morphology identification. It is found that SRAP markers could more really reflect the genetic diversity of endophytic fungi strains from Taxus, and also could be used as a method for identification of endophytic fungi from Taxus. It also suggests that SRAP can be used to establish foundation for further screening of taxol-producing endophytic fungi strains which can produce high levels of paclitaxel.

Distribution and localization of microsatellites in the Perigord black truffle genome and identification of new molecular markers (2010) Fungal Genetics and Biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murat, Claude; Riccioni, C; Belfiori, B

The level of genetic diversity and genetic structure in the Perigord black truffle (Tuber melanosporum Vittad.) has been debated for several years, mainly due to the lack of appropriate genetic markers. Microsatellites or simple sequence repeats (SSRs) are important for the genome organisation, phenotypic diversity and are one of the most popular molecular markers. In this study, we surveyed the T. melanosporum genome (1) to characterise its SSR pattern; (2) to compare it with SSR patterns found in 48 other fungal and three oomycetes genomes and (3) to identify new polymorphic SSR markers for population genetics. The T. melanosporum genomemore » is rich in SSRs with 22,425 SSRs with mono-nucleotides being the most frequent motifs. SSRs were found in all genomic regions although they are more frequent in non-coding regions (introns and intergenic regions). Sixty out of 135 PCR-amplified mono-, di-, tri-, tetra, penta, and hexanucleotides were polymorphic (44%) within black truffle populations and 27 were randomly selected and analysed on 139 T. melanosporum isolates from France, Italy and Spain. The number of alleles varied from 2 to 18 and the expected heterozygosity from 0.124 to 0.815. One hundred and thirty-two different multilocus genotypes out of the 139 T. melanosporum isolates were identified and the genotypic diversity was high (0.999). Polymorphic SSRs were found in UTR regulatory regions of fruiting bodies and ectomycorrhiza regulated genes, suggesting that they may play a role in phenotypic variation. In conclusion, SSRs developed in this study were highly polymorphic and our results showed that T. melanosporum is a species with an important genetic diversity, which is in agreement with its recently uncovered heterothallic mating system.« less

No allelic association between Parkinson`s disease and dopamine D2, D3, and D4 receptor gene polymorphisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanko, S.; Hattori, M.; Dai, X.Y.

1994-12-15

Parkinson`s disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson`s disease. Genetic association studies between Parkinson`s disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson`s disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson`s disease ismore » associated with the dopamine receptor polymorphisms examined. 35 refs., 2 tabs.« less

BDNF and TNF-α polymorphisms in memory.

PubMed

Yogeetha, B S; Haupt, L M; McKenzie, K; Sutherland, H G; Okolicsyani, R K; Lea, R A; Maher, B H; Chan, R C K; Shum, D H K; Griffiths, L R

2013-09-01

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-α rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-α polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-α polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-α and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-α in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis.

PubMed

Cheng, Yang; Zhu, Yun; Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn's disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.

The genetic validation of heterogeneity in schizophrenia.

PubMed

Tsutsumi, Atsushi; Glatt, Stephen J; Kanazawa, Tetsufumi; Kawashige, Seiya; Uenishi, Hiroyuki; Hokyo, Akira; Kaneko, Takao; Moritani, Makiko; Kikuyama, Hiroki; Koh, Jun; Matsumura, Hitoshi; Yoneda, Hiroshi

2011-10-07

Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors. No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39). The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

The long-term evolution of multilocus traits under frequency-dependent disruptive selection.

PubMed

van Doorn, G Sander; Dieckmann, Ulf

2006-11-01

Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic assumptions underlying these approaches are highly idealized and, even worse, predict different consequences of frequency-dependent disruptive selection. Population genetic models, by contrast, enable genotypic evolutionary models, but traditionally assume constant fitness values. Only a minority of these models thus addresses frequency-dependent selection, and only a few of these do so in a multilocus context. An inherent limitation of these remaining studies is that they only investigate the short-term maintenance of genetic variation. Consequently, the long-term evolution of multilocus characters under frequency-dependent disruptive selection remains poorly understood. We aim to bridge this gap between phenotypic and genotypic models by studying a multilocus version of Levene's soft-selection model. Individual-based simulations and deterministic approximations based on adaptive dynamics theory provide insights into the underlying evolutionary dynamics. Our analysis uncovers a general pattern of polymorphism formation and collapse, likely to apply to a wide variety of genetic systems: after convergence to a fitness minimum and the subsequent establishment of genetic polymorphism at multiple loci, genetic variation becomes increasingly concentrated on a few loci, until eventually only a single polymorphic locus remains. This evolutionary process combines features observed in quantitative genetics and adaptive dynamics models, and it can be explained as a consequence of changes in the selection regime that are inherent to frequency-dependent disruptive selection. Our findings demonstrate that the potential of frequency-dependent disruptive selection to maintain polygenic variation is considerably smaller than previously expected.

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

PubMed Central

Kim, Kyung-Seon; Kim, Ghi-Su; Hwang, Joo-Yeon; Lee, Hye-Ja; Park, Mi-Hyun; Kim, Kwang-joong; Jung, Jongsun; Cha, Hyo-Soung; Shin, Hyoung Doo; Kang, Jong-Ho; Park, Eui Kyun; Kim, Tae-Ho; Hong, Jung-Min; Koh, Jung-Min; Oh, Bermseok; Kimm, Kuchan; Kim, Shin-Yoon; Lee, Jong-Young

2007-01-01

Background Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling. Methods We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted. Results We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another. Conclusion Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies. PMID:18036257

Adaptive Role of Inversion Polymorphism of Drosophila subobscura in Lead Stressed Environment

PubMed Central

Kenig, Bojan; Kurbalija Novičić, Zorana; Patenković, Aleksandra; Stamenković-Radak, Marina; Anđelković, Marko

2015-01-01

Local adaptation to environmental stress at different levels of genetic polymorphism in various plants and animals has been documented through evolution of heavy metal tolerance. We used samples of Drosophila subobscura populations from two differently polluted environments to analyze the change of chromosomal inversion polymorphism as genetic marker during laboratory exposure to lead. Exposure to environmental contamination can affect the genetic content within a particular inversion and produce targets for selection in populations from different environments. The aims were to discover whether the inversion polymorphism is shaped by the local natural environments, and if lead as a selection pressure would cause adaptive divergence of two populations during the multigenerational laboratory experiment. The results showed that populations retain signatures from past contamination events, and that heavy metal pollution can cause adaptive changes in population. Differences in inversion polymorphism between the two populations increased over generations under lead contamination in the laboratory. The inversion polymorphism of population originating from the more polluted natural environment was more stable during the experiment, both under conditions with and without lead. Therefore, results showed that inversion polymorphism as a genetic marker reflects a strong signature of adaptation to the local environment, and that historical demographic events and selection are important for both prediction of evolutionary potential and long-term viability of natural populations. PMID:26102201

Adaptive Role of Inversion Polymorphism of Drosophila subobscura in Lead Stressed Environment.

PubMed

Kenig, Bojan; Kurbalija Novičić, Zorana; Patenković, Aleksandra; Stamenković-Radak, Marina; Anđelković, Marko

2015-01-01

Local adaptation to environmental stress at different levels of genetic polymorphism in various plants and animals has been documented through evolution of heavy metal tolerance. We used samples of Drosophila subobscura populations from two differently polluted environments to analyze the change of chromosomal inversion polymorphism as genetic marker during laboratory exposure to lead. Exposure to environmental contamination can affect the genetic content within a particular inversion and produce targets for selection in populations from different environments. The aims were to discover whether the inversion polymorphism is shaped by the local natural environments, and if lead as a selection pressure would cause adaptive divergence of two populations during the multigenerational laboratory experiment. The results showed that populations retain signatures from past contamination events, and that heavy metal pollution can cause adaptive changes in population. Differences in inversion polymorphism between the two populations increased over generations under lead contamination in the laboratory. The inversion polymorphism of population originating from the more polluted natural environment was more stable during the experiment, both under conditions with and without lead. Therefore, results showed that inversion polymorphism as a genetic marker reflects a strong signature of adaptation to the local environment, and that historical demographic events and selection are important for both prediction of evolutionary potential and long-term viability of natural populations.

The First Genetic Map in Sweet Osmanthus (Osmanthus fragrans Lour.) Using Specific Locus Amplified Fragment Sequencing

PubMed Central

He, Yanxia; Yuan, Wangjun; Dong, Meifang; Han, Yuanji; Shang, Fude

2017-01-01

Osmanthus fragrans is an ornamental plant of substantial commercial value, and no genetic linkage maps of this species have previously been reported. Specific-locus amplified fragment sequencing (SLAF-seq) is a recently developed technology that allows massive single nucleotide polymorphisms (SNPs) to be identified and high-resolution genotyping. In our current research, we generated the first genetic map of O. fragrans using SLAF-seq, which is composed with 206.92 M paired-end reads and 173,537 SLAF markers. Among total 90,715 polymorphic SLAF markers, 15,317 polymorphic SLAFs could be used for genetic map construction. The integrated map contained 14,189 high quality SLAFs that were grouped in 23 genetic linkage groups, with a total length of 2962.46 cM and an average distance of 0.21 cM between two adjacent markers. In addition, 23,664 SNPs were identified from the mapped markers. As far as we know, this is the first of the genetic map of O. fragrans. Our results are further demonstrate that SLAF-seq is a very effective method for developing markers and constructing high-density linkage maps. The SNP markers and the genetic map reported in this study should be valuable resource in future research. PMID:29018460

USP38, FREM3, SDC1, DDC, and LOC727982 Gene Polymorphisms and Differential Susceptibility to Severe Malaria in Tanzania.

PubMed

Manjurano, Alphaxard; Sepúlveda, Nuno; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Maxwell, Caroline; Olomi, Raimos; Reyburn, Hugh; Drakeley, Christopher J; Riley, Eleanor M; Clark, Taane G

2015-10-01

Populations exposed to Plasmodium falciparum infection develop genetic mechanisms of protection against severe malarial disease. Despite decades of genetic epidemiological research, the sickle cell trait (HbAS) sickle cell polymorphism, ABO blood group, and other hemoglobinopathies remain the few major determinants in severe malaria to be replicated across different African populations and study designs. Within a case-control study in a region of high transmission in Tanzania (n = 983), we investigated the role of 40 new loci identified in recent genome-wide studies. In 32 loci passing quality control procedures, we found polymorphisms in USP38, FREM3, SDC1, DDC, and LOC727982 genes to be putatively associated with differential susceptibility to severe malaria. Established candidates explained 7.4% of variation in severe malaria risk (HbAS polymorphism, 6.3%; α-thalassemia, 0.3%; ABO group, 0.3%; and glucose-6-phosphate dehydrogenase deficiency, 0.5%) and the new polymorphisms, another 4.3%. The regions encompassing the loci identified are promising targets for the design of future treatment and control interventions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Isolation and characterization of polymorphic microsatellite markers in the black spiny tailed iguana (Ctenosaura pectinata) and their cross-utility in other Ctenosaura.

PubMed

Zarza, Eugenia; Pereyra, Ricardo T; Reynoso, Victor H; Emerson, Brent C

2009-01-01

We isolated and characterized 10 polymorphic microsatellite loci from the Mexican black iguana (Ctenosaura pectinata) and assessed levels of polymorphism in sampling sites located in the northern areas of the species' distribution range. Two to 19 alleles per locus and observed heterozygosity ranging from 0.15 to 0.96 were detected. These markers will be useful to describe population genetic structure, the extent of gene flow in contact zones, to study the mating system of the species and to address conservation genetics issues. Additionally, we evaluated the potential utility of these markers for studies of other species within the genus Ctenosaura (i.e. C. hemilopha, C. similis and C. oaxacana). © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

[ISSR analysis for genetic polymorphism of Aconitum leucostomum from different habitats].

PubMed

Gao, Fu-chun; Sun, Yun; Zhang, Jing; Zhang, Fan

2014-01-01

To investigate the genetic diversities and variations of Aconitum leucostomum,and to supply essential characteristics for identifying Aconitum crude drugs. Plant genome extraction kit was applied to extract DNA,and ultraviolet spectrophotometer was used to detect the concentrations and purity of DNA. 60 ISSR primers were screened to analyze the DNA of Aconitum leucostomum from 10 habitats. Biosoftwares including POPGEN32 and NTSYS-PC were used to analyze the polymorphic bands obtained, and hence to yield the genetic similarity coefficient of the 10 habitats and map the related graphics, and cluster analysis were performed by UPGMA method. 11 primers selected from 60 ISSR primers were used for amplification and a total of 101 DNA bands were obtained, including 89 polymorphic bands,the average percentage of polymorphic bands (PPB) was 88.1%. Shannon information index (I) was 0.5298, the genetic similarity coefficient (H) was 0.3648, observed number of alleles was 1.8911, and effective number of alleles was 1.6555. The genetic identity was from 0.4950 to 0.6931, and the genetic distances were from 0.3666 to 0.7031. According to cluster analysis result of ISSR, the 10 habitats of Aconitum leucostomum were classified into five groups. Germplasm resources of Aconitum leucostomum show abundant polymorphism and higher genetic variation, which might supply molecular level basis, and provide basis for building DNA fingerprint.

Lack of association between ESR1 gene polymorphisms and premature ovarian failure in Serbian women.

PubMed

Li, J; Vujovic, S; Dalgleish, R; Thompson, J; Dragojevic-Dikic, S; Al-Azzawi, F

2014-06-01

It has previously been reported that estrogen receptor-alpha (ERα) gene (ESR1: estrogen receptor 1) polymorphisms are associated with premature ovarian failure (POF). The aim of this study was to investigate whether these genetic polymorphisms of ESR1 are associated with POF in Serbian women. A series of 197 POF cases matched with 547 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. Genomic DNA was extracted from saliva using Oragene® DNA sample collection kits. Two single-nucleotide polymorphisms (SNPs), PvuII and XbaI, in ESR1 were genotyped by dynamic allele-specific hybridization. Haplotype analyses were performed with the restriction fragment length polymorphism method. SNP and haplotype effects were analyzed by logistic regression models. No significant difference was found in the distribution of ESR1 PvuII and XbaI polymorphisms or haplotypes between the POF and control groups. The two ESR1 SNPs, PvuII and XbaI, are not commonly associated with POF in Serbian women and may not contribute to the genetic basis of the condition.

Significant Synergistic Effect of Peroxisome Proliferator–Activated Receptor γ C-2821T and Diabetes on the Risk of Ischemic Stroke

PubMed Central

Hsieh, Fang-I; Lo, Wei-Cheng; Lin, Huey-Juan; Hsieh, Yi-Chen; Lien, Li-Ming; Bai, Chyi-Huey; Tseng, Hung-Pin; Chiou, Hung-Yi

2009-01-01

OBJECTIVE To explore the relationship between the genetic polymorphisms of PPARγ (Pro12Ala, C1431T, and C-2821T) and the risk of ischemic stroke and to investigate whether these genetic polymorphisms of PPARγ would modify the risk of ischemic stroke among patients with hypertension or diabetes. RESEARCH DESIGN AND METHODS The case-control study was conducted with 537 ischemic stroke patients and 537 control subjects. A structured questionnaire was used to collect information on conventional cardiovascular risk factors and laboratory results. The genetic polymorphisms of PPARγ were determined by PCR–restriction fragment–length polymorphism. RESULTS A significant interaction was seen between the −2821C allele and diabetes but not between this allele and hypertension. A markedly elevated risk of ischemic stroke (odds ratio 9.7) was found in the subjects with diabetes and the −2821C allele compared with that in those without these two risk factors. CONCLUSIONS The −2821C allele of PPARγ was a strong predictor of ischemic stroke for diabetic patients. PMID:19651920

avpr1a length polymorphism is not associated with either social or genetic monogamy in free-living prairie voles.

PubMed

Mabry, Karen E; Streatfeild, Craig A; Keane, Brian; Solomon, Nancy G

2011-01-01

Recent discoveries of single-gene influences on social behaviour have generated a great deal of interest in the proximate mechanisms underlying the expression of complex behaviours. Length polymorphism in a microsatellite in the regulatory region of the gene encoding the vasopressin 1a receptor (avpr1a) has been associated with both inter- and intra-specific variation in socially monogamous behaviour in voles (genus Microtus) under laboratory conditions. Here, we evaluate the relationship between avpr1a length polymorphism and social associations, genetic monogamy, and reproductive success in free-living prairie vole (M. ochrogaster) populations. We found no evidence of a relationship between avpr1a microsatellite length and any of our correlates of either social or genetic monogamy in the field. Our results, especially when taken in conjunction with those of recent experimental studies in semi-natural enclosures, suggest that avpr1a polymorphism is unlikely to have been a major influence in the evolution or maintenance of social monogamy in prairie voles under natural conditions.

avpr1a length polymorphism is not associated with either social or genetic monogamy in free-living prairie voles

PubMed Central

Mabry, Karen E.; Streatfeild, Craig A.; Keane, Brian; Solomon, Nancy G.

2010-01-01

Recent discoveries of single-gene influences on social behaviour have generated a great deal of interest in the proximate mechanisms underlying the expression of complex behaviours. Length polymorphism in a microsatellite in the regulatory region of the gene encoding the vasopressin 1a receptor (avpr1a) has been associated with both inter- and intra-specific variation in socially monogamous behaviour in voles (genus Microtus) under laboratory conditions. Here, we evaluate the relationship between avpr1a length polymorphism and social associations, genetic monogamy, and reproductive success in free-living prairie vole (M. ochrogaster) populations. We found no evidence of a relationship between avpr1a microsatellite length and any of our correlates of either social or genetic monogamy in the field. Our results, especially when taken in conjunction with those of recent experimental studies in semi-natural enclosures, suggest that avpr1a polymorphism is unlikely to have been a major influence in the evolution or maintenance of social monogamy in prairie voles under natural conditions. PMID:21442019

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.

Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

PubMed Central

Duconge, Jorge; Cadilla, Carmen L.; Ruaño, Gualberto

2015-01-01

Although the Hispanic population is continuously growing in the United States, they are underrepresented in pharmacogenetic studies. This review addresses the need for compiling available pharmacogenetic data in US Hispanics, discussing the prevalence of clinically relevant polymorphisms in pharmacogenes encoding for drug-metabolizing enzymes. CYP3A5*3 (0.245–0.867) showed the largest frequency in a US Hispanic population. A higher prevalence of CYP2C9*3, CYP2C19*4, and UGT2B7 IVS1+985 A>Gwas observed in US Hispanic vs. non-Hispanic populations. We found interethnic and intraethnic variability in frequencies of genetic polymorphisms for metabolizing enzymes, which highlights the need to define the ancestries of participants in pharmacogenetic studies. New approaches should be integrated in experimental designs to gain knowledge about the clinical relevance of the unique combination of genetic variants occurring in this admixed population. Ethnic subgroups in the US Hispanic population may harbor variants that might be part of multiple causative loci or in linkage-disequilibrium with functional variants. Pharmacogenetic studies in Hispanics should not be limited to ascertain commonly studied polymorphisms that were originally identified in their parental populations. The success of the Personalized Medicine paradigm will depend on recognizing genetic diversity between and within US Hispanics and the uniqueness of their genetic backgrounds. PMID:25431893

Epigenetic changes detected in micropropagated hop plants.

PubMed

Peredo, Elena L; Arroyo-García, Rosa; Revilla, M Angeles

2009-07-01

Micropropagation is a widely used technique in hops (Humulus lupulus L.). However, to the best of our knowledge, the genetic and epigenetic stability of the microplants has never been tested before. In the present study, two hop accessions were established in vitro and micropropagated for 2 years. The genetic and epigenetic stability of the in vitro plants was analyzed with several molecular techniques: random amplified DNA polymorphism (RAPD), retrotransposon microsatellite amplified polymorphism (REMAP), and methylation-sensitive amplification polymorphism (MSAP). No genetic variation among control and treated plants was found, even after 12 cycles of micropropagation. Epigenetic variation was detected, first, when field and in vitro samples were compared. Nearly a 30% of the detected fragments presented the same pattern of alterations in all the vitroplants. Second, lower levels of epigenetic variation were detected among plants from the different subcultures. Part of this detected variation seemed to be accumulated along the 12 sequential subcultures tested.

Genetic discovery in Xylella fastidiosa through sequence analysis of selected randomly amplified polymorphic DNAs.

PubMed

Chen, Jianchi; Civerolo, Edwin L; Jarret, Robert L; Van Sluys, Marie-Anne; de Oliveira, Mariana C

2005-02-01

Xylella fastidiosa causes many important plant diseases including Pierce's disease (PD) in grape and almond leaf scorch disease (ALSD). DNA-based methodologies, such as randomly amplified polymorphic DNA (RAPD) analysis, have been playing key roles in genetic information collection of the bacterium. This study further analyzed the nucleotide sequences of selected RAPDs from X. fastidiosa strains in conjunction with the available genome sequence databases and unveiled several previously unknown novel genetic traits. These include a sequence highly similar to those in the phage family of Podoviridae. Genome comparisons among X. fastidiosa strains suggested that the "phage" is currently active. Two other RAPDs were also related to horizontal gene transfer: one was part of a broadly distributed cryptic plasmid and the other was associated with conjugal transfer. One RAPD inferred a genomic rearrangement event among X. fastidiosa PD strains and another identified a single nucleotide polymorphism of evolutionary value.

The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

PubMed

Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

2007-01-01

Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p < 0.05) and no significant for premature birth, short-birth height and low-birth weight. This is the first study showing the role of the promoter region of the IGF-I gene polymorphism and the level of plasma IGF-I and body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.

PubMed

Zhang, Tao; Liu, Yuan; Hu, Yibo; Zhang, Xiaoqing; Zhong, Lin; Fan, Junwei; Peng, Zhihai

2017-09-05

New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival. Copyright © 2017. Published by Elsevier B.V.

DNA polymorphism in recombining and non-recombing mating-type-specific loci of the smut fungus Microbotryum

PubMed Central

Votintseva, A A; Filatov, D A

2011-01-01

The population-genetic processes leading to the genetic degeneration of non-recombining regions have mainly been studied in animal and plant sex chromosomes. Here, we report population genetic analysis of the processes in the non-recombining mating-type-specific regions of the smut fungus Microbotryum violaceum. M. violaceum has A1 and A2 mating types, determined by mating-type-specific ‘sex chromosomes' that contain 1–2 Mb long non-recombining regions. If genetic degeneration were occurring, then one would expect reduced DNA polymorphism in the non-recombining regions of this fungus. The analysis of DNA diversity among 19 M. violaceum strains, collected across Europe from Silene latifolia flowers, revealed that (i) DNA polymorphism is relatively low in all 20 studied loci (π∼0.15%), (ii) it is not significantly different between the two mating-type-specific chromosomes nor between the non-recombining and recombining regions, (iii) there is substantial population structure in M. violaceum populations, which resembles that of its host species, S. latifolia, and (iv) there is significant linkage disequilibrium, suggesting that widespread selfing in this species results in a reduction of the effective recombination rate across the genome. We hypothesise that selfing-related reduction of recombination across the M. violaceum genome negates the difference in the level of DNA polymorphism between the recombining and non-recombining regions, and may possibly lead to similar levels of genetic degeneration in the mating-type-specific regions of the non-recombining ‘sex chromosomes' and elsewhere in the genome. PMID:21081967

Immunogenetics as a tool in anthropological studies

PubMed Central

Sanchez-Mazas, Alicia; Fernandez-Viña, Marcelo; Middleton, Derek; Hollenbach, Jill A; Buhler, Stéphane; Di, Da; Rajalingam, Raja; Dugoujon, Jean-Michel; Mack, Steven J; Thorsby, Erik

2011-01-01

The genes coding for the main molecules involved in the human immune system – immunoglobulins, human leucocyte antigen (HLA) molecules and killer-cell immunoglobulin-like receptors (KIR) – exhibit a very high level of polymorphism that reveals remarkable frequency variation in human populations. ‘Genetic marker’ (GM) allotypes located in the constant domains of IgG antibodies have been studied for over 40 years through serological typing, leading to the identification of a variety of GM haplotypes whose frequencies vary sharply from one geographic region to another. An impressive diversity of HLA alleles, which results in amino acid substitutions located in the antigen-binding region of HLA molecules, also varies greatly among populations. The KIR differ between individuals according to both gene content and allelic variation, and also display considerable population diversity. Whereas the molecular evolution of these polymorphisms has most likely been subject to natural selection, principally driven by host–pathogen interactions, their patterns of genetic variation worldwide show significant signals of human geographic expansion, demographic history and cultural diversification. As current developments in population genetic analysis and computer simulation improve our ability to discriminate among different – either stochastic or deterministic – forces acting on the genetic evolution of human populations, the study of these systems shows great promise for investigating both the peopling history of modern humans in the time since their common origin and human adaptation to past environmental (e.g. pathogenic) changes. Therefore, in addition to mitochondrial DNA, Y-chromosome, microsatellites, single nucleotide polymorphisms and other markers, immunogenetic polymorphisms represent essential and complementary tools for anthropological studies. PMID:21480890

Estrogen Receptor 1 ( ESR1) Gene Polymorphisms and Obesity Phenotypes in a Population of Young Adults.

PubMed

Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; González-Jiménez, Emilio; Rueda-Medina, Blanca

2017-06-01

Obesity is considered an increasingly serious health problem determined by multiple genetic and environmental factors. Estrogens have been found to play a major role in body weight and adiposity regulation through estrogen receptor 1 ( ESR1). The aim of this study was to determine whether genotype and haplotype frequencies of ESR1 polymorphisms are associated with body composition measures in a population of 572 young adults. A lack of significant association between genotypes of ESR1 gene polymorphisms and obesity phenotypes was seen after adjustment for confounding factors. Linkage disequilibrium (LD) analysis identified a single LD block for the ESR1 gene including PvuII and XbaI single-nucleotide polymorphisms (SNPs) (pairwise r 2 = .66). None of the haplotypes identified revealed statistically significant associations with any of the obesity phenotypes. Our results suggest that polymorphisms of the ESR1 gene do not contribute significantly to the genetic risk for obesity phenotypes in a population of young Caucasian adults.

A Preliminary Study of Gene Polymorphisms Involved in the Neurotransmitters Metabolism of a Homogeneous Spanish Autistic Group

ERIC Educational Resources Information Center

Calahorro, Fernando; Alejandre, Encarna; Anaya, Nuria; Guijarro, Teresa; Sanz, Yolanza; Romero, Auxiliadora; Tienda, Pilar; Burgos, Rafael; Gay, Eudoxia; Sanchez, Vicente; Ruiz-Rubio, Manuel

2009-01-01

Twin studies have shown a strong genetic component for autism. Neurotransmitters, such as serotonin and catecholamines, have been suggested to play a role in the disease since they have an essential function in synaptogenesis and brain development. In this preliminary study, polymorphism of genes implicated in the serotonergic and dopaminergic…

Association of glutathione S-transferase P1 (GSTP1) polymorphism with Tourette syndrome in Taiwanese patients.

PubMed

Shen, Che-Piao; Chou, I-Ching; Liu, Hsin-Ping; Lee, Cheng-Chun; Tsai, Yuhsin; Wu, Bor-Tsang; Hsu, Ban-Dar; Lin, Wei-Yong; Tsai, Fuu-Jen

2014-01-01

The etiology of Tourette syndrome (TS) is multifactorial. TS vulnerability may be associated with genetic and environmental factors. From the genetic point of view, TS is heterogeneous. Previous studies showed that some single-nucleotide polymorphisms (SNPs) of the glutathione-S-transferase P1 (GSTP1) gene can affect cellular proliferation and apoptotic activity and TS is a neurodevelopmental disorder. We guessed that there was a relationship between TS and genetic variants of the GSTP1 gene. Therefore, in this study, we aimed to test the hypothesis that GSTP1 SNPs were associated with TS. We performed a case-control study. One hundred twenty-one TS children and 105 normal children were included in the study. Polymerase chain reaction was used to identify the GSTP1 gene polymorphism at position rs6591256 (A/G, promoter polymorphism) in TS patients and normal children. The polymorphism at position rs6591256 in the GSTP1 gene revealed significant differences in the allele (p=0.0135) and genotype (p=0.0159) distributions between the TS patients and the control group. The A allele was present at a higher frequency than the G allele in the TS patients compared with the control group (odds ratio [OR]=1.91, 95% confidence interval [CI]: 1.14-3.21). The AA genotype was associated with susceptibility to TS with an OR of 2.38 for the AA versus AG genotype (95% CI: 1.29-4.41). These findings suggest that variants in the GSTP1 gene may play a role in susceptibility to TS.

Three Dopaminergic Polymorphisms Are Associated with Academic Achievement in Middle and High School

ERIC Educational Resources Information Center

Beaver, Kevin M.; Vaughn, Michael G.; Wright, John Paul; DeLisi, Matt; Howard, Matthew O.

2010-01-01

Although academic achievement is a heritable construct, to date research has yet to explore its molecular genetic underpinnings. Drawing on data from the National Longitudinal Study of Adolescent Health, the current longitudinal study investigated the associations between polymorphisms in three dopaminergic genes (DAT1, DRD2, and DRD4) and…

Genetic polymorphism and isoenzyme patterns of lactate dehydrogenase in tench (Tinca tinca), crucian carp (Carassius carassius) and carp (Cyprinus carpio).

PubMed

Valenta, M; Slechta, V; Slechtová, V; Kálal, L

1977-01-01

Isoenzyme patterns and the polymorphism of lactate dehydrogenase (LDH) were investigated in 3 fish species of family Cyprinidae, i.e. tench (Tinca tinca), crucian carp (Carassius carassius) and carp (Cyprinus carpio). The isoenzyme patterns were tissue and species specific. In crucian carp subunits with different electrophoretic mobility are present, which are genetically controlled from the B1, B2, A1, A2 and C loci, while the set of loci in carp is B1, B2, A, C1 and C2 and in tench B, A, C. The locus B of LDH in tench, the locus B2 in crucian carp, and the loci B1, C1 and C2 in carp are polymorphic and have two different alleles in each case. The polymorphism did not affect the total LDH activity in the tissues. All the populations investigated were in Hardy-Weinberg equilibrium. The genetic control of the polymorphism in B1 and C1 loci in carp was proved by test matings. The polymorphism in B loci tested in erythrocytes may be utilized as genetic markers in the fish breeding.

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

PubMed

Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

2012-05-01

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore unlikely that its use would be of clinical importance.

The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy

PubMed Central

Wang, Danxin; Sadee, Wolfgang

2012-01-01

CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed. PMID:24466438

Genetic polymorphism of matrix metalloproteinase family and chronic obstructive pulmonary disease susceptibility: a meta-analysis.

PubMed

Zhou, Hongbin; Wu, Yinfang; Jin, Yan; Zhou, Jiesen; Zhang, Chao; Che, Luanqing; Jing, Jiyong; Chen, Zhihua; Li, Wen; Shen, Huahao

2013-10-02

Matrix metalloproteinase (MMP) family is considered to be associated with chronic obstructive pulmonary disease (COPD) pathogenesis, however, no consistent results have been provided by previous studies. In this report, we performed Meta analysis to investigate the association between four kinds of MMP single nucleotide polymorphisms (SNP, MMP1 -1607 1G/2G, MMP3 -1171 5A/6A, MMP9 -1562 C/T, MMP12 -82 A/G) and COPD risk from 21 studies including 4184 cases and 5716 controls. Both overall and subgroup association between SNP and COPD susceptibility were tested. There was no evident association between MMP polymorphisms and COPD susceptibility in general population. On the other hand, subgroup analysis suggested that MMP9 -1562 C/T polymorphism was related to COPD, as we found that C allele carriers were at lower risk in some subgroups stratified by lung function, age and genotype identification method, compared with TT homozygotes. Our results indicated the genotype TT might be one genetic risk factor of severe COPD.

Methodological issues of genetic association studies.

PubMed

Simundic, Ana-Maria

2010-12-01

Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

Single-Nucleotide Polymorphism Markers from De-Novo Assembly of the Pomegranate Transcriptome Reveal Germplasm Genetic Diversity

PubMed Central

Ophir, Ron; Sherman, Amir; Rubinstein, Mor; Eshed, Ravit; Sharabi Schwager, Michal; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Holland, Doron

2014-01-01

Pomegranate is a valuable crop that is grown commercially in many parts of the world. Wild species have been reported from India, Turkmenistan and Socotra. Pomegranate fruit has a variety of health-beneficial qualities. However, despite this crop's importance, only moderate effort has been invested in studying its biochemical or physiological properties or in establishing genomic and genetic infrastructures. In this study, we reconstructed a transcriptome from two phenotypically different accessions using 454-GS-FLX Titanium technology. These data were used to explore the functional annotation of 45,187 fully annotated contigs. We further compiled a genetic-variation resource of 7,155 simple-sequence repeats (SSRs) and 6,500 single-nucleotide polymorphisms (SNPs). A subset of 480 SNPs was sampled to investigate the genetic structure of the broad pomegranate germplasm collection at the Agricultural Research Organization (ARO), which includes accessions from different geographical areas worldwide. This subset of SNPs was found to be polymorphic, with 10.7% loci with minor allele frequencies of (MAF<0.05). These SNPs were successfully used to classify the ARO pomegranate collection into two major groups of accessions: one from India, China and Iran, composed of mainly unknown country origin and which was more of an admixture than the other major group, composed of accessions mainly from the Mediterranean basin, Central Asia and California. This study establishes a high-throughput transcriptome and genetic-marker infrastructure. Moreover, it sheds new light on the genetic interrelations between pomegranate species worldwide and more accurately defines their genetic nature. PMID:24558460

Single-nucleotide polymorphism markers from de-novo assembly of the pomegranate transcriptome reveal germplasm genetic diversity.

PubMed

Ophir, Ron; Sherman, Amir; Rubinstein, Mor; Eshed, Ravit; Sharabi Schwager, Michal; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Holland, Doron

2014-01-01

Pomegranate is a valuable crop that is grown commercially in many parts of the world. Wild species have been reported from India, Turkmenistan and Socotra. Pomegranate fruit has a variety of health-beneficial qualities. However, despite this crop's importance, only moderate effort has been invested in studying its biochemical or physiological properties or in establishing genomic and genetic infrastructures. In this study, we reconstructed a transcriptome from two phenotypically different accessions using 454-GS-FLX Titanium technology. These data were used to explore the functional annotation of 45,187 fully annotated contigs. We further compiled a genetic-variation resource of 7,155 simple-sequence repeats (SSRs) and 6,500 single-nucleotide polymorphisms (SNPs). A subset of 480 SNPs was sampled to investigate the genetic structure of the broad pomegranate germplasm collection at the Agricultural Research Organization (ARO), which includes accessions from different geographical areas worldwide. This subset of SNPs was found to be polymorphic, with 10.7% loci with minor allele frequencies of (MAF<0.05). These SNPs were successfully used to classify the ARO pomegranate collection into two major groups of accessions: one from India, China and Iran, composed of mainly unknown country origin and which was more of an admixture than the other major group, composed of accessions mainly from the Mediterranean basin, Central Asia and California. This study establishes a high-throughput transcriptome and genetic-marker infrastructure. Moreover, it sheds new light on the genetic interrelations between pomegranate species worldwide and more accurately defines their genetic nature.

Microsatellite markers for Leucobryum boninense (Leucobryaceae), endemic to the Bonin Islands, Japan.

PubMed

Oguri, Emiko; Yamaguchi, Tomio; Kajita, Tadashi; Murakami, Noriaki

2013-05-01

Microsatellite primers were developed for Leucobryum boninense, endemic to the Bonin Islands, Japan, to investigate its level of genetic diversity and population genetic structure. • Using next-generation sequencing, 21 primer sets were developed, among which nine loci were polymorphic in the populations of the Bonin Islands. Among these polymorphic loci, the number of alleles per locus ranged from two to 10 (mean = 3.444) and the expected heterozygosity ranged from 0.066 to 0.801 (mean = 0.338). • These results indicate the utility of the nine microsatellite markers that we developed for population genetic studies of L. boninense.

[Genetic aspects of the Stroop test].

PubMed

Nánási, Tibor; Katonai, Enikő Rózsa; Sasvári-Székely, Mária; Székely, Anna

2012-12-01

Impairment of executive control functions in depression is well documented, and performance on the Stroop Test is one of the most widely used markers to measure the decline. This tool provides reliable quantitative phenotype data that can be used efficiently in candidate gene studies investigating inherited components of executive control. Aim of the present review is to summarize research on genetic factors of Stroop performance. Interestingly, only a few such candidate gene studies have been carried out to date. Twin studies show a 30-60% heritability estimate for the Stroop test, suggesting a significant genetic component. A single genome-wide association study has been carried out on Stroop performance, and it did not show any significant association with any of the tested polymorphisms after correction for multiple testing. Candidate gene studies to date pointed to the polymorphisms of several neurotransmitter systems (dopamine, serotonin, acetylcholine) and to the role of the APOE ε4 allele. Surprisingly, little is known about the genetic role of neurothrophic factors and survival factors. In conclusion, further studies are needed for clarifying the genetic background of Stroop performance, characterizing attentional functions.

Genetic and epigenetic variation in Spartina alterniflora following the Deepwater Horizon oil spill.

PubMed

Robertson, Marta; Schrey, Aaron; Shayter, Ashley; Moss, Christina J; Richards, Christina

2017-09-01

Catastrophic events offer unique opportunities to study rapid population response to stress in natural settings. In concert with genetic variation, epigenetic mechanisms may allow populations to persist through severe environmental challenges. In 2010, the Deepwater Horizon oil spill devastated large portions of the coastline along the Gulf of Mexico. However, the foundational salt marsh grass, Spartina alterniflora , showed high resilience to this strong environmental disturbance. Following the spill, we simultaneously examined the genetic and epigenetic structure of recovering populations of S. alterniflora to oil exposure. We quantified genetic and DNA methylation variation using amplified fragment length polymorphism and methylation sensitive fragment length polymorphism (MS-AFLP) to test the hypothesis that response to oil exposure in S. alterniflora resulted in genetically and epigenetically based population differentiation. We found high genetic and epigenetic variation within and among sites and found significant genetic differentiation between contaminated and uncontaminated sites, which may reflect nonrandom mortality in response to oil exposure. Additionally, despite a lack of genomewide patterns in DNA methylation between contaminated and uncontaminated sites, we found five MS-AFLP loci (12% of polymorphic MS-AFLP loci) that were correlated with oil exposure. Overall, our findings support genetically based differentiation correlated with exposure to the oil spill in this system, but also suggest a potential role for epigenetic mechanisms in population differentiation.

Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

PubMed

Bhaskari, J; Premalata, C S; Shilpa, V; Rahul, B; Pallavi, V R; Ramesh, G; Krishnamoorthy, Lakshmi

2016-01-01

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

Contrasting Histories of Three Gene Regions Associated with In(3l)payne of Drosophila Melanogaster

PubMed Central

Hasson, E.; Eanes, W. F.

1996-01-01

In the present report, we studied nucleotide variation in three gene regions of Drosophila melanogaster, spanning >5 kb and showing different degrees of association with the cosmopolitan inversion In(3-L)Payne. The analysis of sequence variation in the regions surrounding the breakpoints and the heat shock 83 (Hsp83) gene locus, located close to the distal breakpoint, revealed the absence of shared polymorphisms and the presence of a number of fixed differences between arrangements, indicating absence of genetic exchange. In contrast, for the esterase-6 gene region, located in the center of the inversion, we observed the presence of shared polymorphisms between arrangements suggesting genetic exchange. In the regions close to the breakpoints, the common St arrangement is 10 times more polymorphic than inverted chromosomes. We propose that the lack of recombination between arrangements in these regions coupled with genetic hitchhiking is the best explanation for the low heterozygosity observed in inverted lines. Using the data for the breakpoints, we estimate that this inversion polymorphism is around 0.36 million yr old. Although it is widely accepted that inversions are examples of balanced polymorphisms, none of the current neutrality tests including our Monte Carlo simulations showed significant departure from neutral expectations. PMID:8978045

[Genetic polymorphism and forensic application of 30 InDel loci of Han population in Beijing].

PubMed

Bai, Ru-Feng; Jiang, Li-Zhe; Zhang, Zhong; Shi, Mei-Sen

2013-12-01

To study the genetic diversities of 30 insertion-deletion (InDel) polymorphisms loci of Han population in Beijing, and to evaluate their forensic application, 210 unrelated healthy individuals of Han population in Beijing were investigated to determine the distributions of allele frequencies by using Investigator DIP system. The PCR products were detected with ABI 3130 XL Genetic Analyzer. Forensic parameters were calculated with relevant statistical analysis software. As a result, after the Bonferroni correction at a 95% significance level, there were no significant departures from Hardy-Weinberg equilibrium or significant linkage disequilibrium between the loci. The power of discrimination (DP) varies between 0.2690 (HLD118) and 0.6330 (HLD45), and the combined discrimination power (TDP) for the 30 InDel loci is 0.999999999985. The combined power of exclusion was 0.98771049 in trio cases (CPE(trio)) and 0.94579456 in duo cases (CPE(duo)). The parentage testing of 32 cases revealed no mutations happened to 30 InDel loci. Multiplex detection of the 30 InDel loci revealed a highly polymorphic genetic distribution in Beijing Han population, which represents a complementary tool in human identification studies, especially in challenging DNA cases.

Genetic polymorphisms of 54 mitochondrial DNA SNP loci in Chinese Xibe ethnic minority group

PubMed Central

Shen, Chun-Mei; Hu, Li; Yang, Chun-Hua; Yin, Cai-Yong; Li, Zhi-Dan; Meng, Hao-Tian; Guo, Yu-Xin; Mei, Ting; Chen, Feng; Zhu, Bo-Feng

2017-01-01

We analyzed the genetic polymorphisms of 54 mitochondrial DNA (mtDNA) variants in Chinese Xibe ethnic minority group. A total of 137 unrelated healthy volunteers from Chinese Xibe group were the objects of our study. Among the selected loci, there were 51 variable positions including transitions and transversions, and single nucleotide transitions were common (83.93%) versus transversions. These variations defined 64 different mtDNA haplotypes exclusive of (CA)n and 9 bp deletion variation. The haplotype diversity and discrimination power in Xibe population were 0.9800 ± 0.004 and 0.9699, respectively. Besides, we compared Xibe group with 18 other populations and reconstructed a phylogenetic tree using Neighbor-Joining method. The result revealed that Xibe group was a close to Xinjiang Han and Yanbian Korean groups. Our data also indicated that Xibe group has a close relationship with Daur and Ewenki groups, which is reflected by the history that Xibe was influenced by Daur and Ewenki groups during the development of these groups. In conclusion, the variants we studied are polymorphic and could be used as informative genetic markers for forensic and population genetic application. PMID:28327596

Genetic differentiation and population structure of five ethnic groups of Punjab (North-West India).

PubMed

Singh, Gagandeep; Talwar, Indu; Sharma, Rubina; Matharoo, Kawaljit; Bhanwer, A J S

2016-12-01

The state of Punjab in the North-West part of India has acted as the main passage for all the major human invasions into the Indian subcontinent. It has resulted in the mixing of foreign gene pool into the local populations, which led to an extensive range of genetic diversity and has influenced the genetic structure of populations in Punjab, North-West India. The present study was conducted to examine the genetic structure, relationships, and extent of genetic differentiation in five Indo-European speaking ethnic groups of Punjab. A total of 1021 unrelated samples belonging to Banias, Brahmins, Jat Sikhs, Khatris, and Scheduled castes were analyzed for four human-specific Ins/Del polymorphic loci (ACE, APO, PLAT, and D1) and three restriction fragment length polymorphisms ESR (PvuII), LPL (PvuII), and T2 (MspI) using Polymerase chain reaction (PCR). All the loci were found to be polymorphic among the studied populations. The frequency of the Alu insertion at APO locus was observed to exhibit the highest value (82.6-96.3 %), whereas D1 exhibited the lowest (26.5-45.6 %) among all the ethnic groups. The average heterozygosity among the studied populations ranged from 0.3816 in Banias to 0.4163 in Khatris. The F ST values ranged from 0.0418 to 0.0033 for the PLAT and LPL loci, respectively, with an average value being 0.0166. Phylogenetic analysis revealed that Banias and Khatris are genetically closest to each other. The Jat Sikhs are genetically close to Brahmins and are distant from the Banias. The Jat Sikhs, Banias, Brahmins, and Khatris are genetically very distant from the Scheduled castes. Overall, Uniform allele frequency distribution patterns, high average heterozygosity values, and a small degree of genetic differentiation in this study suggest a genetic proximity among the selected populations. A low level of genetic differentiation was observed in the studied population groups indicating that genetic drift might have been small or negligible in shaping the genetic structure of North-West Indian Populations.

Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

PubMed

Zhang, H; Ji, W L; Li, M; Zhou, L Y

2015-10-14

Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation, history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species.

Polymorphic Alu insertions among Mayan populations.

PubMed

Herrera, R J; Rojas, D P; Terreros, M C

2007-01-01

The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

Isolation and characterization of 12 microsatellite loci in soapbark, Quillaja saponaria (Quillajaceae)1

PubMed Central

Letelier, Luis; Harvey, Nick; Valderrama, Aly; Stoll, Alexandra; González-Rodríguez, Antonio

2015-01-01

Premise of the study: Microsatellite primers were developed for the endemic Chilean tree Quillaja saponaria (Quillajaceae), a common member of the sclerophyllous Mediterranean forest, to investigate intraspecific patterns of genetic diversity and structure. Methods and Results: Using an enriched library, 12 polymorphic microsatellite loci were developed in Q. saponaria. All loci consisted of dinucleotide repeats. The average number of alleles per locus was 5.3 (2–13), with a total of 64 alleles recorded in 39 individuals from three populations. Conclusions: The microsatellite markers described here are the first characterized for Q. saponaria. The polymorphic loci will be useful in studies of genetic diversity and genetic population differentiation in natural populations of this species. PMID:25995980

Demonstration of protein-based human identification using the hair shaft proteome [Protein-based human identification: A proof of concept using the hair shaft proteome

DOE PAGES

Parker, Glendon J.; Leppert, Tami; Anex, Deon S.; ...

2016-09-07

Human identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 singlemore » nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). Furthermore, this study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.« less

Demonstration of protein-based human identification using the hair shaft proteome [Protein-based human identification: A proof of concept using the hair shaft proteome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, Glendon J.; Leppert, Tami; Anex, Deon S.

Human identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 singlemore » nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). Furthermore, this study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.« less

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PubMed

Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

2010-08-01

Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mating system and extra-pair paternity in the Fan-tailed Gerygone Gerygone flavolateralis in relation to parasitism by the Shining Bronze-cuckoo Chalcites lucidus

PubMed Central

Kuehn, Ralph; Gazda, Małgorzata A.; Sato, Nozomu J.; Okahisa, Yuji; Tanaka, Keita D.; Attisano, Alfredo; Gula, Roman; Ueda, Keisuke; Theuerkauf, Jörn

2018-01-01

Extra-pair copulation can increase genetic diversity and offspring fitness. However, it may also increase intra-nest variability in avian hosts of brood parasites, which can decrease the discrimination ability of host parents towards the parasite. In New Caledonia, the Fan-tailed Gerygone (Gerygone flavolateralis), which is parasitized by the Shining Bronze-cuckoo (Chalcites lucidus), has two nestling morphs, dark and bright, that can occur in monomorphic and polymorphic broods. Gerygone parents recognize and eject parasite nestlings from their nest, but the presence of polymorphic broods may increase the chances of recognition errors. Using 17 microsatellite markers, we investigated the mating system of the Fan-tailed Gerygone to understand the mechanisms underlying nestling polymorphism. We hypothesised that extra-pair copulations would lead to a higher proportion of polymorphic broods caused by higher genetic variability, thus creating a trade-off between genetic benefits and host defence reliability. Extra-pair paternity occurred in 6 of 36 broods, which resulted in 6 of 69 offspring sired by extra-pair males. Broods with and without mixed paternity were comparably often parasitized. Extra-pair paternity did not influence the proportions of bright, dark and polymorphic broods. Compared to bright siblings in polymorphic broods, dark nestlings tended to have lower heterozygosity, particularly in loci associated with skin coloration. The results also suggested that there is no obstacle for genetic exchange between individuals from forest and savannah, possibly due to dispersal of offspring. We conclude that the Fan-tailed Gerygone is a socially monogamous species with a low rate of extra-pair paternity compared to closely related species. Extra-pair paternity increased offspring genetic variability without measurable associated costs by brood parasitism. The results highlight the importance of studying host mating systems to assess the trade-offs between host defence and offspring fitness in co-evolutionary arms races. PMID:29518150

Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility.

PubMed

Li, S-S; Li, J; Xiao, Z; Ren, A-G; Jin, L

2014-03-24

The aim of this study was to explore the relationship between 2 genetic polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and A1298C, and determine the long-term reproductive outcome in infertile men. This was a prospective study conducted in an andrology clinic. Men with a 1-year history of infertility were assessed for the MTHFR polymorphisms at a 5-year follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism between men who did and did not bear children during follow-up. Of the 215 men who were infertile at 1 year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception during the 5-year follow-up, with the highest rate in the first year (32.6%). The MTHFR 677TT genotype (homozygote) was associated with a substantially increased risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type). Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a risk factor for male infertility during 5-year follow-up, whereas a correlation between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility.

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 clinical outcome of the patients. © 2015 Wiley Periodicals, Inc.

Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies

PubMed Central

Gimode, Davis; Odeny, Damaris A.; de Villiers, Etienne P.; Wanyonyi, Solomon; Dida, Mathews M.; Mneney, Emmarold E.; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M.

2016-01-01

Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional breeding programs in order to efficiently optimize productivity. PMID:27454301

Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies.

PubMed

Gimode, Davis; Odeny, Damaris A; de Villiers, Etienne P; Wanyonyi, Solomon; Dida, Mathews M; Mneney, Emmarold E; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M

2016-01-01

Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional breeding programs in order to efficiently optimize productivity.

A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children.

PubMed

Yan, Jingrong; Yin, Ming; Dreyer, ZoAnn E; Scheurer, Michael E; Kamdar, Kala; Wei, Qingyi; Okcu, M Fatih

2012-04-01

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have been implicated in childhood acute lymphoblastic leukemia (ALL) risk, but previously published studies were inconsistent and recent meta-analyses were not adequate. In a meta-analysis of 21 publications with 4,706 cases and 7,414 controls, we used more stringent inclusion method and summarized data on associations between MTHFR C677T and A1298C polymorphisms and childhood ALL risk. We found an overall association between 677T variant genotypes and reduced childhood ALL risk. Specifically, in the dominant genetic model, an association was found in a fixed-effect (TT + CT vs. CC: OR = 0.92; 95% CI = 0.85-0.99) but not random-effect model, whereas such an association was observed in both homozygote genetic model (TT vs. CC: OR = 0.80; 95% CI = 0.70-0.93 by fixed effects and OR = 0.78; 95% CI = 0.65-0.93 by random effects) and recessive genetic model (TT vs. CC + CT: OR = 0.83; 95% CI = 0.72-0.95 by fixed effects and OR = 0.84; 95% CI = 0.73-0.97 by random effects). These associations were also observed in subgroups by ethnicity: for Asians in all models except for the dominant genetic model by random effect and for Caucasians in all models except for the recessive genetic model. However, the A1298C polymorphism did not appear to have an effect on childhood ALL risk. These results suggest that the MTHFR C677T, but not A1298C, polymorphism is a potential biomarker for childhood ALL risk. Copyright © 2011 Wiley Periodicals, Inc.

[Studying the association between genetic polymorphism of growth factors and the development of primary open-angle glaucoma].

PubMed

Kirilenko, M Yu; Tikunova, E V; Sirotina, S S; Polonikov, A V; Bushueva, O Yu; Churnosov, M I

Primary open-angle glaucoma (POAG) is a multifactorial disease, etiopathogenesis of which largely depends on growth factors. Possessing a variety of medical and biological effects, these cytokines may influence the development and progression of POAG. to reveal the role of genetic polymorphisms of growth factors in predisposition to developing POAG that is refractory to local hypotensive therapy. The object of the study were 162 patients with stage II-III POAG, in whom local hypotensive therapy was inefficient, 90 patients with stage II-III POAG well controlled on local hypotensive therapy, and 191 controls. The material for the study was venous blood taken from the cubital vein of a proband. Isolation of genomic DNA was performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of growth factors was performed through allelic discrimination. For that, synthesis of DNA was carried out via polymerase chain reaction (PCR). It is found that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is refractory to local hypotensive therapy. A statistical model for predicting such a risk has been proposed that includes: VEGF-A с.-958C>T genetic marker (rs 833,061), age, concomitant non-inflammatory ocular diseases, microvascular changes in the conjunctiva, the degree of pigmentation of the angle of the anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the model is 90.42%. The T IGFR-1 genetic variant and a combination of the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG that is refractory to local hypotensive therapy.

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

PubMed

Dai, Yi; Wu, Yuquan; Li, Yansheng

2015-01-01

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. 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 χ(2) 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. 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). 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.

X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population.

PubMed

Wang, Liming; Qian, Junfeng; Ying, Chunxiao; Zhuang, Yongwei; Shang, Xingjie; Xu, Fang

2016-12-01

X-ray cross-complementing groups 1 (XRCC1) rs1799782 C>T polymorphisms and colorectal cancer susceptibility were not clear. The purpose of this study was to evaluate the association between XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility by meta-analysis. Related databases of Medline, CNKI, and Wanfang were systematic searched for the studies related to XRCC1 rs1799782 C>T polymorphisms and colorectal cancer risk in Chinese Han population. The genotype distribution of CC, CT and TT were extracted from each included studies in the colorectal cancer patients and healthy control subjects. The odds ratio (OR) and its 95% confidence interval (95% CI) was used to assess the correlation between genetype and colorectal cancer risk. The publications for this study was evaluated by Begg's funnel plot and Egger's line regression test. The median frequency of CC, CT, and TT genotype in cancer group were 48%, 41% and 11%; For control group, they were 51%, 40% and 8%; the pooled results showed that OR = 1.32 (95% CI: 1.041-1.67, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model OR = 1.32 (95% CI: 1.041-1.67, P < 0.05), dominant genetic model OR = 1.21 (95% CI: 1.00-1.46, P < 0.05) and homozygous genetic model OR = 1.43 (95% CI: 1.07-1.91, P < 0.05). The funnel plot was significant asymmetric at the bottom and the Egger's test also indicated significant publication bias (t = 2.43, P = 0.04) for recessive genetic model. But, no publication bias was found in dominant and homozygous model (P > 0.05). Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal.

Development of 101 novel EST-derived single nucleotide polymorphism markers for Zhikong scallop ( Chlamys farreri)

NASA Astrophysics Data System (ADS)

Li, Jiqin; Bao, Zhenmin; Li, Ling; Wang, Xiaojian; Wang, Shi; Hu, Xiaoli

2013-09-01

Zhikong scallop ( Chlamys farreri) is an important maricultured species in China. Many researches on this species, such as population genetics and QTL fine-mapping, need a large number of molecular markers. In this study, based on the expressed sequence tags (EST), a total of 300 putative single nucleotide polymorphisms (SNPs) were selected and validated using high resolution melting (HRM) technology with unlabeled probe. Of them, 101 (33.7%) were found to be polymorphic in 48 individuals from 4 populations. Further evaluation with 48 individuals from Qingdao population showed that all the polymorphic loci had two alleles with the minor allele frequency ranged from 0.046 to 0.500. The observed and expected heterozygosities ranged from 0.000 to 0.925 and from 0.089 to 0.505, respectively. Fifteen loci deviated significantly from Hardy-Weinberg equilibrium and significant linkage disequilibrate was detected in one pair of markers. BLASTx gave significant hits for 72 of the 101 polymorphic SNP-containing ESTs. Thirty four polymorphic SNP loci were predicted to be non-synonymous substitutions as they caused either the change of codons (33 SNPs) or pretermination of translation (1 SNP). The markers developed can be used for the population studies and genetic improvement on Zhikong scallop.

Molecular marker-based genetic diversity analysis of scantly studied Brazilian accessions of a medicinal plant, Morinda citrifolia L. (noni).

PubMed

Bordallo, P N; Monteiro, A M R; Sousa, J A; Aragão, F A S

2017-02-23

Morinda citrifolia L., commonly known as noni, has been used for the treatment of various diseases for over two centuries. It was introduced and widely disseminated in Brazil because of its high market value and ease of adaptation to the soil and climatic conditions of the country. The aim of this study was to estimate the genetic variability of noni accessions from the collection of Embrapa Agroindústria Tropical in Brazil. We evaluated 36 plants of the 13 accessions of noni from the germplasm collection of M. citrifolia. Several methods of DNA extraction were tested. After definition of the method, the DNA of each sample was subjected to polymerase chain reactions using 20 random amplified polymorphic DNA primers. The band patterns on agarose gel were converted into a binary data matrix, which was used to estimate the genetic distances between the plants and to perform the cluster analyses. Of the total number of markers used in this study, 125 (81.1%) were polymorphic. The genetic distances between the genotypes ranged from 0.04 to 0.49. Regardless of the high number of polymorphic bands, the genetic variability of the noni plants evaluated was low since most of the genotypes belonged to the same cluster as shown by the dendrogram and Tocher's cluster analysis. The low genetic diversity among the studied noni individuals indicates that additional variability should be introduced in the germplasm collection of noni by gathering new individuals and/or by hybridizing contrasting individuals.

Polymorphisms in VDR gene in Tunisian postmenopausal women are associated with osteopenia phenotype.

PubMed

Sassi, R; Sahli, H; Souissi, C; Sellami, S; Ben Ammar El Gaaied, A

2015-01-01

Osteopenia is characterized by intermediate values of bone mineral density (BMD) as compared to normal and osteoporotic subjects. BMD, a surrogate phenotype for osteoporosis, is influenced in part by genetic factors. Among the genes associated with BMD, the vitamin D receptor (VDR) was the first gene studied as a potential candidate associated with BMD in adult and postmenopausal bone loss. However, results are controversial. To determine whether VDR polymorphisms ApaI and TaqI are associated with BMD, osteopenia, osteoporosis and low-impact fracture risk in North Africans, these genotypes were analyzed in 566 postmenopausal Tunisian women. In postmenopausal Tunisian women, the GT ApaI genotype seems to be protective against osteoporosis development (p = 0.02; odds ratio = 0.54). Moreover, the presence of the combined GT/TT genotype of ApaI and TaqI polymorphisms is more frequent in normal BMD women than in osteoporotic women (p = 0.00; odds ratio = 0.41). Interestingly, the GG ApaI genotype is associated with osteopenia development (p = 0.02; odds ratio = 1.86) and also the TT TaqI polymorphism (p = 0.02; odds ratio = 1.53). The GG ApaI genotype is associated with a three times risk of vertebral fracture. The ApaI polymorphism showed an association with osteopenia and low-impact vertebral fracture incidence but not with osteoporosis. The TaqI polymorphism is associated specifically with the osteopenia phenotype. The presence of the two polymorphisms increases the risk to develop osteopenia in postmenopausal Tunisian women. Osteopenia seems to be genetically determined. However, osteoporosis is the result of interaction between genetic and environmental factors.

Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic polymorphism.

PubMed

Chan, Betty S H; Sellors, Kate; Chiew, Angela L; Buckley, Nicholas A

2015-02-01

Phenytoin is metabolised in the liver by cytochrome (CYP)2C9 and 2C19 enzymes. Due to saturation of enzyme capacity, the elimination half-life is prolonged at supratherapeutic levels. Genetic polymorphisms of CYP2C9 and 2C19 are reasonably common and further prolong the elimination of phenytoin. There are conflicting reports regarding whether multiple-dose activated charcoal (MDAC) significantly increases the clearance of phenytoin in poisoning. We present 3 patients with phenytoin toxicity and very slow elimination secondary to reduced CYP enzyme function from genetic polymorphisms. MDAC was used in two patients and led to rapid and large reductions in the measured elimination half-lives. This is contrasted with very prolonged elimination in a third patient who did not receive MDAC. MDAC may play a role in the management of chronic phenytoin toxicity, especially in those with very slow endogenous elimination secondary to genetic polymorphisms.

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

PubMed

Sterpone, Silvia; Cozzi, Renata

2010-07-25

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.

Dog-Owner Attachment Is Associated With Oxytocin Receptor Gene Polymorphisms in Both Parties. A Comparative Study on Austrian and Hungarian Border Collies.

PubMed

Kovács, Krisztina; Virányi, Zsófia; Kis, Anna; Turcsán, Borbála; Hudecz, Ágnes; Marmota, Maria T; Koller, Dóra; Rónai, Zsolt; Gácsi, Márta; Topál, József

2018-01-01

Variations in human infants' attachment behavior are associated with single nucleotide polymorphisms (SNPs) in the oxytocin receptor (OXTR) gene, suggesting a genetic component to infant-mother attachment. However, due to the genetic relatedness of infants and their mothers, it is difficult to separate the genetic effects of infants' OXTR genotype from the environmental effects of mothers' genotype possibly affecting their parental behavior. The apparent functional analogy between child-parent and dog-owner relationship, however, offers a way to disentangle the effects of these factors because pet dogs are not genetically related to their caregivers. In the present study we investigated whether single nucleotide polymorphisms of pet dogs' OXTR gene (-213AG,-94TC,-74CG) and their owners' OXTR gene (rs53576, rs1042778, rs2254298) are associated with components of dog-owner attachment. In order to investigate whether social-environmental effects modulate the potential genetic influence on attachment, dogs and their owners from two different countries (Austria and Hungary, N = 135 in total) were tested in a modified version of the Ainsworth Strange Situation Test (SST) and questionnaires were also used to collect information about owner personality and attachment style. We coded variables related to three components of attachment behavior in dogs: their sensitivity to the separation from and interaction with the owner (Attachment), stress caused by the unfamiliar environment (Anxiety), and their responsiveness to the stranger (Acceptance). We found that (1) dogs' behavior was significantly associated with polymorphisms in both dogs' and owners' OXTR gene, (2) SNPs in dogs' and owners' OXTR gene interactively influenced dog-human relationship, (3) dogs' attachment behavior was affected by the country of origin, and (4) it was related to their owners' personality as well as attachment style. Thus, the present study provides evidence, for the first time, that both genetic variation in the OXTR gene and various aspects of pet dogs' environmental background are associated with their attachment to their human caregivers.

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.

[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 passports.

Genetic Diversity and Demographic History of Cajanus spp. Illustrated from Genome-Wide SNPs

PubMed Central

Saxena, Rachit K.; von Wettberg, Eric; Upadhyaya, Hari D.; Sanchez, Vanessa; Songok, Serah; Saxena, Kulbhushan; Kimurto, Paul; Varshney, Rajeev K.

2014-01-01

Understanding genetic structure of Cajanus spp. is essential for achieving genetic improvement by quantitative trait loci (QTL) mapping or association studies and use of selected markers through genomic assisted breeding and genomic selection. After developing a comprehensive set of 1,616 single nucleotide polymorphism (SNPs) and their conversion into cost effective KASPar assays for pigeonpea (Cajanus cajan), we studied levels of genetic variability both within and between diverse set of Cajanus lines including 56 breeding lines, 21 landraces and 107 accessions from 18 wild species. These results revealed a high frequency of polymorphic SNPs and relatively high level of cross-species transferability. Indeed, 75.8% of successful SNP assays revealed polymorphism, and more than 95% of these assays could be successfully transferred to related wild species. To show regional patterns of variation, we used STRUCTURE and Analysis of Molecular Variance (AMOVA) to partition variance among hierarchical sets of landraces and wild species at either the continental scale or within India. STRUCTURE separated most of the domesticated germplasm from wild ecotypes, and separates Australian and Asian wild species as has been found previously. Among Indian regions and states within regions, we found 36% of the variation between regions, and 64% within landraces or wilds within states. The highest level of polymorphism in wild relatives and landraces was found in Madhya Pradesh and Andhra Pradesh provinces of India representing the centre of origin and domestication of pigeonpea respectively. PMID:24533111

Genetic diversity and genetic structure of consecutive breeding generations of golden mandarin fish (Siniperca scherzeri Steindachner) using microsatellite markers.

PubMed

Luo, X N; Yang, M; Liang, X F; Jin, K; Lv, L Y; Tian, C X; Yuan, Y C; Sun, J

2015-09-25

In this study, 12 polymorphic microsatellites were inves-tigated to determine the genetic diversity and structure of 5 consecu-tive selected populations of golden mandarin fish (Siniperca scherzeri Steindachner). The total numbers of alleles, average heterozyosity, and average polymorphism information content showed that the genetic diversity of these breeding populations was decreasing. Additionally, pairwise fixation index FST values among populations and Da values in-creased from F1 generation to subsequent generations (FST values from 0.0221-0.1408; Da values from 0.0608-0.1951). Analysis of molecular variance indicated that most genetic variations arise from individuals within populations (about 92.05%), while variation among populations accounted for only 7.95%. The allele frequency of the loci SC75-220 and SC101-222 bp changed regularly in the 5 breeding generations. Their frequencies were gradually increased and showed an enrichment trend, indicating that there may be genetic correlations between these 2 loci and breeding traits. Our study indicated that microsatellite markers are effective for assessing the genetic variability in the golden mandarin fish breeding program.

Population structure and genetic variation of the endangered species Elaeagnus mollis Diels (Elaeagnaceae).

PubMed

Zhang, J M; Zhang, F

2015-06-01

Elaeagnus mollis Diels is a group of shrubs and dwarf trees endemic to China and are endangered plants. However, the reason why these plants are endangered remains controversial. The current study aimed to explore the endangered status of E. mollis from a genetic perspective and to propose conservation strategies for this species. Using 16 polymorphic allozyme loci, the population genetic structure was investigated for three populations representing the taxa and variants. The variants exhibited relatively high levels of genetic variation compared to other woody shrubs with similar geographic distributions. The overall genetic diversity (HE = 0.352) was elevated compared to long-lived woody angiosperms. The average number of alleles per locus (A), percentage polymorphic loci (P), and observed heterozygosity (HO) were 2.0, 85.2, and 0.371, respectively. Furthermore, gene flow estimates within the population groups were also elevated. The life history and habitats of E. mollis play major roles in the levels of genetic diversity. The results of this study may help to device strategies for preserving the genetic diversity of E. mollis and for promoting planting.

Polymorphisms of Il-10 (-1082) and RANKL (-438) Genes and the Failure of Dental Implants

PubMed Central

Ribeiro, Rodrigo; Melo, Rayanne; Tortamano Neto, Pedro; Vajgel, André

2017-01-01

Background. Genetic polymorphisms in certain cytokines and chemokines have been investigated to understand why some individuals display implant flaws despite having few risk factors at the time of implant. Purpose. To investigate the association of genetic polymorphisms in interleukin- (IL-) 10 [-1082 region (A/G)] and RANKL [-438 region (A/G)] with the failure of dental implants. Materials and Methods. This study included 90 partially edentulous male and female patients who were rehabilitated with a total of 245 Straumann dental implants. An implant was considered a failure if any of the following occurred: mobility, persistent subjective complaint, recurrent peri-implant infection with suppuration, continuous radiolucency around the implant, probing depth ≥ 5 mm, and bleeding on probing. Buccal mucosal cells were collected for analysis of RANKL438 and IL-10. Results. The implant success rate in this population was 34.4%. The mutant allele (G) in RANKL had an incidence of 52.3% and mutant allele (A) in IL-10 was observed in 37.8%. No statistically significant difference was detected between the failure of the implant and the genotypes and allelic frequencies. Conclusion. No association was detected between the genetic polymorphisms of RANKL (-438) and IL-10 (-1082) and the failure of dental implants in the population studied. PMID:28348592

Polymorphisms of Il-10 (-1082) and RANKL (-438) Genes and the Failure of Dental Implants.

PubMed

Ribeiro, Rodrigo; Melo, Rayanne; Tortamano Neto, Pedro; Vajgel, André; Souza, Paulo Roberto Eleutério; Cimões, Renata

2017-01-01

Background . Genetic polymorphisms in certain cytokines and chemokines have been investigated to understand why some individuals display implant flaws despite having few risk factors at the time of implant. Purpose . To investigate the association of genetic polymorphisms in interleukin- (IL-) 10 [-1082 region (A/G)] and RANKL [-438 region (A/G)] with the failure of dental implants. Materials and Methods . This study included 90 partially edentulous male and female patients who were rehabilitated with a total of 245 Straumann dental implants. An implant was considered a failure if any of the following occurred: mobility, persistent subjective complaint, recurrent peri-implant infection with suppuration, continuous radiolucency around the implant, probing depth ≥ 5 mm, and bleeding on probing. Buccal mucosal cells were collected for analysis of RANKL438 and IL-10 . Results . The implant success rate in this population was 34.4%. The mutant allele (G) in RANKL had an incidence of 52.3% and mutant allele (A) in IL-10 was observed in 37.8%. No statistically significant difference was detected between the failure of the implant and the genotypes and allelic frequencies. Conclusion . No association was detected between the genetic polymorphisms of RANKL (-438) and IL-10 (-1082) and the failure of dental implants in the population studied.

Isolation and Characterization of Polymorphic Microsatellite Markers from the Malaria Vector Anopheles fluviatilis Species T (Diptera: Culicidae).

PubMed

Lather, Manila; Sharma, Divya; Dang, Amita S; Adak, Tridibes; Singh, Om P

2015-05-01

Anopheles fluviatilis James is an important malaria vector in India, Pakistan, Nepal, and Iran. It has now been recognized as a complex of at least four sibling species-S, T, U, and V, among which species T is the most widely distributed species throughout India. The taxonomic status of these species is confusing owing to controversies prevailing in the literature. In addition, chromosomal inversion genotypes, which were considered species-diagnostic for An. fluviatilis species T, are unreliable due to the existence of polymorphism in some populations. To study the genetic diversity at population level, we isolated and characterized 20 microsatellite markers from microsatellite-enriched genomic DNA library of An. fluviatilis T, of which 18 were polymorphic while two were monomorphic. The number of alleles per locus among polymorphic markers ranged from 4 to 19, and values for observed and expected heterozygosities varied from 0.352 to 0.857 and from 0.575 to 0.933, respectively. Thirteen markers had cross-cryptic species transferability to species S and U of the Fluviatilis Complex. This study provides a promising genetic tool for the population genetic analyses of An. fluviatilis. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Single-nucleotide polymorphism in populations of sockeye salmon Oncorhynchus nerka from Kamchatka Peninsula].

PubMed

Khrustaleva, A M; Gritsenko, O F; Klovach, N V

2013-11-01

The genetic polymorphism of 45 single-nucleotide polymorphism loci was examined in the four largest wild populations of sockeye salmon Oncorhynchusnerka from drainages of the Asian coast of the Pacific Ocean (Eastern and Western Kamchatka). It was demonstrated that sockeye salmon from the Palana River were considerably different from all other populations examined. The most probable explanation of the observed differences is the suggestion on possible demographic events in the history of this population associated with the decrease in its effective number. To study the origin, colonization patterns, and evolution of Asian sockeye salmon, as well as to resolve some of the applied tasks, like population assignment and genetic identification, a differentiation approach to SNP-marker selection was suggested. Adaptively important loci that evolve under the pressure of balancing (stabilizing) selection were identified, thanks to which the number of loci that provide the baseline classification error rates in the population assignment tests was reduced to 30. It was demonstrated that SNPs located in the MHC2 and GPH genes were affected by diversifying selection. Procedures for selecting single-nucleotide polymorphisms for phylogenetic studies of Asian sockeye salmon were suggested. Using principal-component analysis, 17 loci that adequately reproduce genetic differentiation within arid among the regions of the origin of Kamchatka sockeye salmon, were selected.

Effect of GSTM1 and GSTT1 Polymorphisms on Genetic Damage in Humans Populations Exposed to Radiation From Mobile Towers.

PubMed

Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Kanupriya; Aggarwal, Neeraj K; Kumar, Rajesh; Gupta, Ranjan

2016-04-01

All over the world, people have been debating about associated health risks due to radiation from mobile phones and mobile towers. The carcinogenicity of this nonionizing radiation has been the greatest health concern associated with mobile towers exposure until recently. The objective of our study was to evaluate the genetic damage caused by radiation from mobile towers and to find an association between genetic polymorphism of GSTM1 and GSTT1 genes and DNA damage. In our study, 116 persons exposed to radiation from mobile towers and 106 control subjects were genotyped for polymorphisms in the GSTM1 and GSTT1 genes by multiplex polymerase chain reaction method. DNA damage in peripheral blood lymphocytes was determined using alkaline comet assay in terms of tail moment (TM) value and micronucleus assay in buccal cells (BMN). There was a significant increase in BMN frequency and TM value in exposed subjects (3.65 ± 2.44 and 6.63 ± 2.32) compared with control subjects (1.23 ± 0.97 and 0.26 ± 0.27). However, there was no association of GSTM1 and GSTT1 polymorphisms with the level of DNA damage in both exposed and control groups.

Genetic characterization of Toxoplasma gondii isolates from Portugal, Austria, and Israel reveals higher genetic variability within the type II lineage

USDA-ARS?s Scientific Manuscript database

This study compared genetic diversity of Toxoplasma gondii isolates from Portugal, Austria and Israel. For this, we genotyped 90 T. gondii isolates (16 from Portugal, 67 from Austria and 7 from Israel) using 10 nested PCR-restriction length polymorphism (RFLP) genetic markers and 15 microsatellite (...

Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population.

PubMed

Koishi, Shinko; Yamamoto, Kenji; Matsumoto, Hideo; Koishi, Seiji; Enseki, Youichi; Oya, Akitoshi; Asakura, Arata; Aoki, Yutaka; Atsumi, Mariko; Iga, Tomiei; Inomata, Jyoji; Inoko, Hidetoshi; Sasaki, Tsukasa; Nanba, Eiji; Kato, Nobumasa; Ishii, Tetsuo; Yamazaki, Kosuke

2006-05-01

Autism is now widely accepted as a biological disorder which, by and large, starts before birth. It has been shown that serotonin (5-HT) is associated with several psychological processes and hyperserotoninemia is observed in some autistic patients. The results of previous reports about family-based association studies between the serotonin transporter (5-HTT) gene promoter polymorphism and autism are controversial. In this study, an analysis using the transmission/disequilibrium test (TDT) between the 5-HTT gene promoter polymorphism and autism in 104 trios, all ethnically Japanese, showed no significant linkage disequilibrium (P=0.17). Recently, it has been reported that some haplotypes at the serotonin transporter locus may be associated with the pathogenesis of autism. Therefore, further investigations by haplotype analyses are necessary to confirm the implications of genetic variants of the serotonin transporter in the etiology of autism.

Genetic polymorphism and chronic obstructive pulmonary disease.

PubMed

Yuan, Cunhua; Chang, De; Lu, Guangming; Deng, Xiaowei

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a common chronic disease, and its morbidity and mortality are increasing. There are many studies that have tried to explain the pathogenesis of COPD from genetic susceptibility, to identify the susceptibility of COPD factors, which play a role in early prevention, early detection and the early treatment. However, it is well known that COPD is an inflammatory disease characterized by incomplete reversible airflow limitation in which genes interact with the environment. In recent years, many studies have proved gene polymorphisms and COPD correlation. However, there is less research on the relationship between COPD and genome-wide association study (GWAS), epigenetics and apoptosis. In this paper, we summarized the correlation between gene level and COPD from the following four aspects: the GWAS, the gene polymorphism, the epigenetics and the apoptosis, and the relationship between COPD and gene is summarized comprehensively.

Association of Interleukin-17 polymorphism (-197G/A) in chronic and localized aggressive periodontitis.

PubMed

Chaudhari, Harshal Liladhar; Warad, Shivaraj; Ashok, Nipun; Baroudi, Kusai; Tarakji, Bassel

2016-01-01

Interleukin 17(IL-17) is a pro-inflammatory cytokine produced mainly by Th17 cells. The present study was undertaken to investigate a possible association between IL-17 A genetic polymorphism at (-197A/G) and susceptibility to chronic and localized aggressive periodontitis (LAgP) in an Indian population. The study was carried out on 105 subjects, which included 35 LAgP patients, 35 chronic periodontitis patients and 35 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17 genetic polymorphism at (-197A/G), by using the polymerase chain reaction-restriction fragment length polymorphism method. A statistically significant difference was seen in the genotype distribution among chronic periodontitis patients, LAgP patients and healthy subjects. There was a significant difference in the distribution of alleles among chronic periodontitis patients, LAgP patients and healthy subjects. The odds ratio for A allele versus G allele was 5.1 between chronic periodontitis patients and healthy controls, and 5.1 between LAgp patients and healthy controls. Our study concluded that IL-17 A gene polymorphism at (-197A/G) is linked to chronic periodontitis and LAgP in Indian population. The presence of allele A in the IL-17 gene polymorphism (-197A/G) can be considered a risk factor for chronic periodontitis and LAgP.

Tumor necrosis factor-α -308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura.

PubMed

El Sissy, Maha H; El Sissy, A H; Elanwary, Sherif

2014-07-01

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the cause of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Children with ITP have a T-helper 1-type cytokine pattern with elevated levels of tumor necrosis factor-alpha (TNF-α) as in most autoimmune diseases. Researchers have shown that polymorphism in the TNF-α gene at position -308 affects gene transcriptions with increased TNF-α production. The current case-control study aimed at detecting the frequency of TNF-α -308G/A gene polymorphism as genetic markers in Egyptian children with ITP, and to clear out their possible role in choosing the treatment protocols of therapy, using PCR restriction fragment length polymorphism assay. Ninety-two ITP patients and 100 age and sex-matched healthy controls were recruited in the study. The results obtained revealed that the frequency of TNF-α -308A/A homotype in ITP patients was significantly higher than that of the controls, and conferred almost six-fold increased risk of ITP acquisition. The polymorphic A allele frequency was significantly higher in ITP patients than in the controls, conferring almost two-fold increased ITP risk. In conclusion, our study suggests the possibility that TNF-α -308 gene polymorphism may contribute to the susceptibility of childhood ITP in Egyptian children.

Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration.

PubMed

Sychev, Dmitry A; Zastrozhin, Mikhail S; Miroshnichenko, Igor I; Baymeeva, Natalia V; Smirnov, Valery V; Grishina, Elena A; Ryzhikova, Kristina A; Mirzaev, Karin B; Markov, Dmitry D; Skryabin, Valentin Y; Snalina, Nataliya E; Nosikova, Polina G; Savchenko, Ludmila M; Bryun, Evgeny A

2017-09-26

Haloperidol is used for the treatment of alcohol use disorders in patients with signs of alcohol-related psychosis. Haloperidol therapy poses a high risk of adverse drug reactions (ADR). Contradictory data, which include the effects of genetic polymorphisms in genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate and plasma drug concentration ratio, are described in patients with different genotypes. The primary objective of this study was to investigate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on haloperidol equilibrium concentration in patients with alcohol use disorder. The study included 69 male patients with alcohol use disorder. Genotyping was performed using the allele-specific real-time PCR. CYP2D6 and CYP3A were phenotyped with HPLC-MS using the concentration of endogenous substrate of the enzyme and its urinary metabolites [6-hydroxy-1,2,3,4-tetrahydro-β-carboline(6-HO-THBC) to pinoline ratio for CYP2D6 and 6-β-hydroxycortisol to cortisol ratio for CYP3A]. The equilibrium plasma concentration was determined using LC-MS-MS. Results indicated that both C/D indexes and equilibrium concentration levels depend on CYP2D6 genetic polymorphism, but only in patients receiving haloperidol intramuscular injections [0.26 (0.09; 0.48) vs. 0.54 (0.44; 0.74), p=0.037]. The study demonstrates that CYP2D6 genetic polymorphism (1846G>A) can affect haloperidol concentration levels in patients with alcohol use disorder.

Recipient But Not Donor Adiponectin Polymorphisms Are Associated With Early Posttransplant Hepatic Steatosis in Patients Transplanted for Non-Nonalcoholic Fatty Liver Disease Indications.

PubMed

John, Binu V; Aiken, Taylor; Garber, Ari; Thomas, Dawn; Lopez, Rocio; Patil, Deepa; Konjeti, Venkata Rajesh; Fung, John J; McCollough, Arthur J; Askar, Medhat

2018-06-01

De novo steatosis after liver transplant is common and can occur in up to one-third of patients who are transplanted for liver disease other than for nonalcoholic fatty liver disease. Genetic factors may influence posttransplant steatosis; in a posttransplant setting, donor or recipient genetic factors could also play roles. Genetic polymorphisms in the adiponectin gene have been associated with metabolic syndrome in the pretransplant setting. We aimed to assess the association between donor and recipient adiponectin polymorphisms and early posttransplant hepatic steatosis identified on liver biopsies. Clinical data were collected for 302 liver transplant patients who underwent protocol biopsies for hepatitis C. Of these, 111 patients had available biopsies and donor/recipient DNA. Patients with grade 1 steatosis or greater (35% of patients) were compared with patients without posttransplant steatosis with respect to clinical features and donor/recipient adiponectin polymorphism genotypes. Patients who developed posttransplant steatosis and those without steatosis were similar with respect to individual components of metabolic syndrome. The adiponectin polymorphisms rs1501299 G/G and rs17300539 G/G genotypes in recipients were associated with early posttransplant graft steatosis. We found no associations between graft steatosis and donor adiponectin polymorphisms. Genetic polymorphisms in the adiponectin gene of recipients (but not donors) are associated with early de novo posttransplant hepatic steatosis, independent of components of metabolic syndrome.

Analysis of single nucleotide polymorphisms in case-control studies.

PubMed

Li, Yonghong; Shiffman, Dov; Oberbauer, Rainer

2011-01-01

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variants in the human genome. SNPs are known to modify susceptibility to complex diseases. We describe and discuss methods used to identify SNPs associated with disease in case-control studies. An outline on study population selection, sample collection and genotyping platforms is presented, complemented by SNP selection, data preprocessing and analysis.

Genetic diversity and population structure of a protected species: Polygala tenuifolia Willd.

PubMed

Peng, Yan Qun; Fan, Ling Ling; Mao, Fu Ying; Zhao, Yun Sheng; Xu, Rui; Yin, Yu Jie; Chen, Xin; Wan, De Guang; Zhang, Xin Hui

2018-03-01

Polygala tenuifolia Willd. is an important protected species used in traditional Chinese medicine. In the present study, amplified fragment length polymorphism (AFLP) markers were employed to characterize the genetic diversity in wild and cultivated P. tenuifolia populations. Twelve primer combinations of AFLP produced 310 unambiguous and repetitious bands. Among these bands, 261 (84.2%) were polymorphic. The genetic diversity was high at the species level: percentage of polymorphic loci (PPL)=84.2%, Nei's gene diversity (h)=0.3296 and Shannon's information index (I)=0.4822. Between the two populations, the genetic differentiation of 0.1250 was low and the gene flow was relatively high, at 3.4989. The wild population (PPL=81.9%, h=0.3154, I=0.4635) showed a higher genetic diversity level than the cultivated population (PPL=63.9%, h=0.2507, I=0.3688). The results suggest that the major factors threatening the persistence of P. tenuifolia resources are ecological and human factors rather than genetic. These results will assist with the design of conservation and management programs, such as in natural habitat conservation, setting the excavation time interval for resource regeneration and the substitution of cultivated for wild plants. Copyright © 2018 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

A Web-Based Genetic Polymorphism Learning Approach for High School Students and Science Teachers

ERIC Educational Resources Information Center

Amenkhienan, Ehichoya; Smith, Edward J.

2006-01-01

Variation and polymorphism are concepts that are central to genetics and genomics, primary biological disciplines in which high school students and undergraduates require a solid foundation. From 1998 through 2002, a web-based genetics education program was developed for high school teachers and students. The program included an exercise on using…

[Single nucleotide polymorphism and its application in allogeneic hematopoietic stem cell transplantation--review].

PubMed

Li, Su-Xia

2004-12-01

Single nucleotide polymorphism (SNP) is the third genetic marker after restriction fragment length polymorphism (RFLP) and short tandem repeat. It represents the most density genetic variability in the human genome and has been widely used in gene location, cloning, and research of heredity variation, as well as parenthood identification in forensic medicine. As steady heredity polymorphism, single nucleotide polymorphism is becoming the focus of attention in monitoring chimerism and minimal residual disease in the patients after allogeneic hematopoietic stem cell transplantation. The article reviews SNP heredity characterization, analysis techniques and its applications in allogeneic stem cell transplantation and other fields.

The KCNH2 genetic polymorphism (1956, C>T) is a novel biomarker that is associated with CCB and α,β-ADR blocker response in EH patients in China.

PubMed

He, Fazhong; Luo, Jianquan; Luo, Zhiying; Fan, Lan; He, Yijing; Zhu, Dingliang; Gao, Jinping; Deng, Sheng; Wang, Yan; Qian, Yuesheng; Zhou, Honghao; Chen, Xiaoping; Zhang, Wei

2013-01-01

KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs.

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

PubMed Central

Lind, Abigail L.; Wisecaver, Jennifer H.; Lameiras, Catarina; Wiemann, Philipp; Palmer, Jonathan M.; Keller, Nancy P.; Rodrigues, Fernando; Goldman, Gustavo H.

2017-01-01

Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns. PMID:29149178

Arsenic methylation capacity in relation to nutrient intake and genetic polymorphisms in one-carbon metabolism.

PubMed

Gamboa-Loira, Brenda; Hernández-Alcaraz, César; Gandolfi, A Jay; Cebrián, Mariano E; Burguete-García, Ana; García-Martínez, Angélica; López-Carrillo, Lizbeth

2018-07-01

Nutrients and genetic polymorphisms participating in one-carbon metabolism may explain interindividual differences in inorganic arsenic (iAs) methylation capacity, which in turn may account for variations in susceptibility to iAs-induced diseases. 1) To evaluate the association between polymorphisms in five one-carbon metabolism genes (FOLH1 c.223 T > C, MTHFD1 c.1958 G > A, MTHFR c.665 C > T, MTR c.2756 A > G, and MTRR c.66 A > G) and iAs methylation capacity; 2) To assess if previously reported associations between nutrient intake and iAs methylation capacity are modified by those polymorphisms. Women (n = 1027) exposed to iAs in Northern Mexico were interviewed. Blood and urine samples were collected. Nutrient dietary intake was estimated using a validated food frequency questionnaire. iAs methylation capacity was calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) measured by high performance liquid chromatography (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped by allelic discrimination. Multivariable linear regression models were used to evaluate if genetic polymorphisms modified the associations between iAs methylation capacity parameters and nutrient intake. The median (min-max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) µg/g creatinine in the study population. Significant interactions for iAs metabolism were only found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an increased vitamin B12 intake, as compared to carriers of wild-type TT. Differences in dietary nutrient intake and genetic variants in one-carbon metabolism may jointly influence iAs methylation capacity. Confirmation of these interactions in other populations is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Variation in human genetic polymorphisms, their association with Helicobacter pylori acquisition and gastric cancer in a multi-ethnic country.

PubMed

Schmidt, Heather-Marie A; Ha, Dung Mai; Taylor, Elizabeth F; Kovach, Zsuzsanna; Goh, Khean-Lee; Fock, Kwong Ming; Barrett, Jennifer H; Forman, David; Mitchell, Hazel

2011-12-01

The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients. Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models. The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection. These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Genetic polymorphism of the beta-2 adrenergic receptor in atopic and non-atopic subjects.

PubMed

Potter, P C; Van Wyk, L; Martin, M; Lentes, K U; Dowdle, E B

1993-10-01

To investigate a possible genetic basis for reported differences in beta-2 receptor expression in atopic subjects, DNA from 42 atopic children (22 asthmatics and 22 with allergic rhinitis) and 30 non-atopic subjects was Southern blotted and Ban-1 restriction fragment polymorphisms (RFLPS) were studied using a 2.6 kb probe of the human beta-2 receptor gene. Two alleles 3.1 kb and 2.9 kb were identified. Homozygotes and heterozygotes for the two alleles were found with equal frequency in the atopic patients who had asthma and in those who had allergic rhinitis only. The gene frequencies for the upper and lower alleles were 0.45 and 0.55 respectively. Our studies do not provide evidence for an association between a particular polymorphic form of the human beta-2 receptor gene and atopy.

Molecular phylogeny analysis and species identification of Dendrobium (Orchidaceae) in China.

PubMed

Feng, Shang-Guo; Lu, Jiang-Jie; Gao, Ling; Liu, Jun-Jun; Wang, Hui-Zhong

2014-04-01

Dendrobium plants are important commercial herbs in China, widely used in traditional medicine and ornamental horticulture. In this study, sequence-related amplified polymorphism (SRAP) markers were applied to molecular phylogeny analysis and species identification of 31 Chinese Dendrobium species. Fourteen SRAP primer pairs produced 727 loci, 97% of which (706) showed polymorphism. Average polymorphism information content of the SRAP pairs was 0.987 (0.982-0.991), showing that plenty of genetic diversity exists at the interspecies level of Chinese Dendrobium. The molecular phylogeny analysis (UPGMA) grouped the 31 Dendrobium species into six clusters. We obtained 18 species-specific markers, which can be used to identify 10 of the 31 species. Our results indicate the SRAP marker system is informative and would facilitate further application in germplasm appraisal, evolution, and genetic diversity studies in the genus Dendrobium.

Processing and population genetic analysis of multigenic datasets with ProSeq3 software.

PubMed

Filatov, Dmitry A

2009-12-01

The current tendency in molecular population genetics is to use increasing numbers of genes in the analysis. Here I describe a program for handling and population genetic analysis of DNA polymorphism data collected from multiple genes. The program includes a sequence/alignment editor and an internal relational database that simplify the preparation and manipulation of multigenic DNA polymorphism datasets. The most commonly used DNA polymorphism analyses are implemented in ProSeq3, facilitating population genetic analysis of large multigenic datasets. Extensive input/output options make ProSeq3 a convenient hub for sequence data processing and analysis. The program is available free of charge from http://dps.plants.ox.ac.uk/sequencing/proseq.htm.

Genetic Diversity and Genetic Relationships of Purple Willow (Salix purpurea L.) from Natural Locations

PubMed Central

Prinz, Kathleen; Przyborowski, Jerzy A.

2017-01-01

In this study, the genetic diversity and structure of 13 natural locations of Salix purpurea were determined with the use of AFLP (amplified length polymorphism), RAPD (randomly amplified polymorphic DNA) and ISSR (inter-simple sequence repeats). The genetic relationships between 91 examined S. purpurea genotypes were evaluated by analyses of molecular variance (AMOVA), principal coordinates analyses (PCoA) and UPGMA (unweighted pair group method with arithmetic mean) dendrograms for both single marker types and a combination of all marker systems. The locations were assigned to distinct regions and the analysis of AMOVA (analysis of molecular variance) revealed a high genetic diversity within locations. The genetic diversity between both regions and locations was relatively low, but typical for many woody plant species. The results noted for the analyzed marker types were generally comparable with few differences in the genetic relationships among S. purpurea locations. A combination of several marker systems could thus be ideally suited to understand genetic diversity patterns of the species. This study makes the first attempt to broaden our knowledge of the genetic parameters of the purple willow (S. purpurea) from natural location for research and several applications, inter alia breeding purposes. PMID:29301207

Genes for elite power and sprint performance: ACTN3 leads the way.

PubMed

Eynon, Nir; Hanson, Erik D; Lucia, Alejandro; Houweling, Peter J; Garton, Fleur; North, Kathryn N; Bishop, David J

2013-09-01

The ability of skeletal muscles to produce force at a high velocity, which is crucial for success in power and sprint performance, is strongly influenced by genetics and without the appropriate genetic make-up, an individual reduces his/her chances of becoming an exceptional power or sprinter athlete. Several genetic variants (i.e. polymorphisms) have been associated with elite power and sprint performance in the last few years and the current paradigm is that elite performance is a polygenic trait, with minor contributions of each variant to the unique athletic phenotype. The purpose of this review is to summarize the specific knowledge in the field of genetics and elite power performance, and to provide some future directions for research in this field. Of the polymorphisms associated with elite power and sprint performance, the α-actinin-3 R577X polymorphism provides the most consistent results. ACTN3 is the only gene that shows a genotype and performance association across multiple cohorts of elite power athletes, and this association is strongly supported by mechanistic data from an Actn3 knockout mouse model. The angiotensin-1 converting enzyme insertion/deletion polymorphism (ACE I/D, registered single nucleotide polymorphism [rs]4646994), angiotensinogen (AGT Met235Thr rs699), skeletal adenosine monophosphate deaminase (AMPD1) Gln(Q)12Ter(X) [also termed C34T, rs17602729], interleukin-6 (IL-6 -174 G/C, rs1800795), endothelial nitric oxide synthase 3 (NOS3 -786 T/C, rs2070744; and Glu298Asp, rs1799983), peroxisome proliferator-activated receptor-α (PPARA Intron 7 G/C, rs4253778), and mitochondrial uncoupling protein 2 (UCP2 Ala55Val, rs660339) polymorphisms have also been associated with elite power performance, but the findings are less consistent. In general, research into the genetics of athletic performance is limited by a small sample size in individual studies and the heterogeneity of study samples, often including athletes from multiple-difference sporting disciplines. In the future, large, homogeneous, strictly defined elite power athlete cohorts need to be established though multinational collaboration, so that meaningful genome-wide association studies can be performed. Such an approach would provide unbiased identification of potential genes that influence elite athletic performance.

In silico screening of the chicken genome for overlaps between genomic regions: microRNA genes, coding and non-coding transcriptional units, QTL, and genetic variations.

PubMed

Zorc, Minja; Kunej, Tanja

2016-05-01

MicroRNAs (miRNAs) are a class of non-coding RNAs involved in posttranscriptional regulation of target genes. Regulation requires complementarity between target mRNA and the mature miRNA seed region, responsible for their recognition and binding. It has been estimated that each miRNA targets approximately 200 genes, and genetic variability of miRNA genes has been reported to affect phenotypic variability and disease susceptibility in humans, livestock species, and model organisms. Polymorphisms in miRNA genes could therefore represent biomarkers for phenotypic traits in livestock animals. In our previous study, we collected polymorphisms within miRNA genes in chicken. In the present study, we identified miRNA-related genomic overlaps to prioritize genomic regions of interest for further functional studies and biomarker discovery. Overlapping genomic regions in chicken were analyzed using the following bioinformatics tools and databases: miRNA SNiPer, Ensembl, miRBase, NCBI Blast, and QTLdb. Out of 740 known pre-miRNA genes, 263 (35.5 %) contain polymorphisms; among them, 35 contain more than three polymorphisms The most polymorphic miRNA genes in chicken are gga-miR-6662, containing 23 single nucleotide polymorphisms (SNPs) within the pre-miRNA region, including five consecutive SNPs, and gga-miR-6688, containing ten polymorphisms including three consecutive polymorphisms. Several miRNA-related genomic hotspots have been revealed in chicken genome; polymorphic miRNA genes are located within protein-coding and/or non-coding transcription units and quantitative trait loci (QTL) associated with production traits. The present study includes the first description of an exonic miRNA in a chicken genome, an overlap between the miRNA gene and the exon of the protein-coding gene (gga-miR-6578/HADHB), and the first report of a missense polymorphism located within a mature miRNA seed region. Identified miRNA-related genomic hotspots in chicken can serve researchers as a starting point for further functional studies and association studies with poultry production and health traits and the basis for systematic screening of exonic miRNAs and missense/miRNA seed polymorphisms in other genomes.

Contributions of dopamine-related genes and environmental factors to highly sensitive personality: a multi-step neuronal system-level approach.

PubMed

Chen, Chunhui; Chen, Chuansheng; Moyzis, Robert; Stern, Hal; He, Qinghua; Li, He; Li, Jin; Zhu, Bi; Dong, Qi

2011-01-01

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.

Contributions of Dopamine-Related Genes and Environmental Factors to Highly Sensitive Personality: A Multi-Step Neuronal System-Level Approach

PubMed Central

Chen, Chunhui; Chen, Chuansheng; Moyzis, Robert; Stern, Hal; He, Qinghua; Li, He; Li, Jin; Zhu, Bi; Dong, Qi

2011-01-01

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies. PMID:21765900

Influences of the G2350A polymorphism in the ACE Gene on cardiac structure and function of ball game players

PubMed Central

2012-01-01

Background Except for the I/D polymorphism in the angiotensin I-converting enzyme (ACE) gene, there were few reports about the relationship between other genetic polymorphisms in this gene and the changes in cardiac structure and function of athletes. Thus, we investigated whether the G2350A polymorphism in the ACE gene is associated with the changes in cardiac structure and function of ball game players. Total 85 healthy ball game players were recruited in this study, and they were composed of 35 controls and 50 ball game players, respectively. Cardiac structure and function were measured by 2-D echocardiography, and the G2350A polymorphism in the ACE gene analyzed by the SNaPshot method. Results There were significant differences in left ventricular mass index (LVmassI) value among each sporting discipline studied. Especially in the athletes of basketball disciplines, indicated the highest LVmassI value than those of other sporting disciplines studied (p < 0.05). However, there were no significant association between any echocardiographic data and the G2350A polymorphism in the ACE gene in the both controls and ball game players. Conclusions Our data suggests that the G2350A polymorphism in the ACE gene may not significantly contribute to the changes in cardiac structure and function of ball game players, although sporting disciplines of ball game players may influence the changes in LVmassI value of these athletes. Further studies using a larger sample size and other genetic markers in the ACE gene will be needed. PMID:22239999

Molecular insights of genetic variation in milk thistle (Silybum marianum [L.] Gaertn.) populations collected from southwest Iran.

PubMed

Rafizadeh, Azam; Koohi-Dehkordi, Mehrana; Sorkheh, Karim

2018-06-07

Milk thistle (Silybum marianum) is among the world's popular medicinal plants. Start Codon Targeted (SCoT) marker system was utilized to investigate the genetic variability of 80 S. marianum genotypes from eight populations in Iran. SCoT marker produced 255 amplicons and 84.03% polymorphism was generated. The SCoT marker system's polymorphism information content value was 0.43. The primers' resolving power values were between 4.18 and 7.84. The percentage of polymorphic bands was between 33.3 and 100%. The Nei's gene diversity (h) was 0.19-1.30 with an average 0.72. The Shannon's index (I) ranged from 0.29 to 1.38 with an average value of 0.83. The average gene flow (0.37) demonstrated a high genetic variation among the studied populations. The variation of 42% was displayed by the molecular variance analysis among the populations while a recorded variation of 58% was made within the populations. Current investigation suggested that SCoT marker system could effectively evaluate milk thistle genotypes genetic diversity.

Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women

PubMed Central

Báez, Sergio; Tsuchiya, Yasuo; Calvo, Alfonso; Pruyas, Martha; Nakamura, Kazutoshi; Kiyohara, Chikako; Oyama, Mari; Yamamoto, Masaharu

2010-01-01

AIM: To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC). METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffin block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman® SNP Genotyping Assays or Custom Taqman® SNP Genotyping Assays. RESULTS: The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR: 0.14, 95% CI: 0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR: 5.04, 95% CI: 1.43-17.8). CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs708272 polymorphisms may be related to the risk of developing GBC in Chilean women. PMID:20082485

Forensic molecular genetic diversity analysis of Chinese Hui ethnic group based on a novel STR panel.

PubMed

Fang, Yating; Guo, Yuxin; Xie, Tong; Jin, Xiaoye; Lan, Qiong; Zhou, Yongsong; Zhu, Bofeng

2018-03-26

In present study, the genetic polymorphisms of 22 autosomal short tandem repeat (STR) loci were analyzed in 496 unrelated Chinese Xinjiang Hui individuals. These autosomal STR loci were multiplex amplified and genotyped based on a novel STR panel. There were 246 observed alleles with the allele frequencies ranging from 0.0010 to 0.3609. All polymorphic information content values were higher than 0.7. The combined power of discrimination and the combined probability of exclusion were 0.999999999999999999999999999426766 and 0.999999999860491, respectively. Based on analysis of molecular variance method, genetic differentiation analysis between the Xinjiang Hui and other reported groups were conducted at these 22 loci. The results indicated that there were no significant differences in statistics between Hui group and Northern Han group (including Han groups from Hebei, Henan, Shaanxi provinces), and significant deviations with Southern Han group (including those from Guangdong, Guangxi provinces) at 7 loci, and Uygur group at 10 loci. To sum up, these 22 autosomal STR loci were high genetic polymorphic in Xinjiang Hui group.

Frequency-Dependent Selection: The High Potential for Permanent Genetic Variation in the Diallelic, Pairwise Interaction Model

PubMed Central

Asmussen, M. A.; Basnayake, E.

1990-01-01

A detailed analytic and numerical study is made of the potential for permanent genetic variation in frequency-dependent models based on pairwise interactions among genotypes at a single diallelic locus. The full equilibrium structure and qualitative gene-frequency dynamics are derived analytically for a symmetric model, in which pairwise fitnesses are chiefly determined by the genetic similarity of the individuals involved. This is supplemented by an extensive numerical investigation of the general model, the symmetric model, and nine other special cases. Together the results show that there is a high potential for permanent genetic diversity in the pairwise interaction model, and provide insight into the extent to which various forms of genotypic interactions enhance or reduce this potential. Technically, although two stable polymorphic equilibria are possible, the increased likelihood of maintaining both alleles, and the poor performance of protected polymorphism conditions as a measure of this likelihood, are primarily due to a greater variety and frequency of equilibrium patterns with one stable polymorphic equilibrium, in conjunction with a disproportionately large domain of attraction for stable internal equilibria. PMID:2341034

Interleukin-10 gene -1082 G/A polymorphism in cervical cancer and cervical intraepithelial neoplasia: meta-analysis.

PubMed

Zhang, Shuo; Kong, Ya-Lin; Li, Ya-Li; Yin, Yan-Wei

2014-12-01

To assess the association between polymorphism in the interleukin (IL)-10 promoter region of 1082 G/A and the risk of cervical cancer and/or cervical intraepithelial neoplasia (CIN), using meta-analysis. The electronic literature databases PubMed®, Embase®, Web of Science, CBMdisc and CNKI were searched for relevant studies. The strength of association between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN was measured using pooled odds ratios with 95% confidence intervals in four genetic models: allelic model (A allele versus G allele); additive model (A/A versus G/G); recessive model (A/A versus G/A+G/G); dominant model (A/A+G/A versus G/G). Eight studies involving 1983 cases and 1618 controls were identified and included in the meta-analysis. No significant associations were found between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN in any of the genetic models. IL-10 gene -1082 G/A polymorphism does not appear to be associated with the risk of cervical cancer and/or CIN. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The association between methylenetetrahydrofolate reductase C677 > T polymorphisms and risk of pediatric acute lymphoblastic leukemia in Asia.

PubMed

Lin, Shiguang; Liu, Qin; Zeng, Xiaoming

2014-11-01

The association between methylenetetrahydrofolate reductase (MTHFR) C677 > T polymorphisms and pediatric acute lymphoblastic leukemia (ALL) risk in Asia is controversial. The aim of this meta-analysis was to further assess the relationship between MTHFR C677 > T polymorphisms and pediatric ALL for Chinese children. Studies about the MTHFR C677 > T polymorphisms and pediatric ALL risk were searched in the Medline, PubMed, EMBASE, Wanfang and CNIK databases. The genotype of the case and control group were extracted and pooled by meta-analysis. The association between ALL risk and C677 > T polymorphisms was demonstrated by odds ratio (OR) and its 95% confidence interval (CI). Twelve articles were included in this study with 1803 ALL cases and 4146 controls. In recessive genetic model (TT vs. CC + CT), the OR was 0.37 (95%CI: 0.31-0.43); in dominant genetic model (TT + CT vs. CC) the OR was 0.94 (95%CI: 0.82-1.06); and in the homozygous model the OR was 0.84 (95%CI: 0.69-1.03). The results indicated that Asian children with TT genotype of MTHFR gene may have less risk of developing ALL.

Frequency of genetic polymorphisms of PXR gene in the Brazilian population.

PubMed

Moreira, Ricardo P P; Jorge, Alexander A L; Mendonca, Berenice B; Bachega, Tânia A S S

2011-01-01

PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C>T and -6994T>C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05). We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians.

Pooled genome wide association detects association upstream of FCRL3 with Graves' disease.

PubMed

Khong, Jwu Jin; Burdon, Kathryn P; Lu, Yi; Laurie, Kate; Leonardos, Lefta; Baird, Paul N; Sahebjada, Srujana; Walsh, John P; Gajdatsy, Adam; Ebeling, Peter R; Hamblin, Peter Shane; Wong, Rosemary; Forehan, Simon P; Fourlanos, Spiros; Roberts, Anthony P; Doogue, Matthew; Selva, Dinesh; Montgomery, Grant W; Macgregor, Stuart; Craig, Jamie E

2016-11-18

Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10 -8 ). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10 -4 . Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.

Development and characterization of microsatellite loci in the mistletoe Psittacanthus schiedeanus (Loranthaceae)1

PubMed Central

González, Clementina; Harvey, Nick; Ornelas, Juan Francisco

2015-01-01

• Premise of the study: Microsatellite primers were developed for the parasitic Psittacanthus schiedeanus, a common mistletoe species on cloud forest–adapted tree hosts in Mesoamerica, to investigate intraspecific genetic patterns of diversity and genetic structure. • Methods and Results: Using an enriched library, 10 polymorphic microsatellite loci were developed in P. schiedeanus. All loci consisted of dinucleotide repeats. Average alleles per locus were 12 (4–17), and a total of 120 alleles were recorded across 39 individuals from four populations in Mexico. Primers were tested in 11 additional species, but only amplified successfully in P. calyculatus and P. angustifolius. • Conclusions: The polymorphic loci described will be useful in studies of genetic diversity and genetic population differentiation in natural populations of these parasitic plants, and will provide valuable information to understand the importance of host distribution. PMID:25606357

Molecular diversity of Pakistani mango (Mangifera indica L.) varieties based on microsatellite markers.

PubMed

Nazish, T; Shabbir, G; Ali, A; Sami-Ul-Allah, S; Naeem, M; Javed, M; Batool, S; Arshad, H; Hussain, S B; Aslam, K; Seher, R; Tahir, M; Baber, M

2017-04-05

Understanding the genetic diversity of different Pakistani mango varieties is important for germplasm management and varietal characterization. Microsatellites are efficient and highly polymorphic markers for comparative genome mapping, and were used in the present study to determine the genetic relatedness and variability among 15 indigenous mango cultivars (Mangifera indica L.). Overall, 181 bands were produced using 12 simple sequence repeat (SSR) primers. Out of the 12 primers used, 10 were polymorphic and two were monomorphic. Genetic relatedness among cultivars was assessed by constructing a dendrogram using the unweighted pair group method of arithmetic means. The accessions exhibited coefficients of similarity ranging from 75 to 100%, indicating the frequent use of only a few parent cultivars and the presence of inbreeding. The primers used in the present study were found to be valuable for identifying genetic relationships among mango cultivars.

Genetic diversity in Egyptian and Italian goat breeds measured with microsatellite polymorphism.

PubMed

Agha, S H; Pilla, F; Galal, S; Shaat, I; D'Andrea, M; Reale, S; Abdelsalam, A Z A; Li, M H

2008-06-01

Seven microsatellite markers were used to study genetic diversity of three Egyptian (Egyptian Baladi, Barki and Zaraibi) and two Italian (Maltese and Montefalcone) goat breeds. The microsatellites showed a high polymorphic information content (PIC) of more than 0.5 in most of the locus-breed combinations and indicated that the loci were useful in assessing within- and between-breed variability of domestic goat (Capra hircus). The expected heterozygosity of the breeds varied from 0.670 to 0.792. In the geographically wider distributed Egyptian Baladi breed there were indications for deviations from random breeding. Analysis of genetic distances and population structure grouped the three Egyptian goat breeds together, and separated them from the two Italian breeds. The studied Mediterranean breeds sampled from African and European populations seem to have differentiated from each other with only little genetic exchange between the geographically isolated populations.

Genetic variation in Toll-like receptors and disease susceptibility.

PubMed

Netea, Mihai G; Wijmenga, Cisca; O'Neill, Luke A J

2012-05-18

Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such as MyD88-IRAK4 or TLR3-Unc93b-TRIF-TRAF3, have demonstrated the specific roles of these pathways in host defense against pyogenic bacteria and herpesviruses, respectively. Second, common polymorphisms in genes encoding several TLRs and associated genes have been associated with both infectious and autoimmune diseases. The study of genetic variation in TLRs in various populations combined with information on infection has demonstrated complex interaction between genetic variation in TLRs and environmental factors. This interaction explains the differences in the effect of TLR polymorphisms on susceptibility to infection and autoimmune disease in various populations.

Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway.

PubMed

Mas, Sergi; Blázquez, Ana; Rodríguez, Natalia; Boloc, Daniel; Lafuente, Amalia; Arnaiz, Joan A; Lázaro, Luisa; Gassó, Patricia

2016-11-01

Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics. The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways. Clinical improvement after treatment with fluoxetine in our pediatric population was associated significantly with two polymorphisms located in genes related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2). Although a wide range of candidate genes related to different pathways were assessed, the results show that genetic markers directly related to serotonin have an important effect on fluoxetine response.

Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

PubMed Central

Huang, Hongbin; Peng, Cong; Liu, Yong; Liu, Xu; Chen, Qicong; Huang, Zunnan

2016-01-01

Abstract Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. Methods: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09–1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32–2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26–2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02–1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66–0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03–1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility. Conclusion: The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility. PMID:27749554

Correlations Between COL2A and Aggrecan Genetic Polymorphisms and the Risk and Clinicopathological Features of Intervertebral Disc Degeneration in a Chinese Han Population: A Case-Control Study.

PubMed

Deng, Yu; Tan, Xin-Ti; Wu, Qiang; Wang, Xin

2017-02-01

This case-control study was designed to evaluate the association of three COL2A1 single nucleotide polymorphism (SNPs) (rs1793953, rs2276454, and rs1793937) and Aggrecan variable number of tandem repeat (VNTR) polymorphisms with the risk and clinicopathological features of intervertebral disc degeneration (IVDD) in a Chinese Han population. Data from 295 IVDD patients (case group) and 324 healthy volunteers (control group) were collected between January 2012 and December 2014. Magnetic resonance examinations were conducted on all included subjects. The frequency distributions of the COL2A1 and Aggrecan polymorphisms were detected using direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The genotype and allele frequencies of the COL2A1 genetic polymorphisms (rs1793953 and rs2276454) and the Aggrecan VNTR polymorphisms differed significantly between the case group and the control group (all p < 0.05). The haplotype analysis indicated that the frequencies of ACGL (L, long) and GTCL haplotypes were lower in the case group than in the control group (both p < 0.05). In the case group, the genotype and allele frequencies of the COL2A1 genes, rs1793953 and rs2276454, and Aggrecan VNTR significantly differed in terms of Pfirrmann grades III, IV, and V (all p < 0.05). Personal history of spine sprain or crush injury, history of IVDD in a first-degree relative, and COL2A1 rs2276454 and Aggrecan VNTR presence may be independent risk factors of IVDD (all p < 0.05, odds ratio [OR] >1), whereas tea drinking habit, part-time sports participation, and COL2A1 rs1793953 presence may be protective factors of IVDD (all p < 0.05, OR <1). Our study provides evidence that COL2A1 and Aggrecan genetic polymorphisms may be correlated with the risk and clinicopathological features of IVDD in a Chinese Han population, and ACGL and GTCL haplotypes may be protective factors of IVDD.

Genetic differentiation and geographical relationship of Asian barley landraces using SSRs

USDA-ARS?s Scientific Manuscript database

Genetic diversity in 403 morphologically distinctive landraces of barley (Hordeum vulgare L. subsp. vulgare) originating from seven geographical zones of Asia was studied using simple sequence repeat (SSR) markers. The seven polymorphic SSR markers representing each chromosome chosen for this study ...

Assessing genetic divergence in interspecific hybrids of Aechmea gomosepala and A. recurvata var. recurvata using inflorescence characteristics and sequence-related amplified polymorphism markers.

PubMed

Zhang, F; Ge, Y Y; Wang, W Y; Shen, X L; Yu, X Y

2012-12-03

Conventional hybridization and selection techniques have aided the development of new ornamental crop cultivars. However, little information is available on the genetic divergence of bromeliad hybrids. In the present study, we investigated the genetic variability in interspecific hybrids of Aechmea gomosepala and A. recurvata var. recurvata using inflorescence characteristics and sequence-related amplified polymorphism (SRAP) markers. The morphological analysis showed that the putative hybrids were intermediate between both parental species with respect to inflorescence characteristics. The 16 SRAP primer combinations yield 265 bands, among which 154 (57.72%) were polymorphic. The genetic similarity was an average of 0.59 and ranged from 0.21 to 0.87, indicating moderate genetic divergence among the hybrids. The unweighted pair group method with arithmetic average (UPGMA)-based cluster analysis distinguished the hybrids from their parents with a genetic distance coefficient of 0.54. The cophenetic correlation was 0.93, indicating a good fit between the dendrogram and the original distance matrix. The two-dimensional plot from the principal coordinate analysis showed that the hybrids were intermediately dispersed between both parents, corresponding to the results of the UPGMA cluster and the morphological analysis. These results suggest that SRAP markers could help to identify breeders, characterize F(1) hybrids of bromeliads at an early stage, and expedite genetic improvement of bromeliad cultivars.

Multicenter cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.

PubMed

Terrell, Thomas R; Bostick, Roberd; Barth, Jeffrey; Sloane, Richard; Cantu, Robert C; Bennett, Ellen; Galloway, Leslie; Laskowitz, Daniel; Erlanger, Dave; McKeag, Doug; Valentine, Verle; Nichols, Gregory

2017-01-01

Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome. Limited research has focused on genetic risk for concussion among athletes. We describe the design, methods, and baseline characteristics of this prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, APOE promoter G-219T, and Tau gene exon 6 polymorphisms (Ser53 Pro and Hist47Tyr) with: 1) the risk of prospective concussion; 2) concussion severity; and 3) postconcussion neurocognitive recovery. The prospective cohort study included a final population of 2947 college, high school, and professional athletes. Baseline data collection included a concussion/medical history questionnaire, neuropsychological (NP) testing, and genetic sampling for the genetic polymorphisms. Data collection on new concussions experienced utilized post-concussion history/mental status form, Lovell post-concussion symptom score, Standardized Assessment of Concussion (SAC) and/or the Sports Concussion Assessment Tool (SCAT)-1/SCAT-2, and post-concussion NP testing. This paper is focused on discussing the important methodological considerations, organizational challenges and lessons learned in the completion of a multi-center prospective cohort study. A total of 3740 subjects enrolled, with a total of 335 concussions experienced. Of critical importance to the success of a study of this type is to successfully recruit committed institutions with qualified local study personnel, obtain "buy-in" from study sites, and cultivate strong working relationships with study sites. The use of approved incentives may improve study site recruitment, enhance retention, and enhance compliance with study protocols. Future publications will detail the specific findings of this study. Collaborative research is very likely needed given the nature of this study population.

Influence of Cremophor EL and genetic polymorphisms on the pharmacokinetics of paclitaxel and its metabolites using a mechanism-based model.

PubMed

Fransson, Martin N; Gréen, Henrik; Litton, Jan-Eric; Friberg, Lena E

2011-02-01

The formulation vehicle Cremophor EL has previously been shown to affect paclitaxel kinetics, but it is not known whether it also affects the kinetics of paclitaxel metabolites. This information may be important for understanding paclitaxel metabolism in vivo and in the investigation of the role of genetic polymorphisms in the metabolizing enzymes CYP2C8 and CYP3A4/CYP3A5 and the ABCB1 transporter. In this study we used the population pharmacokinetic approach to explore the influence of predicted Cremophor EL concentrations on paclitaxel (Taxol) metabolites. In addition, correlations between genetic polymorphisms and enzyme activity with clearance of paclitaxel, its two primary metabolites, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel, and its secondary metabolite, 6α-p-3'-dihydroxypaclitaxel were investigated. Model building was based on 1156 samples from a study with 33 women undergoing paclitaxel treatment for gynecological cancer. Total concentrations of paclitaxel were fitted to a model described previously. One-compartment models characterized unbound metabolite concentrations. Total concentrations of 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel were strongly dependent on predicted Cremophor EL concentrations, but this association was not found for 6α-p-3'-dihydroxypaclitaxel. Clearance of 6α-hydroxypaclitaxel (fraction metabolized) was significantly correlated (p < 0.05) to the ABCB1 allele G2677T/A. Individuals carrying the polymorphisms G/A (n = 3) or G/G (n = 5) showed a 30% increase, whereas individuals with polymorphism T/T (n = 8) showed a 27% decrease relative to those with the polymorphism G/T (n = 17). The correlation of G2677T/A with 6α-hydroxypaclitaxel has not been described previously but supports other findings of the ABCB1 transporter playing a part in paclitaxel metabolism.

Impact of Genetic Polymorphisms on 6-Thioguanine Nucleotide Levels and Toxicity in Pediatric Patients with IBD Treated with Azathioprine.

PubMed

Lee, Mi-Na; Kang, Ben; Choi, So Yoon; Kim, Mi Jin; Woo, Sook Young; Kim, Jong-Won; Choe, Yon Ho; Lee, Soo-Youn

2015-12-01

Thiopurine-related toxicity results in discontinuation of therapy in up to 30% of patients with inflammatory bowel disease. Although thiopurine S-methyltransferase (TPMT) is implicated in toxicity, not all toxicity can be attributed to TPMT polymorphisms. We investigated the effects of polymorphisms of genes involved in thiopurine and folate metabolism pathways on 6-thioguanine nucleotide levels and toxicity. Retrospective clinical data and blood samples were collected from 132 pediatric patients with inflammatory bowel disease treated with azathioprine. Eighty-seven genetic polymorphisms of 30 genes were screened using the MassARRAY system, and 70 polymorphisms of 28 genes were selected for further analysis. TPMT genotype (P < 0.001), concurrent use of mesalazine (P = 0.006), ABCC5 (rs2293001) (P < 0.001), ITPA (rs2236206 and rs8362) (P = 0.010 and P = 0.003), and ABCB1 (rs2032582) (P = 0.028) were all associated with the ratio of 6-thioguanine nucleotides to azathioprine dose. ADK (rs10824095) (P = 0.004, odds ratio [OR] = 6.220), SLC29A1 (rs747199) (P = 0.016, OR = 5.681), and TYMS (rs34743033) (P = 0.045, OR = 3.846) were associated with neutropenia. ABCC1 (rs2074087) (P = 0.022, OR = 3.406), IMPDH1 (rs2278294) (P = 0.027, OR = 0.276), and IMPDH2 (rs11706052) (P = 0.034, OR = 3.639) had a significant impact on lymphopenia. This study describes genetic polymorphisms in genes whose products may affect pharmacokinetics and which may predict the relative likelihood of benefit or risk from thiopurine treatment. These findings may serve as a basis for personalized thiopurine therapy in pediatric patients with inflammatory bowel disease, although our data need to be validated in further studies.

Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet

PubMed Central

Curtin, Karen; Slattery, Martha L.; Ulrich, Cornelia M.; Bigler, Jeannette; Levin, Theodore R.; Wolff, Roger K.; Albertsen, Hans; Potter, John D.; Samowitz, Wade S.

2008-01-01

This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case–control study (916 incident colon cancer cases and 1972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylene-tetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP− or CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 and MLH1. The influence of specific dietary factors (folate, methionine, vitamin B12 and alcohol) on these associations was also analyzed. We hypothesized that polymorphisms involved in the provision of methyl groups would be associated with CIMP+ tumors (two or more of five markers methylated), potentially modified by diet. Few associations specific to CIMP+ tumors were observed overall, which does not support the hypothesis that the provision of methyl groups is important in defining a methylator phenotype. However, our data suggest that genetic polymorphisms in MTHFR 1298A > C, interacting with diet, may be involved in the development of highly CpG-methylated colon cancers. AC and CC genotypes in conjunction with a high-risk dietary pattern (low folate and methionine intake and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3–3.4 versus AA/high risk; P-interaction = 0.03). These results provide only limited support for a role of polymorphisms in one-carbon metabolism in the etiology of CIMP colon cancer. PMID:17449906

Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet.

PubMed

Curtin, Karen; Slattery, Martha L; Ulrich, Cornelia M; Bigler, Jeannette; Levin, Theodore R; Wolff, Roger K; Albertsen, Hans; Potter, John D; Samowitz, Wade S

2007-08-01

This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case-control study (916 incident colon cancer cases and 1,972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP- or CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 and MLH1. The influence of specific dietary factors (folate, methionine, vitamin B(12) and alcohol) on these associations was also analyzed. We hypothesized that polymorphisms involved in the provision of methyl groups would be associated with CIMP+ tumors (two or more of five markers methylated), potentially modified by diet. Few associations specific to CIMP+ tumors were observed overall, which does not support the hypothesis that the provision of methyl groups is important in defining a methylator phenotype. However, our data suggest that genetic polymorphisms in MTHFR 1,298A > C, interacting with diet, may be involved in the development of highly CpG-methylated colon cancers. AC and CC genotypes in conjunction with a high-risk dietary pattern (low folate and methionine intake and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3-3.4 versus AA/high risk; P-interaction = 0.03). These results provide only limited support for a role of polymorphisms in one-carbon metabolism in the etiology of CIMP colon cancer.

Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients

PubMed Central

Tsuji, Daiki; Ikeda, Midori; Yamamoto, Keisuke; Nakamori, Harumi; Kim, Yong-Il; Kawasaki, Yohei; Otake, Aki; Yokoi, Mari; Inoue, Kazuyuki; Hirai, Keita; Nakamichi, Hidenori; Tokou, Umi; Shiokawa, Mitsuru; Itoh, Kunihiko

2016-01-01

Abstract Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22–9.69; P = 0.020), CYP2B6∗6 (OR, 4.51; 95% CI, 1.21–16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15–41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06–8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia. PMID:27858847

Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population.

PubMed

Niehaus, D J; Kinnear, C J; Corfield, V A; du Toit, P L; van Kradenburg, J; Moolman-Smook, J C; Weyers, J B; Potgieter, A; Seedat, S; Emsley, R A; Knowles, J A; Brink, P A; Stein, D J

2001-06-01

It has been proposed that the catechol-o-methyl transferase gene (COMT) may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Whereas studies in a North American population showed that the low activity (L) allele of a functional polymorphism in COMT was associated with OCD in male patients, this result was not supported by studies in a Japanese population. The present association study assessed the risk for OCD conferred by this COMT polymorphism in a geographically different patient group, namely, the relatively genetically homogeneous Afrikaner population of South Africa. Fifty-four unrelated OCD patients and fifty-four sex-matched controls were recruited from the same Afrikaner community. Patients and controls were phenotyped (DSM-IV) and genotyped for a NlaIII polymorphism with H (high activity) or L (low activity) alleles in the COMT gene. The H/L genotype was significantly more common than expected in the OCD patient group (P = 0.0017). Replication studies with related individuals may be useful in discovering factors underpinning the H/L genotype abundance in the Afrikaner population. These results emphasise the need for further studies in genetically homogeneous populations to help define the complex etiology of this disease.

Mice, humans and haplotypes--the hunt for disease genes in SLE.

PubMed

Rigby, R J; Fernando, M M A; Vyse, T J

2006-09-01

Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

PubMed

Stafford-Smith, Mark; Podgoreanu, Mihai; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P; Hauser, Elizabeth H; Winn, Michelle P; Milano, Carmelo; Nielsen, Dahlia M; Smith, Mike; Morris, Richard; Newman, Mark F; Schwinn, Debra A

2005-03-01

Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Relationships among genetic makeup, active ingredient content, and place of origin of the medicinal plant Gastrodia tuber.

PubMed

Tao, Jun; Luo, Zhi-yong; Msangi, Chikira Ismail; Shu, Xiao-shun; Wen, Li; Liu, Shui-ping; Zhou, Chang-quan; Liu, Rui-xin; Hu, Wei-xin

2009-02-01

Gastrodia tuber and its component gastrodin have many pharmacological effects. The chemical fingerprints and gastrodin contents of eight Gastrodia populations were determined, and the genomic DNA polymorphism of the populations was investigated. Genetic distance coefficients among the populations were calculated using the DNA polymorphism data. A dendrogram of the genetic similarities between the populations was constructed using the genetic distance coefficients. The results indicated that the genomic DNA of Gastrodia tubers was highly polymorphic; the eight populations clustered into three major groups, and the gastrodin content varied greatly among these groups. There were obvious correlations among genetic makeup, gastrodin content, and place of origin. The ecological environments in Guizhou and Shanxi may be conducive to evolution and to gastrodin biosynthesis, and more suitable for cultivation of Gastrodia tubers. These findings may provide a scientific basis for overall genetic resource management and for the selection of locations for cultivating Gastrodia tubers.

Characterization of microsatellite loci for an Australian epiphytic orchid, Dendrobium calamiforme, using Illumina sequencing1

PubMed Central

Trapnell, Dorset W.; Beasley, Rochelle R.; Lance, Stacey L.; Field, Ashley R.; Jones, Kenneth L.

2015-01-01

Premise of the study: Microsatellite loci were developed for the epiphytic pencil orchid Dendrobium calamiforme for population genetic and phylogeographic investigation of this Australian taxon. Methods and Results: Nineteen microsatellite loci were identified from an Illumina paired-end shotgun library of D. calamiforme. Polymorphism and genetic diversity were assessed in 24 individuals from five populations separated by a maximum distance of ∼80 km. All loci were polymorphic with two to 14 alleles per locus, expected heterozygosity ranging from 0.486 to 0.902, and probability of identity values ranging from 0.018 to 0.380. Conclusions: These novel markers will serve as valuable tools for investigation of levels of genetic diversity as well as patterns of gene flow, genetic structure, and phylogeographic history. PMID:26082878

The BDNFval66met polymorphism and individual differences in temperament in 4-month-old infants: A pilot study.

PubMed

Giusti, Lorenzo; Provenzi, Livio; Tavian, Daniela; Missaglia, Sara; Butti, Niccolò; Montirosso, Rosario

2017-05-01

Individual differences in infants' temperament are under genetic control. We investigated the association between brain-derived-neurotrophic-factor (BDNF val66met ) polymorphism and temperament in 63 full-term infants. Met-carriers (N=25) had lower Regulatory capacities compared to val-homozygotes (N=38). These findings suggest that the BDNF polymorphism affects early temperament individual differences. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between a polymorphism in the IL-12p40 gene and cytomegalovirus reactivation after kidney transplantation.

PubMed

Hoffmann, Thomas W; Halimi, Jean-Michel; Büchler, Mathias; Velge-Roussel, Florence; Goudeau, Alain; Al Najjar, Azmi; Boulanger, Marie-Denise; Houssaini, Tarik Sqalli; Marliere, Jean-Frédéric; Lebranchu, Yvon; Baron, Christophe

2008-05-27

Cytomegalovirus (CMV) infection is associated with a significant rate of morbidity after organ transplantation. The genetic factors influencing its occurrence have been little investigated. IL-12 plays a crucial role in anti-infectious immune responses, especially by stimulating IFNgamma production. An A-to-C single nucleotide polymorphism (SNP) within the 3'-untranslated region of the IL-12p40 gene has been characterized and was reported to be both functionally and clinically relevant. However, the impact of this single nucleotide polymorphism on events after organ transplantation has never been reported. In this study, we investigated the impact of the 3'-untranslated region polymorphism on the occurrence of CMV infection in 469 kidney recipients transplanted at the University Hospital of Tours between 1995 and 2005. The polymorphism was genotyped using the restriction fragment length polymorphism method and CMV infection was determined by pp65 antigenemia. Multifactorial Cox regression analysis demonstrated that the presence of the C allele was an independent risk factor for CMV infection (OR=1.52, P=0.043), the risk being even higher when study was restricted to patients with positive CMV serological status before the graft and who did not receive any CMV prophylaxis (OR=1.88, P=0.028). This study identified a new genetic risk factor for CMV reactivation after kidney transplantation. The results of our study suggest that C carriers might especially benefit from CMV prophylaxis.

Amerindian genetic ancestry and INDEL polymorphisms associated with susceptibility of childhood B-cell Leukemia in an admixed population from the Brazilian Amazon.

PubMed

Carvalho, Darlen C; Wanderley, Alayde V; Amador, Marcos A T; Fernandes, Marianne R; Cavalcante, Giovanna C; Pantoja, Karla B C C; Mello, Fernando A R; de Assumpção, Paulo P; Khayat, André S; Ribeiro-Dos-Santos, Ândrea; Santos, Sidney; Dos Santos, Ney P C

2015-08-20

Acute lymphoblastic leukemia (ALL) is a malignant tumor common in children. Studies of genetic susceptibility to cancer using biallelic insertion/deletion (INDEL) type polymorphisms associated with cancer development pathways may help to clarify etymology of ALL. In this study, we investigate the role of eight functional INDEL polymorphisms and influence of genetic ancestry to B-cell ALL susceptibility in children of Brazilian Amazon population, which has a high degree of inter-ethnic admixture. Ancestry analysis was estimated using a panel of 48 autosomal ancestry informative markers. 130 B-cell ALL patients and 125 healthy controls were included in this study. The odds ratios and 95% confidence intervals were adjusted for confounders. The results indicated an association between the investigated INDEL polymorphisms in CASP8 (rs3834129), CYP19A1 (rs11575899) e XRCC1 (rs3213239) genes in the development of B-cell ALL. The carriers of Insertion/Insertion (Ins/Ins) genotype of the polymorphism in CASP8 gene presented reduced chances of developing B-cell ALL (P=0.001; OR=0.353; 95% CI=0.192-0.651). The Deletion/Deletion (Del/Del) genotype of the polymorphism in CYP19A1 gene was associated to a lower chance of developing B-cell ALL (P=3.35×10 -6 ; OR=0.121; 95% CI=0.050-0.295), while Del/Del genotype of the polymorphism in XRCC1 gene was associated to a higher chance of developing B-cell ALL (P=2.01×10 -4 ; OR=6.559; 95% CI=2.433-17.681). We also found that Amerindian ancestry correlates with the risk of B-cell ALL. For each increase of 10% in the Amerindian ancestry results in 1.4-fold chances of developing B-cell ALL (OR=1.406; 95% IC=1.123-1.761), while each increase of 10% in the European ancestry presents a protection effect in the development of B-cell ALL (OR=0.666; 95% IC=0.536-0.827). The results suggest that genetic factors influence leukemogenesis and might be explored in the stratification of B-cell ALL risk in admixed populations. Copyright © 2015 Z. Published by Elsevier Ltd.. All rights reserved.

Association of TNFα-308, IFNγ+874, and IL10-1082 gene polymorphisms and the risk of non-small cell lung cancer in the population of the South Indian state of Telangana.

PubMed

Peddireddy, Vidyullatha; Badabagni, Siva Prasad; Sulthana, Shehnaz; Kolla, Venkata Karunakar; Gundimeda, Sandhya Devi; Mundluru, Hemaprasad

2016-10-01

Cytokine-mediated inflammation is important in the pathogenesis of non-small cell lung cancer (NSCLC). Genetic polymorphisms in cytokine genes and their association with lung cancer in the Indian population have not been reported. For the first time, we analyzed genetic polymorphisms of TNFα -308 , IFNγ +874 , and IL10 -1082 genes in 246 NSCLC patients and 250 healthy controls in the South Indian population from Telangana using ARMS PCR. IFNγ +874 A/T and IL10 -1082 G/G gene polymorphisms were found to be significantly associated with NSCLC with 1.56- and 1.68-fold disease risk, respectively. There was no association between the risk of NSCLC and TNFα -308 polymorphism. Gene polymorphisms stratified according to smoking revealed that IFNγ +874 A/T polymorphisms in smokers increased the disease risk by 2.91 fold. IL10 -1082 G/G polymorphisms showed 2-fold increased risk among patients who were smokers when compared to the controls. However, there was no association between TNFα -308 , IFNγ +874 , and IL10 -1082 gene polymorphism and the stage of the NSCLC patients. The overall risk associated with the combination of these polymorphisms indicated that the TNFα -308 G/A + IFNγ +874 A/T + IL10 -1082 G/G genotype increased the risk by 1.5 fold. The results of our study indicate an association between cytokine gene polymorphisms and the risk of NSCLC in an Indian population.

Does epigenetic polymorphism contribute to phenotypic variances in Jatropha curcas L.?

PubMed

Yi, Chengxin; Zhang, Shilu; Liu, Xiaokun; Bui, Ha T N; Hong, Yan

2010-11-23

There is a growing interest in Jatropha curcas L. (jatropha) as a biodiesel feedstock plant. Variations in its morphology and seed productivity have been well documented. However, there is the lack of systematic comparative evaluation of distinct collections under same climate and agronomic practices. With the several reports on low genetic diversity in jatropha collections, there is uncertainty on genetic contribution to jatropha morphology. In this study, five populations of jatropha plants collected from China (CN), Indonesia (MD), Suriname (SU), Tanzania (AF) and India (TN) were planted in one farm under the same agronomic practices. Their agronomic traits (branching pattern, height, diameter of canopy, time to first flowering, dormancy, accumulated seed yield and oil content) were observed and tracked for two years. Significant variations were found for all the agronomic traits studied. Genetic diversity and epigenetic diversity were evaluated using florescence Amplified Fragment Length Polymorphism (fAFLP) and methylation sensitive florescence AFLP (MfAFLP) methods. Very low level of genetic diversity was detected (polymorphic band <0.1%) within and among populations. In contrast, intermediate but significant epigenetic diversity was detected (25.3% of bands were polymorphic) within and among populations. More than half of CCGG sites surveyed by MfAFLP were methylated with significant difference in inner cytosine and double cytosine methylation among populations. Principal coordinates analysis (PCoA) based on Nei's epigenetic distance showed Tanzania/India group distinct from China/Indonesia/Suriname group. Inheritance of epigenetic markers was assessed in one F1 hybrid population between two morphologically distinct parent plants and one selfed population. 30 out of 39 polymorphic markers (77%) were found heritable and followed Mendelian segregation. One epiallele was further confirmed by bisulphite sequencing of its corresponding genomic region. Our study confirmed climate and practice independent differences in agronomic performance among jatropha collections. Such agronomic trait variations, however, were matched by very low genetic diversity and medium level but significant epigenetic diversity. Significant difference in inner cytosine and double cytosine methylation at CCGG sites was also found among populations. Most epigenetic differential markers can be inherited as epialleles following Mendelian segregation. These results suggest possible involvement of epigenetics in jatropha development.

Does epigenetic polymorphism contribute to phenotypic variances in Jatropha curcas L.?

PubMed Central

2010-01-01

Background There is a growing interest in Jatropha curcas L. (jatropha) as a biodiesel feedstock plant. Variations in its morphology and seed productivity have been well documented. However, there is the lack of systematic comparative evaluation of distinct collections under same climate and agronomic practices. With the several reports on low genetic diversity in jatropha collections, there is uncertainty on genetic contribution to jatropha morphology. Result In this study, five populations of jatropha plants collected from China (CN), Indonesia (MD), Suriname (SU), Tanzania (AF) and India (TN) were planted in one farm under the same agronomic practices. Their agronomic traits (branching pattern, height, diameter of canopy, time to first flowering, dormancy, accumulated seed yield and oil content) were observed and tracked for two years. Significant variations were found for all the agronomic traits studied. Genetic diversity and epigenetic diversity were evaluated using florescence Amplified Fragment Length Polymorphism (fAFLP) and methylation sensitive florescence AFLP (MfAFLP) methods. Very low level of genetic diversity was detected (polymorphic band <0.1%) within and among populations. In contrast, intermediate but significant epigenetic diversity was detected (25.3% of bands were polymorphic) within and among populations. More than half of CCGG sites surveyed by MfAFLP were methylated with significant difference in inner cytosine and double cytosine methylation among populations. Principal coordinates analysis (PCoA) based on Nei's epigenetic distance showed Tanzania/India group distinct from China/Indonesia/Suriname group. Inheritance of epigenetic markers was assessed in one F1 hybrid population between two morphologically distinct parent plants and one selfed population. 30 out of 39 polymorphic markers (77%) were found heritable and followed Mendelian segregation. One epiallele was further confirmed by bisulphite sequencing of its corresponding genomic region. Conclusion Our study confirmed climate and practice independent differences in agronomic performance among jatropha collections. Such agronomic trait variations, however, were matched by very low genetic diversity and medium level but significant epigenetic diversity. Significant difference in inner cytosine and double cytosine methylation at CCGG sites was also found among populations. Most epigenetic differential markers can be inherited as epialleles following Mendelian segregation. These results suggest possible involvement of epigenetics in jatropha development. PMID:21092236

Potential use of random amplified polymorphic DNA (RAPD) technique to study the genetic diversity in Indian mustard (Brassica juncea) and its relationship to heterosis.

PubMed

Jain, A; Bhatia, S; Banga, S S; Prakash, S; Lakshmikumaran, M

1994-04-01

RAPD assays were performed, using 34 arbitrary decamer oligonucleotide primers and six combinations of two primers, to detect inherent variations and genetic relationships among 12 Indian and 11 exotic B. juncea genotypes. Of 595 amplification products identified, 500 of them were polymorphic across all genotypes. A low level of genetic variability was detected among the Indian genotypes, while considerable polymorphism was present among the exotic ones. Based on the pair-wise comparisons of amplification products the genetic similarity was calculated using Jaccard's similarity coefficients and a dendrogram was constructed using an unweighted pair group method was arithmetical averages (UPGMA). On the basis of this analysis the genotypes were clustered into two groups, A and B. Group A comprised only exotic genotypes, whereas all the Indian genotypes and four of the exotic genotypes were clustered in group B. Almost similar genotypic rankings could also be established by computing as few as 200 amplification products. In general, a high per cent of heterosis was recorded in crosses involving Indian x exotic genotypes. On the other hand, when crosses were made amongst Indian or exotic genotypes, about 80% of them exhibited negative heterosis. Results from this study indicate that, despite the lack of direct correlation between the genetic distance and the degree of heterosis, genetic diversity forms a very useful guide not only for investigating the relationships among Brassica genotypes but also in the selection of parents for heterotic hybrid combinations.

No association between catechol-O-methyltransferase polymorphisms and neurotic disorders among mainland Chinese university students.

PubMed

Kou, Changgui; Meng, Xiangfei; Xie, Bing; Shi, Jieping; Yu, Qiong; Yu, Yaqin; D'Arcy, Carl

2012-07-30

This study investigates the genetic association between catechol-O-methyltransferase (COMT) gene polymorphisms and neurotic disorders. Data were derived from a case-control association study of 255 undergraduates affected by neurotic disorders and 269 matched healthy undergraduate controls. The polymorphisms of eight tag single nucleotide polymorphisms (SNPs) on the COMT gene were tested using polymerase chain reaction (PCR)-based Ligase Detection Reaction (PCR-LDR). The eight tag SNPs on the COMT gene assessed were not associated with neurotic disorders. Our finding suggests that the COMT gene may not be a susceptibility gene for neurotic disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetics of Oxidative Stress in Obesity

PubMed Central

Rupérez, Azahara I.; Gil, Angel; Aguilera, Concepción M.

2014-01-01

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications. PMID:24562334

Genetics of oxidative stress in obesity.

PubMed

Rupérez, Azahara I; Gil, Angel; Aguilera, Concepción M

2014-02-20

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism.

PubMed

Um, Jae-Young; An, Nyeon-Hyoung; Yang, Gui-Bi; Lee, Geon-Mok; Cho, Ju-Jang; Cho, Jae-Woon; Hwang, Woo-Jun; Chae, Han-Jung; Kim, Hyung-Ryong; Hong, Seung-Heon; Kim, Hyung-Min

2005-01-01

Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.

PRKAG3 and CAST genetic polymorphisms and quality traits of dry-cured hams--I. Associations in Spanish dry-cured ham Jamón Serrano.

PubMed

Gou, P; Zhen, Z Y; Hortós, M; Arnau, J; Diestre, A; Robert, N; Claret, A; Čandek-Potokar, M; Santé-Lhoutellier, V

2012-12-01

The functional single polymorphisms identified in the calpastatin (CAST) gene have been related to the rate of meat tenderization and the protein turnover after slaughter, and the Ile199Val polymorphism identified in the coding region of the protein kinase AMP-activated (PRKAG3) gene has been proven to affect ultimate pH in muscle. The aim of the present study was to show the effects of these genetic polymorphisms on the quality traits of Spanish dry-cured ham Jamón Serrano. A tissue sample from 665 crossbreed pigs were genotyped for PRKAG3 Ile199Val, CAST Arg249Lys and CAST Ser638Arg polymorphisms, and a subsample of 120 dry cured hams was selected to perform physico-chemical, rheological, instrumental colour and sensory analyses. Associations between the polymorphisms and several quality traits of dry-cured ham, mainly related to flavour and texture, were found. The genotypes PRKAG3 Ile/Ile, CAST249 Arg/Arg and CAST638 Arg/Arg, and the haplotype CAST 249Arg-638Arg were the most favourable for Jamón Serrano production. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi

Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicitymore » was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of such ethnic heterogeneity in the late toxicities of radiation.« less

Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

PubMed

Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

2015-05-17

No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

Isolation, characterization, and cross-species amplification of polymorphic microsatellite markers for Pilosocereus machrisii (Cactaceae).

PubMed

Perez, Manolo F; Téo, Mariana F; Zappi, Daniela C; Taylor, Nigel P; Moraes, Evandro M

2011-08-01

Microsatellite primers were developed in Pilosocereus machrisii, a columnar cactus with a patchy distribution in eastern tropical South America, to assess its genetic diversity and population structure. Eleven microsatellite markers were developed, of which one was monomorphic among 51 individuals from two populations. The number of alleles per polymorphic locus ranged from two to eight, and the total number of alleles was 57. From the 11 isolated loci, nine were successfully amplified in the other four Pilosocereus species. The results showed that these markers will be useful for studies of genetic diversity, patterns of gene flow, and population genetic structure in P. machrisii, as well as across other congeneric species.

Development of microsatellite markers for Dimorphandra mollis (Leguminosae), a widespread tree from the Brazilian cerrado.

PubMed

Souza, Helena A V; Collevatti, Rosane G; Lemos-Filho, José P; Santos, Fabrício R; Lovato, Maria Bernadete

2012-03-01

Microsatellite markers were developed for Dimorphandra mollis (Leguminosae), a widespread tree in the Brazilian cerrado (a savanna-like vegetation). Microsatellite markers were developed from an enriched library. The analyses of polymorphism were based on 56 individuals from three populations. Nine microsatellite loci were polymorphic, with the number of alleles per locus ranging from three to 10 across populations. The observed and expected heterozygosities per locus and population ranged from 0.062 to 0.850 and from 0.062 to 0.832, respectively. These microsatellites provide an efficient tool for population genetics studies and will be used to assess the genetic diversity and spatial genetic structure of D. mollis.

A highly polymorphic insertion in the Y-chromosome amelogenin gene can be used for evolutionary biology, population genetics and sexing in Cetacea and Artiodactyla

PubMed Central

Macé, Matthias; Crouau-Roy, Brigitte

2008-01-01

Background The early radiation of the Cetartiodactyla is complex, and unambiguous molecular characters are needed to clarify the positions of hippotamuses, camels and pigs relative to the remaining taxa (Cetacea and Ruminantia). There is also a need for informative genealogic markers for Y-chromosome population genetics as well as a sexing method applicable to all species from this group. We therefore studied the sequence variation of a partial sequence of the evolutionary conserved amelogenin gene to assess its potential use in each of these fields. Results and discussion We report a large interstitial insertion in the Y amelogenin locus in most of the Cetartiodactyla lineages (cetaceans and ruminants). This sex-linked size polymorphism is the result of a 460–465 bp inserted element in intron 4 of the amelogenin gene of Ruminants and Cetaceans. Therefore, this polymorphism can easily be used in a sexing assay for these species. When taking into account this shared character in addition to nucleotide sequence, gene genealogy follows sex-chromosome divergence in Cetartiodactyla whereas it is more congruent with zoological history when ignoring these characters. This could be related to a loss of homology between chromosomal copies given the old age of the insertion. The 1 kbp Amel-Y amplified fragment is also characterized by high nucleotide diversity (64 polymorphic sites spanning over 1 kbp in seven haplotypes) which is greater than for other Y-chromosome sequence markers studied so far but less than the mitochondrial control region. Conclusion The gender-dependent polymorphism we have identified is relevant not only for phylogenic inference within the Cetartiodactyla but also for Y-chromosome based population genetics and gender determination in cetaceans and ruminants. One single protocol can therefore be used for studies in population and evolutionary genetics, reproductive biotechnologies, and forensic science. PMID:18925953

Identification of Genetic Polymorphisms of CYP2W1 in the Three Main Chinese Ethnicities: Han, Tibetan, and Uighur.

PubMed

Li, Yanwei; Kang, Xing; Yang, Ge; Dai, Penggao; Chen, Chao; Wang, Huijuan

2016-09-01

CYP2W1 is an orphan member of the cytochrome P450 superfamily. Recently, CYP2W1 has gained great research interest because of its unknown enzymatic function and tumor-specific expression property. This study aims to investigate the genetic polymorphisms of the CYP2W1 gene in Chinese populations and explore the functions of the detected variants. All of the nine exons and exon-intron junction regions of the CYP2W1 gene were sequenced in 150 Chinese subjects, including 50 Han Chinese, 50 Tibetans, and 50 Uighurs. A total of 26 genetic variants were identified in this study, and 19 polymorphisms were detected in each population. Frequency comparison between populations showed that nine variants exhibited significantly different allelic distributions. A total of 12 different haplotypes were inferred from 150 samples by using the genotype data of nine exonic variants found in this study. CYP2W1*1A, *1B, *2, *4, and *6 were detected as the main alleles/haplotypes. Moreover, one, three, and two ethnically specific haplotypes were observed in the Han, Tibetan, and Uighur samples, respectively. Then, the effects of four detected missense mutations (Ala181Thr, Gly376Ser, Val432Ile, and Pro488Leu) on the CYP2W1 protein function were predicted using three in silico tools: Polymorphism Phenotyping v2, Sorts Intolerant from Tolerant, and MutationTaster. The results showed that Gly376Ser and Pro488Leu may have deleterious effects. In summary, this study showed that the genetic pattern of CYP2W1 is interethnically different among the three Chinese populations, and this finding can extend our understanding of population genetics of CYP2W1 in the Chinese population. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.

PubMed

Zhao, Q; Davis, M E; Hines, H C

2004-08-01

The Pit-1 gene was studied as a candidate for genetic markers of growth and carcass traits. Angus beef cattle that were divergently selected for high- or low-blood serum IGF-I concentration were used in this study. The single-strand conformation polymorphism method was used to identify polymorphism in the Pit-1 gene including regions from intron 2 to exon 6. Two polymorphisms, Pit1I3H (HinfI) and Pit1I3NL (NlaIII), were detected in intron 3 of the Pit-1 gene. One polymorphism, Pit1I4N (BstNI), was found in intron 4, and a single nucleotide polymorphism, Pit1I5, was found in intron 5. The previously reported polymorphism in exon 6, Pit1E6H (HinfI), was also studied in 416 Angus beef cattle. Associations of the polymorphisms with growth traits, carcass traits, and IGF-I concentration were analyzed using a general linear model procedure. No significant associations were observed between these polymorphisms and growth and carcass traits.

APOE polymorphism as a potential determinant of functional fitness in the elderly regardless of nutritional status.

PubMed

Snejdrlova, Michaela; Kalvach, Zdenek; Topinkova, Eva; Vrablik, Michal; Prochazkova, Renata; Kvasilova, Marie; Lanska, Vera; Zlatohlavek, Lukas; Prusikova, Martina; Ceska, Richard

2011-01-01

Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly. © 2011 Neuroendocrinology Letters

Association of brain-derived neurotrophic factor valine to methionine polymorphism with sexual dysfunction following selective serotonin reuptake inhibitor treatment in female patients with major depressive disorder.

PubMed

Nazree, Nur Elia; Mohamed, Zahurin; Reynolds, Gavin P; Mohd Zain, Shamsul; Masiran, Ruziana; Sidi, Hatta; Chong, Lu Ann; Hway, Anne Yee; Adlan, Aida Syarinaz; Zainal, Nor Zuraida

2016-12-01

The occurrence of female sexual dysfunction (FSD) in patients with major depressive disorder (MDD) receiving selective serotonin reuptake inhibitors (SSRIs) treatment gives negative impacts on patients' quality of life and causes treatment discontinuation. We aimed to investigate whether genetic polymorphism of identified candidate gene is associated with FSD in our study population. This is a cross-sectional study. A total of 95 female patients with MDD who met the criteria of the study were recruited and were specifically assessed on the sexual function by trained psychiatrists. Patients' DNA was genotyped for BDNF Val66Met polymorphism using real-time polymerase chain reaction. The prevalence of FSD in this study is 31.6%. In the FSD group, patients with problematic marriage were significantly more frequent compared with patients who did not have problematic marriage (P = 0.009). Significant association was detected in the lubrication domain with BDNF Val66Met polymorphism (P = 0.030) using additive genetic model, with even stronger association when using the recessive model (P = 0.013). This study suggested that there was no significant association between BDNF Val66Met with FSD. However, this polymorphism is significantly associated with lubrication disorder in patients treated with SSRIs. © 2015 Wiley Publishing Asia Pty Ltd.

Genetic Characterization of the Fish Piaractus brachypomus by Microsatellites Derived from Transcriptome Sequencing.

PubMed

Jorge, Paulo H; Mastrochirico-Filho, Vito A; Hata, Milene E; Mendes, Natália J; Ariede, Raquel B; de Freitas, Milena Vieira; Vera, Manuel; Porto-Foresti, Fábio; Hashimoto, Diogo T

2018-01-01

The pirapitinga, Piaractus brachypomus (Characiformes, Serrasalmidae), is a fish from the Amazon basin and is considered to be one of the main native species used in aquaculture production in South America. The objectives of this study were: (1) to perform liver transcriptome sequencing of pirapitinga through NGS and then validate a set of microsatellite markers for this species; and (2) to use polymorphic microsatellites for analysis of genetic variability in farmed stocks. The transcriptome sequencing was carried out through the Roche/454 technology, which resulted in 3,696 non-redundant contigs. Of this total, 2,568 contigs had similarity in the non-redundant (nr) protein database (Genbank) and 2,075 sequences were characterized in the categories of Gene Ontology (GO). After the validation process of 30 microsatellite loci, eight markers showed polymorphism. The analysis of these polymorphic markers in farmed stocks revealed that fish farms from North Brazil had a higher genetic diversity than fish farms from Southeast Brazil. AMOVA demonstrated that the highest proportion of variation was presented within the populations. However, when comparing different groups (1: Wild; 2: North fish farms; 3: Southeast fish farms), a considerable variation between the groups was observed. The F ST values showed the occurrence of genetic structure among the broodstocks from different regions of Brazil. The transcriptome sequencing in pirapitinga provided important genetic resources for biological studies in this non-model species, and microsatellite data can be used as the framework for the genetic management of breeding stocks in Brazil, which might provide a basis for a genetic pre-breeding programme.

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis.

PubMed

Boeddha, Navin P; Emonts, Marieke; Cnossen, Marjon H; de Maat, Moniek P; Leebeek, Frank W; Driessen, Gertjan J; Hazelzet, Jan A

2017-02-01

The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Molecular-genetic correlates of infant attachment: A cautionary tale

PubMed Central

Booth-Laforce, Cathryn; Belsky, Jay; Burt, Keith B.; Groh, Ashley M.

2014-01-01

This paper advises caution in relation to the increasing interest in molecular-genetic association studies in developmental psychology based on a set of empirical examples from the NICHD Study of Early Child Care and Youth Development (SECCYD) that highlight the fragility of effects reported in the literature on the molecular-genetic correlates of infant attachment. Specifically, this paper updates and provides three extensions to results reported in Luijk et al. (2011), which recently failed to replicate evidence from smaller-sample studies that a set of dopaminergic, serotonergic, and oxytonergic markers are significantly associated with infant attachment security or disorganization. First, we report here that the average effect of “usual suspect” polymorphisms on infant attachment security and disorganization in the SECCYD is approximately zero. Second, because Luijk et al. (2011) reported data based exclusively on the White infants in the SECCYD, this paper reveals that the average effect of polymorphisms featured in this literature is also of trivial magnitude in the non-White sub-sample (cf. Chen, Barth, Johnson, Gotlib, & Johnson, 2011). Third, this paper attempts, but fails, to replicate a recent finding by Raby et al. (2012) suggesting that, although molecular-genetic polymorphisms might not be implicated in security versus insecurity, the serotonin transporter gene contributes to variation in emotional distress during the Strange Situation Procedure. Implications for future research on the genetics of developmental phenotypes in general and attachment in particular are discussed, with a focus on statistical power and model-based theory testing. PMID:23421800

Genetic factors contribute to bleeding after cardiac surgery.

PubMed

Welsby, I J; Podgoreanu, M V; Phillips-Bute, B; Mathew, J P; Smith, P K; Newman, M F; Schwinn, D A; Stafford-Smith, M

2005-06-01

Postoperative bleeding remains a common, serious problem for cardiac surgery patients, with striking inter-patient variability poorly explained by clinical, procedural, and biological markers. We tested the hypothesis that genetic polymorphisms of coagulation proteins and platelet glycoproteins are associated with bleeding after cardiac surgery. Seven hundred and eighty patients undergoing aortocoronary surgery with cardiopulmonary bypass were studied. Clinical covariates previously associated with bleeding were recorded and DNA isolated from preoperative blood. Matrix Assisted Laser Desorption/Ionization, Time-Of-Flight (MALDI-TOF) mass spectroscopy or polymerase chain reaction were used for genotype analysis. Multivariable linear regression modeling, including all genetic main effects and two-way gene-gene interactions, related clinical and genetic predictors to bleeding from the thorax and mediastinum. Nineteen candidate polymorphisms were assessed; seven [GPIaIIa-52C>T and 807C>T, GPIb alpha 524C>T, tissue factor-603A>G, prothrombin 20210G>A, tissue factor pathway inhibitor-399C>T, and angiotensin converting enzyme (ACE) deletion/insertion] demonstrate significant association with bleeding (P < 0.01). Adding genetic to clinical predictors results improves the model, doubling overall ability to predict bleeding (P < 0.01). We identified seven genetic polymorphisms associated with bleeding after cardiac surgery. Genetic factors appear primarily independent of, and explain at least as much variation in bleeding as clinical covariates; combining genetic and clinical factors double our ability to predict bleeding after cardiac surgery. Accounting for genotype may be necessary when stratifying risk of bleeding after cardiac surgery.

Genetic Analysis of Termite Colonies in Wisconsin.

PubMed

Arango, R A; Marschalek, D A; Green, F; Raffa, K F; Berres, M E

2015-06-01

The objective of this study was to document current areas of subterranean termite activity in Wisconsin and to evaluate genetic characteristics of these northern, peripheral colonies. Here, amplified fragment-length polymorphism was used to characterize levels of inbreeding, expected heterozygosity, and percent polymorphism within colonies as well as genetic structure among populations sampled. Genetic analysis revealed two species of termites occur in Wisconsin, Reticulitermes flavipes (Kollar) and Reticulitermes tibialis Banks, both found in the southern half of the state. Colonies of both species in Wisconsin are thought to represent the northern boundary of their current distributions. Measurements of within colony genetic variation showed the proportion of polymorphic loci to be between 52.9-63.9% and expected heterozygosity to range from 0.122-0.189. Consistent with geographical isolation, strong intercolony genetic differences were observed, with over 50% of FST values above 0.25 and the remaining showing moderate levels of genetic differentiation. Combined with low levels of inbreeding in most collection locations (FIS 0.042-0.123), we hypothesize termites were introduced numerous times in the state, likely by anthropogenic means. We discuss the potential effects of these genetic characteristics on successful colony establishment of termites along the northern boundary compared with termites in the core region of their distribution. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

G-protein beta 3 subunit polymorphisms and essential hypertension: a case-control association study in northern Han Chinese

PubMed Central

Li, Mei; Zhang, Bei; Li, Chuang; Liu, Jie-Lin; Wang, Li-Juan; Liu, Ya; Wang, Zuo-Guang; Wen, Shao-Jun

2015-01-01

Objective To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recruited 731 hypertensive patients and 673 control subjects (the calculated power value was > 0.8). Genotyping was performed to identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models (additive, dominant and recessive models). Results The genotype distribution and allele frequencies of C825T, C1429T and G(-350)A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C1429T and G(-350)A polymorphisms and the risk of essential hypertension in any genetic model. Linkage disequilibrium was only detected between C825T and C1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C1429T and G(-350)A] were not significantly associated with essential hypertension in northern Han Chinese population. PMID:25870615

Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique.

PubMed

Toral Ibañez, Manuel; Caru, Margarita; Herrera, Miguel A; Gonzalez, Luis; Martin, Luis M; Miranda, Jorge; Navarro-Cerrillo, Rafael M

2009-02-01

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was constructed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geographic origin.

Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique*

PubMed Central

Toral Ibañez, Manuel; Caru, Margarita; Herrera, Miguel A.; Gonzalez, Luis; Martin, Luis M.; Miranda, Jorge; Navarro-Cerrillo, Rafael M.

2009-01-01

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was constructed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geographic origin. PMID:19235269

Genetic analysis of 430 Chinese Cynodon dactylon accessions using sequence-related amplified polymorphism markers.

PubMed

Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

2014-10-21

Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260-1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53-0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars.

Genetic variation at microsatellite loci in the tropical herb Aphelandra aurantiaca (Acanthaceae).

PubMed

Suárez-Montes, Pilar; Tapia-López, Rosalinda; Núñez-Farfán, Juan

2015-11-01

To assess the effect of forest fragmentation on genetic variation and population structure of Aphelandra aurantiaca (Acanthaceae), a tropical and ornamental herbaceous perennial plant, we developed the first microsatellite primers for the species. Fourteen microsatellite markers were isolated and characterized from A. aurantiaca genomic libraries enriched for di-, tri-, and tetranucleotide repeat motifs. Polymorphism was evaluated in 107 individuals from four natural populations. Twelve out of 14 genetic markers were polymorphic. The number of alleles per locus ranged from two to 12, and the observed and expected heterozygosities ranged from 0.22 to 0.96 and from 0.20 to 0.87, respectively. Fixation indices ranged from -0.41 to 0.44. These newly developed microsatellite markers for A. aurantiaca will be useful for future population genetic studies, specifically to detect the possible loss of genetic diversity due to habitat fragmentation.

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

2014-02-14

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.

[Meta-analysis on relationship between single nucleotide polymorphism of rs2231142 in ABCG2 gene and gout in East Asian population].

PubMed

Wu, Lei; He, Yao; Zhang, Di

2015-11-01

To systematically evaluate the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout in East Asian population. The literature retrieval was conducted by using English databases (Medline, EMbase), Chinese databases (CNKI, Vip, Wanfang, SinaMed) and others to collect the published papers on the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout by the end of December 2014. Meta-analysis was performed with software Stata 12.0. Nine studies were included. There were significant associations between increased risk of gout and single nucleotide polymorphism of rs2231142, the combined OR was 2.04 (95%CI: 1.82-2.28) for A allele and C allele, 1.97 (95%CI: 1.57-2.48) for CA and CC, 3.71 (95%CI: 3.07-4.47) for AA and CC. Sex and region specific subgroup analysis showed less heterogeneity. There is significant association between gout and single nucleotide polymorphism of rs2231142 in East Asian population, and A allele is a high risk gene for gout.

Meta-analysis of the rs2075650 polymorphism and risk of Alzheimer disease.

PubMed

He, Ya; Li, Chen; Yang, Ying; Li, Yizhou; Wang, Yuan; Yang, Hua; Jin, Tianbo; Chen, Songsheng

2016-10-01

Several researchers have suggested that the rs2075650 polymorphism is significantly associated with an increased risk of developing Alzheimer disease (AD) in European. However, some others found inconsistent results in Asian (Chinese and Korean). We addressed the controversy through performing a meta-analysis of the relationship between rs2075650 in TOMM40 (translocase of outer mitochondrial membrane 40 homologue) and Alzheimer disease. We selected eight case-control studies involving 4290 cases of Alzheimer disease and 5556 healthy individuals. The association between the TOMM40 rs2075650 polymorphism and Alzheimer disease was examined by overall odds ratio (OR) with a 95 % confidence interval (CI). We used different genetic model analysis, sensitivity analysis, and assessments of bias in our meta-analysis. The pooled analysis showed the inconsistent results that TOMM40 rs2075650 polymorphism was associated with Alzheimer disease in European and Korean population in all genetic models, but there was no significant association between the TOMM40 rs2075650 polymorphism and Alzheimer disease risk in Chinese population. We conclude that rs2075650 in TOMM40 gene may increase the risk of Alzheimer disease.

Genetic basis of inter-individual variability in the effects of exercise on the alleviation of lifestyle-related diseases

PubMed Central

Mori, Masayuki; Higuchi, Keiichi; Sakurai, Akihiro; Tabara, Yasuharu; Miki, Tetsuro; Nose, Hiroshi

2009-01-01

Habitual exercise training, including a high-intensity interval walking programme, improves cardiorespiratory fitness and alleviates lifestyle-related diseases, such as obesity, hypertension and dyslipidaemia. However, the extent of improvement has been shown to differ substantially among individuals for various exercise regimens. A body of literature has demonstrated that gene polymorphisms could account for the inter-individual variability in the improvement of risk factors for lifestyle-related diseases following exercise training. However, the fractions of the variability explained by the polymorphisms are small (∼5%). Also, it is likely that the effects of gene polymorphisms differ with exercise regimens and subject characteristics. These observations suggest the necessity for further studies to exhaustively identify such gene polymorphisms. More importantly, the physiological and molecular genetic mechanisms by which gene polymorphisms interact with exercise to influence the improvements of risk factors for lifestyle-related diseases differentially remain to be clarified. A better understanding of these issues should lead to more effective integration of exercise to optimize the treatment and management of individuals with lifestyle-related diseases. PMID:19736300

Genetically-determined polymorphism of nonspecific esterases and phosphoglucomutase in eight introduced breeds of the silkworm, Bombyx mori, raised in Bulgaria.

PubMed

Staykova, Teodora

2008-01-01

Isoenzymes are very suitable markers for the study of the inter-breed diversity of the silkworm Bombyx mon L. (Lepidoptera: Bombycidae). More than 250 breeds are raised in Bulgaria, which are not very well studied with regard to their isoenzymic polymorphism. Polymorphism of nonspecific esterases from pupal haemolymph was analyzed, as well as of phosphoglucomutase from different organs of larvae, pupae and imago, from eight introduced breeds. Electrophoresis in polyacrylamide gels was used. A polylocus control of nonspecific esterases, and possible monolocus control of phosphoglucomutase was ascertained. Biallele and triallele polymorphism of phosphoglucomutase locus and in three of the esterase loci was determined. The allelic frequencies of the polymorphic loci in each breed were analyzed. Inter-breed differences were found in different allelic frequencies, different heterozygosity and polymorphism.

Genetic diversity in wild populations of Paulownia fortune.

PubMed

Li, H Y; Ru, G X; Zhang, J; Lu, Y Y

2014-11-01

The genetic diversities of 16 Paulownia fortunei populations involving 143 individuals collected from 6 provinces in China were analyzed using amplified fragment length polymorphism (AFLP). A total of 9 primer pairs with 1169 polymorphic loci were screened out, and each pair possessed 132 bands on average. The percentage of polymorphic bands (98.57%), the effective number of alleles (1.2138-1.2726), Nei's genetic diversity (0.1566-0.1887), and Shannon's information index (0.2692-0.3117) indicated a plentiful genetic diversity and different among Paulownia fortunei populations. The genetic differentiation coefficient between populations was 0.2386, while the gene flow was 1.0954, and the low gene exchange promoted genetic differentiation. Analysis of variance indicated that genetic variation mainly occurred within populations (81.62% of total variation) rather than among populations (18.38%). The 16 populations were divided by unweighted pair-group method with arithmetic means (UPGMA) into 4 groups with obvious regionalism, in which the populations with close geographical locations (latitude) were clustered together.

Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline.

PubMed

Pappas, Derek J; Marin, Wesley; Hollenbach, Jill A; Mack, Steven J

2016-03-01

Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

TNFalpha -308 C-->t and -863 C-->a polymorphisms and spermiogram characteristics.

PubMed

Kurz, Christine; Bentz, Eva-Katrin; Denschlag, Dominik; Berner, Isabel; Keck, Christoph; Tempfer, Clemens B; Pietrowski, Detlef

2008-01-01

Genetic factors may play a role in male infertility. In a prospective case-control study, we assessed the allele and genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms, detected by PCR of sperm DNA, of 577 Caucasian men recruited in an infertility clinic. Semen sampling was performed and spermiogram results were correlated to genetic data. The allele frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were not significantly different between non-normozoospermic (n = 447) and normozoospermic (n = 130) men [758/894 (85%) and 134/894 (15%) vs. 213/269 (82%) and 43/260 (18%), p = 0.5, odds ratio (OR) 1.1, 95% confidence interval (CI) 0.74-1.76, and 749/894 (84%) and 145/894 (16%) vs. 212/260 (82%) and 48/260 (18%), p = 0.4, OR 1.2, 95% CI 0.78-1.76, respectively]. The genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were also not significantly different between non-normozoospermic and normozoospermic men. In addition, mutant alleles were not overrepresented in subgroups of men with the oligoasthenoteratozoospermia syndrome and asthenozoospermia. The TNFalpha -308 C-->T and -863 C-->A polymorphisms are not associated with spermiogram characteristics and do not represent molecular markers for genetic susceptibility to male infertility. Copyright 2008 S. Karger AG, Basel.

Extensive shared polymorphism at non-MHC immune genes in recently diverged North American prairie grouse

USGS Publications Warehouse

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2018-01-01

Gene polymorphisms shared between recently diverged species are thought to be widespread and most commonly reflect introgression from hybridization or retention of ancestral polymorphism through incomplete lineage sorting. Shared genetic diversity resulting from incomplete lineage sorting is usually maintained for a relatively short period of time, but under strong balancing selection it may persist for millions of years beyond species divergence (balanced trans-species polymorphism), as in the case of the major histocompatibility complex (MHC) genes. However, balancing selection is much less likely to act on non-MHC immune genes. The aim of this study was to investigate the patterns of shared polymorphism and selection at non-MHC immune genes in five grouse species from Centrocercus and Tympanuchus genera. For this purpose, we genotyped five non-MHC immune genes that do not interact directly with pathogens, but are involved in signaling and regulate immune cell growth. In contrast to previous studies with MHC, we found no evidence for balancing selection or balanced trans-species polymorphism among the non-MHC immune genes. No haplotypes were shared between genera and in most cases more similar allelic variants sorted by genus. Between species within genera, however, we found extensive shared polymorphism, which was most likely attributable to introgression or incomplete lineage sorting following recent divergence and large ancestral effective population size (i.e., weak genetic drift). Our study suggests that North American prairie grouse may have attained relatively low degree of reciprocal monophyly at nuclear loci and reinforces the rarity of balancing selection in non-MHC immune genes.

Polymorphisms of glutathione peroxidase 1 (GPX1 Pro198Leu) and catalase (CAT C-262T) in women with spontaneous abortion.

PubMed

Sabet, Eliza Eskafi; Salehi, Zivar; Khodayari, Siamak; Zarafshan, Samin Sabouhi; Zahiri, Ziba

2014-10-01

About 10%-15% of conceptions are lost spontaneously prior to 20 weeks. Apart from the clinical problems, genetic variations have also been proposed as a susceptibility factor to miscarriage. Glutathione peroxidase 1 (GPX1) and catalase (CAT) encode two antioxidant enzymes that detoxify H2O2 and protect the cells from oxidative damage. A functional polymorphism at codon 198 of the GPX1 gene causes a C/T substitution in exon 2, which encodes for either proline or leucine (Pro198Leu). The CAT gene has a polymorphic site in the promoter region at position -262 (C-262T) which alters the expression and enzyme blood levels, leading to some pathological clinical conditions. In this study, we evaluated the association of these two polymorphisms with the risk of spontaneous abortion. Genomic DNA from 105 cases with spontaneous abortion and 90 healthy women were genotyped using allele-specific PCR (AS-PCR) and polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The genetic distributions for GPX1 did not differ significantly between cases and controls (p = 0.680). However, C-262T polymorphism was significantly associated with the risk of the disease (OR, 5.50; 95% CI, 1.43-21.09; p = 0.012). In conclusion, this study indicates that CAT -262T/T genotype confers less susceptibility to spontaneous abortion, while GPX1 Pro198Leu polymorphism may not be correlated with the disease.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis.

PubMed

López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A; Huaranga, Marco A Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A

2017-01-06

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

PubMed Central

López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A.; Huaranga, Marco A. Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J.; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J. Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

2017-01-01

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA. PMID:28059143

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

Colon tumor mutations and epigenetic changes associated with genetic polymorphism: Insight into disease pathways

PubMed Central

Slattery, Martha L.; Wolff, Roger K.; Curtin, Karen; Fitzpatrick, Frank; Herrick, Jennifer; Potter, John D.; Caan, Bette J.; Samowitz, Wade S.

2010-01-01

Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP positive and MSI tumors, with the strongest associations among aspirin users. The Fok1 Vitamin D Receptor (VDR) polymorphism was associated with CIMP positive/Ki-ras mutated tumors; the Poly A and CDX2 VDR polymorphisms were associated only with Ki-ras mutated tumors. NAT2 was associated with CIMP positive/Ki-ras mutated tumors but not with MSI tumors. The TCF7L2 rs7903146 polymorphism was associated with p53 mutated tumors. Most associations varied by recent aspirin/NSAID use: IL6 rs1800796 and rs1800795 polymorphisms were associated inversely with tumor mutations in the presence of aspirin/NSAIDs; POMC significantly reduced risk of Ki-ras- mutated tumors when aspirin/NSAIDs were not used; the TCF7L2 rs7903146 was associated with reduced risk of Ki-ras-mutated tumors in the presence of aspirin and increased risk in the absence of aspirin. These data, although exploratory, identify specific tumor subsets that may be associated with specific exposures/polymorphism combinations. The important modifying effects of aspirin/NSAIDs on associations with genetic polymorphisms reinforce the underlying role of inflammation in the etiology of colon cancer. PMID:18992263

Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target.

PubMed

Witkiewicz, Agnieszka K; Costantino, Christina L; Metz, Richard; Muller, Alexander J; Prendergast, George C; Yeo, Charles J; Brody, Jonathan R

2009-05-01

The recently discovered indoleamine 2,3-dioxygenase-2 (IDO2) gene has 2 functional polymorphisms that abolish its enzymatic activity. We hypothesize that expression of the IDO2 enzyme in primary pancreatic ductal adenocarcinomas (PDA) can help cancer cells evade immune detection. Because the IDO2 enzyme might be the preferential target of d-1-methyl-tryptophan, a clinical lead inhibitor of IDO currently being evaluated in phase I trials, we sequenced IDO2 in 36 pancreatic specimens and evaluated its expression. We found that 58% (21 of 36) of cases were heterozygous for the R248W polymorphism; 28% (10 of 36) were homozygous wild-type; and only 14% (5 of 36) were homozygous for the functionally inactive polymorphism. As for the Y359STOP polymorphism, we found that 27% (10 of 36) of cases were heterozygous, 62% (22 of 36) were homozygous wild-type, and only 11% (4 of 36) were homozygous for this functionally inactive allele. Ruling out the possibility of compound polymorphic variants, we estimated 75% of our resected patient cohort had an active IDO2 enzyme, with a conservative estimate that 58% of the patients had at least 1 functional allele. IDO2 was expressed in PDA tissue from each genetically polymorphic subgroup. We also detected IDO2 protein expression in the genetically distinct pancreatic cancer cell lines after exposure with interferon-gamma. This is the first study to report IDO2 expression in PDA and related cancers indicating that IDO2 genetic polymorphisms do not negate interferon-gamma-inducible protein expression. Taken together, our data strongly suggest that the clinical lead compound d-1-methyl-tryptophan might be useful in treatment of PDA.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

PubMed

Albrechtsen, A; Grarup, N; Li, Y; Sparsø, T; Tian, G; Cao, H; Jiang, T; Kim, S Y; Korneliussen, T; Li, Q; Nie, C; Wu, R; Skotte, L; Morris, A P; Ladenvall, C; Cauchi, S; Stančáková, A; Andersen, G; Astrup, A; Banasik, K; Bennett, A J; Bolund, L; Charpentier, G; Chen, Y; Dekker, J M; Doney, A S F; Dorkhan, M; Forsen, T; Frayling, T M; Groves, C J; Gui, Y; Hallmans, G; Hattersley, A T; He, K; Hitman, G A; Holmkvist, J; Huang, S; Jiang, H; Jin, X; Justesen, J M; Kristiansen, K; Kuusisto, J; Lajer, M; Lantieri, O; Li, W; Liang, H; Liao, Q; Liu, X; Ma, T; Ma, X; Manijak, M P; Marre, M; Mokrosiński, J; Morris, A D; Mu, B; Nielsen, A A; Nijpels, G; Nilsson, P; Palmer, C N A; Rayner, N W; Renström, F; Ribel-Madsen, R; Robertson, N; Rolandsson, O; Rossing, P; Schwartz, T W; Slagboom, P E; Sterner, M; Tang, M; Tarnow, L; Tuomi, T; van't Riet, E; van Leeuwen, N; Varga, T V; Vestmar, M A; Walker, M; Wang, B; Wang, Y; Wu, H; Xi, F; Yengo, L; Yu, C; Zhang, X; Zhang, J; Zhang, Q; Zhang, W; Zheng, H; Zhou, Y; Altshuler, D; 't Hart, L M; Franks, P W; Balkau, B; Froguel, P; McCarthy, M I; Laakso, M; Groop, L; Christensen, C; Brandslund, I; Lauritzen, T; Witte, D R; Linneberg, A; Jørgensen, T; Hansen, T; Wang, J; Nielsen, R; Pedersen, O

2013-02-01

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Genetic Confirmation of Mungbean (Vigna radiata) and Mashbean (Vigna mungo) Interspecific Recombinants using Molecular Markers.

PubMed

Abbas, Ghulam; Hameed, Amjad; Rizwan, Muhammad; Ahsan, Muhammad; Asghar, Muhammad J; Iqbal, Nayyer

2015-01-01

Molecular confirmation of interspecific recombinants is essential to overcome the issues like self-pollination, environmental influence, and inadequacy of morphological characteristics during interspecific hybridization. The present study was conducted for genetic confirmation of mungbean (female) and mashbean (male) interspecific crosses using molecular markers. Initially, polymorphic random amplified polymorphic DNA (RAPD), universal rice primers (URP), and simple sequence repeats (SSR) markers differentiating parent genotypes were identified. Recombination in hybrids was confirmed using these polymorphic DNA markers. The NM 2006 × Mash 88 was most successful interspecific cross. Most of true recombinants confirmed by molecular markers were from this cross combination. SSR markers were efficient in detecting genetic variability and recombination with reference to specific chromosomes and particular loci. SSR (RIS) and RAPD identified variability dispersed throughout the genome. In conclusion, DNA based marker assisted selection (MAS) efficiently confirmed the interspecific recombinants. The results provided evidence that MAS can enhance the authenticity of selection in mungbean improvement program.

Does Marriage Moderate Genetic Effects on Delinquency and Violence?

PubMed Central

Li, Yi; Liu, Hexuan; Guo, Guang

2015-01-01

Using data from the National Longitudinal Study of Adolescent to Adult Health (N = 1,254), the authors investigated whether marriage can foster desistance from delinquency and violence by moderating genetic effects. In contrast to existing gene–environment research that typically focuses on one or a few genetic polymorphisms, they extended a recently developed mixed linear model to consider the collective influence of 580 single nucleotide polymorphisms in 64 genes related to aggression and risky behavior. The mixed linear model estimates the proportion of variance in the phenotype that is explained by the single nucleotide polymorphisms. The authors found that the proportion of variance in delinquency/violence explained was smaller among married individuals than unmarried individuals. Because selection, confounding, and heterogeneity may bias the estimate of the Gene × Marriage interaction, they conducted a series of analyses to address these issues. The findings suggest that the Gene × Marriage interaction results were not seriously affected by these issues. PMID:26549892

Genetic Polymorphism of Inosine Triphosphate Pyrophosphatase Is a Determinant of Mercaptopurine Metabolism and Toxicity During Treatment for Acute Lymphoblastic Leukemia

PubMed Central

Stocco, G; Cheok, MH; Crews, KR; Dervieux, T; French, D; Pei, D; Yang, W; Cheng, C; Pui, C-H; Relling, MV; Evans, WE

2009-01-01

The influence of genetic polymorphism in inosine triphosphate pyrophosphatase (ITPA) on thiopurine-induced adverse events has not been investigated in the context of combination chemotherapy for acute lymphoblastic leukemia (ALL). This study investigated the effects of a common ITPA variant allele (rs41320251) on mercaptopurine metabolism and toxicity during treatment of children with ALL. Significantly higher concentrations of methyl mercaptopurine nucleotides were found in patients with the nonfunctional ITPA allele. Moreover, there was a significantly higher probability of severe febrile neutropenia in patients with a variant ITPA allele among patients whose dose of mercaptopurine had been adjusted for TPMT genotype. In a cohort of patients whose mercaptopurine dose was not adjusted for TPMT phenotype, the TPMT genotype had a greater effect than the ITPA genotype. In conclusion, genetic polymorphism of ITPA is a significant determinant of mercaptopurine metabolism and of severe febrile neutropenia, after combination chemotherapy for ALL in which mercaptopurine doses are individualized on the basis of TPMT genotype. PMID:18685564

Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.

PubMed

Stocco, G; Cheok, M H; Crews, K R; Dervieux, T; French, D; Pei, D; Yang, W; Cheng, C; Pui, C-H; Relling, M V; Evans, W E

2009-02-01

The influence of genetic polymorphism in inosine triphosphate pyrophosphatase (ITPA) on thiopurine-induced adverse events has not been investigated in the context of combination chemotherapy for acute lymphoblastic leukemia (ALL). This study investigated the effects of a common ITPA variant allele (rs41320251) on mercaptopurine metabolism and toxicity during treatment of children with ALL. Significantly higher concentrations of methyl mercaptopurine nucleotides were found in patients with the nonfunctional ITPA allele. Moreover, there was a significantly higher probability of severe febrile neutropenia in patients with a variant ITPA allele among patients whose dose of mercaptopurine had been adjusted for TPMT genotype. In a cohort of patients whose mercaptopurine dose was not adjusted for TPMT phenotype, the TPMT genotype had a greater effect than the ITPA genotype. In conclusion, genetic polymorphism of ITPA is a significant determinant of mercaptopurine metabolism and of severe febrile neutropenia, after combination chemotherapy for ALL in which mercaptopurine doses are individualized on the basis of TPMT genotype.

Genetics of osteoporosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urano, Tomohiko; Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655

Highlights: • Single-nucleotide polymorphisms (SNPs) associated with osteoporosis were identified. • SNPs mapped close to or within VDR and ESR1 are associated with bone mineral density. • WNT signaling pathway plays a pivotal role in regulating bone mineral density. • Genetic studies will be useful for identification of new therapeutic targets. - Abstract: Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which increases susceptibility to fractures. BMD is a complex quantitative trait with normal distribution and seems to be genetically controlled (in 50–90% of the cases), according to studies onmore » twins and families. Over the last 20 years, candidate gene approach and genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with low BMD, osteoporosis, and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding nuclear receptors and WNT-β-catenin signaling proteins. Understanding the genetics of osteoporosis will help identify novel candidates for diagnostic and therapeutic targets.« less

Human genetic mapping studies using single sperm typing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hubert, R.S.

1993-01-01

Sperm typing is a powerful technique that uses the polymerase chain reaction (PCR) to analyze DNA sequences within single sperm cells in order to construct genetic maps. This methodology was used to estimate the recombination fraction between D3S2 and D3S2 which was found to be 0.28 (95% CI = 0.20-0.36). Pedigree analysis was unable to determine genetic distance between these two markers due to their low informativeness. We also showed that dinucleotide and tetranucleotide repeat polymorphisms can be analyzed in single cells without using radioactivity or denaturing gels. This provides a rich new source of DANA polymorphisms for genetic mappingmore » by sperm typing. In addition, an approach that uses the sperm typing methodology is described that can define the physical boundaries of meiotic recombination hotspots. The hotspot at 4p16.3 near the Huntington disease gene was localized to an interval between D4S10 and D4S126. These studies demonstrated the usefulness of sperm typing as a tool for the study of human genetic.« less

Various pharmacogenetic aspects of antiepileptic drug therapy: a review.

PubMed

Mann, Michael W; Pons, Gerard

2007-01-01

Pharmacogenetics concerns the influence of an individual's genetic background on the pharmacokinetics and pharmacodynamics of xenobiotics. Much of the pharmacogenetic data in the field of epilepsy deals with the pharmacokinetics of antiepileptic drugs (AEDs). In particular, two polymorphisms of cytochrome P450 2C9 are known to slow down the metabolism of phenytoin to a degree that increases the risk of the neurotoxic adverse effects of this drug among carriers of these polymorphisms. A significant number of patients with epilepsy do not respond to AEDs and such pharmacoresistance is a major, largely unsolved, problem that is likely to be multifactorial in nature. In this regard, genetic factors may influence transmembrane drug transporter proteins, thereby modifying the intracerebral penetration of AEDs. Monogenic idiopathic epilepsies are rare and frequently associated with ion channel mutations; however, to date, a consistent relationship between changes in channel properties and clinical phenotype has not been established nor has any association between genotype and response to specific treatment options. Polymorphisms of drug targets may represent another genetic facet in epilepsy: a recent study demonstrated for the first time a polymorphism of a drug target (the alpha-subunit of a voltage-gated sodium channel) associated in clinical practice with differing response to two classic AEDs. Adverse drug reactions and teratogenicity of AEDs remain a major concern. Whole-genome single nucleotide polymorphism profiling might in the future help to determine genetic predisposing factors for adverse drug reactions. Recently, in Han Chinese treated with carbamazepine and presenting with Stevens-Johnson syndrome, a strong association was found with HLA B*1502. If genetically targeted drug development becomes more affordable/cost efficient in the near future, the development of new drugs for relatively rare diseases could become economically viable for the pharmaceutical industry. The synergy of lower trial costs and efficacy-based prescribing may reduce the cost of medical treatment for a particular disease. This hypothetical advantage of the practical use of pharmacogenetics is, however, counterbalanced by several possible dangers, including illicit data mining and the development of a human 'genetic underclass' with the risk of exclusion from, for example employment or health insurance, because of an 'unfavourable' genetic profile.

Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.

PubMed

Bek, S; Nielsen, J V; Bojesen, A B; Franke, A; Bank, S; Vogel, U; Andersen, V

2016-09-01

Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis. A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis. There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

PubMed Central

Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

Background The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. Methods A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Results Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. Conclusions The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted. PMID:26023918

Effect of personality type on pharmacodynamics through changing pharmacokinetics.

PubMed

Xu, Feng

2007-01-01

A few studies have showed that there is an association between the genetic polymorphisms of drug-metabolizing enzyme, CYP2D6, to persons with different personality type. More and more evidences suggested that personality type is kind of behavioral or psychological factor which might influence the pharmacodynamics as well as patient's gender, age, disease, and genetic background. We hypothesized that personality affect the pharmacodynamics through changing pharmacokinetic mediated by different polymorphism of drug-metabolizing enzymes. Since many major diseases, from cancer to infectious disease, are involved with risky Type A personality, we appeal for attention to the clinical pharmacologist and psychiatrists further to study personality pharmacokinetics for individualized medicine.

Identification and characterization of microsatellite markers from the tropical sea cucumber, Stichopus horrens (Selenka).

PubMed

Shangguan, J B; Li, Z B; Yuan, Y; Huang, Y S

2015-10-28

Tropical commercial sea cucumber Stichopus horrens is extensively distributed throughout the tropical Indo-Pacific region, and wild stocks have been severely depleted over the past decade. In this study, we used the microsatellite enrichment library of S. horrens to identify and characterize 13 microsatellite loci, including 11 polymorphic loci and 2 monomorphic loci. Among the 11 polymorphic loci, the number of alleles was 3-8. The observed and expected heterozygosity varied from 0.1364 to 0.8966 and from 0.1653 to 0.7551, respectively. Additionally, all 11 polymorphic loci showed moderate and high polymorphism with the polymorphism information content (0.271-0.7311). A total of 9 polymorphic loci were in Hardy-Weinberg equilibrium, except for 2 loci (adjusted P = 0.004545). Linkage disequilibrium was not detected in any pairs of polymorphic loci. The present study will be useful for studying genetic structure, population conservation, and breeding of wild S. horrens; moreover, our results contribute to the phylogeny and evolutionary research of Holothuroidea.

Genetic characterization of the dihydrofolate reductase gene of Pneumocystis jirovecii isolates from Portugal.

PubMed

Costa, Marina C; Esteves, Francisco; Antunes, Francisco; Matos, Olga

2006-12-01

The aim of the present study was to evaluate the genetic variation of Pneumocystis jirovecii dihydrofolate reductase (DHFR) gene in an immunocompromised Portuguese population and to investigate the possible association between DHFR genotypes and P. jirovecii pneumonia (PcP) prophylaxis with co-trimoxazole. One hundred and thirty-eight P. jirovecii isolates were submitted to DHFR genetic characterization by PCR and sequencing. In the studied population, 72.7% of the patients presented sequences identical to the wild-type sequence of the P. jirovecii DHFR gene and 27.3% presented point substitutions. A total of nine substitution sites were identified; four synonymous substitutions at nucleotide positions 201, 272, 312 and 381 were detected in 31 patients. Five non-synonymous substitutions were observed, leading to the DHFR mutations Leu-13-->Ser, Asn-23-->Ser, Ser-31-->Phe, Met-52-->Leu and Ala-67-->Val. With the exception of the polymorphism at position 312 and the mutation at codon 52, all polymorphisms were reported in this study for the first time. Our results suggest that DHFR gene polymorphisms are frequent in the Portuguese immunocompromised population but do not seem to be associated with PcP prophylaxis failure (P = 0.748 and P = 0.730).

Genetic markers, genotyping methods & next generation sequencing in Mycobacterium tuberculosis

PubMed Central

Desikan, Srinidhi; Narayanan, Sujatha

2015-01-01

Molecular epidemiology (ME) is one of the main areas in tuberculosis research which is widely used to study the transmission epidemics and outbreaks of tubercle bacilli. It exploits the presence of various polymorphisms in the genome of the bacteria that can be widely used as genetic markers. Many DNA typing methods apply these genetic markers to differentiate various strains and to study the evolutionary relationships between them. The three widely used genotyping tools to differentiate Mycobacterium tuberculosis strains are IS6110 restriction fragment length polymorphism (RFLP), spacer oligotyping (Spoligotyping), and mycobacterial interspersed repeat units - variable number of tandem repeats (MIRU-VNTR). A new prospect towards ME was introduced with the development of whole genome sequencing (WGS) and the next generation sequencing (NGS) methods, where the entire genome is sequenced that not only helps in pointing out minute differences between the various sequences but also saves time and the cost. NGS is also found to be useful in identifying single nucleotide polymorphisms (SNPs), comparative genomics and also various aspects about transmission dynamics. These techniques enable the identification of mycobacterial strains and also facilitate the study of their phylogenetic and evolutionary traits. PMID:26205019

Microsatellite markers for Senna spectabilis var. excelsa (Caesalpinioideae, Fabaceae)1

PubMed Central

López-Roberts, M. Cristina; Barbosa, Ariane R.; Paganucci de Queiroz, Luciano; van den Berg, Cássio

2016-01-01

Premise of the study: Senna spectabilis var. excelsa (Fabaceae) is a South and Central American tree of great ecological importance and one of the most common species in several sites of seasonally dry forests. Our goal was to develop microsatellite markers to assess the genetic diversity and structure of this species. Methods and Results: We designed and assessed 53 loci obtained from a microsatellite-enriched library and an intersimple sequence repeat library. Fourteen loci were polymorphic, and they presented a total of 39 alleles in a sample of 61 individuals from six populations. The mean values of observed and expected heterozygosities were 0.355 and 0.479, respectively. Polymorphism information content was 0.390 and the Shannon index was 0.778. Conclusions: Polymorphism information content and Shannon index indicate that at least nine of the 14 microsatellite loci developed are moderate to highly informative, and potentially useful for population genetic studies in this species. PMID:26819856

Isolation and characterization of 30 microsatellite loci for Cunninghamia lanceolata (Taxodiaceae)1

PubMed Central

Wang, Si-Si; Zhang, Yang; Liu, De-Chen; Sun, Xiao-Wei; Wang, Rong; Li, Yuan-Yuan

2017-01-01

Premise of the study: To quantify the population-level genetic characteristics of Cunninghamia lanceolata (Taxodiaceae), an important timber conifer, we developed 30 pairs of microsatellite primers based on the nuclear genome. Methods and Results: Using the streptavidin-biotin capture system, we developed 14 polymorphic and 16 monomorphic microsatellites. Polymorphisms were detected in 14 loci using 94 individual trees that were collected from three C. lanceolata populations in Hubei and Zhejiang provinces and in Chongqing Municipality, China. There were three to 30 alleles per locus, and the observed and expected heterozygosities ranged from 0.0313–0.8333 and from 0.0313–0.9246, respectively. Cross-species amplification showed that two to seven polymorphic loci were functional in three of the five related species that were collected. Conclusions: Our newly developed microsatellite primers provide neutral molecular markers that are beneficial to future studies of population genetics and germplasm conservation of C. lanceolata. PMID:28989826

Uncovering Local Trends in Genetic Effects of Multiple Phenotypes via Functional Linear Models.

PubMed

Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Barondess, David A; Tong, Xiaoren; Jadhav, Sneha; Lu, Qing

2016-04-01

Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear model approach. In this work we extend previous developments to allow inclusion of multiple traits and adjustment for additional covariates. Our functional approach is unique in that it provides a nuanced depiction of effects and interactions for the variables in the model by representing them as curves varying over a genetic region. We demonstrate flexibility and competitive power of our approach by contrasting its performance with commonly used statistical tools and illustrate its potential for discovery and characterization of genetic architecture of complex traits using sequencing data from the Dallas Heart Study. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Epigenetic Variability in the Genetically Uniform Forest Tree Species Pinus pinea L

PubMed Central

Sáez-Laguna, Enrique; Guevara, María-Ángeles; Díaz, Luis-Manuel; Sánchez-Gómez, David; Collada, Carmen; Aranda, Ismael; Cervera, María-Teresa

2014-01-01

There is an increasing interest in understanding the role of epigenetic variability in forest species and how it may contribute to their rapid adaptation to changing environments. In this study we have conducted a genome-wide analysis of cytosine methylation pattern in Pinus pinea, a species characterized by very low levels of genetic variation and a remarkable degree of phenotypic plasticity. DNA methylation profiles of different vegetatively propagated trees from representative natural Spanish populations of P. pinea were analyzed with the Methylation Sensitive Amplified Polymorphism (MSAP) technique. A high degree of cytosine methylation was detected (64.36% of all scored DNA fragments). Furthermore, high levels of epigenetic variation were observed among the studied individuals. This high epigenetic variation found in P. pinea contrasted with the lack of genetic variation based on Amplified Fragment Length Polymorphism (AFLP) data. In this manner, variable epigenetic markers clearly discriminate individuals and differentiates two well represented populations while the lack of genetic variation revealed with the AFLP markers fail to differentiate at both, individual or population levels. In addition, the use of different replicated trees allowed identifying common polymorphic methylation sensitive MSAP markers among replicates of a given propagated tree. This set of MSAPs allowed discrimination of the 70% of the analyzed trees. PMID:25084460

Epigenetic variability in the genetically uniform forest tree species Pinus pinea L.

PubMed

Sáez-Laguna, Enrique; Guevara, María-Ángeles; Díaz, Luis-Manuel; Sánchez-Gómez, David; Collada, Carmen; Aranda, Ismael; Cervera, María-Teresa

2014-01-01

There is an increasing interest in understanding the role of epigenetic variability in forest species and how it may contribute to their rapid adaptation to changing environments. In this study we have conducted a genome-wide analysis of cytosine methylation pattern in Pinus pinea, a species characterized by very low levels of genetic variation and a remarkable degree of phenotypic plasticity. DNA methylation profiles of different vegetatively propagated trees from representative natural Spanish populations of P. pinea were analyzed with the Methylation Sensitive Amplified Polymorphism (MSAP) technique. A high degree of cytosine methylation was detected (64.36% of all scored DNA fragments). Furthermore, high levels of epigenetic variation were observed among the studied individuals. This high epigenetic variation found in P. pinea contrasted with the lack of genetic variation based on Amplified Fragment Length Polymorphism (AFLP) data. In this manner, variable epigenetic markers clearly discriminate individuals and differentiates two well represented populations while the lack of genetic variation revealed with the AFLP markers fail to differentiate at both, individual or population levels. In addition, the use of different replicated trees allowed identifying common polymorphic methylation sensitive MSAP markers among replicates of a given propagated tree. This set of MSAPs allowed discrimination of the 70% of the analyzed trees.

Population structure and genotypic variation of Crataegus pontica inferred by molecular markers.

PubMed

Rahmani, Mohammad-Shafie; Shabanian, Naghi; Khadivi-Khub, Abdollah; Woeste, Keith E; Badakhshan, Hedieh; Alikhani, Leila

2015-11-01

Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter-retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. Copyright © 2015 Elsevier B.V. All rights reserved.

[A meta-analysis on the association between genetic polymorphisms of osteoprotegerin and cardiovascular disease].

PubMed

Xin, J Y; Cong, H L

2018-06-24

Objective: To explore the association between genetic polymorphisms of rs2073617T/C (950T/C) and rs2073618G/C(1181G/C) in the osteoprotegerin gene and cardiovascular disease with meta-analysis. Methods: A computer-based search for the study of relationship between genetic polymorphisms of rs2073617T/C and rs2073618G/C in the osteoprotegerin gene and cardiovascular disease were performed in electronic databases including China National Knowledge Infrastructure(CNKI), China Biomedical Literature Database, Wanfang Database, Chinese Journal Full-text Database, Embase, PubMed, and Cochrane Library, supplemented by manual search, from the beginning of library to February 28, 2017. The quality of the included studies were assessed by the Newcastle-Ottawa Scale (NOS) scoring system. Data were analyzed using STATA 12.0 software. Results: Eleven clinical case-control studies that enrolled 2 115 patients with cardiovascular disease and 1 467 healthy subjects were included.The results indicated that osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C might be closely associated with the susceptibility to cardiovascular disease(rs2073617T/C allele model: OR= 0.79, 95% CI 0.73-0.87, P= 0.001;rs2073618G/C M allele and W allele: OR= 0.83, 95% CI 0.74-0.92, P= 0.001). The osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C were significantly related to the incidence of coronary artery disease and acute coronary syndrome(coronary artery disease allele model: OR= 0.83, 95% CI 0.75-0.92, P= 0.001; acute coronary syndrome allele model: OR= 0.73, 95% CI 0.62-0.85, P< 0.001). However, there was no significant correlation between the genetic polymorphisms of these two sites and the lesion vessel number of coronary artery (rs2073617T/C allele model: OR= 1.00, 95% CI 0.81-1.24, P= 0.985;rs2073618G/C allele model: OR= 0.98, 95% CI 0.80-1.21, P= 0.626). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-ligase detection reaction(PCR-LDR) evidenced the association between osteoprotegerin gene polymorphisms and cardiovascular disease(allele model: OR= 0.79, 95% CI 0.72-0.86, P< 0.001), but no obvious relationship was found with fluorogenic quantitative detection and molecularprobe(allele model: OR= 0.86, 95% CI 0.65-1.12, P= 0.263). Conclusion: This meta-analysis indicates that the osteoprotegerin gene polymorphisms of rs2073617T/C and rs2073618G/C may be closely related to the increased risk of cardiovascular disease.

Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.

PubMed

Sanhueza, Jorge A; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A

2016-12-01

Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety ( 5HTT , CRH2R , ACE , NK1R , 5HT1AR and CRF-BP ) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms ( 5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

Polymorphisms for ghrelin with consequences on satiety and metabolic alterations.

PubMed

Perret, Jason; De Vriese, Carine; Delporte, Christine

2014-07-01

To understand the current trend of ghrelin genetic variations on the control of satiety, eating behaviours, obesity, and metabolic alterations, and its development over the last 18 months. Several polymorphisms of the ghrelin gene, its receptor gene and ghrelin's acylating enzyme, ghrelin O-acyl transferase, have been identified and studied over the last decade in relation to control of satiety, obesity, eating behaviours, metabolic syndrome, glucose homeostasis, and type 2 diabetes. However, the effects described are either small or nonsignificant and often subjected to contradictory conclusions between studies. In the last 18 months, several of these areas of investigations have been revisited under more controlled conditions or have been subjected to meta-analysis. The effects of ghrelin gene polymorphism, is a complex area of investigation, due to ghrelin's interplay with a host of various factors part of an integrative network. However, taken together, results suggest that there are no or nonsignificant effects of the common genetic variants. A better understanding of the network, probably by a systems biology type approach, will be necessary to assign the exact role played by gene polymorphism of the component of the ghrelin axis.

Dog obesity--the need for identifying predisposing genetic markers.

PubMed

Switonski, M; Mankowska, M

2013-12-01

Incidence of overweight and obesity in dogs exceeds 30%, and several breeds are predisposed to this heritable phenotype. Rapid progress of canine genomics and advanced knowledge on the genetic background of human obesity bring a unique opportunity to perform such studies in dogs. Natural candidate genes for obesity are these encoding adipokines. Extended studies in humans indicated that polymorphisms of three of them, i.e. ADIPOQ, IL1 and TNF, are associated with predisposition to obesity. On the other hand, the use of genome-wide association studies revealed an association between human obesity and polymorphism of more than 50 other genes. Until now only few preliminary reports on polymorphism of canine FTO, MC4R, MC3R and PPARG genes have been published. Since the dog is a valuable model organism for human diseases one can foresee that such studies may also contribute to an in-depth understanding of human obesity pathogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

PubMed Central

Viatte, Sebastien; Massey, Jonathan; Bowes, John; Duffus, Kate; Eyre, Stephen; Barton, Anne; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew W.; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Tim D.; Valdes, Ana M.; Wallis, Gillian A.; Wilkinson, J. Mark; Zeggini, Eleftheria

2016-01-01

Objective Genetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study. Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA. PMID:26895230

Meta-analyses of four polymorphisms of lipoprotein lipase associated with the risk of Alzheimer's disease.

PubMed

Ren, Liang; Ren, Xingxing

2016-04-21

We evaluated the contributions of four polymorphisms of the lipoprotein lipase (LPL) gene to the risk of Alzheimer's disease (AD). Through a comprehensive literature search for genetic variants of LPL involved in AD association studies, we found four polymorphisms for the current meta-analyses. These polymorphisms were Asn291Ser(rs268), PvuII(rs285), HindIII(rs320) and Ser447Ter(rs328). In total, eight studies with 5064 cases and 5016 controls were retrieved for the meta-analyses of the four genetic variants. The analyses showed that Asn291Ser(rs268) (OR=2.34, 95% CI=1.05-5.25, P=0.04), HindIII(rs320) (OR=1.44, 95% CI=1.17-1.78, P=0.0006), and Ser447Ter(rs328) (OR=0.80, 95% CI=0.66-0.98, P=0.03) were significantly associated with a risk of AD. No association was found between the PvuII(rs285) polymorphism and the risk of AD. Our results showed that Asn291Ser(rs268), HindIII(rs320) and Ser447Ter(rs328) polymorphisms of LPL were associated with a risk of AD. Asn291Ser(rs268) and HindIII(rs320) were predisposing factors of AD, whereas Ser447Ter(rs328) showed a protective effect for AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The presence of IL-8 +781 T/C polymorphism is associated with the parameters of severe Clostridium difficile infection.

PubMed

Czepiel, Jacek; Biesiada, Grażyna; Dróżdż, Mirosław; Gdula-Argasińska, Joanna; Żurańska, Justyna; Marchewka, Jakub; Perucki, William; Wołkow, Paweł; Garlicki, Aleksander

2018-01-01

There is large variation in the clinical manifestations of Clostridium difficile infection (CDI). We also still can not predict which patients are more susceptible to reinfection with CDI. The aim of our study was to evaluate the effect of gene single nucleotide polymorphisms (SNP) of proinflammatory cytokines, specifically IL-1β, IL-8 on the development, clinical course and recurrence of CDI. We performed a prospective study of adults (130 people ≥ 18 years) including 65 patients with CDI treated in tertiary hospital and 65 healthy persons. The following 3 variants were analyzed for the occurrence of gene polymorphisms in patients with CDI versus the control group: IL-1β +3953 A/G (rs1143634), IL-1β -31 A/G (rs1143627), and IL-8 +781 T/C (rs2227306). Then, we assessed the correlation between these genetic polymorphisms and biochemical parameters important in CDI course, CDI severity as well as CDI recurrence. The presence of genetic polymorphisms of IL-1β +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C polymorphism is associated with the severe CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systematic screening for CYP3A4 genetic polymorphisms in a Han Chinese population.

PubMed

Hu, Guo-Xin; Dai, Da-Peng; Wang, Hao; Huang, Xiang-Xin; Zhou, Xiao-Yang; Cai, Jie; Chen, Hao; Cai, Jian-Ping

2017-03-01

To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28-*34. This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.

The Correlation between the CLEC16A Gene and Genetic Susceptibility to Type 1 Diabetes in Chinese Children.

PubMed

Sang, Yanmei; Zong, Wei; Yan, Jie; Liu, Min

2012-01-01

Objective. The CLEC16A gene is related to the genetic susceptibility to T1DM with racial variability. This study investigated the association between CLEC16A gene polymorphisms and T1DM in Chinese children. Methods. 131 Chinese children with T1DM were selected for study, and 121 healthy adult blood donors were selected as normal controls. PCR and mass spectrometry was used to study the distributions of 17 CLEC16A alleles in patients and controls. The relationship between CLEC16A gene polymorphisms and T1DM was studied. Results. The distributions of two polymorphisms (rs12921922, rs12931878) of CLEC16A in T1DM and healthy controls were significantly different, while the distributions of other CLEC16A polymorphisms show no significant differences. The alleles of rs12921922 are C and T. The frequency of the T allele was significantly increased in patients versus healthy controls. The alleles of rs12931878 are A and C. The frequencies of the A allele are significantly increased in T1DM patients versus healthy controls. Conclusion. Two polymorphisms in the CLEC16A gene correlate with increased susceptibility to T1DM in Chinese children, revealing that it was another new gene that correlates with susceptibility to T1DM in multiple populations.