... and Families Resources for Health Professionals What glossary definitions help with understanding Floating-Harbor syndrome? autosomal ; autosomal dominant ; brachydactyly ; cell ; clinodactyly ; cryptorchidism ; deficiency ; gene ; motor ; mutation ; ...
This article is meant to serve as a summary of scientific advances from the past 5 years with regard to genetic polymorphisms in sepsis. It is also meant to highlight some of the discoveries that may improve our ability to identify vulnerable patients at earlier time points in sepsis, when interventions are more likely to have a positive effect. The article begins with an overview of polymorphism studies and a discussion of candidate gene versus genome-wide association studies. Next, an overview of polymorphisms associated with sepsis is presented. The overview includes detailed descriptions of E-selectin, apolipoprotein E, and C-reactive protein polymorphisms and a table in which numerous other sepsis-related polymorphisms are introduced. An examination of consortia-based projects that have the potential to catalyze sepsis research is included as is a preview of technological advancements that are likely to strongly influence sepsis studies in the near future. The article concludes with a brief consideration of ethical and social issues relevant to human genomic studies. PMID:19892256
Namath, Allen; Patterson, Andrew J
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), ?-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.
Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna
During the last years, publications upon potential association between genetic polymorphisms and clinical outcomes have exponentially increased. Conflicting results between similar studies have contributed to seriously distrust the validity of this approach. This review emphasizes on intrinsic properties of SNP and methodological prerequisites for such studies. PMID:21975537
Courivaud, Cécile; Saas, Philippe; Ducloux, Didier
Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis.\\u000a The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer.\\u000a To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility
Mohammad Masoudi; Iraj Saadat; Shahpour Omidvari; Mostafa Saadat
The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature. Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.
Histamine is a biogenic amine that plays an essential role in controlling many physiological functions, both in the central nervous system (CNS) and the peripheral nervous system (PNS). Most of these physiological effects are mediated through interactions with four histamine receptor subtypes, all of which are members of the larger family of rhodopsin-like class A G-protein coupled receptors (GPCRs) (Leurs et al., 2011; Lim et al., 2009). Here, we focus on the genetic variations and polymorphisms localized on the genes encoding for human histamine receptors where it provides an up to date collection of all polymorphisms found on genes encoding the histamine receptor subtypes and their association to diseases. PMID:24012610
Micallef, Stephany; Stark, Holger; Sasse, Astrid
Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794
Savas, Sevtap; Liu, Geoffrey; Xu, Wei
According to pulsed-field gel electrophoresis (PFGE) typing, 4,12:a:- Salmonella enterica isolates from harbor porpoises are highly diverse. However, porpoise isolates belong to only two multilocus sequence types within the eBurst group 18 (eBG18) genetic cluster, which also includes S. enterica serovars Bispebjerg and Abortusequi. Isolates of other, serologically similar serovars belong to unrelated eBGs. These assignments to eBGs were supported by eBG-specific sequences of the flagellar gene fliC. PMID:23042176
Haase, Jana K; Brown, Derek J; Weill, François-Xavier; Mather, Henry; Foster, Geoffrey; Brisse, Sylvain; Wain, John; Achtman, Mark
Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), ?-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093
Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval
In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10?8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17–1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10?14) and rs12617313 (P = 7.48 × 10?12), both highly correlated with rs9679290 (r2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10?9, per-allele OR = 1.28, 95% CI: 1.18–1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.
Han, Summer S.; Yeager, Meredith; Moore, Lee E.; Wei, Ming-Hui; Pfeiffer, Ruth; Toure, Ousmane; Purdue, Mark P.; Johansson, Mattias; Scelo, Ghislaine; Chung, Charles C.; Gaborieau, Valerie; Zaridze, David; Schwartz, Kendra; Szeszenia-Dabrowska, Neonilia; Davis, Faith; Bencko, Vladimir; Colt, Joanne S.; Janout, Vladimir; Matveev, Vsevolod; Foretova, Lenka; Mates, Dana; Navratilova, M.; Boffetta, Paolo; Berg, Christine D.; Grubb, Robert L.; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Burdett, Laurie; Brisuda, Antonin; McKay, James D.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Rosenberg, Philip S.; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Tucker, Margaret A.; Chanock, Stephen J.; Toro, Jorge R.
In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. PMID:22113997
Han, Summer S; Yeager, Meredith; Moore, Lee E; Wei, Ming-Hui; Pfeiffer, Ruth; Toure, Ousmane; Purdue, Mark P; Johansson, Mattias; Scelo, Ghislaine; Chung, Charles C; Gaborieau, Valerie; Zaridze, David; Schwartz, Kendra; Szeszenia-Dabrowska, Neonilia; Davis, Faith; Bencko, Vladimir; Colt, Joanne S; Janout, Vladimir; Matveev, Vsevolod; Foretova, Lenka; Mates, Dana; Navratilova, M; Boffetta, Paolo; Berg, Christine D; Grubb, Robert L; Stevens, Victoria L; Thun, Michael J; Diver, W Ryan; Gapstur, Susan M; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Burdett, Laurie; Brisuda, Antonin; McKay, James D; Fraumeni, Joseph F; Chatterjee, Nilanjan; Rosenberg, Philip S; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Tucker, Margaret A; Chanock, Stephen J; Toro, Jorge R
Abstract The genetic origin of the three common variants of the human apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981, and since the mid 1980s these are probably the most-studied protein variants in human races. They have been related to a number of age-related diseases, including Alzheimer disease, as well as to healthy aging and longevity. The gene variants underlying these protein isoforms, known as ?2, ?3, and ?4, are allelic forms of the APOE gene, resulting from different haplotypes at the APOE locus (19q13.31). In particular, they result from three of the four haplotypes expected by the combinations of the alleles of the two single-nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known as ?3r, has been identified in only two Caucasian families from Italy and in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant is rare, and it encodes a protein isoform, identified as E3r, showing identical physical characteristics to E3, that conversely, is the most common form of apoE in humans. In this review article, we report the identification of the haplotype ?3r in a third Caucasian family from Italy, and then attempt to re-examine the current knowledge regarding the APOE polymorphism, taking into account this fourth haplotype. We also focus on the commonly accepted hypothesis for the evolution of the common APOE gene variants, in which we include the ?3r haplotype, previously not considered. PMID:21958003
Seripa, Davide; D'Onofrio, Grazia; Panza, Francesco; Cascavilla, Leandro; Masullo, Carlo; Pilotto, Alberto
Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344\\/N × LEW\\/N, BN\\/SsN × LEW\\/N, and DA\\/Bkl × F344\\/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers
Yan-Ping Ding; Elaine F. Remmers; Ying Du; Ryan E. Longman; Ellen A. Goldmuntz; Hongbin Zha; Shigeru Kotake; Grant W. Cannon; Marie M. Griffiths; Ronald L. Wilder
Background The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts.
Kang, Hae Ji; Bennett, Shannon N.; Sumibcay, Laarni; Arai, Satoru; Hope, Andrew G.; Mocz, Gabor; Song, Jin-Won; Cook, Joseph A.; Yanagihara, Richard
Increasing sophistication in methods used to account for human variability in susceptibility to toxicants has been one of the success stories in the continuing evolution of risk assessment science. Genetic polymorphisms have been suggested as an important contributor to overall human variability. Recently, data on polymorphisms in metabolic enzymes have been integrated with physiologically based pharmacokinetic (PBPK) modeling as an
L. T. Haber; A. Maier; P. R. Gentry; H. J. Clewell; M. L. Dourson
At its broadest sense, to say that a phenotype is epigenetic suggests that it occurs without changes in DNA sequence, yet is heritable through cell division and occasionally from one organismal generation to the next. Since gene regulatory changes are oftentimes in response to environmental stimuli and may be retained in descendent cells, there is a growing expectation that one's experiences may have consequence for subsequent generations and thus impact evolution by decoupling a selectable phenotype from its underlying heritable genotype. But the risk of this overbroad use of “epigenetic” is a conflation of genuine cases of heritable non-sequence genetic information with trivial modes of gene regulation. A look at the term “epigenetic” and some problems with its increasing prevalence argues for a more reserved and precise set of defining characteristics. Additionally, questions arising about how we define the “sequence independence” aspect of epigenetic inheritance suggest a form of genome evolution resulting from induced polymorphisms at repeated loci (e.g., the rDNA or heterochromatin).
Maggert, Keith A.
THE Kimura theory1 that protein polymorphism is mainly due to random genetic drift acting on a number of neutral isoalleles has been recently discussed by many authors2-4. The electrophoretic study of populations of the same species having different geographical origin and showing great fluctuations in number offers possibilities for testing the relative importance of natural selection and genetic drift in
Luciano Bullini; MARIO COLUZZI
Genetic variation of proteins (protein polymorphism) is widespread among many animal species. The biological significance of protein polymorphism has been the subject of many studies. This variation has a supporting function for population genetic studies as a source of genetic markers. In farm animals it is used in population genetics and in parentage control, mostly together with blood group polymorphism.In
R. C. Buis
Phenotypic polymorphism is a consequence of developmental plasticity, in which the trajectories of developing organisms diverge\\u000a under the influence of cues. Environmental and genetic phenotype determination are the two main categories of polymorphic\\u000a development. Even though both may evolve as a response to varied environments, they are traditionally regarded as fundamentally\\u000a distinct phenomena. They can however be joined into a
Inter-individual variability in drug response is well known. Genetic polymorphism in genes encoding drug-metabolizing enzymes\\u000a results in variation in drug metabolism and in turn drug response. The cytochrome P450 enzymes (CYP) play a central role in\\u000a the metabolism of many therapeutic agents. CYP2C19 gene polymorphism is widely studied in Caucasians, African, and Oriental populations; however, far less is known about
Yogita Ghodke; Kalpana Joshi; Yashendra Arya; Anjali Radkar; Aditi Chiplunkar; Pooja Shintre; Bhushan Patwardhan
The genetic basis of color polymorphism is explored in the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera: Sternorrhyncha), in which two color morphs have been described (pink or green). Laboratory crosses and a Mendelian genetic analysis reveal that color polymorphism in pea aphids is determined by a single biallelic locus, which we name colorama, with alleles P and p, pink being dominant to green. The putative genotypes are Pp or PP for pink morphs, and pp for green morphs. This locus is shown to be autosomal. Last, there was no evidence of influence of the direction of the cross on color inheritance, thus showing that cytoplasmic effects and/or maternally-inherited symbionts play no role in the inheritance of color polymorphism in pea aphids. The existence of a simple genetic determinism for color polymorphism in a system in which genetic investigation is possible may facilitate investigations on the physiological and molecular mechanisms of genetically-based color morph variation, and the establishment of a link between this locus and fitness in a range of ecological conditions.
Caillaud, Marina C.; Losey, John E.
The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations in North India were examined for 10 polymorphic Alu insertions (PAIs). The investigated PAIs exhibit high levels of polymorphism and average heterozygosity. Limited interpopulation variance and genetic flow in the present study suggest admixture. The results of this study demonstrate that, contrary to common belief, the caste system has not provided an impermeable barrier to genetic exchange among Indian groups. PMID:19341319
Tripathi, Manorama; Tripathi, Piyush; Chauhan, Ugam Kumari; Herrera, Rene J; Agrawal, Suraksha
Amplified fragment length polymorphism (AFLP) analysis was used to study the genetic variation within and among populations\\u000a of genus Olea. A group of genotypes, all of them cultivated varieties of a single species, Olea europaea, was compared with wild olives and with a group of individuals belonging to different Olea species. Five primer combinations were used which produced about 290
A. Angiolillo; M. Mencuccini; L. Baldoni
Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45%
Cheah Yoke-Kqueen; Son Radu
The goal of this DOD Breast Concept award was to identify and functionally characterize common genetic polymorphisms in the human UDP- glucuronosyltransferase gene, UGT1A9. We had previously determined that UGT1A9, a metabolic enzyme expressed predominant...
R. B. Raftogianis
Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE. PMID:23042179
Lúquez, Carolina; Raphael, Brian H; Joseph, Lavin A; Meno, Sarah R; Fernández, Rafael A; Maslanka, Susan E
Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE.
Raphael, Brian H.; Joseph, Lavin A.; Meno, Sarah R.; Fernandez, Rafael A.; Maslanka, Susan E.
The usefulness of the results so far published on genetics of primary hypertension for establishing the clinical impact of candidate gene polymorphisms is weakened by the scanty information regarding: a) the functional effect of the gene variants of interest in humans; b) the regulatory genetic network (RGN) where the gene is operating with all the interacting environmental-biological factors and the respective hierarchical organization; c) the consistency between the natural history of the established pathophysiological mechanisms underlying hypertension and the new molecular mechanism detected with genetics; d) the limitations regarding the translation of animal data to human due to the differences among species of the genetic molecular mechanisms underlying similar organ function changes in the different species. Of course, not all these information are available for adducin polymorphisms. In this review, being aware of their importance, the evaluation of the clinical impact of adducin has been focused on data obtained together with the interacting genetic-environmental or biological factors. Adducin polymorphisms and endogenous ouabain (EO) were detected by a top-down approach in rodents after having demonstrated, at cellular and kidney level, that an increase in tubular Na reabsorption could underlies the transition from normotension to hypertension both in rodents and humans. Therefore, we hypothesized that adducin polymorphisms and EO may operate within the triggering RGN that initiates the increase in blood pressure in both species. The distinction between triggering RGN and the secondary RGN is important both to limit the level of genetic complexity arising from secondary changes, and to detect the molecular target to develop tailored therapeutic approach. The pharmacogenomic approach, both in rodents or humans, with newly discovered and never treated hypertension, may be useful to strengthen the "causation" of genetic mechanism. Mutant adducin increases tubular reabsorption: diuretics, because of their effect on overall tubular reabsorption, or rostafuroxin, because of its selective inhibition of the adducin and ouabain effects, may be used for this purpose. Indeed the pharmacogenomic approach with both drugs have provided data consistent with the role of adducin and EO. Taken together, all these findings indicate a clear impact of adducin polymorphism and EO in a subset of patients when the appropriate environmental, biological or genetic context is taken into account. The size of this impact is variable and affected by the context. PMID:20382219
Citterio, Lorena; Lanzani, Chiara; Manunta, Paolo; Bianchi, Giuseppe
Background Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. Methods DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt?1607), MMP2(nt?955), MMP3(nt?1612), MMP9(nt?1562), MMP10(nt+180), MMP12(nt?82), MMP13(nt?77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt?1296), TGFB1(nt?509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. Results Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (?2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 (P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN (P = .0169) and TIMP3 (P = .0023) in cases with a family history of AAA. Conclusions These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt?1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual’s risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.
Ogata, Toru; Shibamura, Hidenori; Tromp, Gerard; Sinha, Moumita; Goddard, Katrina A. B.; Sakalihasan, Natzi; Limet, Raymond; MacKean, Gerald L.; Arthur, Claudette; Sueda, Taijiro; Land, Susan; Kuivaniemi, Helena
The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.
Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T. [Molecular Tool, Inc., Baltimore, MD (United States)] [and others
Interactions between polymorphisms at different quantitative trait loci (QTLs) are thought to contribute to the genetics of many traits, and can dramatically impact the power of genetic studies to detect QTLs1. Interacting loci have been identified in many organisms1–5. However, the prevalence of interactions6–8, and the nucleotide changes underlying them9,10, are largely unknown. Here we search for naturally occurring genetic interactions in a large set of quantitative phenotypes—the levels of all transcripts in a cross between two strains of S. cerevisiae7. For each transcript, we searched for secondary loci that interact with primary QTLs detected by their individual effects. Such locus pairs were estimated to play a role in the inheritance of 57% of transcripts; statistically significant pairs were identified for 225 transcripts. Among these, 67% of secondary loci had individual effects too small to be significant in a genome-wide scan. Engineered polymorphisms in isogenic strains confirmed an interaction between the mating-type locus MAT and the pheromone response gene GPA1. Our results suggest that genetic interactions are widespread in the genetics of transcript levels, and that many QTLs will be missed by single-locus tests but can be detected by two-stage tests that allow for interactions.
Brem, Rachel B.; Storey, John D.; Whittle, Jacqueline; Kruglyak, Leonid
Background Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. Methods and Findings A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n?=?914 controls vs. 1262 cases, Mantel-Haenszel 2x2 ?2?=?7.47, P?=?0.006, odds ratio?=?0.86, 95%CI 0.77–0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n?=?557, Pearson's 2×2 ?2?=?17.34, P?=?0.00003, odds ratio?=?0.42, 95%CI 0.27–0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. Conclusion This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.
Vannberg, Fredrik O.; Tosh, Kerrie; Floyd, Sian; Jackson-Sillah, Dolly; Crampin, Amelia; Sichali, Lifted; Bah, Boubacar; Gustafson, Per; Aaby, Peter; McAdam, Keith P. W. J.; Bah-Sow, Oumou; Lienhardt, Christian; Sirugo, Giorgio; Fine, Paul; Hill, Adrian V. S.
As complex common diseases, asthma and allergic diseases are caused by the interaction of multiple genetic variants with a variety of environmental factors. Candidate-gene studies have examined the involvement of a very large list of genes in asthma and allergy, demonstrating a role for more than 100 loci. These studies have elucidated several themes in the biology and pathogenesis of these diseases. A small number of genes have been associated with asthma or allergy through traditional linkage analyses. The publication of the first asthma-focused genome-wide association (GWA) study in 2007 has been followed by nearly 30 reports of GWA studies targeting asthma, allergy, or associated phenotypes and quantitative traits. GWA studies have confirmed several candidate genes and have identified new, unsuspected, and occasionally uncharacterized genes as asthma susceptibility loci. Issues of results replication persist, complicating interpretation and making conclusions difficult to draw, and much of the heritability of these diseases remains undiscovered. In the coming years studies of complex diseases like asthma and allergy will probably involve the use of high-throughput next-generation sequencing, which will bring a tremendous influx of new information as well as new problems in dealing with vast datasets.
March, Michael E; Sleiman, Patrick MA; Hakonarson, Hakon
Low birth weight (LBW) infants have increased susceptibility to perinatal complications. An immature and impaired vascular system may possibly participate in these complications. There is evidence that supports the notion that vascular endothelial growth factor (VEGF), which is an essential regulator of embryonic angiogenesis, plays a central role in the pathogenesis of perinatal complications. We aimed to test whether functional genetic polymorphisms of VEGF are associated with the risk of preterm birth or perinatal morbidity. We enrolled 128 LBW infants (< or = 1500 grams). VEGF T-460C, VEGF C-2578A and VEGF G+405C polymorphisms were determined by real-time PCR or PCR-RFLP, respectively. Their genotypes were compared with VEGF genotypes of 200 healthy, term neonates. The prevalence of the VEGF+405 C allele was higher in LBW infants than in healthy, term neonates (OR [95% CI]: 1.29 [1.01-1.65]). Carrier state for the VEGF -2578A allele was an independent risk factor for enterocolitis necrotisans (NEC) (adjusted OR [95% CI]: 2.77 [1.00-7.65]). The carrier state for the VEGF -2578AA genotype was associated with a decreased risk of acute renal failure (ARF) (adjusted OR [95% CI]: 0.2 [0.05-0.78]). These results suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C-2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF. PMID:17353160
Bányász, Ilona; Bokodi, Géza; Vásárhelyi, Barna; Treszl, András; Derzbach, László; Szabó, András; Tulassay, Tivadar; Vannay, Adám
Antithrombotic therapy, including anticoagulants as well as antiplatelet drugs, is an important component in the treatment of cardiovascular disease. Variability in response to such medications, of which pharmacogenetic response is a major source, can decrease or enhance the benefits expected. This review is a comprehensive assessment of the literature published to date on the effects of genetic polymorphisms on the actions of a variety of antithrombotic medications, including warfarin, clopidogrel, prasugrel, and aspirin. Literature evaluating surrogate markers in addition to the impact of pharmacogenetics on clinical outcomes has been reviewed. The results of the studies are conflicting as to what degree pharmacogenetics will affect medication management in cardiovascular disease. Additional research is necessary to discover, characterize, and prospectively evaluate genetic and non-genetic factors that impact antithrombotic treatment in order to maximize the effectiveness and limit the harmful effects of these valuable agents.
Lanham, Kena J; Oestreich, Julie H; Dunn, Steven P; Steinhubl, Steven R
Analysis of GM polymorphism has been performed on 1,806 individuals representing three sympatric ethnic groups--Bedik, Fulani, and Mandenkalu--of eastern Senegal. Haplotype frequencies estimated by maximum likelihood have been used to compute common genetic pools between the three samples and a number of other sub-Saharan African populations. Despite extreme linguistic and sociocultural differentiations and very high levels of endogamy, especially in the Bedik and Niokholo Mandenkalu, the three populations share about 90%-95% of their haplotype frequencies in a system which commonly provides strong genetic differentiations. This supports the view that, despite its importance at a large continental scale level, as it is discussed for a set of populations from many regions of sub-Saharan Africa, sociocultural differentiation usually has little effect on local genetic diversity.
Blanc, M; Sanchez-Mazas, A; Van Blyenburgh, N H; Sevin, A; Pison, G; Langaney, A
To ascertain whether there are chemical and genetic relationships among some Thymus species and also to determine correlation between these two sets of data, the essential-oil composition and genetic variability of six populations of Thymus including: T. daenensis ?ELAK. (two populations), T. fallax FISCH. & C.A.MEY., T. fedtschenkoi RONNIGER, T. migricus KLOKOV & DES.-SHOST., and T. vulgaris L. were analyzed by GC and GC/MS, and also by randomly amplified polymorphic DNA (RAPD). Thus, 27 individuals were analyzed using 16 RAPD primers, which generated 264 polymorphic scorable bands and volatiles isolated by distillation extraction were subjected to GC and GC/MS analyses. The yields of oils ranged from 2.1 to 3.8% (v/w), and 34 components were identified, amounting to a total percentage of 97.8-99.9%. RAPD Markers allowed a perfect distinction between the different species based on their distinctive genetic background. However, they did not show identical clustering with the volatile-oil profiles. PMID:23776024
Rustaiee, Ali Reza; Yavari, Alireza; Nazeri, Vahideh; Shokrpour, Majid; Sefidkon, Fatemeh; Rasouli, Musa
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....
Objective Multiple chemical sensitivity (MCS) is a chronic medical condition characterized by symptoms that the affect an individual’s response to low-level chemical exposure. In this study, we identified a chemical sensitive population (CSP) and investigated the effect of genetic polymorphisms on their risk of chemical sensitivity. Methods A quick environment exposure sensitivity (QEESI) questionnaire was used to survey 324 Japanese male workers whose DNA samples had been collected and stored. The following genes, which encode enzymes affecting the metabolic activation of a large number of xenobiotic compounds, were selected and analyzed in order to determine their influence on genetic predisposition to CSP: cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S-transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and superoxide dismutase (SOD) 2. Results Significant case-control distributed differences were observed in SOD2 polymorphisms and allele frequency distribution in high chemical sensitive subjects. Both the significant adjusted OR of 4.30 (95% CI, 1.23–15.03) and 4.53 (95% CI, 1.52-13.51) were observed in SOD2 Ala/Ala and Val/Ala compared to Val/Val and in SOD2 Ala/Ala compared to Val/Ala compared to Val/Val genetic analysis in the high chemical sensitivity case-control study. Conclusions We observed that high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.
Cui, Xiaoyi; Lu, Xi; Hiura, Mizue; Oda, Masako; Miyazaki, Wataru; Katoh, Takahiko
A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity. In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.
We report construction of an initial genetic linkage map for the black tiger shrimp, Penaeus monodon. Mapping was carried out using polymorphic markers derived from 23 Amplified Fragment Length Polymorphism (AFLP) primer pairs. These were analysed on three reference families of known pedigree. A total of 673 polymorphic AFLP loci that conformed to expected Mendelian segregation ratios were scored in
Kate Wilson; Yutao Li; Vicki Whan; Sigrid Lehnert; Keren Byrne; Stephen Moore; Siriporn Pongsomboon; Anchalee Tassanakajon; George Rosenberg; Elizabeth Ballment; Zahra Fayazi; Jennifer Swan; Matthew Kenway; John Benzie
C-reactive protein (CRP) produced locally within esophageal cancer is associated with the prognosis and the rate of recurrence. CRP genetic polymorphisms reportedly affect serum CRP concentrations; however, there are no reports of an association between genetic polymorphisms and tumoral CRP expression. This study enrolled 73 Japanese patients classified with Stage IIA-IV thoracic esophageal squamous cell cancer, and also investigated their CRP genetic polymorphisms using DNA extracted from their peripheral blood. The study then assessed the association between CRP genetic polymorphisms and tumoral CRP expression. The results revealed a significant association between the CRP 1846C>T genetic polymorphism and tumoral CRP expression. This finding suggests that tumoral CRP production controlled by CRP genetics significantly influences tumor behavior. PMID:22911253
Motoyama, Satoru; Nakatsu, Toshinobu; Miura, Masatomo; Hinai, Yudai; Minamiya, Yoshihiro; Ogawa, Jun-ichi
Objectives/Hypothesis Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP). Study Design Case control study. Methods Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression. Results The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-? (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals’ odds of susceptibility to nasal polyps increasing almost twofold (odds ratio, 1.86; confidence interval, 1.4–3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups. Conclusions TNF-?-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-? is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.
Bernstein, Joel M.; Anon, Jack B.; Rontal, Michael; Conroy, Jeffrey; Wang, Chong; Sucheston, Lara
The polymorphism distributions of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, and FGA) were investigated in a Tibetan population by multiplex PCR amplification using five fluorochromes (6FAM, VIC, NED, PET, LIZ). Gene frequency, discrimination power (DP), heterozygosity (H), polymorphism information content (PIC) and probability of paternity exclusion (EPP) were calculated, and all loci were tested for Hardy-Weinberg equilibrium. Results indicate that the gene frequency of these 15 STR loci is in Hardy-Weinberg equilibrium. The DP is at 0.7555-0.9602, H is at 0.5651-0.8530, PIC is at 0.5528-0.8456, and EPP is at 0.3811-0.8549. Cumulative DP of the 15 STR is 0.99999999, and cumulative EPP is 0.999999997. Therefore, these 15 STR loci can be used as genetic markers of Tibetan populations in anthropological studies, linkage analysis of genetic diseases, individual identification and paternity testing in forensic medicine. PMID:18779127
Li, Ning; Su, Yu-Hong; Xi, Huan-Jiu; Ren, Fu; Huang, Ke-Qiang; Xiao, Yan-Jie; Wen, You-Feng; Li, Chun-Shan; Li, Chang-Yong; Wang, Kun; Cheng, Jian-Guo
Complex chemical mixtures are transported by train from Russia to Finland for further shipment. Here, we studied if exposure to genotoxic components among these substances could affect chromosomal aberrations (CAs) in peripheral lymphocytes of workers handling the tank cars. An initial survey among 48 railroad workers and 39 referents (male smokers and nonsmokers) showed an elevation of CAs. A campaign was started to reduce exposures through preventive measures. Five years later, 51 tank car workers and 40 age-matched referents (all nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5, XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR). No increase in CAs was seen in the exposed group, suggesting that the preventive measures had been successful. However, a positive association existed between exposure duration and CA level among the exposed subjects. The level of chromosome-type breaks was actually lower in the exposed workers than the referents, particularly among MTHFR wild-type homozygotes or XRCC3 codon 241 variant allele carriers, suggesting modulation of CA frequency by folate metabolism and DNA repair. An interaction was observed between the occupational exposure and MTHFR, EPHX1, and MTR genotypes in determining CA level. The NAT2, ERCC2 exon 10, and XRCC1 codon 194 polymorphisms also affected CA frequency. Our findings suggest that handling of tank cars containing complex chemical mixtures poses a genotoxic risk, which may be reduced by preventive measures. Several genetic polymorphisms seem to modify the genotoxic effect or baseline CA level. PMID:19177501
Catalán, Julia; Heilimo, Iiris; Falck, Ghita C-M; Järventaus, Hilkka; Rosenström, Päivi; Nykyri, Erkki; Kallas-Tarpila, Tarja; Pitkämäki, Leena; Hirvonen, Ari; Norppa, Hannu
Background, aim, and scope The possibility of gene transfer from genetically modified oilseed rape (OSR) to its cultivated or wild relatives is of concern\\u000a since its commercial cultivation, because of its potential weediness and impact on the environment. Introgression of modified\\u000a genes can affect conservation of agricultural crops, because there are many cultivars and wild Brassicaceae that may cross\\u000a with genetically
Masaharu Kawata; Kikuko Murakami; Toyohisa Ishikawa
For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. Variants leading to reduced or increased enzymatic activity as compared to the wild-type alleles have been identified. This review tries to define potential fields in the therapy of major medical conditions where genotyping (or phenotyping) of genetically polymorphic DMEs might be beneficial for drug safety or
D Tomalik-Scharte; A Lazar; U Fuhr; J Kirchheiner
To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421
J. Y. Choi; A. Shin; S. K. Park; H. W. Chung; S. I. Cho; C. S. Shin; H. Kim; K. M. Lee; K. H. Lee; C. Kang; D. Y. Cho; D. Kang
A genetic linkage map of tef was constructed with amplified fragment length polymorphism (AFLP) markers using F5 recombinant inbred lines (RILs) derived by single seed descent from the intraspecific cross of ’Kaye Murri’×’Fesho’. A total\\u000a of 192 EcoRI\\/MseI primer combinations were screened for parental polymorphism. Around three polymorphic fragments per primer combination were\\u000a detected, indicating a low polymorphism level in
G. Bai; H. Tefera; M. Ayele; H. T. Nguyen
Expression pattern analysis has been revealed that glutathione S-transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls (P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history (P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives. PMID:21113667
Masoudi, Mohammad; Saadat, Iraj; Omidvari, Shahpour; Saadat, Mostafa
Thorough assessment of modern genetic diversity and interpopulation affinities within the African continent is essential for understanding the processes that have been at work during the course of worldwide human evolution. Regardless of whether autosomal, Y-chromosome, or mtDNA markers are used, allele- or haplotype-frequency data from African populations are necessary in setting the framework for the construction of global population phylogenies. In the present study we analyze genetic differentiation and population structure in a data set of nine African populations using 12 polymorphic Alu insertions (PAls). Furthermore, to place our findings within a global context, we also examined an equal number of non-African groups. Frequency data from 456 individuals presented for the first time in this work plus additional data obtained from the literature indicate an overall pattern of higher intrapopulation diversity in sub-Saharan populations than in northern Africa, a prominent differentiation between these two locations, an appreciably high degree of transcontinental admixture in Egypt, and significant discontinuity between Morocco and the Iberian peninsula. Moreover, the topologies of our phylogenetic analyses suggest that out of the studied sub-Saharan groups, the southern Bantu population of Sotho/ Tswana presents the highest level of antiquity, perhaps as a result of ancestral or acquired Khoisan genetic signals. Close affinities of eastern sub-Saharan populations with Egypt in the phylogenetic trees may indicate the existence of gene flow along the Nile River. PMID:16596946
Terreros, Maria C; Martinez, Laisel; Herrera, Rene J
For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markers is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.
Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.
Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Shortly thereafter, we identified the 677C-->T variant and showed that it encoded a thermolabile enzyme with reduced activity. Currently, a total of 41 rare but deleterious mutations in MTHFR, as well as about 60 polymorphisms have been reported. The 677C-->T (Ala222Val) variant has been particularly noteworthy since it has become recognized as the most common genetic cause of hyperhomocysteinemia. The disruption of homocysteine metabolism by this polymorphism influences risk for several complex disorders, including cardiovascular disease, neural tube defects and some cancers. We describe here the complex structure of the MTHFR gene, summarize the current state of knowledge on rare and common mutations in MTHFR and discuss some relevant findings in a mouse model for MTHFR deficiency. PMID:17349292
Leclerc, Daniel; Rozen, Rima
Background Filaggrin is a key protein that facilitates the formation of skin barrier by forming a stratum corneum. Mutations in the gene encoding filaggrin (FLG) have recently been reported in patients with ichthyosis vulgaris (IV). Interestingly, there are ethnic differences between FLG mutations identified in Asians and Europeans, and few FLG mutations are overlapping between Chinese and Japanese IV patients. Objective The aim of this study was to investigative the genetic polymorphism of FLG in Korean IV patients. Methods Genomic DNA was extracted from whole venous blood specimen of Korean patients with IV and a control group, and the full sequence of FLG was determined via overlapping long-range polymerase chain reaction method. Results Analysis of base sequence previously unreported reveal new nonsense mutation p.Y1767X in a Korean IV patient, and additional new single nucleotide polymorphisms. Conclusion On the basis of this study, it is anticipated that analysis of FLG gene sequence be extended to other dermatoses associated with FLG, such as atopic dermatitis.
Kim, Eun Joo; Jeong, Mi Sook; Li, Kapsok; Park, Mi Kyung; Lee, Mi-Kyung; Yoon, Yoosik; Cho, Dae-Yeon
Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.
Constantin, Jean-Michel; Mira, Jean-Paul; Guerin, Renaud; Cayot-Constantin, Sophie; Lesens, Olivier; Gourdon, Florence; Romaszko, Jean-Pierre; Linval, Philippe; Laurichesse, Henri; Bazin, Jean-Etienne
The present invention is based on the discovery of genetic polymorphisms that are associated with cardiovascular disorders, particularly acute coronary events such as myocardial infarction and stroke, and genetic polymorphisms that are associated with responsiveness of an individual having a cardiovascular disorder to treatment of the disorder with statin. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.
For Pearl Harbor, ILM created vistas of period battleships under attack and CG planes in combat at Pearl Harbor and in other battles. Simulation software was written for the huge billowing smoke from destroyed battleship row and new rigid body software was developed for the destruction of planes and ships. Other developments included: new environmental lighting techniques to enhance the
Safe Harbor was created as a response to the European Commission's Directive on Data Privacy which was launched in October 1998 and prohibits the transfer of personal data to countries outside of the European Union that do not meet the EU's standards for privacy protection. Because the United States has significantly lower standards for privacy protection, the Directive on Data Privacy would have prohibited many transactions between the US and EU nations. Safe Harbor is a framework of US organizations that have agreed to comply with the Directive. The Safe Harbor Website contains a basic overview of the initiative which explains its history and mission. Safe Harbor documents include privacy principles, an in-depth collection of FAQs, information on how Safe Harbor is enforced, and other documents from both the US and the EU.
Random amplified polymorphic DNA (RAPD) analysis using 10-mer oligonucleotide primers efficiently differentiated sugarcane cultivars and proved suitable for detecting gross genetic change such as that which can occur in sugarcane subjected to prolonged tissue culture, for example in protoplast-derived callus. However, RAPD analysis was not sufficiently sensitive to detect smaller genetic changes that occur during sugarcane genetic transformation. The length
P. W. J. Taylor; J. R. Geijskes; H.-L. Ko; T. A. Fraser; R. J. Henry; R. G. Birch
The present invention is based on the discovery of genetic polymorphisms that are associated with venous thrombosis. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.
Stressors such as heat, cold, toxins, and oxygen deprivation are known to induce heat shock proteins. Genetic polymorphisms associated with heat shock protein genes have been associated with decreased male and female fertility. Our objectives were to 1) confirm single nucleotide polymorphisms (SNP) ...
Single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (InDels) are becoming important genetic markers for major crop species. We amplified genomic regions corresponding to 678 unigenes across 12 maize inbred lines. The amplification products from 592 unigenes were sequenced (17...
Simple sequence repeats (SSRs), consisting of tandemly repeated multiple copies of mono-, di-, tri-, or tetranucleotide motifs, are ubiquitous in eukaryotic genomes and are frequently used as genetic markers, taking advantage of their length polymorphism. We have examined the polymorphism of such sequences in the chloroplast genomes of plants, by using a PCR-based assay. GenBank searches identified the presence of
W. Powell; M. Morgante; R. McDevitt; G. G. Vendramin; J. A. Rafalski
Genetic and environmental factors are involved in prostate cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and pro- gression of sporadic PCa. One hundred and thirty-three PCa patients and 157 age-matched healthy controls
ILKE HACER ONEN; ABDULLAH EKMEKCI; MUZAFFER EROGLU; ECE KONAC; SULEYMAN YESIL; HASAN BIRI
Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. The aims of this study were to identify the factors affecting MPO serum concentration, to study the familial resemblance of MPO levels and to investigate the association between newly described MPO polymorphisms as well
Aline Hoy; David Trégouët; Brigitte Leininger-Muller; Odette Poirier; Mickaël Maurice; Catherine Sass; Gérard Siest; Laurence Tiret; Sophie Visvikis
Inflammation is the mainstay of atherosclerosis and is an important governing factor at all stages of the disease process from lesion formation to plaque build-up and final end-stage rupture and thrombosis. An overview of the numerous clinico-epidemiological studies on the association between inflammatory gene polymorphisms and Cardiovascular disease (CVD) and its co-morbidities have shown that the risk associated with any single genotype is modest while the haplotypes, especially those defined on the basis of tag-SNP approach, have better coverage of the gene and show moderately higher impact on disease risk. Nevertheless, even these associations have been inconsistent with low cross-race repeatability. This has been attributed to many plausible causes such as clinical heterogeneity, sample selection criteria, variable genetic landscapes across different ethnic groups, confounding effect of co-morbidities etc. On the other hand, unbiased studies such as the family-based linkage and case-control based associations that have taken into account, thousands of genotypic markers spanning the whole genome, have had the ability to identify novel genetic loci for coronary artery disease. These studies have shown that many inflammatory genes are involved in the regulation of specific biomarkers of inflammation that collectively contribute to the disease-associated risk. In addition, there appears to be considerable cross talk between the different biochemical and metabolic processes. Therefore, consideration of all these factors can build towards an ‘atherosclerotic bionetwork’ that can refine our quest for developing a robust risk stratification tool for cardiovascular disease.
Shanker, Jayashree; Kakkar, Vijay V
The genetic structure of a gramineous weed (Alopecurus myosuroides Huds.) was investigated by an electrophoretic survey of seven enzyme systems on 19 susceptible and herbicide-resistant populations collected in different countries. The results indicate that Alopecurus myosuroides is an allogamous self-incompatible plant with a high level of genetic polymorphism (60 per cent of loci polymorphic, average heterozygosity = 0.21) and with
Bruno Chauvel; Jacques Gasquez
BACKGROUND: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the
Hoirun Nisa; Suminori Kono; Guang Yin; Kengo Toyomura; Jun Nagano; Ryuichi Mibu; Masao Tanaka; Yoshihiro Kakeji; Yoshihiko Maehara; Takeshi Okamura; Koji Ikejiri; Kitaroh Futami; Takafumi Maekawa; Yohichi Yasunami; Kenji Takenaka; Hitoshi Ichimiya; Reiji Terasaka
Because of conflicting results about the association between azoospermic patients with Klinefelter syndrome (KFS) and azoospermia factor (AZF) polymorphism, and because nothing is known about the association of KFS with partial AZFc deletions, an association study was performed in Tunisian KFS patients. A total of 29 azoospermic patients and 13 fertile men were enrolled in this study. The classical microdeletions were found in six out of nine KFS patients (67%). Gr/Gr deletions and b2/b3 deletions are partial AZFc deletions. One KFS patient without classical microdeletions had a gr/gr deletion. This deletion (gr/gr) was observed in four out of 18 azoospermic patients without chromosomal abnormalities. In addition, two b2/b3 and one AZFc deletion were identified in this group. All KFS patients had elevated plasma FSH and LH concentrations, but normal plasma testosterone concentration. The testis biopsy of three samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions or partial AZFc deletions were found in the fertile group. It is concluded that in the patient population KFS patients may harbour Y microdeletions, and screening for these should be part of the diagnostic work-up, particularly in those considering assisted reproductive techniques. However, partial AZFc deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KFS subjects. PMID:19909597
Hadjkacem-Loukil, Lobna; Ghorbel, Myriam; Bahloul, Ali; Ayadi, Hammadi; Ammar-Keskes, Leila
Current mouse lines efficient for human cell xenotransplantation are backcrossed into NOD mice to introduce its multiple immunodeficient phenotypes. Our positional genetic study has located the NOD-specific polymorphic Sirpa as a molecule responsible for its high xenograft efficiency: it recognizes human CD47 and the resultant signaling may cause NOD macrophages not to engulf human grafts. In the present study, we established C57BL/6.Rag2(nullIl2rgnull) mice harboring NOD-Sirpa (BRGS). BRGS mice engrafted human hematopoiesis with an efficiency that was equal to or even better than that of the NOD.Rag1(nullIl2rgnull) strain, one of the best xenograft models. Consequently, BRGS mice are free from other NOD-related abnormalities; for example, they have normalized C5 function that enables the evaluation of complement-dependent cytotoxicity of antibodies against human grafts in the humanized mouse model. Our data show that efficient human cell engraftment found in NOD-based models is mounted solely by their polymorphic Sirpa. The simplified BRGS line should be very useful in future studies of human stem cell biology. PMID:23293079
Yamauchi, Takuji; Takenaka, Katsuto; Urata, Shingo; Shima, Takahiro; Kikushige, Yoshikane; Tokuyama, Takahito; Iwamoto, Chika; Nishihara, Mariko; Iwasaki, Hiromi; Miyamoto, Toshihiro; Honma, Nakayuki; Nakao, Miki; Matozaki, Takashi; Akashi, Koichi
. Many rat strains have been employed in the genetic study of quantitative traits such as blood pressure. In such genetic studies,\\u000a it is essential to prepare rat genetic maps fine enough to identify the genes regulating quantitative traits. However, it\\u000a is not an easy task to isolate a sufficient number of genetic markers polymorphic between a particular pair of
Chiho Matsumoto; Toru Nabika; Tomoji Mashimo; Norihiro Kato; Yukio Yamori; Junichi Masuda
Many polyphenisms are examples of adaptive phenotypic plasticity where a single genotype produces distinct phenotypes in response to environmental cues. Such alternative phenotypes occur as winged and wingless parthenogenetic females in the pea aphid (Acyrthosiphon pisum). However, the proportion of winged females produced in response to a given environmental cue varies between clonal genotypes. Winged and wingless phenotypes also occur in males of the sexual generation. In contrast to parthenogenetic females, wing production in males is environmentally insensitive and controlled by the sex-linked, biallelic locus, aphicarus (api). Hence, environmental or genetic cues induce development of winged and wingless phenotypes at different stages of the pea aphid life cycle. We have tested whether allelic variation at the api locus explains genetic variation in the propensity to produce winged females. We assayed clones from an F2 cross that were heterozygous or homozygous for alternative api alleles for their propensity to produce winged offspring. We found that clones with different api genotypes differed in their propensity to produce winged offspring. The results indicate genetic linkage of factors controlling the female wing polyphenism and male wing polymorphism. This finding is consistent with the hypothesis that genotype by environment interaction at the api locus explains genetic variation in the environmentally cued wing polyphenism. PMID:15817441
Braendle, Christian; Friebe, Ilvy; Caillaud, Marina C; Stern, David L
Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence
S. M. Bergevoet; H. M. J. Roelofs; Z. van Hooijdonk; R. H. M. te Morsche; Th. Wobbes; J. B. de Kok; F. M. Nagengast; W. H. M. Peters
As an example of advanced testing in the field of metabolism in an industrial environment, the introduction of some novel approaches, including the use of genetically engineered cell lines for assessing CYP 2D6-related polymorphic effects is illustrated. In this paper, it is demonstrated that novel in vitro test systems can be developed by using these genetically engineered cell lines for
S Coecke; A Bogni; I Langezaal; A Worth; T Hartung; M Monshouwer
Genetic linkage maps were constructed for both maize and tomato, utilizing restriction fragment length polymorphisms (RFLPs) as the source of genetic markers. In order to detect these RFLPs, unique DNA sequence clones were prepared from either maize or tomato tissue and hybridized to Southern blots containing restriction enzyme-digested genomic DNA from different homozygous lines. A subsequent comparison of the RFLP
T. Helentjaris; M. Slocum; S. Wright; A. Schaefer; J. Nienhuis
Random amplified polymorphic DNA (RAPD) marker-based analysis was carried out to study the extent of genetic polymorphism between populations of the two endangered Himalayan poppy species, Meconopsis paniculata and M. Simplicifolia. Of the 90 primers tested, 38 revealed marked inter-species genetic polymorphism between individuals of the two species from geographically isolated populations. However, intra-species genetic homogeneity was also evident with
Irshad M. Sulaiman; Seyed E. Hasnain
A role for the N-acetyltransferase 2 (NAT2) genetic polymorphism in cancer risk has been the subject of numerous studies. Although comprehensive reviews of the NAT2 acetylation polymorphism have been published elsewhere, the objective of this paper is to briefly highlight some important features of the NAT2 acetylation polymorphism that are not universally accepted to better understand the role of NAT2 polymorphism in carcinogenic risk assessment. NAT2 slow acetylator phenotype(s) infer a consistent and robust increase in urinary bladder cancer risk following exposures to aromatic amine carcinogens. However, identification of specific carcinogens is important as the effect of NAT2 polymorphism on urinary bladder cancer differs dramatically between monoarylamines and aryldiamines. Misclassifications of carcinogen exposure and NAT2 genotype/phenotype confound evidence for a real biological effect. Functional understanding of the effects of NAT2 genetic polymorphisms on metabolism and genotoxicity, tissue-specific expression and the elucidation of the molecular mechanisms responsible are critical for interpretation of previous and future human molecular epidemiology investigations into the role of NAT2 polymorphism on cancer risk. Although associations have been reported for various cancers, this paper focuses on urinary bladder cancer, a cancer in which a role for NAT2 polymorphism was first proposed and for which evidence is accumulating that the effect is biologically significant with important public health implications.
Hein, David W.
Aim To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE) and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC). Method This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, ?429T/C, ?374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. Results All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. Conclusion The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.
Hua, Feng; Wang, Bin; Mao, Wei; Feng, Xueren
This issue of "Loblolly Magazine" was written in observance of the 50th anniversary of the U.S. entrance into World War II. The publication features interviews conducted by East Texas high school students with Clarence Otterman, one of the few survivors of the crew of the USS Arizona, which was bombed during the attack on Pearl Harbor, and with a…
Johnson, Jennifer, Ed.
Molecular genetics techniques provide an accurate and cost-effective way to identify hatchery strains and to measure genetic variation in fish populations. In this study, we sought to identify genetic differences at the mitochondrial DNA (mtDNA) level in two of the three hatchery strains of Michigan brown trout Salmo trutta by using restriction fragment length polymorphisms (RFLPs) of segments of mtDNA
Todd J. Tiano; Catherine M. Willis; Amy A. Noble; Mark R. Luttenton; Alexey G. Nikitin
Ornithine decarboxylase (ODC), the first enzyme in the biosynthesis of polyamines, has increased activity in breast cancer\\u000a tissue compared with benign and normal tissues. The ODC gene contains a single nucleotide polymorphism in which a guanine is substituted for an adenine. This study investigated\\u000a whether the ODC +316 G > A polymorphism (rs2302615) was associated with the risk of developing breast cancer.
Iain Brown; Susan Halliday; Heather Greig; Steven D. Heys; Heather M. Wallace; Andrew C. Schofield
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA methylation and synthesis. Two functional, common polymorphisms (C677T and A1298C) are known in the MTHFR gene. MTHFR activity is lowered in individuals with the 677TT genotype and is somewhat reduced in those with the 1298CC genotype. We reviewed the consistency of reported associations of these polymorphisms with colorectal cancer and adenoma with consideration of the effects of nutritional status. A total of 16 studies have addressed the association between MTHFR C677T polymorphism and colorectal cancer in 10 countries. Decreased risk of colorectal cancer associated with the 677TT genotype has fairly consistently been observed, with few exceptions. This decrease was observable in people with either high or low folate status. Alteration in the thymidylate pool associated with MTHFR activity is postulated as an underlying mechanism. Studies on the A1298C polymorphism are limited, and their results are variable. Almost all of seven studies of colorectal adenoma have found no association between C677T polymorphism and adenoma, but the 677TT genotype seems to be related to increased risk when folate status is poor. Reduced availability of methyl groups for DNA methylation might be more relevant to adenoma formation. Although the underlying mechanisms still remain to be clarified, epidemiological findings regarding MTHFR C677T polymorphism provide strong evidence that adequate folate status confers protection from colorectal cancer. PMID:16128738
Kono, Suminori; Chen, Kun
Context: The polymorphism of class II HLA genes modulates the genetic risk for several endocrine autoimmune diseases. The consti- tutive class II expression on antigen-presenting cells is under the control of the MHC class II transactivator, encoded by the MHC2TA gene, which is mapped to chromosome 16p13. The MHC2TA 168 A3G single nucleotide polymorphism (rs3087456) has been sug- gested to
Mehran Ghaderi; Giovanni Gambelunghe; Cristina Tortoioli; Annalisa Brozzetti; Ken Jatta; Baback Gharizadeh; Annamaria De Bellis; Francesca Pecori Giraldi; Massimo Terzolo; Corrado Betterle
A meta-analysis of association studies was performed to assess whether the reported genetic polymorphisms in cytokine genes are risk factors for recurrent miscarriage (RM). The electronic PubMed database was searched for case–control studies on immunity-related genes in RM. Investigations of a single polymorphism\\/gene involvement in RM reported more than five times were selected. Aggregating data from seven case-control studies on
Igor Medica; Sasa Ostojic; Nina Pereza; Andrej Kastrin; Borut Peterlin
In order to understand genetic polymorphisms among Entamoeba histolytica strains in a limited geographic area and among restricted social populations, we studied nucleotide polymorphism in DNA regions that do not encode proteins (locus 1-2 and locus 5-6) and in genes coding for chitinase and for serine-rich E. histolytica protein. Thirty E. histolytica isolates from domestically infected Japanese amebiasis patients (male
Ali Haghighi; Seiki Kobayashi; Tsutomu Takeuchi; Gohta Masuda; Tomoyoshi Nozaki
The UDP-glucuronosylatransferase 1A1 (UGT1A1) gene is involved in the metabolism of estrogen and detoxification of potential carcinogens. The number of TA repeats in\\u000a the promoter region of UGT1A1 has been linked to breast cancer risk, but results varied by race. We performed a comprehensive assessment of genetic polymorphisms\\u000a in the UGT1A1 gene, and examined these polymorphisms and TA repeats in
Dezheng Huo; Hee-Jin Kim; Clement A. Adebamowo; Temidayo O. Ogundiran; Effiong E. Akang; Oladapo Campbell; Adeniyi Adenipekun; Qun Niu; Lise Sveen; James D. Fackenthal; Donna Lee Fackenthal; Soma Das; Nancy Cox; Anna Di Rienzo; Olufunmilayo I. Olopade
Purpose To examine the relationship between nonarteritic anterior ischemic optic neuropathy (NAION) and genetic polymorphisms of enzymes influencing endothelial function. Methods The subjects were 34 patients with NAION (mean age, 62.4 years old; 59% male) and 102 controls (mean age, 63.8 years old; 66% male). Genetic polymorphisms were investigated in three candidate genes associated with endothelial function: endothelin-1 (ET-1), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR). The genotype distributions in the patients with NAION were compared with those in the controls. Results There were no significant differences in the genotype distributions of the ACE I/D and MTHFR C677T polymorphisms between the NAION and control groups (p=0.261 and p=0.354, respectively), whereas the genotype distribution of the G/T (Lys198Asn) polymorphism of the ET-1 gene varied significantly between the groups (p=0.009). After adjusting for covariates, individuals with the TT genotype of the Lys198Asn polymorphism were more likely to develop NAION compared with those with the GG genotype (odds ratio=4.43, 95% confidence interval 1.33–14.73, p=0.015). Conclusions We found an increased prevalence of a G/T polymorphism of the ET-1 gene in patients with NAION. Our data suggest that this polymorphism may be an important risk factor in developing NAION in the Japanese population.
Shikishima, Keigo; Matsushima, Masato; Tsuneoka, Hiroshi
Polymorphisms have been identified in several HSP70 genes, which may affect HSP70 repair efficiency. We investigated the association of the polymorphisms in HSPA1A, HSPA1B, and HSPA1L genes in the HSPs repair pathway with the risk of cataract in a Chinese population. The study included 415 cataract patients and 386 controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism method. HSPA1B 1267 A/A genotype seems to have a protective role against cataract (p?=?0.014, odds ratio (OR)?=?0.664, 95 % confidence intervals (CI)?=?0.480-0.919), and the G allele (p?=?0.057, OR?=?1.216, 95 % CI?=?0.999-1.479) does not seem to have a deleterious role in the development of cataract. Haplotypes with frequencies of GAT were significantly different than those of controls (p?=?0.005). In HSPA1A G190C and HSPA1L T2437C polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared to controls. We conclude that the A/A genotype of HSPA1B A1267G polymorphism seem to have a protective role against age-related cataract. PMID:23666708
Zhang, Yi; Gong, Jianying; Zhang, Lan; Xue, Daxi; Liu, Hanruo; Liu, Ping
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.
Ren, Jing; Sun, Daokun; Chen, Liang; You, Frank M.; Wang, Jirui; Peng, Yunliang; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua
Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity. PMID:23538839
Ren, Jing; Sun, Daokun; Chen, Liang; You, Frank M; Wang, Jirui; Peng, Yunliang; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua
The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits. PMID:15682872
In the present study six different populations of L. orbonalis were collected and subjected to analysis of genetic variability in terms of carboxylesterase isozyme pattern and DNA polymorphism using RAPD-PCR. Pattern of carboxylesterase revealed a similar isozyme cluster in the populations namely, sivaganga (population-3), dindigal (population-4), virudhunagar (population-5) and coimbatore (population-6). Similarly, the populations of L. orbonalis recorded 3 distinct randomly amplified polymorphic DNA markers in all populations grouped above. This pattern of genetic variability in the populations was also supported by the analysis of the similarity indices and UPGMA dendrogram. PMID:15991581
Karthikeyan, K A M; Vijayakumar, I; Murali, P; Suresh, P; Janarthanan, S
We investigated the effects of genetic factors on the prognosis of cerebral infarction in young adults in Taiwan. Because ischemic stroke with arterial occlusion or undetermined etiology is more likely to be related to a genetic prothrombotic state, 231 patients younger than 50 years (mean age 44.6 years, range 25 to 49 years) with acute ischemic stroke due to large artery atherosclerosis (n=90), small artery occlusion (n=114) or undetermined cause (n=27) were recruited and prospectively followed up for pre-determined outcome. On each patient, we screened the PlA1/PlA2 polymorphism of the platelet glycoprotein IIIa gene, 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene, G10976A polymorphism of the factor VII gene, C677T polymorphism of the methylenetetrahydrofolate reductase gene, and 27 base-pair repeat polymorphism of the endothelial nitric oxide synthase gene. End points were the composite outcome events of stroke, myocardial infarction, and death from all causes. During a mean duration follow-up of 29 months, composite outcome events occurred in 33 patients. There was a higher annual incidence rate of composite outcome events during the first year (9.1%, 95% CI 5.9-13.9%) than in the subsequent 2 years (2.6%, 95% CI 1.2-5.6%, p=0.038). None of the genetic polymorphism was associated with the composite outcome events. Past history of coronary artery disease or cerebrovascular disease was the only independent predictor of the composite outcome events (HR 3.71, 95% CI 1.69-8.14, p=0.001) at the Cox regression analysis. Our data indicate that the prothrombotic genetic polymorphisms do not have a significant influence on the prognosis in young ischemic stroke due to arterial occlusion or undetermined causes in Taiwan. PMID:15351855
Yeh, Poh-Shiow; Lin, Huey-Juan; Li, Yi-Heng; Lin, Kao-Chang; Cheng, Tain-Junn; Chang, Chia-Yu; Ke, Der-Shin
Because of conflicting results about the association between azoospermic patients with Klinefelter syndrome (KFS) and azoospermia factor (AZF) polymorphism, and because nothing is known about the association of KFS with partial AZFc deletions, an association study was performed in Tunisian KFS patients. A total of 29 azoospermic patients and 13 fertile men were enrolled in this study. The classical microdeletions
Lobna Hadjkacem-Loukil; Myriam Ghorbel; Ali Bahloul; Hammadi Ayadi; Leila Ammar-Keskes
Cultivated peanut possesses an extremely narrow genetic basis. Polymorphism is considerably difficult to identify with the\\u000a use of conventional biochemical and molecular tools. For the purpose of obtaining considerable DNA polymorphisms and fingerprinting\\u000a cultivated peanut genotypes in a convenient manner, start codon targeted polymorphism technique was used to study genetic\\u000a diversity and relatedness among 20 accessions of four major botanical
Faqian Xiong; Ruichun Zhong; Zhuqiang Han; Jing Jiang; Liangqiong He; Weijian Zhuang; Ronghua Tang
5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. A novel polymorphic site in MTHFR (G1793A) could influence the homocysteine levels and was first described in 2002. Investigations revealed that this allele was associated with susceptibility to several cancers, but its distribution around the world was not adequate. To study the prevalence of the mutant frequency in Chinese populations, 923 healthy individuals from 13 Chinese populations distributing widely from north to south were collected. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), with the digestion of restriction endonuclease BsrBI. Of the 923 individuals, 82.1% were GG homozygous, 17.2% were GA heterozygous and 0.7% were AA homozygous. The frequency of the MTHFR 1793A allele in all tested individuals was 9.3%, which was slightly lower than indicated by HapMap (10%, Beiing Han, 45 samples). The frequencies of A allele were generally higher in southern China than that in northern China, and the frequencies had significant variance in 13 Chinese populations (X2 = 26.315, P = 0.010). Summarizing of the MTHFR G1793A allele polymorphism, including control groups in the case-control studies, we found only 20 normal peoples with AA homozygous (7 Chineses, 1 Caucasian, 2 Java Indonesias, 2 non-Hispanic whites, 6 Irish women, 2 Indians). The Java Indonesias and Ashkenzai Jevish had the highest (26.6%) and the lowest (1.3%) 1793A frequency, respectively. Together with our previous data, the MTHFR G1793A polymorphism was in linkage disequilibrium with both C677T and A1298C polymorphism sites in Chinese population, but not as strong as presented by HapMap. PMID:18409008
Mao, Renfang; Fan, Yihui; Chen, Feng; Fu, Songbin
Polymorphisms provide one of the most useful tools for understanding the maintenance of genetic and phenotypic variation in nature. We have previously described a genetically based polymorphism in dorsal patterning that is expressed by female brown anole lizards, Anolis sagrei, which occur in Bar, Diamond and intermediate Diamond-Bar morphs. Previous studies of island populations in The Bahamas support a role for selection in maintaining the polymorphism, but the agents responsible for this selection remain unclear. We tested two main hypotheses regarding the importance of predation as a selective agent that maintains the polymorphism within populations. First, we tested whether correlational selection favours different combinations of morph, locomotor performance and escape behaviour by measuring morph-specific natural selection on sprint speed, running endurance and the propensity of females to either 'freeze' or 'run' in response to attempted capture. Morphs did not differ in any of these traits, nor did correlational selection consistently favour any particular combinations of morph and antipredator behaviour. Second, we experimentally excluded bird and snake predators from two entire island populations, allowed these predators access to two additional islands and then measured subsequent differences in natural selection on morphs in each population. Predators reduced the survival of Bar and Diamond females, but not of genetically intermediate Diamond-Bar females. These results provide limited evidence that predation may play a role in maintaining this polymorphism, although the functional traits that could account for differential susceptibility to predation remain unclear. PMID:22913414
Calsbeek, R; Cox, R M
There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD. The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and b2-adrenoreceptor. A total
J. Brøgger; V. M. Steen; H. G. Eiken; A. Gulsvik; P. Bakke
We used sequence polymorphism of the mitochondrial DNA D-loop (968 bp excluding the tandem repeat region) to determine genetic diversity of horses inhabiting Cheju (a southern island of Korea). Seventeen haplotypes with frequencies from 1.5 to 21.5% were found among 65 Cheju horse samples. Genetic diversity (h) of the 17 haplotypes was calculated to be 0.91, indicating that the extant
Y. H. Yang; K. I. Kim; E. G. Cothran; A. R. Flannery
Chub mackerel, Scomber japonicus, is a species of major importance to fisheries, particularly in eastern Asia. To aid in the sustainable management of this\\u000a fisheries resource, we isolated eight novel microsatellite loci from the fish and examined their polymorphisms to estimate\\u000a genetic variability. Genetic variability differed at each locus. The number of alleles ranged from 5 to 14, and observed
Hyung Kee Cha; Hye Suck An; Jung Hwa Choi; Sukyung Kang; Jung Youn Park; Kyung Kil Kim
Analysis of isozyme variation was carried out for 27 natural populations ofCeratopteris thalictroides in Japan. Of fifteen enzyme loci examined, eight loci were genetically polymorphic. At six loci,Lap, Pgi-2, Pgm-3, Pgm-4, Idh-2, and Skd-2, a marked genetic differentiation was observed between populations to the south of Okinawa Island and those to the north\\u000a of the island. Okinawa Island contained a
Yasuyuki Watano; Shigeo Masuyama
In addition to tumor invasion and angiogenesis, matrix metalloproteinase (MMP)9 also contributes to carcinogenesis and tumor\\u000a growth. Genetic variation that may influence MMP9 expression was evaluated among participants of the Shanghai Breast Cancer\\u000a Genetics Study (SBCGS) for associations with breast cancer susceptibility. In stage 1, 11 MMP9 single nucleotide polymorphisms (SNPs) were genotyped by the Affymetrix Targeted Genotyping System and\\/or
Alicia Beeghly-FadielWei; Wei Lu; Xiao-Ou Shu; Jirong Long; Qiuyin Cai; Yongbin Xiang; Yu-Tang Gao; Wei Zheng
The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformation polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. 37 refs., 2 figs., 1 tab.
Nielsen, D.A.; Goldman, D. (National Inst. on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)); Dean, M. (National Cancer Inst., Frederick, MD (United States))
The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformational polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. Images Figure 1
Nielsen, D A; Dean, M; Goldman, D
Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and
Asiah Osman; Barbara Jordan; Philip A. Lessard; Norwati Muhammad; M. Rosli Haron; Norifiza Mat Riffin; Anthony J. Sinskey; ChoKyun Rha; David E. Housman
The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations
Manorama Tripathi; Piyush Tripathi; Ugam Kumari Chauhan; Rene J. Herrera; Suraksha Agrawal
5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. A novel polymorphic site in\\u000a MTHFR (G1793A) could influence the homocysteine levels and was first described in 2002. Investigations revealed that this allele\\u000a was associated with susceptibility to several cancers, but its distribution around the world was not adequate. To study the\\u000a prevalence of the mutant frequency in Chinese populations,
Renfang Mao; Yihui Fan; Feng Chen; Songbin Fu
We study the form of polymorphisms that can be maintained by the joint effects of generation overlap and randomly fluctuating selection, acting on a quantitative trait affecting offspring viability. The genetic system can be single locus or multilocus, haploid or diploid. Selection is assumed to be stabilizing with a randomly fluctuating optimum, and we assume additive allelic effects without epistasis.
The fission yeast Schizosaccharomyces pombe is widely used as a model eukaryote for cell and molecular studies but little is known of natural genetic variation in this species. In order to obtain informative molecular markers, imperfect tandem repeats, identified through bioinformatic methods, were tested for length polymorphism in six wild-type strains of Sch. pombe isolated from different substrates and geographical
Ann-Marie Patch; Stephen J. Aves
Frequencies of ?-casein gene alleles were determined in 1316 animals from the Brazilian Bos indicus genetic groups (Sin- dhi cows, Gyr sires, Gyr cows, Guzerat sires, Guzerat cows, Nel- lore sires, and Gyr x Holstein crossbreds) by means of polymerase chain reaction-restriction fragment length polymorphism analysis using two independent restriction nucleases (Hinf I and HaeIII). The genotyping of ?-casein alleles
A. L. S. Azevedo; C. S. Nascimento; R. S. Steinberg; M. R. S. Carvalho; M. G. C. D. Peixoto; R. L. Teodoro; R. S. Verneque; S. E. F. Guimaraes; M. A. Machado
This study is the first to document genetic differences among Pacific lampreys Lampetra tridentata across much of their range. We examined collections of migrating adult Pacific lampreys from the Naka River, Japan; Moose River, Alaska; and six Pacific Northwest locations (North Fork Toutle, Willamette, Deschutes, John Day, Rogue, and Klamath rivers) based on variation at 180 polymorphic loci among the
Binbin Lin; Ziping Zhang; Yilei Wang; Kenneth P. Currens; Adrian Spidle; Yuji Yamazaki; David A. Close
The results of genetical studies of osteal plate polymorphism of threespine stickleback Gasterosteusaculeatus reported to date (Munzing 1959; Hagen and Gilbertson 1973; Avise 1976) are discussed and proposed inheritance models are considered. Results of crosses between the morphs of G. aculeatus from the White Sea are presented. An attempt has been made by the author to devise a unifying model
V. V. Ziuganov
Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication as- sociated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who
Allison E. Ashley-Koch; Laine Elliott; Melanie E. Kail; Laura M. De Castro; Jude Jonassaint; Terry L. Jackson; Jennifer Price; Kenneth I. Ataga; Marc C. Levesque; J. Brice Weinberg; Eugene P. Orringer; Ann Collins; Jeffery M. Vance; Marilyn J. Telen
Target region amplification polymorphism (TRAP) is a fairly new PCR-based molecular marker technique which uses gene-based in- formation for primer design. The objective of this study was to eval- uate the utility of TRAP markers for assessing genetic diversity and interrelationships in sugarcane germplasm collections. Thirty geno- types from the genera Saccharum, Miscanthus, and Erianthus were used in the study.
S. Alwala; A. Suman; J. A. Arro; J. C. Veremis; C. A. Kimbeng
BACKGROUND: The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of
Camilla F Skjelbred; Mona Sæbø; Anette Hjartåker; Tom Grotmol; Inger-Lise Hansteen; Kjell M Tveit; Geir Hoff; Elin H Kure
RAPD analysis was applied to onion (Allium cepa) and otherAllium species in order to assess the degree of polymorphism within the genus and to investigate if this approach was suitable for genetic studies of onion. Seven cultivars ofA. cepa, including shallot, and single cultivars of Japanese bunching onion (A. fistulosum), chive (A. schoenoprasum), leek (A. ampeloprasum), and a wild relative
Susan E. Wilkie; Peter G. Isaac; Robert J. Slater
Our objective was to examine if Sequence related amplified polymorphisms (SRAPs) could be used to detect genetic diversity among a set of alfalfa populations representing original sources of Medicago germplasm and public domain cultivars. Fifteen different populations were examined, including 9 NPGS...
Genomic research requires many molecular markers for construction of the genetic linkage map and for marker-assisted selection (MAS). Amplified fragment length polymorphism (AFLP) markers are inherited with Mendelian expectations in catfish and, thus, are suitable for use in gene mapping and MAS. To identify large numbers of AFLP markers, 64 primer combinations were tested to generate AFLP patterns between channel
Zhanjiang Liu; Ping Li; Huseyin Kucuktas; Amy Nichols; Guo Tan; Xinmin Zheng; Brad J. Argue; Rex A. Dunham; D. Roger Yant
Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. E. Nizankowska-Mogilnicka, L. Adamek, P. Grzanka, T.B. Domagala, M. Sanak, M. Krzanowski, A. Szczeklik. #ERS Journals Ltd 2003. ABSTRACT: Frequently an inherited predisposition to thrombosis remains clinically silent until an additional environmental factor intervenes. The present study aimed to assess distribution of inherited risk factors of venous thrombosis in
E. Nizankowska-Mogilnicka; L. Adamek; P. Grzanka; T. B. Domagala; M. Sanak; M. Krzanowski; A. Szczeklik
Genetic diversity among Fusarium moniliformeisolates was analysed using vegetative compatibility group (VCG) and random amplified polymorphic DNA (RAPD) techniques. In the first experiment, RAPD was used to analyse a set of 43 isolates collected from different corn growing areas in Israel and the US. The isolates were assigned to 27 different VCGs. Thirty-two RAPD haplotypes were also detected by analysing
R. HUANG; M. GALPERIN; Y. LEVY; R. PERL-TREVES
The diadem butterfly, Hypolimnas misippus, shows various anomalies in its presumed Batesian mimetic relationship with the distasteful danaine, Danaus chrysippus. If these anomalies are to be resolved and if reports of sexual selection in female diadems are to be correctly interpreted, an understanding of the genetics of the colour pattern polymorphism is essential. In an earlier study we developed a
Ian J Gordon; David A S Smith
RAPD markers were used to assess genetic fidelity of 23 micropropagated plants of a single clone (L34) of Populus deltoides. Eleven arbitrary 10-base primers were successfully used to amplify DNA from in vivo and in vitro material. Of these, 5 distinguished a total of 13 polymorphisms common across 6 micropropagated plants. Apart from these 6 plants, the amplification products were
Vijay Rani; Ajay Parida; S. N. Raina
Vascular Endothelial Growth Factor (VEGF) is the main player in angiogenesis. Because of its crucial role in this process, the study of the genetic factors controlling VEGF variability may be of particular interest for many angiogenesis-associated diseases. Although some polymorphisms in the VEGF gene have been associated with a susceptibility to several disorders, no genome-wide search on VEGF serum levels
Daniela Ruggiero; Cyril Dalmasso; Teresa Nutile; Rossella Sorice; Laura Dionisi; Mario Aversano; Philippe Bröet; Anne-Louise Leutenegger; Catherine Bourgain; Marina Ciullo; Amanda Toland
Carriers of the short allele of a functional 5? promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele
Lukas Pezawas; Andreas Meyer-Lindenberg; Emily M Drabant; Beth A Verchinski; Karen E Munoz; Bhaskar S Kolachana; Michael F Egan; Venkata S Mattay; Ahmad R Hariri; Daniel R Weinberger
We have used random amplified polymorphic DNA (RAPD) markers to study genetic variation in Alstroemeria. The first objective was to examine the discriminatory power of RAPD markers in different genotypes of Alstroemeria obtained by traditional breeding. All genotypes examined, including commercial Alstroemeria varieties, could be distinguished on the basis of their RAPD profiles. Progeny plants could be distinguished from their
E. Anastassopoulos; M. Keil
A polymorphic DNA marker has been found genetically linked, in a set of 39 human families, to an autosomal recessive gene that causes cystic fibrosis (CF), a disease affecting one in 2000 Caucasian children. The DNA marker (called D0CRI-917) is also linked to the PON locus, which by independent evidence is linked to the CF locus. The best estimates of
Lap-Chee Tsui; Manuel Buchwald; David Barker; Jeffrey C. Braman; Robert Knowlton; James W. Schumm; Hans Eiberg; Jan Mohr; Dara Kennedy; Natasa Plavsic; Martha Zsiga; Danuta Markiewicz; Gita Akots; Valerie Brown; Cynthia Helms; Thomas Gravius; Carol Parker; Kenneth Rediker; Helen Donis-Keller
We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are
Gane Ka-Shu Wong; Bin Liu; Jun Wang; Yong Zhang; Xu Yang; Zengjin Zhang; Qingshun Meng; Jun Zhou; Dawei Li; Jingjing Zhang; Peixiang Ni; Songgang Li; Longhua Ran; Heng Li; Jianguo Zhang; Ruiqiang Li; Shengting Li; Hongkun Zheng; Wei Lin; Guangyuan Li; Xiaoling Wang; Wenming Zhao; Jun Li; Chen Ye; Mingtao Dai; Jue Ruan; Yan Zhou; Yuanzhe Li; Ximiao He; Yunze Zhang; Jing Wang; Xiangang Huang; Wei Tong; Jie Chen; Jia Ye; Chen Chen; Ning Wei; Guoqing Li; Le Dong; Fengdi Lan; Yongqiao Sun; Zhenpeng Zhang; Zheng Yang; Yingpu Yu; Yanqing Huang; Dandan He; Yan Xi; Dong Wei; Qiuhui Qi; Wenjie Li; Jianping Shi; Miaoheng Wang; Fei Xie; Jianjun Wang; Xiaowei Zhang; Pei Wang; Yiqiang Zhao; Ning Li; Ning Yang; Songnian Hu; Changqing Zeng; Weimou Zheng; Bailin Hao; LaDeana W. Hillier; Shiaw-Pyng Yang; Wesley C. Warren; Richard K. Wilson; Mikael Brandström; Hans Ellegren; Richard P. M. A. Crooijmans; Jan J. van der Poel; Henk Bovenhuis; Martien A. M. Groenen; Ivan Ovcharenko; Laurie Gordon; Lisa Stubbs; Susan Lucas; Tijana Glavina; Andrea Aerts; Pete Kaiser; Lisa Rothwell; John R. Young; Sally Rogers; Brian A. Walker; Andy van Hateren; Jim Kaufman; Nat Bumstead; Susan J. Lamont; Huaijun Zhou; Paul M. Hocking; David Morrice; Dirk-Jan de Koning; Andy Law; Neil Bartley; David W. Burt; Henry Hunt; Hans H. Cheng; Ulrika Gunnarsson; Per Wahlberg; Leif Andersson; Ellen Kindlund; Martti T. Tammi; Björn Andersson; Caleb Webber; Chris P. Ponting; Ian M. Overton; Paul E Boardman; Haizhou Tang; Simon J. Hubbard; Stuart A. Wilson; Jun Yu; Jian Wang; HuanMing Yang
Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187 156 extensively annotated matured mRNA transcripts from 36 073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion–insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/.
Shimada, Makoto K.; Matsumoto, Ryuzou; Hayakawa, Yosuke; Sanbonmatsu, Ryoko; Gough, Craig; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Imanishi, Tadashi; Gojobori, Takashi
Background Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm. Findings A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties. Conclusions The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop.
Abstract Myeloperoxidase (MPO) is a member of the mammalian peroxidase superfamily and plays specific roles in host defense. This study aimed to explore the association between one polymorphism of MPO and hypertension risk. Study subjects were recruited from Taipei City Hospital, Zhongxiao Branch, Taipei Medical University Hospital and Taipei Municipal WanFang Hospital. Participants completed questionnaires and provided blood samples. In this study we considered hypertension to be present among subjects that had blood pressures above 140/90 mmHg, or who had previously received treatment for hypertension. The polymorphism of MPO investigated in this study was constructed by performing a restriction fragment length polymorphism following polymerase chain reaction. This study found the odds ratio and 95% confidence interval for hypertension among subjects with the MPO -463 GA/AA genotype to be 1.97 (1.23-3.16) when compared with those with the GG genotype after multivariate adjustment. Participants with a body mass index (BMI) ? 24 kg/m(2) and with MPO -463 GA/AA genotype had a 4.60-fold increased risk of hypertension compared with those with a BMI < 24 kg/m(2) and with the GG genotype. This is the first study to conclude that the MPO -463 GA/AA genotype was associated with hypertension. In addition, we also detected that subjects with the MPO -463 GA/AA genotype that had higher BMIs and positive diabetes status tended to have higher risks of hypertension than subjects with the MPO -463 GA/AA genotype that had normal BMIs and were not diabetic. PMID:23384293
Liu, Yi-Chien; Chung, Chi-Jung; Shiue, Horng-Sheng; Cheng, Ya-Yun; Huang, Shiau-Rung; Su, Chien-Tien; Hsueh, Yu-Mei
Plasmodium vivax, a protozoan malaria parasite of humans, represents a major public health concern in the Republic of Korea (= South Korea). However, little is known about the genetic properties and population structures of the P. vivax isolates circulating in South Korea. This article reviews known polymorphic genetic markers in South Korean isolates of P. vivax and briefly summarizes the current issues surrounding the gene and population structures of this parasite. The critical genetic characteristics of major antigens of the parasite, such as circumsporozoite protein (CSP), merozoite surface protein 1 (MSP-1) and MSP-3, Duffy binding protein (DBP), apical membrane antigen 1 (AMA-1), and GAM-1, are also discussed. PMID:19885335
Hwang, Seung-Young; Kim, So-Hee; Kho, Weon-Gyu
Recent development of DNA markers provides powerful tools for population genetic analyses. Amplified fragment length polymorphism (AFLP) markers result from a poly- merase chain reaction (PCR)-based DNA fingerprinting technique that can detect multiple restriction fragments in a single polyacrylamide gel, and thus are potentially useful for population genetic studies. Because AFLP markers have to be analysed as dominant loci in
G. Yan; J. Romero-Severson; M. Walton; D. D. CHADEEand; D. W. Severson
Intense selection on isolated populations can cause loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that polychlorinated biphenyls (PCBs), have acted as strong selective agents on populations of a non-migratory fish, Fundulus heteroclitus, indigenous to heavily contaminated sites. To evaluate population genetic structure and test for effects of
Amy M. McMillan; Mark J. Bagley; Suzanne A. Jackson; Diane E. Nacci
Asbestos, a known occupational pollutant, may upregulate the activity of inducible nitric oxide synthase (iNOS) and thus the production of nitric oxide (NO). This study investigated whether iNOS?(CCTTT)n polymorphism is associated with an increased asbestosis risk in exposed workers. The study cohort consisted of 262 cases with asbestosis and 265 controls with no asbestos-related disease. For each subject the cumulative asbestos exposure data were available. The number of CCTTT repeats was determined following PCR amplification of the iNOS promoter region. Logistic regression was performed to estimate asbestosis risk. The OR of asbestosis was 1.20 (95%? CI = 0.85–1.69) for the LL genotype compared to the combined SL and SS genotypes and 1.26 (95% CI = 0.86–1.85) for the LL genotype compared to the SL genotype. The results of this study are borderline significant and suggest a possible role of iNOS?(CCTTT)n polymorphism in the risk of asbestosis; however, further studies are needed.
Franko, Alenka; Dodic-Fikfak, Metoda; Arneric, Niko; Dolzan, Vita
The use of bacterial artificial chromosomes (BACs) provides a consistent and high targeting efficiency of homologous recombination in embryonic stem (ES) cells, facilitated by long stretches of sequence homology. Here, we introduce a BAC targeting method which employs restriction fragment length polymorphisms (RFLPs) in targeted polymorphic C57BL/6/Cast/Ei F1 mouse ES cell lines to identify properly targeted ES cell clones. We demonstrate that knockout alleles can be generated either by targeting of an RFLP located in the open reading frame thereby disrupting the RFLP and ablating gene function, or by introduction of a transcription stop cassette that prematurely stops transcription of an RFLP located downstream of the stop cassette. With both methods we have generated Rnf12 heterozygous knockout ES cells, which were identified by allele specific PCR using genomic DNA or cDNA as a template. Our results indicate that this novel strategy is efficient and precise, by combining a high targeting efficiency with a convenient PCR based readout and reliable detection of correct targeting events.
Barakat, Tahsin Stefan; Rentmeester, Eveline; Sleutels, Frank; Grootegoed, J. Anton; Gribnau, Joost
Alterations in lipoproteins are involved in the pathophysiology of Alzheimer's disease (AD). For sporadic AD, the Apolipoprotein E (APOE) is recognized as a sole genetic risk factor. Apolipoprotein A1 (APOA1) has been suggested to bind amyloid ? and promoter polymorphisms of the APOA1 gene were likely to affect the onset of the disease. Apolipoprotein D (APOD) expression is upregulating in AD brain and evidences showed APOD polymorphisms affect the risk for AD. The aim of this study was to investigate whether polymorphisms of both APOA1 and APOD genes are associated with early-onset AD (EOAD) and late-onset AD (LOAD). Common single nucleotide polymorphisms (SNPs) of the two genes were analyzed using a case-control study design. There were no associations between the two SNPs of the APOA1 gene and the onset of AD. No synergetic associations were found among the APOA1 SNPs, APOE and the risk for AD. Rs7659, 3' UTR polymorphism of the APOD gene was associated with EOAD in APOE?4 (-) subgroup. We were unable to show any impact of the other two SNPs of the APOD gene on the risk for AD. Our results suggest that the variation of the APOD gene modifies the risk for AD. Further association studies for APOD 3' UTR polymorphisms with other ethnic groups would be needed. PMID:23690001
Shibata, Nobuto; Nagata, Tomoyuki; Shinagawa, Shunichiro; Ohnuma, Tohru; Shimazaki, Hiromi; Komatsu, Miwa; Kuerban, Bolati; Tomson, Katrin; Nakayama, Kazuhiko; Yamada, Hisashi; Arai, Heii
Background Temporomandibular disorder (TMD) is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD. Methods A case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women) were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Genotyping of 20 Single Nucleotide Polymorphisms (SNPs), divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype) were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR) with a 95% of confidence interval were calculated. Results Six of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1) rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002), allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013), allele T of Methylentetrahydrofolate Dehydrogenase (MTHFD) rs2236225 (OR = 3.09; 95%CI 1.27, 7.50; p = 0.016) and allele A of Methionine Synthase Reductase (MTRR) rs1801394 (OR = 2.35; 95CI 1.10, 5.00; p = 0.037). An inflammatory oxidative stress enzyme, Gluthatione S-Tranferase Mu-1(GSTM1), null allele (OR = 2.21; 95%CI 1.24, 4.36; p = 0.030) and a neurotransmission receptor, Dopamine Receptor D4 (DRD4), long allele of 48 bp-repeat (OR = 3.62; 95%CI 0.76, 17.26; p = 0.161). Conclusions Some genetic polymorphisms related to folates metabolism, inflammatory oxidative stress, and neurotransmission responses to pain, has been significantly associated to TMD syndrome
The primary goal of this project is to identify non-hormonal dietary risk and genetic susceptibility factors for breast cancer in African-American women. This project initial will assess the role of dietary fat, cholesterol, cooking practices (e.g., of fa...
The ploidy of Trypanosoma cruzi is until now undetermined although analysis of isoenzymes, molecular karyotype and DNA content suggest diploidy in a very plastic genome. Also, there has been no convincing demonstration of genetic exchange and it has been proposed that reproduction is clonal. We have compared 18 T. cruzi stocks and clones from the same area or host by
Anna Rosa Bogliolo; Liana Lauria-Pires; Wendy C. Gibson
BACKGROUND: Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. CASE PRESENTATION: A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and
Jean-Michel Constantin; Jean-Paul Mira; Renaud Guerin; Sophie Cayot-Constantin; Olivier Lesens; Florence Gourdon; Jean-Pierre Romaszko; Philippe Linval; Henri Laurichesse; Jean-Etienne Bazin
The goal of this DOD Breast Concept award was to identify and functionally characterize common genetic polymorphisnis in the human UDP- glucuronosyltransferase gene, UGTlA9. We had previously determined that UGTlA9, a metabolic enzyme expressed predominan...
R. B. Raftogianis
In an attempt to compare intrinsic and extrinsic genetic diversity of the lyssavirus genotypes, 69 rabies virus isolates from various part of the world were partially sequenced and compared to 13 representative isolates of the 6 lyssavirus genotypes. The analysis of their phylogenetic relationships, performed on the complete nucleoprotein (N) coding gene (1350 bases), established that the rabies virus isolates
Bachir Kissi; Noël Tordo; Hervé Bourhy
Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...
Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...
Background: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. Methods: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. Results: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of ?3, ?4, or ?5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. Conclusions: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.
Richardson, M; Powell, E; Barrie, H; Clouston, A; Purdie, D; Jonsson, J
Dinucleotide microsatellites have been characterized and used as genetic markers in rice. Screening of a rice genomic library with poly(dG-dA)·(dC-dT) and poly(dG-dT)·(dC-dA) probes indicated that (GA)n repeats occurred, on average, once every 225 kb and (GT)n repeats once every 480 kb. DNA sequencing of ten randomly selected microsatellites indicated that the numbers of repeats ranged from 12 to 34 and
Kun-Sheng Wu; Steven D. Tanksley
Background It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. Results In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ?800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ?400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk. Conclusions Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation.
BACKGROUND: Genetic variants of the organic cation transporter (OCT1) gene could influence interindividual variation in clinical response to metformin therapy. The genetic basis for the single-nucleotide polymorphism (SNP) of OCT1 gene has been established in other populations, but it remains to be elucidated in the Indian population. This study is focused on OCT1 gene variants rs2282143 (P341L, 1022C>T), rs628031 (M408V, 1222A>G) and rs622342 (1386C>A) frequency distributions in the South Indian Tamilian population. MATERIALS AND METHODS: A total of 112 unrelated healthy subjects of South Indian Tamilian origin, aged 18–60 years, of either sex were recruited for the study. Genotyping was determined using the quantitative real time-polymerase chain reaction and polymerase chain reaction followed by restriction fragment length polymorphism methods. RESULTS: Allele frequencies of rs2282143, rs628031and rs622342 polymorphisms were 8.9%, 80.3% and 24.5%, respectively. Interethnic differences in the genotype and allele frequencies of OCT1 gene polymorphism were observed when compared with other major populations. The SNPs rs2282143, T allele and rs628031, G allele were more common in Asians (5.5–16.8% and 76.2–81%) and African Americans (8.2% and 73.5%) than in Caucasians (0–2% and 57.4–60%). CONCLUSION: This is the first time the frequency of OCT1 gene polymorphism was determined in the Indian population, and is similar to the frequencies observed in African-Americans and other Asian populations but different from those in Caucasians. The data observed in this study would justify further pharmacogenetic studies to potentially evaluate the role of OCT1 gene polymorphism in the therapeutic efficacy of metformin.
Umamaheswaran, Gurusamy; Praveen, Ramakrishnan G.; Arunkumar, Annan S.; Das, Ashok K.; Shewade, Deepak G.; Adithan, Chandrasekaran
Eotaxin family (Eotaxin 1,2 and 3) recruits and activates CCR3-bearing cells such as eosinophil, mast cells, and Th2 lymphocytes that play a major role in allergic disorders. We examined the polygenetic effects of the Eotaxin gene family in a Korean population. Gene-gene interactions were tested using a multistep approach with multifactor dimensionality reduction (MDR) method between asthmatics and normal controls. The overall best MDR model of the main effect single nucleotide polymorphisms (SNPs) included EOT2 + 1272A > G and EOT3 + 77C > T (model 1) [testing accuracy 0.597, cross-validation consistency (CVC) 10/10, P < 0.001]. The overall best MDR model of the SNPs with no main effects included EOT2 + 304C > A, EOT3 + 716A > G, and EOT3 + 1579G > A (model 2) (testing accuracy 0.616, CVC 10/10, P < 0.001). Model 3 was obtained by including the MDR variables for models 1 and 2. This new composite model predicted asthma with better accuracy than either model 1 or model 2 (testing accuracy 0.643, CVC 10/10, P < 0.001). The detection of statistical interaction models is one evidence of gene-gene interactions among Eotaxin genes, and this interaction is thought to influence the development of asthma. Although the models are limited to determining statistical interactions within a population, they may be useful for identifying groups at high risk of developing asthma. PMID:18712274
Lee, June-Hyuk; Moore, Jason H; Park, Sung-Woo; Jang, An-Soo; Uh, Soo-Taek; Kim, Yong Hoon; Park, Choon-Sik; Park, Byung Lae; Shin, Hyoung Doo
The usefulness of random amplified polymorphic DNA markers (RAPD) was assayed in an attempt to discriminate among species, strains and individuals within the genus Schistosoma. Depending on the species, 40-50 arbitrary decamer oligonucleotides were used as primers to amplify total DNA by the polymerase chain reaction (PCR). An important polymorphism was observed among 5 species, allowing a phylogenetic tree to be outlined. These differences can be used for rapid and accurate identification. A limited but easily detectable polymorphism was revealed among 3 strains of a single species (Schistosoma mansoni). Minor differences were observed among individuals of a single strain. A RAPD marker allows sexual discrimination between individuals from the terminal spined-egg species group. Although a limited number of strains have been examined, the results already indicate clearly that RAPD markers constitute a powerful tool for the analysis of genetic variability. This new tool will considerably extend the information available from morphology, isozyme and limited restriction fragment length polymorphism data and opens the way to genetic analysis of these species. PMID:8341320
Barral, V; This, P; Imbert-Establet, D; Combes, C; Delseny, M
Endometriosis is a sex steroids-dependent disease. It has been postulated that certain genetic polymorphisms involved in sex steroids biosynthesis and metabolisms may be associated with increased risk of developing endometriosis. Despite a deluge of reports of positive associations of endometriosis with numerous polymorphisms involving sex steroids production and metabolism, the results are often conflicting. We performed a meta-analysis of 12
Eryngium alpinum L. is an endangered species found across the European Alps. In order to obtain base-line data for the conservation of this species, we investigated levels of genetic diversity within and among 14 populations from the French Alps. We used the amplified fragment length polymorphism (AFLP) technique with three primer pairs and scored a total of 62 unambiguous, polymorphic
M. Gaudeul; P. Taberlet; I. Till-Bottraud
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. PMID:15723179
Chen, Jianchi; Civerolo, Edwin L; Jarret, Robert L; Van Sluys, Marie-Anne; de Oliveira, Mariana C
The original goal of this project is to determine the frequency of genetic polymorphisms for carcinogen metabolism and the p53 mutational spectra in a previously conducted breast cancer study designed to assess nutritional risk factors, seeking to identif...
P. G. Shields
Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infection and persistently normal transaminases (PNALT). A total of 121 PNALT patients did not receive any antiviral treatment but underwent periodic clinical monitoring, including repeat biopsies, for a median of 120 months. IL6-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C polymorphisms were related to histologic fibrosis progression. Among patients whose grading and staging scores increased at the end of the follow-up ?2 Ishak points (N = 60 and N = 26, respectively), IL-6 -174G>C genotype frequencies were GG 37/66, GC 21/45, CC 2/10 (p = 0.041) and GG 18/66, GC 8/45, CC 0/10 (p = 0.040), respectively. The following frequencies were observed for the 572G>C polymorphism: GG 50/105, GC 10/16, CC 0/0, and GG 19/105, GC 7/16, CC 0/0, respectively. Grading progression was independently associated with carriage of the G allele in -174G>C polymorphism (oddd ratio = 5.07%, 95% confidence interval = 0.959-26.8, p = 0.023). Staging progression was independently associated with carriage of the C allele in -572G>C polymorphism (odd ratio = 4.60%, 95% confidence interval 1.42-14.8, p = 0.012). IL-6 polymorphisms influence histologic progression of HCV in patients with PNALT. PMID:20655350
Falleti, Edmondo; Fabris, Carlo; Vandelli, Carmen; Colletta, Cosimo; Cussigh, Annarosa; Smirne, Carlo; Fontanini, Elisabetta; Cmet, Sara; Minisini, Rosalba; Bitetto, Davide; Toniutto, Pierluigi; Pirisi, Mario
BACKGROUND: We previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of the CysLTR2 gene. METHODS: We measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics having ht1+\\/+ and ht2+\\/+. A gel retardation assay was
Jeong-Ah Shin; Hun Soo Chang; Se-Min Park; An-Soo Jang; Sung Woo Park; Jong Sook Park; Soo-Taek Uh; Gune Il Lim; Taiyoun Rhim; Mi-Kyeong Kim; Inseon S Choi; Il Yup Chung; Byung Lae Park; Hyoung Doo Shin; Choon-Sik Park
Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens has been proposed to play a protective role in estrogen-induced genotoxic carcinogenesis. We have taken a comprehensive approach to test the hypothesis that genetic variation in COMT might influence breast cancer risk. Fifteen COMT single nucleotide polymorphisms (SNPs) select- ed on the basis of in-depth resequencing of the COMT gene were genotyped in 1,482
Yuan Ji; Janet Olson; Jianping Zhang; Michelle Hildebrandt; Liewei Wang; James Ingle; William Miller; J. Michael Dixon; Hiltrud Brauch; Michel Eichelbaum; Christina Justenhoven; Ute Hamann; Thomas Bruning; Shan Wang-Gohrke; Daniel Schaid; Richard Weinshilboum; H. Lee Moffitt
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic a ctivation of procarcinogens such as N- nitrosoamines and low molecular weight organi c compounds. The purpose of this study is to determine whether CYP450 2E1
Lin Cai; Shun-Zhang Yu; Zuo-Feng Zhang
Blood pressure is influenced by multiple genetic loci whose identities are largely unknown. A restriction fragment length polymorphism (RFLP) in the renin gene was found between Dahl salt-hypertension--sensitive (S) and Dahl salt-hypertension--resistant (R) rats. In an F2 population derived from crossing S and R rats, the renin RFLP cosegregated with blood pressure. One dose of the S-rat renin allele was
John P. Rapp; Sue-May Wang; Howard Dene
Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2
Akira Yokoyama; Tai Omori
Smoking and the consumption of alcohol are the main risk factors for head and neck cancer. However, interindividual variation in the activity of enzymes involved in the detoxification of tobacco smoke (pro)carcinogens, such as microsomal epoxide hydrolase (mEH), glutathione-S-transferases (GSTs) and uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGTs), may influence the process of carcinogenesis. Genetic polymorphisms of these enzymes may alter their activity
M. Lacko; M. B. Oude Ophuis; W. H. M. Peters; J. J. Manni
Objective To study the function of the rennin- angiotensin-aldoterone system(RAAS) under high altitude hypoxia environment and objective to investigate the effects of high altitude hypoxia on the angiotensin conversion enzyme 2(ACE2) Genetics polymorphisms. Methods Forty male adult Sprague Dawley( SD) rats, under high altitude hypoxia environment were divided randomly into 4 groups: the control group(D group, Xi'an area 5m above
Wenhua Li; Liu Zhong
The development and mapping of genetic markers based upon expressed sequence tag polymorphisms (ESTPs) in loblolly pine (Pinus taeda L.) are reported. The new markers were generated by PCR-amplification of loblolly pine genomic DNAs with primers designed\\u000a from sequenced cDNAs. The cDNA libraries were constructed from RNAs expressed in the needles of loblolly pine seedlings or\\u000a in the xylem from
B. Temesgen; G. R. Brown; D. E. Harry; C. S. Kinlaw; M. M. Sewell; D. B. Neale
Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined\\u000a presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary\\u000a embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate\\u000a reductase (MTHFR) C677T and A1298C, and plasminogen activator
Juergen Ringwald; Annika Berger; Werner Adler; Cornelia Kraus; Rocco P. Pitto
Background: Folate is an important micronutrient molecule participating in DNA synthesis, methylation and repair mechanisms. Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. The aim of
Nongnuch Sirachainan; Siranee Wongruangsri; Saowanee Kajanachumpol; Samart Pakakasama; Anannit Visudtibhan; Issarang Nuchprayoon; Apasri Lusawat; Suchart Phudhicharoenrat; Shanop Shuangshoti; Suradej Hongeng
Health policy is increasingly confronted with the demand for financing genetic testing on inherited susceptibility to disease.\\u000a Tests on polymorphism\\/SNP associated with multicausal and chronic conditions are already offered in private commercial institutions\\u000a or in academic hospitals. The increasing pressure on public health services to offer SNP testing leads to first methodological\\u000a approaches for a generally valid regulatory framework applicable
Background Chronic inflammation is an important mechanism for the development and progression of prostate cancer. To better understand the potential relationship between genes in the inflammation pathway and prostate cancer (PC) risk, we evaluated variants in 16 candidate genes. Methods A total of 143 tagging and amino acid altering single nucleotide polymorphisms (SNPs) were genotyped in Caucasian and African American men participating in one of two population-based, case-control studies (n = 1,458 cases and 1,351 controls). The relative risk of prostate cancer was estimated using logistic and polytomous regression models. Results Ten SNPs in seven genes (CXCL12, IL4, IL6, IL6ST, PTGS2, STAT3, and TNF) were nominally associated (p<0.05) with risk of PC in Caucasians. The most significant effect on risk was seen with rs11574783 in the IL6ST gene (odds ratio, OR=0.08, 95% CI 0.01–0.63). Cumulatively, four SNPs in genes IL4, IL6ST, PTGS2, and STAT3 conferred a three-fold elevation in PC risk among men carrying the maximum number of high-risk alleles (OR=2.97, 95% CI 1.41–6.25, ptrend = 0.0003). Risk estimates for seven SNPs varied significantly according to disease aggressiveness (phomogeneity<0.05), with SNPs in AKT1, PIK3R1 and STAT3 independently associated with more aggressive PC; OR=5.1 (95% CI 2.29–11.40, ptrend = 3.8×10?5) for carriers of all high-risk genotypes. Conclusions These results suggest that variants in genes within the inflammation pathway may play a role in the development of PC, however further studies are needed to replicate our findings. Impact These results underline the potential importance of the inflammation pathway in PC development and progression.
Kwon, Erika M.; Salinas, Claudia A.; Kolb, Suzanne; Fu, Rong; Feng, Ziding; Stanford, Janet L.; Ostrander, Elaine A.
Background The receptor activator of NF-?B (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. Methods Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the ?2-tests for 2 x 2 and 2 x 3 tables. Results The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). Conclusions This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population.
Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second biggest cause of cancer death in men of the Western world. Higher incidences of PCa occur in men from North America, Oceania and Western countries, whereas men from Asia and North Africa have a much lower PCa incidence rate. Investigations into this population disparity of PCa incidence, in order to identify potential preventive factors or targets for the therapeutic intervention of PCa, have found differences in both environmental and genetic variations between these populations. Environmental variations include both diet and lifestyle, which vary widely between populations. Evidence that diet comes into play has been shown by men who immigrate from Eastern to Western countries. PCa incidence in these men is higher than men in their native countries. However the number of immigrants developing PCa still doesn't match native black/white men, therefore genetic factors also contribute to PCa risk, which are supported by familial studies. There are a number of genetic polymorphisms that are differentially presented between Western and Eastern men, which are potentially associated with PCa incidence. Androgen and its receptor (AR) play a major role in PCa development and progression. In this study, we focus on genes involved in androgen biosynthesis and metabolism, as well as those associated with AR pathway, whose polymorphisms affect androgen level and biological or physiological functions of androgen. While many of the genetic polymorphisms in this androgen/AR system showed different frequencies between populations, contradictory evidences exist for most of these genes investigated individually as to the true contribution to PCa risk. More accurate measurements of androgen activity within the prostate are required and further studies need to include more African and Asian subjects. As many of these genetic polymorphisms may contribute to different steps in the same biological/physiological function of androgen and AR pathway, an integrated analysis considering the combined effect of all the genetic polymorphisms may be necessary to assess their contribution to PCa initiation and progression. PMID:23593537
Li, Jie; Mercer, Emma; Gou, Xin; Lu, Yong-Jie
Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case–control
T Zheng; T R Holford; S H Zahm; P H Owens; P Boyle; Y Zhang; B Zhang; J P Wise; L P Stephenson; F Ali-Osman
Alternative male mate-securing strategies are widespread among animal taxa, but there are few well-documented examples of genetic polymorphisms for them. In the Japanese calopterygid damselfly Mnais costalis, males occur as either orange-winged territorial fighter males, or clear-winged non-territorial sneaker males. It has previously been suggested that this behavioral polymorphism is genetically controlled. However, there was no direct evidence for this.
We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency. ?? 2011 The Authors.
Talbot, S. L.; Palmer, A. G.; Sage, G. K.; Sonsthagen, S. A.; Swem, T.; Brimm, D. J.; White, C. M.
Indonesian native chickens are considered an important genetic resource, particularly with respect to their excellent traits for meat and egg production. However, few molecular genetic studies of these native chickens have been conducted. We analyzed the genetic diversity and differentiation of 4 populations of Indonesian native chickens: Black Kedu (BK), Kedu (KD), Kampung (LOC), and Arab (AR). Blood samples from 188 individuals were collected in central and western Java. Genomic DNA was genotyped using 98 autosomal SNP markers, of which 87 were found to be polymorphic. The proportion of polymorphic loci and the average heterozygosity of each population were in the range of 0.765 to 0.878 and 0.224 to 0.263, respectively. The 4 populations of Indonesian chickens appeared to be derived from 3 genetic populations (K = 3): maximum likelihood clustering showed that the BK variety and AR breed were each assigned to a distinct cluster, whereas the LOC ecotype and KD variety were admixed populations with similar proportions of membership. Principal components analysis revealed that eigenvector 1 separated BK and AR from the other 2 populations. Neighbor-joining trees constructed from pairwise distance matrix (F(ST)) estimates, for individuals and between populations, corroborated that the LOC ecotype and KD variety were related closely, whereas the BK variety and AR breed diverged at greater distances. These results also confirmed the usefulness of SNP markers for the study of genetic diversity. PMID:22010231
Riztyan; Katano, T; Shimogiri, T; Kawabe, K; Okamoto, S
As environments change, animals update their internal representations of the external world. New information about the environment is learned and retained whereas outdated information is disregarded or forgotten. Retroactive interference (RI) occurs when the retrieval of previously learned information is less available owing to the acquisition of recently acquired information. Even though RI is thought to be a major cause of forgetting, its functional significance is still under debate. We find that natural allelic variants of the Drosophila melanogaster foraging gene known to affect rover and sitter behaviour differ in RI. More specifically, rovers who were previously shown to experience greater environmental heterogeneity while foraging display RI whereas sitters do not. Rover responses are biased towards more recent learning events. These results provide an ecological context to investigate the function of forgetting via RI and a suitable genetic model organism to address the evolutionary relevance of cognitive tasks. PMID:20667877
Reaume, Christopher J; Sokolowski, Marla B; Mery, Frederic
Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus–host relationship.
Kang, Hae Ji; Kosoy, Michael Y.; Shrestha, Sanjaya K.; Shrestha, Mrigendra P.; Pavlin, Julie A.; Gibbons, Robert V.; Yanagihara, Richard
Genetic diversity among 45 Indian mustard (Brassica juncea L.) genotypes comprising 37 germplasm collections, five advance breeding lines and three improved cultivars was investigated at the DNA level using the random amplified polymorphic DNA (RAPD) technique. Fifteen primers used generated a total of 92 RAPD fragments, of which 81 (88%) were polymorphic. Of these, 13 were unique to accession 'Pak85559'. Each primer produced four to nine amplified products with an average of 6.13 bands per primer. Based on pairwise comparisons of RAPD amplification products, Nei and Li's similarity coefficients were calculated to evaluate the relationships among the accessions. Pairwise similarity indices were higher among the oilseed accessions and cultivars showing narrow ranges of 0.77-0.99. An unweighted pair-group method with arithmetic averages cluster analysis based on these genetic similarities placed most of the collections and oilseed cultivars close to each other, showing a low level of polymorphism between the accessions used. However, the clusters formed by oilseed collections and cultivars were comparatively distinct from that of advanced breeding lines. Genetically, all of the accessions were classified into a few major groups and a number of individual accessions. Advanced breeding lines were relatively divergent from the rest of the accessions and formed independent clusters. Clustering of the accessions did not show any pattern of association between the RAPD markers and the collection sites. A low level of genetic variability of oilseed mustard was attributed to the selection for similar traits and horticultural uses. Perhaps close parentage of these accessions further contributed towards their little diversity. The study demonstrated that RAPD is a simple and fast technique to compare the genetic relationship and pattern of variation among the gene pool of this crop. PMID:18713372
Khan, Muhammad Ayub; Rabbani, Malik Ashiq; Munir, Muhammad; Ajmal, Saifullah Khan; Malik, Muhammad Azim
Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses. PMID:18421701
Bersano, A; Ballabio, E; Bresolin, N; Candelise, L
Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk. PMID:22131055
Kim, Dojung; Lee, Young-Joo; Ryu, Heui-Young; Lee, Jin-Hee; Kim, Hyun-Kyung; Kim, Eunhee; Moon, Jae-Dong; Chang, Dong Deuk; Yoon, Hae-Seong
Background Plasmodium vivax Duffy binding protein (PvDBP) plays an essential role in erythrocyte invasion and a potential asexual blood stage vaccine candidate antigen against P. vivax. The polymorphic nature of PvDBP, particularly amino terminal cysteine-rich region (PvDBPII), represents a major impediment to the successful design of a protective vaccine against vivax malaria. In this study, the genetic polymorphism and natural selection at PvDBPII among Myanmar P. vivax isolates were analysed. Methods Fifty-four P. vivax infected blood samples collected from patients in Myanmar were used. The region flanking PvDBPII was amplified by PCR, cloned into Escherichia coli, and sequenced. The polymorphic characters and natural selection of the region were analysed using the DnaSP and MEGA4 programs. Results Thirty-two point mutations (28 non-synonymous and four synonymous mutations) were identified in PvDBPII among the Myanmar P. vivax isolates. Sequence analyses revealed that 12 different PvDBPII haplotypes were identified in Myanmar P. vivax isolates and that the region has evolved under positive natural selection. High selective pressure preferentially acted on regions identified as B- and T-cell epitopes of PvDBPII. Recombination may also be played a role in the resulting genetic diversity of PvDBPII. Conclusions PvDBPII of Myanmar P. vivax isolates displays a high level of genetic polymorphism and is under selective pressure. Myanmar P. vivax isolates share distinct types of PvDBPII alleles that are different from those of other geographical areas. These results will be useful for understanding the nature of the P. vivax population in Myanmar and for development of PvDBPII-based vaccine.
Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n?=?39) and NS (n?=?30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms. PMID:22412972
Thu, Kelsie L; Vucic, Emily A; Chari, Raj; Zhang, Wei; Lockwood, William W; English, John C; Fu, Rong; Wang, Pei; Feng, Ziding; MacAulay, Calum E; Gazdar, Adi F; Lam, Stephen; Lam, Wan L
Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of “null” alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy–Weinberg equilibrium. Locus-by-locus FST, analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data.
Coates, Brad Steven; Bayles, Darrell O.; Wanner, Kevin W.; Robertson, Hugh M.; Hellmich, Richard L.; Sappington, Thomas W.
Flavin-containing monooxygenase 3 (FMO3) is a hepatic microsomal enzyme that oxidizes a host of drugs, xenobiotics and other chemicals. Numerous variants in the gene encoding FMO3 have been identified, some of which result in altered enzymatic activity and, consequently, altered substrate metabolism. Studies also implicate individual and ethnic differences in the frequency of FMO3 polymorphisms. In addition, new variants continue to be identified with potentially important clinical implications. For example, the role of FMO3 variants in the pathophysiology of gastrointestinal diseases is an evolving area of research. Two commonly occurring polymorphisms of FMO3, E158K and E308G, have been associated with a reduction in polyp burden in patients with familial adenomatous polyposis who were treated with sulindac sulfide, an FMO3 substrate. These findings suggest a potential role for prospective genotyping of common FMO3 polymorphisms in the treatment of disease states that involve the use of drugs metabolized by FMO3. This review summarizes the current state of research on the genetic polymorphisms of FMO3, with a focus on their clinical implications in gastrointestinal diseases.
Hisamuddin, Irfan M; Yang, Vincent W
The relationships between behavioural trait data and the genotype of 15 polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26-item questionnaire on the dog's behaviour, distributed to the dog's owners, through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis of the questionnaire items extracted eight factors accounting for 66.8% of the variance. An association analysis between these factors and genetic polymorphisms indicated that the polymorphism of c.471T>C in the solute carrier family 1 (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene was significantly associated with Factor 1, referred to as 'aggression to strangers'. This association remained stable in separate analyses of data from surveys obtained from the hospitals and those obtained from the magazine. The results suggest that the c.471T>C polymorphism is associated with some types of aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are necessary to extend these findings to dogs in general. PMID:19397510
Takeuchi, Y; Kaneko, F; Hashizume, C; Masuda, K; Ogata, N; Maki, T; Inoue-Murayama, M; Hart, B L; Mori, Y
Many species of frog exhibit striking color and pattern polymorphisms, but the genetic bases of these traits are not known for most species. The coqui frog, Eleutherodactylus coqui, a species endemic to the island of Puerto Rico, exhibits a wide variety of color and pattern polymorphisms including 4 discrete stripe patterns on its dorsal surface and an unstriped morph. We conducted breeding experiments to determine the mode of inheritance for these 5 dorsal color patterns in E. coqui. We analyzed results from 14 different cross types, which included 1519 offspring from 71 clutches. We found that color patterns segregate at ratios consistent with a single autosomal locus, 5-allele model, in which all alleles coding for stripes are codominant and the allele coding for the unstriped morph is recessive. We propose that this locus be named "stripes" with alleles B (interocular bar), L (dorsolateral stripes), N (narrow middorsal stripe), W (wide middorsal stripe), and u (unstriped). The results of this experiment suggest the genetic basis of stripe patterns in this well-studied species and provide a model for studying the evolution and maintenance of this phenotypic polymorphism. PMID:20643755
O'Neill, Eric M; Beard, Karen H
DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL.
Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa
Globe artichoke ( Cynara cardunculus L. var. scolymus L.) is a diploid (2 n=2 x=34), predominantly cross-pollinated plant native to the Mediterranean basin, and Italy contains the richest primary cultivated 'gene pool'. Commercial production is mainly based on perennial cultivation of vegetatively propagated clones that are highly heterozygous and segregate widely when progeny-tested. Analysis of the artichoke genome by means of molecular markers has been limited to a few studies; here we report on the genetic relatedness among 118 artichoke accessions, including clones belonging to the same varietal type, two accessions of cultivated cardoon ( C. cardunculus L. var. altilis DC.) and four accessions of wild cardoon [ C. cardunculus L. var. sylvestris (Lamk) Fiori] as measured by amplified fragment length polymorphism (AFLP). Eight primer combinations yielded a total of 667 bands, of which 519 were polymorphic. Genetic similarities among accessions were calculated according to Jaccard's Similarity Index and used to construct a dendrogram based on the unweighted pair group method using arithmetic averages. Our results demonstrate that AFLP markers can be useful in evaluating Cynara cardunculus genetic diversity and in classifying accessions to phylogenetic groups based on their genetic similarity values. Genetic variation among artichoke clones belonging to the same varietal type was in some cases higher than that found among accessions differently named and coming from different areas. The lowest Jaccard's Similarity Index found within a varietal type can be considered as a threshold for the identification of accessions which share an analogous genetic background. This will enable the selection of representatives in order to develop and manage a germplasm 'core collection' as well as the identification of suitable material for future artichoke breeding efforts. PMID:14968303
Lanteri, S; Saba, E; Cadinu, M; Mallica, G M; Baghino, L; Portis, E
Summary Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5 to the insulin gene on chromosome 11 and diabetic nephropathy. This was
L. J. Raffel; C. M. Vadheim; M.-P. Roth; R. Klein; S. E. Moss; J. I. Rotter
Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1 *2/ADA2 *2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings. PMID:20943049
Sebastiani, G D; Bottini, N; Greco, E; Saccucci, P; Canu, G; Lucarelli, P; Gloria-Bottini, F; Fontana, L
The paper deals with the hereditary predisposition of the hemostatic system to the severe course of acute disseminated intravascular coagulation (DIC). The results of evaluation of some types of genetic polymorphisms of the factors of coagulation and of the fibrinolytic system are recent and important for clinical application. Analysis of mortality in the fulminant course of acute DIC showed significant differences in the detection rates of the variants of genetic polymorphism in the type I plasminogen activator inhibitor gene, which is indicative of the possible genetic determination of acute DIC. PMID:17564003
Vorob'eva, N A; Kapustin, S I
Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage?/CD34+/CD38?/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations.
Will, Britta; Zhou, Li; Vogler, Thomas O.; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D.; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M.; Ye, B. Hilda; List, Alan F.; Steidl, Christian
Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage(-)/CD34(+)/CD38(-)/CD90(+)) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872
Will, Britta; Zhou, Li; Vogler, Thomas O; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M; Ye, B Hilda; List, Alan F; Steidl, Christian; Steidl, Ulrich; Verma, Amit
In the present study, 10 short tandem repeats (STR) (HPRTB, DXS6789, DXS6799, DXS6804, DXS7130, DXS7132, DXS7133, DXS7423, DXS7424, and DXS8378) on X chromosome were investigated among four ethnic populations (431 individuals) in northwest of China, in order to learn about the genetic diversity, forensic suitability, and possible genetic affinities of the populations. The polymorphism information content (PIC) values for the ten loci range from 0.340 to 0.810, and the observed heterozygosity values for the ten loci range from 0.397 to 0.860, the results indicated that the ten loci have a moderate degree of variability in the four populations, and each population has its own characteristics of genetic structure. A Neighbor-joining (NJ) tree constructed on the basis of the generated data shows very low genetic distance between Han, Mongolian and Tibetan, Dongxiang and Tu as well as between Salar and Bonan populations. Our results based on genetic distance analysis are consistent with the results of earlier studies based on linguistics and the immigration history and origin of these populations. These STR loci on the X chromosome studied here are not only useful in showing significant genetic variation between the populations, but also are suitable for human identity testing among the four populations. PMID:21809023
Sun, Ruifang; Zhu, Yongsheng; Zhu, Feng; Kuang, Wenjian; Feng, Jiali; Tian, Zhao; Chai, Zhaoqin; Liu, Yao; Li, Shengbin
All evolutionary change can be traced to alterations in allele frequencies in populations over time. DNA sequencing on a massive scale now permits us to follow the genetic consequences as our species has diverged from our close relatives and as we have colonized different parts of the world and adapted to them. But it has been difficult to disentangle natural selection from many other factors that alter frequencies. These factors include mutation and intragenic reciprocal recombination, gene conversion, segregation distortion, random drift, and gene flow between populations (these last two are greatly influenced by splits and coalescences of populations over time). The first part of this review examines recent studies that have had some success in dissecting out the role of natural selection, especially in humans and Drosophila. Among many examples, these studies include those that have followed the rapid evolution of traits that may permit adaptation to high altitude in Tibetan and Andean populations. In some cases, directional selection has been so strong that it may have swept alleles close to fixation in the span of a few thousand years, a rapidity of change that is also sometimes encountered in other organisms. The second part of the review summarizes data showing that remarkably few alleles have been carried completely to fixation during our recent evolution. Some of the alleles that have not reached fixation may be approaching new internal equilibria, which would indicate polymorphisms that are maintained by balancing selection. Finally, the review briefly examines why genetic polymorphisms, particularly those that are maintained by negative frequency dependence, are likely to have played an important role in the evolution of our species. A method is suggested for measuring the contribution of these polymorphisms to our gene pool. Such polymorphisms may add to the ability of our species to adapt to our increasingly complex and challenging environment. PMID:21718163
Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies of MTHFR 677T and MTHFR 1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies of MTHFR at position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93-5.89) and 2.75 (95% CI 0.95-12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS and MTHFR 1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work. PMID:18057532
Meguid, Nagwa A; Dardir, Ahmed A; Khass, Mohamed; Hossieny, Lamia El; Ezzat, Afaf; El Awady, Mostafa K
Cathepsin S (CTSS) played an important role in the etiology of cardiovascular disease and metabolic syndrome. Few studies had been reported on the association between the polymorphisms of CTSS and metabolic disorders in Asian population. Therefore we explored the association between the polymorphisms of CTSS and metabolic disorders in a Chinese Han population. The subjects were a Chinese Han cohort with 1160 participants, and the genotyping was performed with PCR-RFLP. Polymorphism rs16827671 was associated with BMI and serum total cholesterol (P=0.001; P=0.02, respectively). Subjects with CT genotype of rs16827671 had a higher risk of hypercholesterolemia (OR=1.64, 95% CI: 1.15-2.33, P=0.006) compared with TT genotype. Subjects with AG genotype of rs11576175 had lower risks of hypertriglyceridemia and borderline hypercholesterolemia (OR=0.52, 95% CI: 0.36-0.73, P=0.0001; OR=0.52, 95% CI: 0.35-0.77, P=0.001, respectively) compared with GG genotype. Compared with the haplotype TG, haplotype TA had a lower risk of hypertriglyceridemia and a higher risk of borderline hypercholesterolemia (OR=0.62, 95% CI: 0.44-0.88, P=0.002; OR=1.59, 95% CI: 1.10-2.31, P=0.008, respectively), and haplotype CA had a lower risk of hypercholesterolemia (OR=0.35, 95% CI: 0.18-0.68, P=0.002). In conclusion, we found that the genetic polymorphisms of CTSS were associated with metabolic disorders in a Chinese Han population, which would enrich the knowledge on genetic mechanisms of the pathogenesis of metabolic disorders. PMID:23747398
Ou, Zejin; Wang, Guanghai; Li, Qiang; Ma, Zuliang; Lin, Danmiao; Dai, Meng; Zou, Fei
The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. PMID:22924548
Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M
We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.
Escalante, A A; Lal, A A; Ayala, F J
Background: This study aims to determine the association of some genetic polymorphisms in the relationship of air pollutants on the serum levels of thrombomodulin (TM) and tissue factor (TF) in a population-based sample of children and adolescents. Materials and Methods: This cross-sectional study was conducted among 110 participants (52.8% girls) with a mean age of 12.7 + 2.3 years, in Isfahan, Iran. Genotypes of TM G33-A and + 5466A > G polymorphisms were determined by the polymerase chain reaction – restriction length fragment polymorphism method (PCR-RFLP). The enzyme-linked immunosorbent assay (ELISA) was used for measurement of serum TM and TF. Results: The following genotypes were identified for TM: GG in 69.2%, GA in27.2%, and AA in 3.6% of the participants. Considering TF, 108 participants were homozygous for the + 5466A allele, and two subjects had + 5466AG genotype. The mean pollution standards index (PSI) value was at a moderate level; the mean particulate matter measured up to 10 ?m (PM10); and ozone (O3), nitrogen dioxide, and sulfur dioxide were considerably high. The mean serum TF and TM levels were not significantly different among the participants with the aforementioned genotypes. Among participants exposed to high quartiles of O3, PM10, and PSI, the TM-33G / A polymorphism (GA + AA genotype) increased the Odds ratio (OR) of the low serum TM level. There was no statistically significant association in the areas of low pollution. Conclusion: The findings of our study support the synergistic effect of the TM-33G / A polymorphism and air pollutants on factors associated with the onset of the atherosclerosis. This might be confirmatory evidence for gene-environment interaction, and related effects on atherogenesis from early life.
Poursafa, Parinaz; Kelishadi, Roya; Haghjooy-Javanmard, Shaghayegh; Rafiei, Laleh; Keramatian, Kasra
Purpose Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of tumor metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. Experimental Design NME1 genotypes were analyzed in a cohort of 1134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. Results Single nucleotide polymorphisms (SNPs) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality (HR =1.4, 95% CI =1.1–1.9) as compared to those carrying the wild-type allele, and the association was more evident in patients with an early stage cancer (HR=1.7, 95% CI =1.2–2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR=1.3, 95% CI, 1.0–1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. Conclusion Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival.
Qu, Shimian; Long, Jirong; Cai, Qiuyin; Shu, Xiao-Ou; Cai, Hui; Gao, Yu-Tang; Zheng, Wei
Background Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal function decline. Methodology/Principal Findings We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerular filtration rate (eGFR) over an 11-year period in 2578 Caucasian participants of the Nurses' Health Study. Logistic regression was used to examine the associations between genotype and risk of eGFR decline of ?25%. Results After 11 years between creatinine measurements, the eGFR declined by ?25% in 423 of 2578 (16%) women. The angiotensinogen (AGT) A-20C polymorphism was associated with a higher risk of renal function decline when two risk alleles were present than if one or no alleles were present (CC vs AA and AC) OR 1.83 (95% CI 1.02–3.26; p?=?0.04). The angiotensin II type 1 receptor (AT1R) A1166C polymorphism was marginally associated with a higher risk of renal function decline when two risk alleles were present (CC vs AA, OR?=?1.41; 95% CI 0.98–2.01; p?=?0.06). The alpha-adducin G460W polymorphism was associated with a lower risk of renal function decline when any number of risk alleles were present (WG vs GG, OR?=?0.78, 95% CI 0.61–0.99, p?=?0.04; WW vs GG, OR?=?0.46; 95% CI 0.20–1.07, p?=?0.07). Linear regression analysis with change in eGFR as the outcome showed a larger decline of 3.5 (95% CI 0.5 to 6.4, p?=?0.02) ml/min/1.73 m2 in AGT A-20C CC homozygotes. No other polymorphisms were significantly associated with renal function decline or absolute change in eGFR over the study period. Conclusions Genetic variants in the angiotensinogen, angiotensin II type 1 receptor and alpha-adducin genes may contribute to loss of renal function in the general female Caucasian population.
Cooper Worobey, Cynthia; Fisher, Naomi D. L.; Cox, David; Forman, John P.; Curhan, Gary C.
Genetic variation in the five taxonomic groups of the Stylosanthes guianensis (Aubl.) Sw. complex was investigated using random amplified polymorphic DNA markers (RAPDs). DNA samples from four plants of each of 45 accessions within the S. guianensis species complex were analyzed using 20 oligonucleotides of random sequence. Little variation was found within each of the 18 accessions (1-7% of total RAPD bands in pairwise comparisons) and none within each of the other 27 accessions. However, higher levels of polymorphisms were observed both within (index of genetic distance = 1 - F = 0.16-0.248) and between (1 - F = 0.254-0.408) the five taxa. This level of differentiation at the DNA level supported an earlier classification of the taxa as distinct species. A phenogram based on band sharing was constructed to show genetic relationships among the taxa studied. This phenogram corroborated the description of relationships based on morphological-agronomic characteristics, seed protein patterns, rhizobial affinities, crossability, and pollen stainability of the hybrids. In this phenogram, the most similar species were S. grandiflora and S. hippocampoides (1 - F = 0.264), with S. acuminata also showing closest similarity to these two species (1 - F = 0.277 and 0.283, respectively). Stylosanthes gracilis accessions showed the closest similarity (1 - F = 0.296) to S. guianensis ssp. guianensis accessions. Lowest similarity values (1 - F = 0.335-0.411) were found between these two species and S. grandiflora, S. acuminata, and S. hippocampoides. PMID:8458571
Kazan, K; Manners, J M; Cameron, D F
Purpose. Genetic polymorphisms of MICA and DEPDC5 have been reported to correlate with progression to hepatocellular carcinoma (HCC) in chronic hepatitis C patients. However, correlation of these genetic variants with HCC recurrence following hepatectomy has not yet been clarified. Methods. Ninety-six consecutive HCC patients who underwent hepatectomy, including 64 patients who were hepatitis C virus (HCV) positive, were genotyped for MICA (rs2596542) and DEPDC5 (rs1012068). Recurrence-free survival rates (RFS) were compared for each genotype. Results. Five-year HCC recurrence-free survival (RFS) rates following hepatectomy were 20.7% in MICA GG allele carriers, 38.7% in GA, and 20.8% in AA, respectively (P = 0.72). The five-year RFS rate was 23.8% in DEPDC5 TT allele carriers and 31.8% in TG/GG, respectively (P = 0.47). The survival rates in all (including HCV-negative) patients were also similar among each MICA and DEPDC5 genotype following hepatectomy. Among HCV-positive patients carrying the DEPDC5 TG/GG allele, low fibrosis stage (F0-2) occurred more often compared with TT carriers (P < 0.05). Conclusions. Neither MICA nor DEPDC5 genetic polymorphism correlates with HCC recurrence following hepatectomy. DEPDC5 minor genotype data suggest a high susceptibility for HCC development in livers, even those with low fibrosis stages.
Motomura, Takashi; Ono, Yuki; Shirabe, Ken; Fukuhara, Takasuke; Konishi, Hideyuki; Mano, Yohei; Toshima, Takeo; Yoshiya, Shohei; Muto, Jun; Ikegami, Toru; Yoshizumi, Tomoharu; Maehara, Yoshihiko
Currently, quantitative prediction of the impact of genetic polymorphism and drug-drug interactions mediated by cytochromes, based on in vivo data, is made by two separate methods and restricted to a single cytochrome. We propose a unified approach for describing the combined impact of drug-drug interactions and genetic polymorphism on drug exposure. It relies on in vivo data and uses the following three characteristic parameters: one for the victim drug, one for the interacting drug, and another for the genotype. These parameters are known for a wide range of drugs and genotypes. The metrics of interest are the ratio of victim drug area under the curve (AUC) in patients with genetic variants taking both drugs, to the AUC in patients with either variant or wild-type genotype taking the victim drug alone. The approach was evaluated by external validation, comparing predicted and observed AUC ratios found in the literature. Data were found for 22 substrates, 30 interacting drugs, and 38 substrate-interacting drug couples. The mean prediction error of AUC ratios was 0.02, and the mean prediction absolute error was 0.38 and 1.34, respectively. The model may be used to predict the variations in exposure resulting from a number of drug-drug-genotype combinations. The proposed approach will help (1) to identify comedications and population at risk, (2) to adapt dosing regimens, and (3) to prioritize the clinical pharmacokinetic studies to be done. PMID:24027036
Tod, Michel; Nkoud-Mongo, Christina; Gueyffier, François
Twenty-one physically mapped, polymorphic markers have been developed from a chromosome 12-specific cosmid library. The markers consist of CA repeat-containing sequence-tagged sites (STSs) derived from cosmid clones mapped by fluorescence in situ hybridization (FISH). Three methods for determining the sequence flanking CA microsatellites were used, including one using degenerate primer sets for direct sequence analysis. Oligonucleotide primer pairs suitable for use in polymerase chain reaction (PCR) were selected from the sequences flanking the CA microsatellite and were tested for their ability to generate unique PCR products. The informativeness of these STSs as genetic markers was determined by typing 10 unrelated individuals who are part of the Centre d'Etude du Polymorphisme Humaine (EPH) pedigrees. Eleven of the 21 FISH-mapped, polymorphic STSs are heterozygous in 7 or more of the individuals tested. Since these markers are derived from physically mapped cosmids, genetic linkage analysis with them will facilitate the integration of the developing physical and genetic maps of chromosome 12. 29 refs., 4 figs., 2 tabs.
LeBlanc-Straceski, J.M.; Kissel, H.; Murtaugh, L.; Kucherlapati, R.; Montogmery, K.T.; Krauter, K.S. (Albert Einstein College of Medicine, Bronx, NY (United States)); Tsai, P.; Ward, D.C. (Yale Univ. Medical School, New Haven, CT (United States))
Background The enzyme phosphoenolpyruvate carboxykinase, PEPCK, occurs in its guanosine-nucleotide-using form in animals and a few prokaryotes. We study its natural genetic variation in Colias (Lepidoptera, Pieridae). PEPCK offers a route, alternative to pyruvate kinase, for carbon skeletons to move between cytosolic glycolysis and mitochondrial Krebs cycle reactions. Results PEPCK is expressed in both cytosol and mitochondrion, but differently in diverse animal clades. In vertebrates and independently in Drosophila, compartment-specific paralogous genes occur. In a contrasting expression strategy, compartment-specific PEPCKs of Colias and of the silkmoth, Bombyx, differ only in their first, 5?, exons; these are alternatively spliced onto a common series of following exons. In two Colias species from distinct clades, PEPCK sequence is highly variable at nonsynonymous and synonymous sites, mainly in its common exons. Three major amino acid polymorphisms, Gly 335 ? Ser, Asp 503 ? Glu, and Ile 629 ? Val occur in both species, and in the first two cases are similar in frequency between species. Homology-based structural modelling shows that the variants can alter hydrogen bonding, salt bridging, or van der Waals interactions of amino acid side chains, locally or at one another?s sites which are distant in PEPCK?s structure, and thus may affect its enzyme function. We ask, using coalescent simulations, if these polymorphisms? cross-species similarities are compatible with neutral evolution by genetic drift, but find the probability of this null hypothesis is 0.001???P???0.006 under differing scenarios. Conclusion Our results make the null hypothesis of neutrality of these PEPCK polymorphisms quite unlikely, but support an alternative hypothesis that they are maintained by natural selection in parallel in the two species. This alternative can now be justifiably tested further via studies of PEPCK genotypes? effects on function, organismal performance, and fitness. This case emphasizes the importance, for evolutionary insight, of studying gene-specific mechanisms affected by natural genetic variation as an essential complement to surveys of such variation.
The authors have constructed a 2.4-cM resolution genetic linkage map for chromosome 7q that is bounded by centromere and telomere polymorphisms and contains 66 loci (88 polymorphic systems), 38 of which are uniquely placed with odds for order of at least 1000:1. Ten genes are included in the map and 11 markers have heterozygosities of at least 70%. This map is the first to incorporate several highly informative markers derived from a telomere YAC clone HTY146 (locus D7S427), including HTY146c3 (HET 92%). The telomere locus markers span at least 200 kb of the 7q terminus and no crossovers within the physical confines of the locus were observed in approximately 240 jointly informative meioses. The sex-equal map length is 158 cM and the largest genetic interval between uniquely localized markers in this map is 11 cM. The female and male map lengths are 181 and 133 cM, respectively. The map is based on the CEPH reference pedigrees and includes over 4000 new genotypes, the previously reported data plus 29 allele systems from the published CEPH version 5 database, and was constructed using the program package CRI-MAP. This genetic linkage map can be considered a baseline map for 7q, and will be useful for defining the extent of chromosome deletions previously reported for breast and prostate cancers, for developing additional genetic maps such as index marker and 1-cM maps, and ultimately for developing a fully integrated genetic and physical map for this chromosome. 63 refs., 4 figs., 1 tab.
Helms, C.; Mishra, S.K.; Burgess, A.K.; Ramachandra, S.; Tierney, C.; Dorsey, D.; Donis-Keller, H. (Washington Univ. School of Medicine, St. Louis, MO (United States)); Riethman, H. (Wistar Institute, Philadelphia, PA (United States))
Genetic diversity and structure were analyzed in 10 accessions belonging to Banco Ativo de Germoplasma de Capsicum located at Federal University of Piauí in northwestern Brazil that receives pepper samples grown in community gardens in various regions and Brazilian states. Selections were made from seeds of C. chinense (4 accessions), C. annuum (5 accessions), and C. baccatum (1 accession). Samples consisting of leaves were collected from 4-10 plants of each accession (a total of 85 plants). Native polyacrylamide gel electrophoresis was used to identify ?- and ?-esterase polymorphisms. Polymorphism was clearly detected in 5 loci. Sixteen alleles were found at 5 ?/?-esterase loci of the three Capsicum species. In the C. chinense samples, the highest HO and HE values were 0.3625 and 0.4395, respectively, whereas in C. annuum samples, HO and HE values were 0.2980 and 0.3310, respectively; the estimated HO and HE values in C. chinense samples were higher than those detected in C. annuum samples. A deficit of homozygous individuals was found in C. chinense (FIS = -0.6978) and C. annuum (FIS = 0.7750). Genetic differentiation between C. chinense and C. annuum at these loci was high (FST = 0.1867) indicating that C. chinense and C. annuum are genetically structured species for ?/?- esterase isozymes. The esterase analysis showed high genetic diversity among the C. chinense and C. annuum samples and very high genetic differentiation (FST = 0.6321) among the C. chinense and C. annuum samples and the C. baccatum accession. PMID:23661440
Monteiro, E R; Bronzato, A R; Orasmo, G R; Lopes, A C A; Gomes, R L F; Mangolin, C A; Machado, M F P S
Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T
Ana Lívia Silva Galbiatti; Lidia Maria Rebolho Batista da Silva; Mariangela Torreglosa Ruiz-Cintra; Luis Sérgio Raposo; José Victor Maníglia; Érika Cristina Pavarino; Eny Maria Goloni-Bertollo
Genetic polymorphism of glycine-rich ?-glycoprotein (GBG) was studied in populations from northern and southern Italy, respectively. Gene frequencies were as follows: northern Italy (n = 431): GbS = 0.7675, GbF = 0.2049, GbS0.7 = 0.0127, GbF1 = 0.0139; southern Italy (n = 161): GbS = 0.7050, GbF = 0.2360, GbS0.7 = 0.0373, GbF1 = 0.0217. Comparison of these two populations
R. Scherz; R. Pflugshaupt; R. Bütler; F. Peyretti
Construction of a Genetic Linkage Map Based on Amplified Fragment Length Polymorphism Markers and Development of Sequence-Tagged Site Markers for Marker-Assisted Selection of the Sporeless Trait in the Oyster Mushroom (Pleurotus eryngii)
A large number of spores from fruiting bodies can lead to allergic reactions and other problems during the cultivation of edible mushrooms, including Pleurotus eryngii (DC.) Quél. A cultivar harboring a sporulation-deficient (sporeless) mutation would be useful for preventing these problems, but traditional breeding requires extensive time and labor. In this study, using a sporeless P. eryngii strain, we constructed a genetic linkage map to introduce a molecular breeding program like marker-assisted selection. Based on the segregation of 294 amplified fragment length polymorphism markers, two mating type factors, and the sporeless trait, the linkage map consisted of 11 linkage groups with a total length of 837.2 centimorgans (cM). The gene region responsible for the sporeless trait was located in linkage group IX with 32 amplified fragment length polymorphism markers and the B mating type factor. We also identified eight markers closely linked (within 1.2 cM) to the sporeless locus using bulked-segregant analysis-based amplified fragment length polymorphism. One such amplified fragment length polymorphism marker was converted into two sequence-tagged site markers, SD488-I and SD488-II. Using 14 wild isolates, sequence-tagged site analysis indicated the potential usefulness of the combination of two sequence-tagged site markers in cross-breeding of the sporeless strain. It also suggested that a map constructed for P. eryngii has adequate accuracy for marker-assisted selection.
Ueda, Jun; Obatake, Yasushi; Murakami, Shigeyuki; Fukumasa, Yukitaka; Matsumoto, Teruyuki
Construction of a genetic linkage map based on amplified fragment length polymorphism markers and development of sequence-tagged site markers for marker-assisted selection of the sporeless trait in the oyster mushroom (Pleurotus eryngii).
A large number of spores from fruiting bodies can lead to allergic reactions and other problems during the cultivation of edible mushrooms, including Pleurotus eryngii (DC.) Quél. A cultivar harboring a sporulation-deficient (sporeless) mutation would be useful for preventing these problems, but traditional breeding requires extensive time and labor. In this study, using a sporeless P. eryngii strain, we constructed a genetic linkage map to introduce a molecular breeding program like marker-assisted selection. Based on the segregation of 294 amplified fragment length polymorphism markers, two mating type factors, and the sporeless trait, the linkage map consisted of 11 linkage groups with a total length of 837.2 centimorgans (cM). The gene region responsible for the sporeless trait was located in linkage group IX with 32 amplified fragment length polymorphism markers and the B mating type factor. We also identified eight markers closely linked (within 1.2 cM) to the sporeless locus using bulked-segregant analysis-based amplified fragment length polymorphism. One such amplified fragment length polymorphism marker was converted into two sequence-tagged site markers, SD488-I and SD488-II. Using 14 wild isolates, sequence-tagged site analysis indicated the potential usefulness of the combination of two sequence-tagged site markers in cross-breeding of the sporeless strain. It also suggested that a map constructed for P. eryngii has adequate accuracy for marker-assisted selection. PMID:22210222
Okuda, Yasuhito; Ueda, Jun; Obatake, Yasushi; Murakami, Shigeyuki; Fukumasa, Yukitaka; Matsumoto, Teruyuki
Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no\\u000a relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study\\u000a is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected\\u000a CAD [156 patients with a previous myocardial infarction (MI), 307 without MI].
Xavier Jeunemaitre; François Ledru; Salvatore Battaglia; Marie-Thérèse Guillanneuf; Dominique Courbon; Cécile Dumont; Olivier Darmon; Louis Guize; Jean-Léon Guermonprez; Benoît Diebold; Pierre Ducimetière
Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE
Hongwei Wan; Yong Zhou; Ping Yang; Bo Chen; Guiqing Jia; Xiaoting Wu
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.
Zhou, Hongbin; Wu, Yinfang; Jin, Yan; Zhou, Jiesen; Zhang, Chao; Che, Luanqing; Jing, Jiyong; Chen, Zhihua; Li, Wen; Shen, Huahao
We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.
Kanazawa, Tetsufumi; Kikuyama, Hiroki; Okugawa, Gaku; Uenishi, Hiroyuki; Miyamoto, Toshio; Matsumoto, Naoki; Koh, Jun; Shinosaki, Kazuhiro; Kishimoto, Toshifumi; Yoneda, Hiroshi; Kinoshita, Toshihiko
Background Some polymorphisms of the neurotrophin family have previously been investigated as candidate genes for Alzheimer's disease (AD). In the present study, we examined whether neurotrophin-3 (NTF-3) polymorphisms are genetic risk factors in patients with AD. Methods From a sample of 507 subjects, we recruited 248 age-matched subjects divided into 2 groups: AD patients (n = 143) and normal controls (NCs) (n = 105). We identified 3 representative NTF-3 single nucleotide polymorphisms (SNPs): rs6332, rs6489630, and rs4930767. Next, we statistically compared the allele frequencies of each SNP between the AD and NC groups in the early-onset (<65 years) cases under a more limited age-matched condition. Results We found a significant association between rs6332 and the total group of AD patients (p = 0.013) and significant associations between both rs6332 (p = 0.033) and rs6489630 (p = 0.035) and early-onset AD patients. Conclusion These results suggest that NTF-3 SNPs may not only be associated with AD itself, but also with early-onset AD in Japanese patients, assuming that the NTF-3 gene may have age-related effects on neurodegenerative diseases.
Nagata, Tomoyuki; Shibata, Nobuto; Shinagawa, Shunichiro; Nakayama, Ritsuko; Kuerban, Bolati; Ohnuma, Tohru; Arai, Heii; Nakayama, Kazuhiko; Yamada, Hisashi
Coumarin anticoagulants, which include warfarin, acenocoumarol and phenprocoumon, are among the most widely prescribed drugs worldwide. There is now a large body of published data showing that genotype for certain common polymorphisms in the genes encoding the target vitamin K epoxide reductase (G-1639A/C1173T) and the main metabolizing enzyme CYP2C9 (CYP2C9*2 and *3 alleles) are important determinants of the individual coumarin anticoagulant dose requirement. Additional less common polymorphisms in these genes together with polymorphisms in other genes relevant to blood coagulation such as the cytochrome P450 CYP4F2, gamma-glutamyl carboxylase, calumenin and cytochrome P450 oxidoreductase may also be significant predictors of dose, especially in ethnic groups such as Africans where there have been fewer genetic studies compared with European populations. Using relevant genotypes to calculate starting dose may improve safety during the initiation period. Various algorithms for dose calculation, which also take patient age and other characteristics into consideration, have been developed for all three widely used coumarin anticoagulants and are now being tested in ongoing large randomised clinical trials. One recently completed study has provided encouraging results suggesting that calculation of warfarin dose on the basis of individual patient genotype leads to few adverse events and a higher proportion of time within the therapeutic coagulation rate window, but these findings still need confirmation. PMID:23376975
Daly, Ann K
The equilibrium sequence diversity of genes within a population and the rate of sequence divergence between populations or species depends on a variety of factors, including expression pattern, mutation rate, nature of selection, random drift, and mating system. Here, we extend population genetic theory developed for maternal-effect genes to predict the equilibrium polymorphism within species and sequence divergence among species for genes with social effects on fitness. We show how the fitness effects of genes, mating system, and genetic system affect predicted gene polymorphism. We find that, because genes with indirect social effects on fitness effectively experience weaker selection, they are expected to harbor higher levels of polymorphism relative to genes with direct fitness effects. The relative increase in polymorphism is proportional to the inverse of the genetic relatedness between individuals expressing the gene and their social partners that experience the fitness effects of the gene. We find a similar pattern of more rapid divergence between populations or species for genes with indirect social effects relative to genes with direct effects. We focus our discussion on the social insects, organisms with diverse indirect genetic effects, mating and genetic systems, and we suggest specific examples for testing our predictions with emerging sociogenomic tools. PMID:19245396
Linksvayer, Timothy A; Wade, Michael J
The equilibrium sequence diversity of genes within a population and the rate of sequence divergence between populations or species depends on a variety of factors, including expression pattern, mutation rate, nature of selection, random drift, and mating system. Here, we extend population genetic theory developed for maternal-effect genes to predict the equilibrium polymorphism within species and sequence divergence among species for genes with social effects on fitness. We show how the fitness effects of genes, mating system, and genetic system affect predicted gene polymorphism. We find that, because genes with indirect social effects on fitness effectively experience weaker selection, they are expected to harbor higher levels of polymorphism relative to genes with direct fitness effects. The relative increase in polymorphism is proportional to the inverse of the genetic relatedness between individuals expressing the gene and their social partners that experience the fitness effects of the gene. We find a similar pattern of more rapid divergence between populations or species for genes with indirect social effects relative to genes with direct effects. We focus our discussion on the social insects, organisms with diverse indirect genetic effects, mating and genetic systems, and we suggest specific examples for testing our predictions with emerging sociogenomic tools.
Linksvayer, Timothy A.; Wade, Michael J.
Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age ? 49 years (P<0.001), male gender (P=0.03), tobacco habit (P<0.001), MTHFR 1298AC/CC (P=0.028), MTR 2756AG/GG (P=0.010) and RFC1 80AG/GG (P=0.015) genotypes were associated with an increased risk of HNSCC. There were interactions between lower survival and CBS 844ins68 (P=0.005); age ? 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P=0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. PMID:22051736
Galbiatti, Ana Lívia Silva; da Silva, Lidia Maria Rebolho Batista; Ruiz-Cintra, Mariangela Torreglosa; Raposo, Luis Sérgio; Maníglia, José Victor; Pavarino, Erika Cristina; Goloni-Bertollo, Eny Maria
Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations. PMID:23872234
Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J
Genotype polymorphism studies at 15 highly polymorphic short tandem repeat (STR) loci were carried out in three genetically important minor caste groups (Yadav, Kurmi and Baniya) of Bihar, a eastern state of India to evaluate their significance in human identification and population genetics study. The selected communities practice endogamy. Despite of same geographical area, the physical features of Yadavs and Baniyas resemble North Indian Indo-Caucasoids whereas Kurmis resemble more to Indo-Austroloids. Among the chosen 15 loci, two are penta-nucleotide repeat: Penta-D and Penta-E, and 13 are tetra-nucleotide repeat: vWA D8S1179, TPOX, FGA, D5S818, D13S317, D7S820, D16S539, D3S1358, THO1, CSF1PO, D21S11, D18S51 and are validated for other population of India and world for forensic testing and human population study. Thirteen of these STR loci are present in the combined DNA index system (CODIS) [J. Forensic Sci. 44 (1999) 1277] and world-wide data is available. PMID:12427452
Ashma, R; Kashyap, V K
Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism. First molecular genetic studies underline the influence of polymorphisms located on genes coding for the receptors of the neuropeptides, oxytocin and vasopressin. However, the proportion of variance explained by these gene loci is rather low indicating that additional genetic variants must be involved. Pharmacological studies show that the dopaminergic system interacts with oxytocin and vasopressin. The present experimental study tests a dopaminergic candidate polymorphism for altruistic behaviour, the functional COMT Val158Met SNP. N?=?101 healthy Caucasian subjects participated in the study. Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r?=?0.32, P???0.001). Carriers of at least one Val allele donated about twice as much money as compared with those participants without a Val allele (P?=?0.01). Cooperativeness and the Val allele of COMT additively explained 14.6% of the variance in donation behaviour. Results indicate that the Val allele representing strong catabolism of dopamine is related to altruism. PMID:21030481
Reuter, Martin; Frenzel, Clemens; Walter, Nora T; Markett, Sebastian; Montag, Christian
The efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) patients has significantly increased in the last 20 years; as a result, the focus of research is slowly shifting from trying to increase survival rates to reduce chemotherapy-related toxicity. At the present time, the cornerstone of therapy for ALL is still formed by a reduced number of drugs with a highly toxic profile. In recent years, a number of genetic polymorphisms have been identified that can play a significant role in modifying the pharmacokinetics and pharmacodynamics of these drugs. The best example is that of the TPMT gene, whose genotyping is being incorporated to clinical practice in order to individualize doses of mercaptopurine. However, there are additional genes that are relevant for the metabolism, activity, and/or transport of other chemotherapy drugs that are widely use in ALL, such as methotrexate, cyclophosphamide, vincristine, L-asparaginase, etoposide, cytarabine, or cytotoxic antibiotics. These genes can also be affected by genetic alterations that could therefore have clinical consequences. In this review we will discuss recent data on this field, with special focus on those polymorphisms that could be used in clinical practice to tailor chemotherapy for ALL in order to reduce the occurrence of serious adverse effects.
Gervasini, Guillermo; Vagace, Jose M.
A systematic study has been conducted of all available reports in PubMed and OMIM (Online Mendelian Inheritance in Man) to examine the genetic and molecular basis of quantitative genetic loci (QTL) of diabetes with the main focus on genes and polymorphisms. The major question is, What can the QTL tell us? Specifically, we want to know whether those genome regions differ from other regions in terms of genes relevant to diabetes. Which genes are within those QTL regions, and, among them, which genes have already been linked to diabetes? whether more polymorphisms have been associated with diabetes in the QTL regions than in the non-QTL regions. Our search revealed a total of 9038 genes from 26 type 1 diabetes QTL, which cover 667,096,006 bp of the mouse genomic sequence. On one hand, a large number of candidate genes are in each of these QTL; on the other hand, we found that some obvious candidate genes of QTL have not yet been investigated. Thus, the comprehensive search of candidate genes for known QTL may provide unexpected benefit for identifying QTL genes for diabetes.
Gao, Peng; Jiao, Yan; Xiong, Qing; Wang, Cong-Yi; Gerling, Ivan; Gu, Weikuan
Trichophyton mentagrophytes is a common cosmopolitan dermatophyte species composed of two varieties: T. mentagrophytes var. interdigitale (anthropophilic form) and T. mentagrophytes var. mentagrophytes (zoophilic form). We used a random amplified polymorphic DNA (RAPD) method to study the genetic diversity of 46 clinical isolates of the T. mentagrophytes complex collected from 38 patients with different geographical origins (Europe, Africa, South America). The T. mentagrophytes were isolated either from a unique lesion for 31 patients, including two patients living together, or from at least two sites for seven patients. Only one primer of 15 primers tested showed DNA polymorphism in the isolates, producing 23 distinct patterns belonging to three clusters. There was no specific cluster grouping isolates from the same geographical origin. The same pattern is shared by all the four T. mentagrophytes var. mentagrophytes and 13 of 42 T. mentagrophytes var. interdigitale. An identity of strains responsible for several lesions in seven individuals suggests an homogeneous T. mentagrophytes population in the case of multiple lesions. In contrast, the dissimilarity of two strains recovered from two patients living together argues against person-to-person transmission in that case. This study indicates that RAPD can be successfully applied to show genetic diversity among T. mentagrophytes isolates. PMID:10354019
Kac, G; Bougnoux, M E; Feuilhade De Chauvin, M; Sene, S; Derouin, F
Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study. PMID:23198514
Landau, Mark E; Kenney, Kimbra; Deuster, Patricia; Gonzalez, Rodney S; Contreras-Sesvold, Carmen; Sambuughin, Nyamkhishig; O'Connor, Francis G; Campbell, William W
Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis. PMID:18563616
Arsova-Sarafinovska, Zorica; Matevska, Nadica; Eken, Ayse; Petrovski, Daniel; Banev, Saso; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Erdem, Onur; Sayal, Ahmet; Aydin, Ahmet; Dimovski, Aleksandar J
Vitiligo is an acquired depigmentary disorder of the skin, characterized by multiple susceptibility loci and genetic heterogeneity. The etiology of vitiligo is unknown but several hypotheses, including an autoimmune origin, have been proposed. Tumor necrosis factor (TNF)-?, a pleiotropic proinflammatory cytokine, has been shown to play a critical role in several autoimmune diseases including vitiligo. The aim of present study was to determine the association of TNF-? and -? gene polymorphisms with vitiligo in Saudi patients. TNF-? and -? genes were amplified in 123 Saudi patients and 200 matched controls using polymerase chain reaction to search for polymorphisms involved at positions -308, and intron 1 +252. The frequency of the TNF-? (-308) GA genotype was higher and the frequencies of the GG and AA genotypes were significantly lower in vitiligo patients compared to controls. These findings suggested that genotype GA-positive individuals at position -308 of TNF-? are susceptible to vitiligo, whereas the GG and AA genotypes might exert a protective effect. The frequency of allele A (TNF-? 2-allele) was significantly higher and that of allele G (TNF-? 1-allele) was lower in vitiligo patients compared to controls, indicating an association of allele A with susceptibility to vitiligo in Saudi patients. The results of our examination of TNF-? (intron 1 +252) polymorphisms showed a significant increase in the frequency of the GG genotype and allele G (TNF-? 1-allele) in vitiligo patients, suggesting a susceptibility of the GG genotype and allele G for vitiligo. By contrast, the high frequency of the GA genotype in controls might indicate a protective effect. The results of the present study strongly support a link between TNF-? (-308) and -? (intron 1 +252) polymorphisms and vitiligo in Saudi patients. PMID:23884763
Al-Harthi, F; Zouman, A; Arfin, M; Tariq, M; Al-Asmari, A
Background In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Methods Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Results Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. Conclusion The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P. falciparum and P. vivax is therefore essential also in Honduras.
TXN2 encodes human thioredoxin 2, a small redox protein important in cellular antioxidant defenses, as well as in the regulation of apoptosis. Txn2 knockout mice fail to complete neural tube closure by E10.5 and die in utero. We hypothesized that genetic variation in human TXN2 gene may alter the function of the encoded protein in a manner associated with an increased risk for neural tube defects (NTDs). A DNA re-sequencing effort of the human TXN2 gene was taken. After a variation in the promoter was identified, the transcriptional activity of different alleles was investigated. The possible association between these variations and the risk of spina bifida was further evaluated in a subset of samples obtained from a large population-based case-control study in California in two different ethnicity groups, non-Hispanic white and Hispanic white. We identified a novel promoter insertion polymorphism located 9 base pairs upstream of the transcription start site of exon 1(-9 insertion). The GA, G and GGGA insertions were associated with a marked decrease of transcriptional activity when overexpressed in both U2-OS (an osteosarcoma cell line) and 293 cells (derived from human embryonic kidney). Further analysis revealed that the GA insertion was associated with increased spina bifida risk for Hispanic whites. Our study revealed a novel Ins/Del polymorphism in the human TXN2 gene proximal promoter region that altered the transcriptional activity and is associated with spina bifida risk. This polymorphism may be a genetic modifier of spina bifida risk in this California population. PMID:19165900
Wen, Shu; Lu, Wei; Zhu, Huiping; Yang, Wei; Shaw, Gary M; Lammer, Edward J; Islam, Ana; Finnell, Richard H
The genetic diversity of 47 clinical and reference strains of Candida glabrata from several geographical origins and diverse clinical disorders, with different antifungal susceptibilities, as well as their genetic relationships were studied through multilocus enzyme electrophoresis (MLEE) and randomly amplified polymorphic DNA (RAPD) techniques. The genetic diversity estimated for 11 MLEE loci measured as average heterozygosity (h) was 0.055. A high level of genetic relatedness among isolates was established by cluster analysis. Forty-nine RAPD markers were analyzed, and the average genetic diversity among isolates, estimated by Shannon's index (Ho), was 0.372. The ?ST values estimated through an analysis of molecular variance to assess genetic differentiation among isolates revealed no genetic differentiation among them. Our results revealed very low genetic diversity among isolates, a lack of differentiation, and no association with their geographic origin and the clinical characteristics.
Boldo, Xavier M.; Villa-Tanaca, Lourdes; Zuniga, Gerardo; Hernandez-Rodriguez, Cesar
The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma
The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy±surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes (MTHFR C677T, MTR A2756G, TS tandem repeat polymorphism) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy. The genotypes were correlated with tumour response to polychemotherapy, radiochemotherapy and with overall survival. Tumours with the MTR wild-type genotype (2756AA) showed a median survival time of 16 months, whereas tumours with an MTR variant genotype (2756AG/2756GG) showed a median survival time of 42 months (P=0.0463). No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene. Among tumours treated with radiochemotherapy and subsequent resection, MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype (P=0.0442). In contrast, no significant relationship between clinically determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed. In conclusion, pretherapeutic determination of the MTR A2756G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas. Determination of MTHFR C677T and TS tandem repeat polymorphism has no predictive value.
Sarbia, M; Stahl, M; von Weyhern, C; Weirich, G; Puhringer-Oppermann, F
Genetic diversity of Plasmodium populations has been more extensively documented in Colombia for Plasmodium falciparum than for Plasmodium vivax. Recently, highly variable microsatellite markers have been described and used in population-level studies of genetic variation of P. vivax throughout the world. We applied this approach to understand the genetic structure of P. vivax populations and to identify recurrence-associated haplotypes. In this, three microsatellite markers of P. vivax were amplified and the combined size of the fragments was used to establish genotypes. Patients from an ongoing treatment efficacy trial who were kept either in endemic or non-endemic regions in the northwest of Colombia were included in the study. In total 58 paired clinical isolates, were amplified. A total of 54 haplotypes were observed among the two regions. Some haplotypes were exclusive to the endemic region where the highest degree of polymorphism was detected. In addition, we confirmed the different genotypes of recurrent-relapsing and primary infection isolates suggesting the activation of heterologous hypnozoite populations. We conclude that analysis of the three microsatellites is a valuable tool to establish the genetic characteristics of P. vivax populations in Colombia. PMID:21497586
Restrepo, Eliana; Imwong, Mallika; Rojas, Winston; Carmona-Fonseca, Jaime; Maestre, Amanda
To understand the effects of the interaction between genetic polymorphisms and obesity on the risk of hypertriglyceridemia\\u000a (HTG), two polymorphisms, an SstI polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in the HTG group) or\\u000a without HTG (257 cases in the control group). Our
Yu-Lin Ko; Yu-Shien Ko; Shy-Meeng Wu; Ming-Sheng Teng; Fu-Ru Chen; Tsu-Shiu Hsu; Chen-Wen Chiang; Ying-Shiung Lee
Background Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. Methods and Results In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006) and earlier age of onset (P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases (P = 0.01) and tumor size (P = 0.01). Conclusion Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.
Hoyal, Carolyn R; Kammerer, Stefan; Roth, Richard B; Reneland, Richard; Marnellos, George; Kiechle, Marion; Schwarz-Boeger, Ulrike; Griffiths, Lyn R; Ebner, Florian; Rehbock, Joachim; Nelson, Matthew R; Braun, Andreas
Genes influence quantitative variations in plasma lipoprotein concentrations. For example, intake of dietary saturated fat and cholesterol raises the average serum cholesterol concentration, leading to a higher risk of coronary artery disease in populations. However, not all individuals within the population are susceptible: genetic factors appear to render individuals either "dietary responsive" or "dietary nonresponsive." In this review, we focus on current knowledge about the influence of genetic polymorphisms in certain genes on the lipoprotein response to dietary fat and cholesterol. Our preliminary studies in the Dietary Intervention Study in Children suggest a significant dose-response relation between the decrease in LDL cholesterol from baseline to 36 mo of follow-up in both the intervention group (who consumed a low-fat, low-cholesterol diet) and the usual care group (who consumed a regular diet) and the presence of the APOA1*A allele at the M1 site and the + site at the M2 site of the gene encoding apolipoprotein (apo) A-I. The DNA polymorphisms on the genes encoding apo A-IV, apo B, apo C-III, apo E, lipoprotein lipase, cholesteryl ester transfer protein, lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol O:-acyltransferase), and LDL receptor were found by others to be associated with the plasma lipoprotein response to dietary intervention. Possible mechanisms involved in these effects are discussed and certain discrepancies in the literature about some genetic effects on responsiveness are analyzed. An improved understanding of the influence of specific genes on lipoprotein responsiveness to dietary fat and cholesterol may allow us to identify and counsel certain individuals to avoid high-fat diets so that they may reduce their risk of developing hyperlipidemia and coronary artery disease. PMID:11063469
Ye, S Q; Kwiterovich, P O
In investigating the genetic marker for population genetics of Japanese macaques by electrophoresis, the author found the erythrocyte lacate dehydrogenase (LDH) polymorphism existing in some troops. There were four kinds of variations which seemed to be controlled by two loci, controlling A and B subunits of this enzyme. The variant phenotypes were named LDH-Amac2-1 LDH-Bmac1-1, LDH-Amac3-1 LDH-Bmac1-1, LDH-Amac 1-1 LDH-Bmac2-1,
Background Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer. Methods We analyzed associations among OGG1 Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese. Results The results showed that the MUTYH His/His genotype compared with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31–7.00, p = 0.010), whereas there was no significant increase for the Gln/His genotype (adjusted OR 1.35, 95%CI 0.70–2.61, p = 0.376). The MUTYH His/His genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95–6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89–11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1 Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH His/His genotype compared with the Gln/Gln genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22–12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60–11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also no significant risk for lung cancer. Conclusion Our findings suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.
Miyaishi, Aiko; Osawa, Kayo; Osawa, Yasunori; Inoue, Natsuko; Yoshida, Kana; Kasahara, Mayumi; Tsutou, Akimitsu; Tabuchi, Yoshiki; Sakamoto, Kazuo; Tsubota, Noriaki; Takahashi, Juro
We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosomes segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome. 39 refs., 5 figs., 4 tabs.
Lynch, T.J.; Brickner, J.; Orias, E.; Nakano, K.J. [Univ. of California, Santa Barbara, CA (United States)
We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosome segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome.
Lynch, T. J.; Brickner, J.; Nakano, K. J.; Orias, E.
Random amplified polymorphic DNA (RAPD) markers were used to detect polymorphism and to examine relationships among four table grape clones from northwestern Paraná, in southern Brazil. The 10 primers used for RAPD fingerprints generated 126 reproducible fragments, of which 63, 68, 76, and 72 were polymorphic in cultivars Italia, Rubi, Benitaka, and Brasil, respectively. Among the primers, OPP-08 generated the highest number of fragments, whereas OPE-15 was the most efficient for discriminating polymorphic fragments. The distribution of the clones by cluster analysis indicated that there were no differences in RAPD markers between the colored mutant and the original clone (cultivar Italia), supporting the hypothesis that the non-colored and the colored mutant are the same cultivar. However, we found high levels of polymorphism within and between the cultivars Italia, Rubi, Benitaka, and Brasil (65.1%), contrary to a previous hypothesis that the four clones are genetically uniform. This confirmed our expectation of genetic variation among the clones and within each clone. We conclude that the primers are useful for analyzing the development of the genetic diversity within each of these clones. PMID:19224464
Maia, S H Z; Mangolin, C A; Collet, S A O; Machado, M F P S
Background The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs) constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation. Results We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR) approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194). We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI) database (n = 29967) and a control set of sequences (coding region) not associated with SNP sites randomly selected from the NCBI database (n = 29967). We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level of p ? 0.05. Significant models (p << 0.001) were detected for each SNP type examined in the larger NCBI dataset. Importantly, the flanking region models were elongated or truncated depending on the nucleotide change. Additionally, nucleotide distributions differed significantly at motif sites relative to the type of variation observed. The MDR approach effectively discerned specific sites within the flanking regions of observed SNPs and their respective identities, supporting the collective contribution of these sites to SNP genesis. Conclusion The present study represents the first use of this computational methodology for modeling nonlinear patterns in molecular genetics. MDR was able to identify distinct nucleotide patterning around sites of mutations dependent upon the observed nucleotide change. We discovered one flanking region set that included five nucleotides clustered around a specific type of SNP site. Based on the strongly associated patterns identified in this study, it may become possible to scan genomic databases for such clustering of nucleotides in order to predict likely sites of future SNPs, and even the type of polymorphism most likely to occur.
Arehart, Eric; Gleim, Scott; White, Bill; Hwa, John; Moore, Jason H
The aim of this study was to determine the genetic diversity of Plasmodium falciparum by analyzing the polymorphism of the msp-1 and msp-2 genes and the multiplicity of infection in children with uncomplicated malaria in southern Benin. Blood samples of children with fever or history of fever with thick smear positive P. falciparum were collected on filter paper. After extraction of DNA by Chelex®, the samples underwent nested PCR. 93 isolates from children were genotyped. For the msp-1 gene, the K1 and R033 sequences were the most represented in the study population with 85.2% and 83% prevalence, respectively. Regarding the msp-2 gene, the FC27 family was more highly represented with 99% prevalence against 81.5% for 3D7. Mixed infections accounted for 80.4% of the samples. Twenty-five alleles were identified for msp-1 and 28 for msp-2. Fourteen and ten alleles belonged to the K1 (100–500 bp) and MAD20 (100–500 bp) families, respectively. The RO33 sequence did not show any polymorphism, with only one variant (160 bp) detected. The msp-2 gene was present as 16 FC27 family fragments (250–800 bp) and 12 of the 3D7 family (350–700 bp). The multiplicity of infection was estimated at 3.8 for msp-1 and 3.9 for msp-2 with 77 (87.5%) and 84 (91.3%) samples harboring more than one parasite genotype for msp-1 and msp-2, respectively. The multiplicity of infection (MOI) was influenced neither by age nor by parasite density. This study shows a significant diversity of P. falciparum in southern Benin with an MOI unaffected by age or by parasite density.
Ogouyemi-Hounto, Aurore; Gazard, Dorothee Kinde; Ndam, Nicaise; Topanou, Elsa; Garba, Olivia; Elegbe, Pancras; Hountohotegbe, Tatiana; Massougbodji, Achille
Frequency-dependent disease impacts may contribute to the maintenance of genetic diversity and sexual reproduction in plant\\u000a populations. In earlier work with experimental wheat (Triticum aestivum) populations at a single density, we found that stripe rust (caused by Puccinia striiformis) created frequency-dependent selection on its host but competitive interactions between host genotypes reduced the potential\\u000a for disease to maintain genetic polymorphisms
Christopher C. Mundt; Johanne Brunet; Kathryn E. Sackett
The random amplified polymorphic DNA (RAPD) technique was used to evaluate genetic affinities among eight red mullet (Mullus barbatus L., 1758) samples from the Mediterranean Sea. Twenty-nine random primers were used. Despite the variability which was found\\u000a within samples, no specific RAPD marker for the discrimination of the populations was detected. The data analysis revealed\\u000a that the genetic diversity among
Z. Mamuris; A. P. Apostolidis; A. J. Theodorou; C. Triantaphyllidis
5-Fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5'-untranslated region (5'-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing. PMID:22496803
Ghosh, Soma; Hossain, M Zulfiquer; Borges, Michael; Goggins, Michael G; Ingersoll, Roxann G; Eshleman, James R; Klein, Alison P; Kern, Scott E
Aims The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility. Methods Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes. Results A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR?=?0.71, 95% CI?=?0.55–0.92, P?=?0.01), IL2RA rs11594656 (OR?=?0.86, 95% CI?=?0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR?=?0.71, 95% CI?=?0.55–0.92, P?=?0.01). APOA5 ?1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR?=?1.27, 95% CI?=?1.03–1.57, P?=?0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C. Conclusion Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 ?1131T/C are risky factors of T1D and T2D, respectively.
Wang, Qinwen; Xu, Leiting; Bu, Shizhong; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting; Liu, Qiong; Ye, Meng; Mai, Yifeng; Duan, Shiwei
The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.
Bashash, Morteza; Shah, Amil; Hislop, Greg; Treml, Martin; Bretherick, Karla; Janoo-Gilani, Rozmin; Leach, Stephen; Le, Nhu
Many species show changes in distribution and phenotypic trait variation in response to climatic warming. Evidence of genetically based trait responses to climate change is, however, less common. Here, we detected evolutionary variation in the landscape-scale distribution of a genetically based chemical polymorphism in Mediterranean wild thyme (Thymus vulgaris) in association with modified extreme winter freezing events. By comparing current data on morph distribution with that observed in the early 1970s, we detected a significant increase in the proportion of morphs that are sensitive to winter freezing. This increase in frequency was observed in 17 of the 24 populations in which, since the 1970s, annual extreme winter freezing temperatures have risen above the thresholds that cause mortality of freezing-sensitive morphs. Our results provide an original example of rapid ongoing evolutionary change associated with relaxed selection (less extreme freezing events) on a local landscape scale. In species whose distribution and genetic variability are shaped by strong selection gradients, there may be little time lag associated with their ecological and evolutionary response to long-term environmental change. PMID:23382198
Thompson, John; Charpentier, Anne; Bouguet, Guillaume; Charmasson, Faustine; Roset, Stephanie; Buatois, Bruno; Vernet, Philippe; Gouyon, Pierre-Henri
The origin of Pacific islanders is still an open issue in human population genetics. To address this topic we analyzed a set of 18 Alu insertion polymorphisms in a total of 176 chromosomes from native Easter Island inhabitants (Rapanui). Available genealogical records allowed us to subdivide the total island sample into two groups, representative of the native population living in the island around 1900, and another formed by individuals with some ancestors of non-Rapanui origin. Significant genetic differentiation was found between these groups, allowing us to make some biodemographic and historical inferences about the origin and evolution of this geographically isolated island population. Our data are consistent with equivalent and recent contributions from Amerindian and European migrants to the 1900s Rapanui population, with an accelerated increase in the European gene flow during the 20(th) century, especially since the 1960s. Comparative analysis of our results with other available Alu variation data on neighbouring populations supports the "Voyaging Corridor" model of Polynesian human settlement, which indicates that pre-Polynesians are mainly derived from Southeast Asian and Wallacean populations rather than from Taiwan or the Philippines. This study underlines the importance of sampling and taking into account historical information in genetic studies to unravel the recent evolution of human populations. PMID:17044858
González-Pérez, E; Esteban, E; Via, M; García-Moro, C; Hernández, M; Moral, P
Recent studies of genetically controlled enzyme variation lead to an estimation that at least 30 to 60% of the structural genes are polymorphic in natural populations of many vertebrate and invertebrate species. Some authors have argued that a substantial proportion of these polymorphisms cannot be maintained by natural selection because this would result in an unbearable genetic load. If many polymorphisms are maintained by heterotic natural selection, individuals with much greater than average proportion of homozygous loci should have very low fitness. We have measured in Drosophila melanogaster the fitness of flies homozygous for a complete chromosome relative to normal wild flies. A total of 37 chromosomes from a natural population have been tested using 92 experimental populations. The mean fitness of homozygous flies is 0.12 for second chromosomes, and 0.13 for third chromosomes. These estimates are compatible with the hypothesis that many (more than one thousand) loci are maintained by heterotic selection in natural populations of D. melanogaster.
Tracey, Martin L.; Ayala, Francisco J.
Allergic rhinitis is a chronic inflammatory disease that is assumed to be due to an interaction between different genetic and/or environmental factors. A disintegrin and metalloprotease domain 33 (ADAM33) has been extensively studied as a susceptibility gene in asthma and has been linked to bronchial hyper-responsiveness. In this study, we investigated the association between ADAM33 single nucleotide polymorphisms and the incidence of allergic rhinitis among the Jordanian population. We conducted a case-control association study on 120 adult individuals diagnosed with allergic rhinitis and 128 normal healthy controls. 8 single-nucleotide polymorphisms in ADAM33 were genotyped using PCR-RFLP method. No significant differences in the allelic frequencies of all SNPs tested between AR patients and the control volunteers were found, although S2 C/G SNP showed a tendency toward significance with P=0.06. On the genotype level significant association were found in the following genotypes: T1 AA, T1 AG, T2 GG, T2 AG, T+1 GG, T+1 AG, V4 CG, S2 CC, S2 CG, Q-1AA. Seven haplotypes were present only within AR patients and eight haplotypes were completely absent from the AR patients. Three haplotypes exhibited significant association with AR P?0.05, two of them were present only in AR patients. In conclusion, the polymorphisms in the ADAM33 gene are associated with susceptibility to AR in the Jordanian population. Furthermore, the haplotype of the tested SNPs were also associated with the risk of AR. PMID:24035932
Zihlif, Malek; Mahafza, Tareq; Obeidat, Nathir M; Froukh, Tawfiq; Shaban, Mazen; Al-Akhras, Fatima M; Zihlif, Nadwa; Naffa, Randa
Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor 4G/5G polymorphisms between 50 patients with symptomatic DVT within 3 weeks after elective THA and an asymptomatic control group of 85 patients. We found no major difference for the presence of a single mutation between the groups. Factor V Leiden and homozygous MTHFR C667T mutations were of borderline significance with odds ratios (95% confidence intervals) of 3.73 (0.89-15.63) and 2.93 (0.92-9.29), respectively. Patients with homozygous or combined heterozygous status of MTHFR C677T and A1298C mutation had a higher frequency of DVT after elective THA (odds ratio, 2.86; 95% confidence interval, 1.32-6.35) than those with wild-type. The presence of a single mutation may not further increase the already high risk for symptomatic DVT after THA, whereas combinations of mutations of distinct polymorphisms might be important. However, prospective studies with a larger number of patients are needed before we would recommend preoperative screening. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18800213
Ringwald, Juergen; Berger, Annika; Adler, Werner; Kraus, Cornelia; Pitto, Rocco P
The strategy of therapy and prognosis of reproductive system neoplasia generally depend on the steroid receptor status of tumor. The causes of formation of steroid receptor-free tumors are to be investigated. The genetic polymorphism of CYP19 (aromatase), CYP17 (17-hydroxylase; 17,20-lyase), CYP1B1 (4-estrogen hydroxylase) and COMT (catechol-O-methyl transferase) was studied in a total of 254 patients with breast and endometrial cancer, with particular reference to the association of certain polymorphisms and receptor status of tumor. It was found that the lack of estrogen receptor (ER) in breast tumor was due to a deficit in the A3A6 allele (p(0.01), while the absence of progesterone receptors was associated with a lower incidence of the A1A1 and A1A2 variants (p = 0.022) of tetranucleotide repeats in the CYP19 gene. In the same patients, receptor-negative tumors occurred more often (p = 0.032) than in combinations of higher level of 4-hydroxylase estradiol of S-allele in position 48 (Gly/Arg) of the CYP1B1 gene. Moreover, endometrial carcinoma patients tended to reveal (p = 0.058) an increased ratio of A6A7-CYP19 to allele A1-containing variant. No other distinctions between R(+) and R(-) tumors were identified. It is suggested that peculiar polymorphisms of steroidogenic enzymes may moderately influence the genesis of R(-) neoplasms which may be associated with either the rate of estrogen biosynthesis or, as in the case of CYP1B1, with formation of genotoxic derivatives of estrogens. The latter point is to be investigated further. PMID:15176218
Berstein, L M; Zimarina, T S; Tsyrlina, E V; Kovalevski?, A Iu; Imianitov, E N
In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC. PMID:16740934
Huard, Richard C; Fabre, Michel; de Haas, Petra; Lazzarini, Luiz Claudio Oliveira; van Soolingen, Dick; Cousins, Debby; Ho, John L
Genetic exchange among populations of asexual filamentous fungi is presumed to be limited to isolates in the same vegetative compatibility group (VCG). To test this hypothesis, we compared the distribution of single nucleotide polymorphisms (SNP's) in Aspergills flavus isolates from six different V...
Oral cancer ranks first among all cancers in males and is the third most common among females in India. Tobacco-derived carcinogens are involved in the development of oral cancer. Environment–gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study looked at the significance of genetic polymorphisms
T. T Sreelekha; K Ramadas; M Pandey; G Thomas; K. R Nalinakumari; M. R Pillai
Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the ethnic groups inhabiting South and East Siberia, including Altaians, Buryats, Tuvinians, Todjins, Tofalars, Yakuts, and Evenks were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E\\/G, G, A, B, and F) and Caucasoid (H, HV, I, J, K,
M. V. Derenko; B. A. Malyarchuk; G. A. Denisova; I. K. Dambueva; V. T. Kakpakov; Ch. M. Dorzhu; F. A. Luzina; E. A. Lotosh; U. N. Ondar; M. I. Kaplina; I. A. Zakharov
Amplified fragment length polymorphism (AFLP) fingerprinting of clinical isolates of Chlamydia trachomatis serovars D, E, and F showed a low percentage of genetic heterogeneity, but clear differences were found. Isolates from index patients and partners had identical AFLP patterns and AFLP markers. Characterization of these AFLP markers could give more insight into the differences in virulence and clinical course of C. trachomatis infections.
Morre, Servaas A.; Ossewaarde, Jacobus M.; Savelkoul, Paul H. M.; Stoof, Jeroen; Meijer, Chris J. L. M.; van den Brule, Adriaan J. C.
Cotton genome complexity was investigated with a saturated molecular genetic map that combined several sets of microsatellites or simple sequence repeats (SSR) and the first major public set of single nucleotide polymorphism (SNP) markers in cotton genomes (Gossypium spp.), and that was constructed ...
The objective of the present study was to assess the utility of molecular marker data generated by Sequence Related Amplified Polymorphisms (SRAPs) to assess genetic relationships among semi-dormant and non-dormant modern alfalfa cultivars using bulked DNAs. Marker data was also used to examine rel...
In order to carry out preimplantation genetic diagnosis (PGD) for ?-thalassaemia, we have applied direct sequencing of single cell PCR products to detect mutations and polymorphic loci within the ?-globin gene. Conventional duplex PCR was used to amplify two regions of the ?-globin gene with an amplification efficiency of 79% for blastomeres. Sequencing data were obtained for 100% of amplified
Nicole D. Hussey; Tenielle Davis; Jenny R. Hall; Michael F. Barry; Rogan Draper; Robert J. Norman; Zbigniew Rudzki
Background Apart from allergic mechanisms, a lack or mutation of metabolic enzymes may cause adverse drug reactions. Patch testing has rarely been useful in cutaneous adverse drug reactions (CADRs) induced by diphenylhydantoin (DPH). Genetic polymorphisms leading to altered metabolic processes of cytochrome P 450 (CYP) 2C9, a main metabolic enzyme for DPH, may be the pathological mechanism for certain cases
Ai-Young Lee; Min-Jung Kim; Won-Young Chey; Jun Choi; Byung-Gun Kim
The response to lipid-lowering drugs is modified by a number of factors like age, gender, concomitant disease and genetic determinants. Even within homogenous groups of patients, individual responses vary greatly. Until now, no clinical or biochemical parameter exists which predicts whether a subject will respond well to a particular lipid-lowering drug or, in the extreme case, will develop adverse, life-threatening effects (e.g., myositis or rhabdomyolysis). The recent advances in the human genome project promises to have a great impact on our understanding of lipid and lipoprotein metabolism and of the individual response to lipid-lowering drugs. Monogenetic disorders of the lipid metabolism produce severe clinical phenotypes, such as Tangier disease, but have a minor role in the evaluation of cardiovascular risk in the general population. On the other hand, several polymorphisms in genes involved in lipoprotein metabolism (e.g., apolipoprotein E) are associated with the plasma levels of lipoproteins, explaining a substantial fraction of the variance of LDL or HDL concentrations. In combination, the knowledge of these polymorphisms, further variants yet to be discovered and variants within the genes involved in the metabolism of lipid-lowering drugs will in the future allow these drugs to be selected according to the patients needs and thus increase both efficacy and cost-effectiveness of lipid-lowering regimes. PMID:11368750
Hoffmann, M M; Winkelmann, B R; Wieland, H; März, W
Human Papillomavirus infection is considered as the main etiological factor of cervical cancer (ICC), although, the role of host genetic factors in ICC susceptibility has been increasing. Immunological response is crucial for the prevention of viral associated diseases. Interleukin 1 receptor antagonist (IL-1RN) is considered to be an important regulator of host immunity and several studies have shown a potential role of a 86 bp VNTR polymorphism within intron 2 of the IL-1RN gene in host immune response variability. We investigated the role of this polymorphism in cervical cancer development in Portugal with a case-control study developed with peripheral blood samples from 196 healthy women and 340 women with cervical lesions from the Northern Region of Portugal. We observed that IL-1RN Allele 2 homozygosis was significantly higher in cases than in controls. In fact, IL-1RN A2*A2 homozygous revealed to be associated with an increased risk of HSIL + ICC (OR = 1.90; 95 % IC 1.13-3.21; p = 0.015). Furthermore, we also observed that median age of onset of HSIL + ICC was significantly different (46.0 vs 52.0) in IL-1RN A2*A2 homozygous comparing to non-A2*A2 (p = 0.028). Our results indicated that IL-1RN A2 allele is associated with an increased susceptibility to cervical cancer development, probably by increasing predisposition to shorter immune responses. PMID:23053980
Sousa, Hugo; Santos, Alexandra M; Catarino, Raquel; Pinto, Daniela; Moutinho, José; Canedo, Paulo; Machado, José Carlos; Medeiros, Rui
Aims Impaired S-mephenytoin 4?-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population. Methods Study subjects were 142 healthy, unrelated Malaysians aged 18–29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5?-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. Results Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P ? 0.05). Conclusions Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.
Yang, Y S; Wong, L P; Lee, T C; Mustafa, A M; Mohamed, Z; Lang, Chim C
Genetic characterization of the Jeju horse (JH) was performed to construct a correct pedigree of the JH family. A total of 111 horses including 79 JH were genotyped using 20 microsatellite loci. The number of alleles varied from 5 to 11 (mean 7.45) in the JH. The observed heterozygosity and expected heterozygosity ranged from 0.293 to 0.891 and from 0.357 to 0.841, respectively. The polymorphic information contents (PIC) ranged from 0.335 to 0.816. AHT4, ASB2, ASB17, ASB23, CA425, HMS2, HMS3, HTG10, LEX3 and VHL20 loci had relatively high PIC values (> 0.7). The total exclusion probability (PE) of the 20 microsatellite loci was 0.9999 in the JH. These results provide basic information for developing an accurate pedigree and will be useful in making decisions regarding conservation of the JH. PMID:18981670
Choi, Sung-Kyoon; Cho, Chang-Yeon; Yeon, Sung-Heum; Cho, Byung-Wook; Cho, Gil-Jae
Genetic variation at 12 allozyme loci (10 of them being polymorphic ones) has been studied in the archive-clone plantation of 23 Pinus sylvestris plus-trees and their seed progeny in the south-east of Ukraine. More than a half of clones had 4-8 heterozygous loci, whereas their seed progeny was marked by a lower variation than maternal trees. Seed progeny was obtained at a high outcrossing rate (t(m) = 95%). The clone progeny was characterized by a high percentage of abnormal allele segregation in megagametophytes. There was also a high frequency of significant deviation in distribution of seed embryo genotypes from the theoretically expected one according to the Hardy-Weinberg law. PMID:20201411
Korshikov, I I; Demkovich, A E
Summary We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines - contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb.
We describe a genetic polymorphism of human neutral alpha-glucosidase C, detected in lymphoid cells by a combination of starch gel electrophoresis and isoelectric focusing. The seven phenotypes observed appear to result from the expression of four different alleles. The distribution of the observed phenotypes fits the expected distribution predicted from calculated gene frequencies in Hardy-Weinberg equilibrium. Family studies are consistent with autosomal inheritance of the gene. The product of one of the alleles is unusual in that it is "silent," with an estimated gene frequency of .174 in an outbred white population. Approximately one-third of the population is heterozygous "null." Homozygosity for the allele has not been associated with any obvious disease state. This is the third example of a "null" allele which has a substantial gene frequency in an outbred population but does not appear to result in disease in the homozygous state. Images Fig. 1 Fig. 2
Martiniuk, F; Hirschhorn, R
It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results. PMID:21660264
Nunobiki, Osamu; Ueda, Masatsugu; Toji, Eisaku; Yamamoto, Michiko; Akashi, Kyoko; Sato, Naomi; Izuma, Shinji; Torii, Kiyo; Tanaka, Ichiro; Okamoto, Yoshiaki; Noda, Sadamu
It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.
Nunobiki, Osamu; Ueda, Masatsugu; Toji, Eisaku; Yamamoto, Michiko; Akashi, Kyoko; Sato, Naomi; Izuma, Shinji; Torii, Kiyo; Tanaka, Ichiro; Okamoto, Yoshiaki; Noda, Sadamu
We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines--contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb.
Wong, G K; Hillier, L; Brandstrom, M; Croojmans, R; Ovcharenko, I; Gordon, L; Stubbs, L; Lucas, S; Glavina, T; Kaiser, P; Gunnarsson, U; Webber, C; Overton, I
Most social Hymenoptera are characterized by simple haploid sex determination and environment-based caste differentiation. This appears to be strikingly different in the queen-polymorphic ant Vollenhovia emeryi. Almost all long- and short-winged queens from a population in Central Japan were homozygous at three microsatellite loci, whereas workers were mostly heterozygous, suggesting either a complex system of genetic caste determination or, more likely, the production of female sexuals from unfertilized eggs by thelytokous parthenogenesis and of workers from fertilized eggs. Furthermore, male genotypes were not compatible with those of the queens and had exclusively the paternal allele found in the sterile, heterozygous workers, probably because males are produced from fertilized eggs after the exclusion of maternal nuclear DNA as recently reported for Wasmannia auropunctata. The genus Vollenhovia might provide an interesting model system to trace the evolution of unusual caste and sex determination systems.
Ohkawara, Kyohsuke; Nakayama, Megumi; Satoh, Atsumi; Trindl, Andreas; Heinze, Jurgen
HarborTides.com is a neat, user-friendly facility for tide information for over 2,500 harbors in the US (and Bermuda). Users may browse by state or search by zip code for information on high and low tides, sunrise and sunset, and longitude and latitude for every harbor. After filling out a form for free membership, users can also print out monthly tide tables.
Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are known to play a role in DNA methylation, synthesis, and repair. The genetic mutations in MTHFR and TYMS genes may have influences on their respective enzyme activities. Data on the association studies of the MTHFR and TYMS genetic polymorphisms and risk of hepatocellular carcinoma (HCC) are sparse. MTHFR and TYMS genotypes were determined on 365 HCC cases and 457 healthy control subjects among Hispanic and non-Hispanic whites and African-Americans in Los Angeles County, California, and among Chinese in the city of Nanning, Guangxi, China. Relative to the high-activity genotype, each low-activity genotype of MTHFR was associated with a statistically nonsignificant 30% to 50% reduction in risk of HCC. Relative to the TYMS3?UTR +6/+6 genotype, individuals with 1 or 2 copies of the deletion allele had a statistically significant 50% reduction in risk of HCC. When we examined HCC risk by the total number of mutant alleles in the 3 polymorphic loci of MTHFR/TYMS (range, 0-4), there was a monotonic decrease in risk with increasing number of mutant alleles (P for trend = 0.003). Individuals possessing the maximum number of mutant alleles (i.e., 4) had an odds ratio of 0.46 (95% confidence interval = 0.23-0.93) for HCC compared with those with no or only 1 mutant allele. Conclusion This study supports the hypothesis that reduced MTHFR activity and enhanced TYMS activity, both of which are essential elements in minimizing uracil misincorporation into DNA, may protect against the development of HCC.
Yuan, Jian-Min; Lu, Shelly C.; Van Den Berg, David; Govindarajan, Sugantha; Zhang, Zhen-Quan; Mato, Jose M.; Yu, Mimi C.
We have studied genetic variation at 30–32 loci coding for enzymes in natural populations of five species of Drosophila. The average proportion of heterozygous loci per individual is 17.7 ± 0.4%. The average proportion of polymorphic loci per population is 69.2 ± 2.6% or 49.8 ± 2.2%, depending on what criterion of polymorphism is used. The following generalizations are advanced: (1) The amount of genetic polymorphism varies considerably from locus to locus. (2) At a given locus, populations of the same species are very similar in the amount and pattern of genetic variation. (3) However, at some loci large differences sometimes occur between local populations of the same species. (4) The amount of variation at a given locus is approximately the same in all five species. (5) When different species are compared, the pattern of the variation is either essentially identical or totally different at a majority of loci. We have tested the hypothesis that protein polymorphisms are selectively neutral by examining four predictions derived from the hypothesis. Our results are at variance with every one of the predictions. We have measured the amount of genetic differentiation, D, between taxa of various degrees of evolutionary divergence. The average value of D is 0.033 for local populations, 0.228 for subspecies, 0.226 for semispecies, 0.538 for sibling species, and 1.214 for morphologically distinguishable species. Our results indicate that a substantial degree of genetic differentiation (22.8 allelic substitutions for every 100 loci) occurs between allopatric populations that have diverged to the point where they might become different species if they were to become sympatric. However, very little additional genetic change is required for the development of complete reproductive isolation. After the speciation process is completed, species continue to diverge genetically from each other.
Ayala, Francisco J.; Tracey, Martin L.; Barr, Lorraine G.; McDonald, John F.; Perez-Salas, Santiago
We have asked here how the remarkable variation in maize haplotype structure affects recombination. We compared recombination across a genetic interval of 9S in 2 highly dissimilar heterozygotes that shared 1 parent. The genetic interval in the common haplotype is ?100 kb long and contains 6 genes interspersed with gene-fragment-bearing Helitrons and retrotransposons that, together, comprise 70% of its length. In one heterozygote, most intergenic insertions are homozygous, although polymorphic, enabling us to determine whether any recombination junctions fall within them. In the other, most intergenic insertions are hemizygous and, thus, incapable of homologous recombination. Our analysis of the frequency and distribution of recombination in the interval revealed that: (i) Most junctions were circumscribed to the gene space, where they showed a highly nonuniform distribution. In both heterozygotes, more than half of the junctions fell in the stc1 gene, making it a clear recombination hotspot in the region. However, the genetic size of stc1 was 2-fold lower when flanked by a hemizygous 25-kb retrotransposon cluster. (ii) No junctions fell in the hypro1 gene in either heterozygote, making it a genic recombination coldspot. (iii) No recombination occurred within the gene fragments borne on Helitrons nor within retrotransposons, so neither insertion class contributes to the interval's genetic length. (iv) Unexpectedly, several junctions fell in an intergenic region not shared by all 3 haplotypes. (v) In general, the ability of a sequence to recombine correlated inversely with its methylation status. Our results show that haplotypic structural variability strongly affects the frequency and distribution of recombination events in maize.
He, Limei; Dooner, Hugo K.
Polyporus umbellatus (Pers.) Fries is an endangered medicinal fungus in China with in vivo anticancer activity, but its genetic information is lacking. Eight natural P. umbellatus strains collected from 7 provinces in China were subjected to sequence-related amplified polymorphism markers to estimate the level and pattern of genetic diversity. Forty-nine primer combinations generated 1219 highly reproducible and discernible loci, among which 1023 were polymorphic. The percentage of polymorphism varied from 35.71 to 96.30 with an average of 83.92. Genetic identity among all strains ranged from 0.15 to 0.78 with an average of 0.46. The unweighted pair group method with arithmetic mean dendrogram clustered 8 strains into 3 clusters, and the clustering pattern showed 3 groups. Principal coordinate analysis further indicated that the genetic diversity of P. umbellatus strains was unevenly distributed and instead displayed a clustered distribution pattern. A relatively high level of genetic diversity was maintained in 8 natural P. umbellatus strains, but its abundance might be subjected to environmental heterogeneity, and the population structure of co-evolved Armillaria species may be selected by nature under the specific microenvironment. PMID:23315801
Zhang, Y; Kang, Y; Qin, Y; Zhou, Z; Lei, M; Guo, H
We have initiated research to determine the genetic basis of a male wing polymorphism in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae). Previous studies showed that this polymorphism is controlled by a single biallelic locus, which we name aphicarus (api), on the X chromosome. Our objectives were to confirm that api segregates as a polymorphism of a single gene on the X chromosome, and to obtain molecular markers flanking api that can be used as a starting point for high-resolution genetic and physical mapping of the target region, which will ultimately allow the cloning of api. We have established an F2 population segregating for api and have generated X-linked AFLP markers. The segregation pattern of api in the F2 population shows that the male wing polymorphism segregates as a polymorphism of a single gene, or set of closely linked genes on the X chromosome. Using a subset of 78 F2 males, we have constructed a linkage map of the chromosomal region encompassing api using seven AFLP markers. The map spans 74.1 cM and we have mapped api to an interval of 10 cM. In addition, we confirmed X linkage of our AFLP markers and api by using one X-linked marker developed in an earlier study. Our study presents the first mapping of a gene with known function in aphids, and the results indicate that target gene mapping in aphids is feasible. PMID:15674387
Braendle, C; Caillaud, M C; Stern, D L
Background Merozoite surface protein-1 (MSP-1) and MSP-2 of Plasmodium falciparum are potential vaccine candidate antigens for malaria vaccine development. However, extensive genetic polymorphism of the antigens in field isolates of P. falciparum represents a major obstacle for the development of an effective vaccine. In this study, genetic polymorphism of MSP-1 and MSP-2 among P. falciparum field isolates from Myanmar was analysed. Methods A total of 63 P. falciparum infected blood samples, which were collected from patients attending a regional hospital in Mandalay Division, Myanmar, were used in this study. The regions flanking the highly polymorphic characters, block 2 for MSP-1 and block 3 for MSP-2, were genotyped by allele-specific nested-PCR to analyse the population diversity of the parasite. Sequence analysis of the polymorphic regions of MSP-1 and MSP-2 was also conducted to identify allelic diversity in the parasite population. Results Diverse allelic polymorphism of MSP-1 and MSP-2 was identified in P. falciparum isolates from Myanmar and most of the infections were determined to be mixed infections. Sequence analysis of MSP-1 block 2 revealed that 14 different alleles for MSP-1 (5 for K1 type and 9 for MAD20 type) were identified. For MSP-2 block 3, a total of 22 alleles (7 for FC27 type and 15 for 3D7 type) were identified. Conclusion Extensive genetic polymorphism with diverse allele types was identified in MSP-1 and MSP-2 in P. falciparum field isolates from Myanmar. A high level of mixed infections was also observed, as was a high degree of multiplicity of infection.
The anti-platelet agent clopidogrel bisulfate (sold under the trade name Plavix in the United States) is a widely prescribed medication for the prevention of blood clots in patients with acute coronary syndrome, in those who have suffered other cardiovascular disease-related events such as ischemic stroke, and in patients who are undergoing percutaneous coronary intervention. Response to clopidogrel varies substantially due to genetic and acquired factors. Patients who experience recurrent cardiovascular ischemic or thrombotic events while taking clopidogrel are typically described as non-responsive or resistant. The drug's oxidation is mainly dependent on the cytochrome P450 enzyme 2C19 (CYP2C19). Patients with certain genetic variants in CYP2C19 have been found to have lower levels of the active metabolite, less platelet inhibition, and greater risk of major adverse cardiovascular events such as heart attack, stroke, and death. Testing for CYP2C19 polymorphisms may identify patients who will not respond adequately to the standard clopidogrel regimen and who should, consequently, be given an alternate treatment strategy. This article outlines the evidence concerning pharmacogenetic testing for clopidogrel response, including data on clinical validity and clinical utility, and summarizes the currently available tests marketed for this purpose.
Ned, Renee M.
Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes, embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymorphism array analyses of 55 RMS samples including eight RMS-derived cell lines. The ERMS subtype was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of ARMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was detected in 45.5% of ARMS that had been unrecognized in RMS to date. Novel amplifications were also detected, including IRS2 locus in two fusion-positive tumors, and KRAS or NRAS loci in three ERMS cases. Of note, gain of 13q was significantly associated with good patient outcome in ERMS. We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort. These findings enhance our understanding of the genetic mechanisms underlying RMS pathogenesis and support further studies for therapeutic development of RMS. PMID:23578105
Nishimura, Riki; Takita, Junko; Sato-Otsubo, Aiko; Kato, Motohiro; Koh, Katsuyoshi; Hanada, Ryoji; Tanaka, Yukichi; Kato, Keisuke; Maeda, Daichi; Fukayama, Masashi; Sanada, Masashi; Hayashi, Yasuhide; Ogawa, Seishi
Applying a combined technology for the detection of allotypic variation of the fourth component of human complement (C4), including immunofixation with anti-C4 and C4-dependent lysis after agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of C4 to separate the C4A and B alpha-chains, and the determination of Rodgers (Rg) and Chido (Ch) determinants of C4 in serum and at the blotted C4 alpha-chains, we detected rare human C4 allotypes and studied the genetic linkage. Partial inhibitors (p.i.) of anti-Rg and anti-Ch sera were found; the C4A51 allotype characterized as Rg p.i. and the C4A1 and C4B51 allotypes as Ch p.i. were genetically inherited. The C4A1 allotype has a unique Rg- Ch+ C4A alpha-chain. Duplicated C4A loci, A*3, A*2, and A*5, A*2 were both associated with a C4BQO and the HLA haplotype A3-Cw4-Bw35-DR1. These additions to the already known extensive C4 polymorphism may help to sort out their significance for the biological functions of human C4. PMID:6201442
Rittner, C; Giles, C M; Roos, M H; Démant, P; Mollenhauer, E
Molecular genetic studies were carried out on three isolates of Trichinella nelsoni (from Kenya, Tanzania and South Africa) and three isolates of Trichinella T8 (from South Africa and Namibia) from sylvatic carnivores and from a sylvatic swine. A probe (pT7.3) specific for T. nelsoni was obtained by screening a pUC18 genomic library. The pT7.3 sequence was 346 bp in length with an AT content of 70%. The sequence is present approximately 200 times per haploid genome. Southern blot analysis of Hind III digested DNAs of the three isolates of T. nelsoni revealed that the hybridisation patterns of the isolates from Kenya and Tanzania were identical and that they differed from that of the isolate from South Africa, indicating the presence of polymorphism in this species. A pUC18 genomic library of Trichinella T8 was also screened, and one clone (pT8.3) was found to be specific for homologous DNA by dot blot, but Southern blot analysis of DNA samples from eight genotypes showed different hybridisation signals for both Trichinella T8 and Trichinella britovi DNAs. No differences in the nucleotide sequences of the expansion segment V were observed for the T. nelsoni isolates. However, they differed from those of Trichinella T8. The presence of Trichinella T8 in Africa south of the Sahara and its genetic relationship with T. britovi remain unclear and warrant detailed investigations. PMID:10779583
La Rosa, G; Pozio, E
Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD. To date, one study has evaluated the association between a single CETP SNP and AD. In this study, we examined three CETP SNPs to evaluate the genetic association of CETP with late onset AD on two study cohorts: the Religious Orders Study (ROS) series, including 85 AD and 70 non-AD individuals, and the University of Kentucky (UKY) series, including 78 AD and 84 non-AD individuals. Significant association between CETP genotypes or haplotypes and late onset AD was not detected in these two study cohorts. Moreover, the CETP genotypes and haplotypes were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E4 (apoE4). In summary, CETP genetic variants were not associated with AD in two series. PMID:15882786
Zhu, Haiyan; Gopalraj, Rangaraj K; Kelly, Jeremiah F; Bennett, David A; Estus, Steven
Chemokines represent central players of the innate and adaptive immunity and are involved in the regulation of inflammatory events occurring during infectious complications or during graft vs. host disease (GvHD). Patients after allogeneic stem cell transplantation (alloSCT) are at a high risk for the development of acute GvHD or to suffer from fungal infections. Susceptibility to fungal infections and the course of GvHD can be genetically influenced by single nucleotide polymorphisms (SNPs), which regulate expression or biological activity of chemokines, and therefore have an impact on the outcome of invasive aspergillosis and GvHD. High lightened studies of abetting factors for GvHD revealed SNPs in TNFA, IL-6, IL-10, INF-?, CCL2, CCL5 (RANTES), IL-1Ra, IL-23R, IL-7Ralpha, IL-10RB, and CCR9 genes as prevalent considerable. Furthermore, additional SNPs were described to be significantly associated with fungal infections (Aspergillus fumigatus, Candida albicans), including markers in CCL3, CCL4, CCL20, CXCL2, CXCL8, CXCL10, CCR1, and CCR2. This review summarizes the current knowledge about the growing number of genetic markers in chemokine genes and their relevance for patients after alloSCT. PMID:20397074
Loeffler, Juergen; Ok, Michael; Morton, Oliver C; Mezger, Markus; Einsele, Hermann
Recent evidences suggest that common functional polymorphisms in the promoter region of the Calpain-10 gene may have an impact on an individual's susceptibility to polycystic ovary syndrome (PCOS), but individually published results are inconclusive. Our meta-analysis is aimed to provide a more precise estimation of the relationships between Calpain-10 genetic polymorphisms and PCOS risk. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from inception through April 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio (OR) with 95% confidence interval (CI) was calculated. Fourteen case-control studies were included with a total of 2123 PCOS patients and 3612 healthy controls. Nine common SNPs in the Calpain-10 gene were addressed. Our meta-analysis indicated that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene might be associated with increased PCOS risk. However, no statistically significant association was observed in UCSNP-43, UCSNP-22, UCSNP-43, UCSNP-45, UCSNP-56, UCSNP-58, and UCSNP-110 polymorphisms. Further subgroup analysis by ethnicity revealed that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms might decrease the risk of PCOS among Asian populations, but not among Caucasian populations. The current meta-analysis indicates that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene may be risk factors for PCOS, especially among Asian populations. PMID:23994294
Shen, Wenjing; Li, Tianren; Hu, Yanjie; Liu, Hongbo; Song, Min
This United States Geological Survey (USGS) site is designed to summarize and make available results of scientific research conducted in Boston Harbor, Massachusetts since 1985. A computer image of the harbor indicates ecosystem zones with descriptions (watershed, estuary, inner shelf, and basin), sewage outfall sites, and rock types. Links are provided for more information on this region.
Little is known about the genetic foundations of colony social organization. One rare example in which a single major gene is implicated in the expression of alternative social organizations involves the presumed odorant-binding protein gene Gp-9 in fire ants. Specific amino acid substitutions in this gene invariably are associated with the expression of monogyny (single queen per colony) or polygyny (multiple queens per colony) in fire ant species of the Solenopsis richteri clade. These substitutions are hypothesized to alter the abilities of workers to recognize queens and thereby regulate their numbers in a colony. We examined whether these same substitutions underlie the monogyny/polygyny social polymorphism in the distantly related fire ant S. geminata. We found that Gp-9 coding region sequences are identical in the polygyne and monogyne forms of this species, disproving our hypothesis that one or a few specific amino acid replacements in the protein are necessary to induce transitions in social organization in fire ants. On the other hand, polygyne S. geminata differs genetically from the monogyne form in ways not mirrored in the two forms of S. invicta, a well-studied member of the S. richteri clade, supporting the conclusion that polygyny did not evolve via analogous routes in the two lineages. Specifically, polygyne S. geminata has lower genetic diversity and different gene frequencies than the monogyne form, suggesting that the polygyne form originated via a founder event from a local monogyne population. These comparative data suggest an alternative route to polygyny in S. geminata in which loss of allelic variation at genes encoding recognition cues has led to a breakdown in discrimination abilities and the consequent acceptance of multiple queens in colonies.
Ross, Kenneth G; Krieger, Michael J B; Shoemaker, D DeWayne
This study estimated the population pharmacokinetics of risperidone and its active metabolite, 9-hydroxyrisperidone, according to genetic polymorphisms in the metabolizing enzyme (CYP2D6) and transporter (ABCB1) genes in healthy subjects. Eighty healthy subjects who received a single oral dose of 2 mg risperidone participated in this study. However, eight subjects with rare genotype variants in CYP2D6 alleles were excluded from the final model built in this study. We conducted the population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2D6 alleles and ABCB1 (2677G>T/A and 3435C>T) on the population pharmacokinetics of risperidone and 9-hydroxyrisperidone. A two-compartment model with a first-order absorption and lag time fitted well to serum concentration-time curve for risperidone. 9-hydroxyrisperidone was well described by a one-compartment model as an extension of the parent drug (risperidone) model with first-order elimination and absorption partially from the depot. Significant covariates for risperidone clearance were genetic polymorphisms of CYP2D6*10, including CYP2D6*1/*10 (27.5 % decrease) and CYP2D6*10/*10 (63.8 % decrease). There was significant difference in the absorption rate constant (k ( a )) of risperidone among the CYP2D6*10 genotype groups. In addition, combined ABCB1 3435C>T and CYP2D6*10 genotypes had a significant (P < 0.01) effect on the fraction of metabolite absorbed from the depot. The population pharmacokinetic model of risperidone and 9-hydroxyrisperidone including the genetic polymorphisms of CYP2D6*10 and ABCB1 3435C>T as covariates was successfully constructed. The estimated contribution of genetic polymorphisms in CYP2D6*10 and ABCB1 3435C>T to population pharmacokinetics of risperidone and 9-hydroxyrisperidone suggests the interplay of CYP2D6 and ABCB1 on the pharmacokinetics of risperidone and 9-hydroxyrisperidone according to genetic polymorphisms. PMID:22623266
Yoo, Hee-Doo; Cho, Hea-Young; Lee, Sang-No; Yoon, Hwa; Lee, Yong-Bok
Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ? 1.1?kg/m(2)) and MC4R variants (effect size ? 0.64?kg/m(2)). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes. PMID:19822564
Cha, Seongwon; Koo, Imhoi; Park, Byung L; Jeong, Sangkyun; Choi, Sun M; Kim, Kil S; Shin, Hyoung D; Kim, Jong Y
Immigration has been the principal source of population growth in Australia since European settlement began in 1788. As a result, the Australian gene pool has been constantly evolving, particularly over the last 50 years, during which peoples from many European and Asian countries have arrived in large numbers. Three highly polymorphic DNA loci (D1S80, HLA-DQA1, and human THO1) are used to assess the level of diversity among six immigrant subpopulations that compose significant elements in present-day Australia, namely, Asians, Italians, Greeks, Slavs, Middle Easterners, and a "general white" sample. Asian migrants are the most distinctive of the groups at all three loci, possessing the highest frequencies of alleles HLA-DQA1*3 and D1S80*27, *28, and *30, and an exceptionally high frequency of THO1*9. The European-derived groups cluster together separately from Asians, but Greeks are characterized by their frequencies of HLA-DQA1*2 and *4 and THO1*8. Middle Easterners lie on the fringe of the European cluster. When the results of the present study are combined with worldwide data for each of the three DNA markers, these hypervariable loci, especially D1S80 and THO1, are able to differentiate the major groups of humans. The level of population differentiation revealed by RST values for the three DNA markers is similar to or even less than the values recorded for the less polymorphic classical genetic markers. Therefore these three DNA markers are highly suitable for both forensic purposes and the investigation of population relationships. PMID:8754256
Robinson, S L; Gutowski, S J; van Oorschot, R A; Fripp, Y; Mitchell, J
Trial-and-error method has been used extensively in the breeding of Discus. There is limited knowledge on the genetic structure of its species complex and also the genetic basis of its stock constitution and management. Random Amplified Polymorphic DNA (RAPD) fingerprinting was used to assess the genetic diversity among four wild forms of Discus: Symphysodon discus (Heckel), S. aequiefasciata aequiefasciata (Wild
Tieh Ling Koh; Gideon Khoo; Li Qun Fan; Violet Pan Eng Phang
BackgroundThe association of vitamin D receptor (VDR) gene polymorphisms to the lumbar degenerative disc disease has been previously studied; however, the role of VDR gene polymorphisms in cervical spondylosis remains unknown.
Zhan Chao Wang; Xiong Sheng Chen; Da Wei Wang; Jian Gang Shi; Lian Shun Jia; Guang Hui Xu; Jian Hou Huang; Lei Fan
Understanding the genetics of a polymorphic trait is important to predict its likely evolution. In Collinsia heterophylla, the upper petal lip colour can be either be white or white with a purple band, while the lower petal lip colour is invariably purple. Because the corolla is only partly polymorphic, the polymorphism can not have evolved due to a mutation where a pigment was lost in the entire plant, which is common in other polymorphic species. In a previous study, high frequency of the purple band was found in populations with darker flowers, indicating possible selection for this trait. In this study, I determined inheritance of the colour polymorphism using two populations (one with only white morph and other with both morphs). I conducted experimental crosses within and between floral morphs to determine whether patterns of segregation in offspring conform to single-gene predictions. Data from F1, F2, F3 and backcross progeny are consistent with a genetic model of one major locus with presence of the band being completely dominant, as indicated in earlier studies using distantly related populations. A novel finding in this study was that the two morphs did not show a difference in seed germination frequency or seedling survival. This trait can thus be valuable as a genetic marker. Even though more thorough ecological data are needed to understand the potential selection pressures on upper petal lip colour in C. heterophylla, its simple inheritance may indicate the possibility of fast evolutionary response to selective forces acting on this trait. PMID:19700859
Microsatellites were evaluated as genetic markers for the mitochondrial genome (mtDNA) of Phytophthora cinnamomi for population studies. Two (A)n microsatellite loci were cloned from the mtDNA of P. cinnamomi. Amplification products from these loci showed little polymorphism among Phytophthora isolates due to their location in coding regions of mtDNA. A further three (A)n microsatellite loci obtained from the complete mtDNA sequence of P. infestans were also not highly polymorphic, although located in non-coding mtDNA. The presence of the (A)n microsatellites was not conserved in the genus Phytophthora. Unlike those of the chloroplast genome of plants, (A)n microsatellite loci of mtDNA do not have potential as highly polymorphic markers in Phytophthora. PMID:9673029
Dobrowolski, M P; Tommerup, I C; O'Brien, P A
The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion\\/deletion (I\\/D) polymorphism
Nozomi Kato; Yuji Tatara; Mitsuru Ohishi; Yasushi Takeya; Miyuki Onishi; Yoshihiro Maekawa; Hiromi Rakugi
The Buck Harbor study has investigated the history and existing conditions at Bucks Harbor, located at Machiasport, Maine. The study has addressed and evaluated several options for the future development of Bucks Harbor. One of the key factors recognized ...
Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1? (IL-1?), IL-6 (IL-6), and tumor necrosis factor-? (TNF-?) 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-1? C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-? 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. PMID:21660081
Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong
Obesity and insulin resistance is a common finding in patients with polycystic ovary syndrome (PCOS). Significant number of PCOS women experience insulin resistance that is irrespective of the degree of obesity suggesting possible genetic basis. Therefore, several polymorphisms of the genes encoding for the insulin (INS), insulin receptor (INSR) or insulin receptor substrates (IRS) involved in postreceptor signaling have been explored for their association with abnormal sensitivity to insulin in PCOS. The aim of the present study was to determine whether selected polymorphisms of INS, INSR and IRS-1 are associated with the development of PCOS as well as with increased insulin resistance in Croatian women with PCOS. The study enrolled 150 women with PCOS and 175 control women. The diagnosis of PCOS was based on Rotterdam consensus criteria. Each subject underwent an evaluation of body mass index (BMI), hirsutism, acne and menstrual cycle abnormalities as well as follicular stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, androstendione, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), fasting glucose and fasting insulin. Insulin resistance (IR) was quantified using the homeostatic model assessment of IR (HOMA-IR). Molecular analyses for the genetic polymorphisms were preformed. There was a significant difference in clinical and biochemical characteristics of the studied groups except for BMI and fasting glucose levels. No significant differences were observed in the genotype and allele distribution of the VNTR INS, C/T INSR, Gly792Arg IRS-1 polymorphisms between cases and controls. Moreover, no association was found between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and parameters of insulin resistance in PCOS patients. In conclusion, our data does not support an association between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and susceptibility to PCOS or insulin resistance in Croatian women with PCOS. PMID:23697264
Skrgati?, Lana; Baldani, Dinka Pavici?; Gersak, Ksenija; Cerne, Jasmina Ziva; Ferk, Polonca; Cori?, Mario
Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca(2+)/H(+)-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na(+) channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K(+) channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors. PMID:24068186
Fedele, Francesco; Mancone, Massimo; Chilian, William M; Severino, Paolo; Canali, Emanuele; Logan, Suzanna; De Marchis, Maria Laura; Volterrani, Maurizio; Palmirotta, Raffaele; Guadagni, Fiorella
Two new genetic polymorphisms (Pe and Po) are found in human parotid saliva. Each polymorphism is determined by the autosomal inheritance of one expressed (dominant) and one unexpressed (recessive) allele. Autosomal inheritance is supported by studies of 63 families including 264 children for Pe and 57 families including 242 children for Po. For randomly collected salivas, gene frequencies in 317
Edwin A. Azen; Pao-Lo Yu
The uncoupling protein (UCP) family has been suggested as a possible determinant affecting obesity risk given their function in the regulation of energy metabolism. In an effort to elucidate the effects of UCP family polymorphisms on obesity phenotypes, we genotyped 10 polymorphisms in UCP2 and UCP3 among overweight female subjects (n=458), and genetic effects on BMI and changes after a
Yoosik Yoon; Byung Lae Park; Min Ho Cha; Kil Soo Kim; Hyun Sub Cheong; Yoo Hyun Choi; Hyoung Doo Shin
A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-? plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-? gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting. PMID:22819972
Lahey, Benjamin B; Michalska, Kalina J; Liu, Chunyu; Chen, Qi; Hipwell, Alison E; Chronis-Tuscano, Andrea; Waldman, Irwin D; Decety, Jean
A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-? plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-? gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting.
Lahey, Benjamin B.; Michalska, Kalina J.; Liu, Chunyu; Chen, Qi; Hipwell, Alison E.; Waldman, Irwin D.; Decety, Jean
Background and aims—The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer disease, the association between the restriction fragment length polymorphism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease was investigated. ?Patients and methods—One hundred and seventy seven unrelated controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reaction (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC polymorphism with peptic ulcer and Helicobacter pylori infection was also examined. ?Results—Four alleles, 480 (allele 1), 450 (allele 2), 400 (allele 3), and 310 bp (allele 4), were detected by PCR. The frequency of allele 4 was significantly higher in patients with gastric body ulcer than in controls (?2=9.92, p<0.005). Genotypes containing allele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ulcer. The relative risk of gastric body ulcer associated with the presence of allele 4, compared with its absence, was 4.63 and was statistically significant (?2=14.84, p<0.005). There were no significant differences in the allelic frequencies between H pylori positive and H pylori negative groups in controls, patients with gastric body ulcer, or patients with gastric angular or antral ulcer. Both in H pylori negative and H pylori positive cases, there was an increased frequency of allele 4 in patients with gastric body ulcer compared with controls. ?Conclusions—These results suggest that there is a significant association between this genetic polymorphism at the PGC gene locus and gastric body ulcer. There are differences in the genetic aetiology between gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric body ulcer; this genetic predisposition is not associated with H pylori infection. ?? Keywords: pepsinogen C; gastric ulcer; genetic heterogeneity; restriction fragment length polymorphism; Helicobacter pylori
Ohtaki, Y; Azuma, T; Konishi, J; Ito, S; Kuriyama, M
BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.
Furuya, K.; Yamaguchi, E.; Itoh, A.; Hizawa, N.; Ohnuma, N.; Kojima, J.; Kodama, N.; Kawakami, Y.
Cow milk allergy is the most frequent allergy in the first years of life. Milk from other mammalian species has been suggested as a possible nutritional alternative to cow milk, but in several cases, the clinical studies showed a high risk of cross-reactivity with cow milk. In the goat species, ?S?-casein (?S?-CN), coded by the CSN1S1 gene, is characterized by extensive qualitative and quantitative polymorphisms. Some alleles are associated with null (i.e., CSN1S1 0(1)) or reduced (i.e., CSN1S1 F) expression of the specific protein. The aim of this work was to obtain new information on goat milk and to evaluate its suitability for allergic subjects, depending on the genetic variation at ?s?-CN. Individual milk samples from 25 goats with different CSN1S1 genotypes were analyzed by sodium dodecyl sulfate PAGE and immunoblotting, using monoclonal antibodies specific for bovine ?-CN and sera from children allergic to cow milk. A lower reaction was observed to 2 goat milk samples characterized by the CSN1S1 0(1)0(1) and 0(1)F genotypes. Moreover, a fresh food skin prick test, carried out on 6 allergic children, showed the lack of positive reaction to the 0(1)0(1) milk sample and only one weak reactivity to the 0(1)F sample. The risk of cross-reactivity between cow and goat milk proteins suggests the need for caution before using goat milk for infant formulas. However, we hypothesize that it can be used successfully in the preparation of modified formulas for selected groups of allergic patients. The importance of taking the individual goat CN genetic variation into account in further experimental studies is evident from the results of the present work. PMID:21257068
Ballabio, C; Chessa, S; Rignanese, D; Gigliotti, C; Pagnacco, G; Terracciano, L; Fiocchi, A; Restani, P; Caroli, A M
The relationship between alternans and arrhythmogenicity was studied in genetically modified murine hearts modeling catecholaminergic polymorphic ventricular tachycardia (CPVT) during Langendorff perfusion, before and after treatment with catecholamines and a ?-adrenergic antagonist. Heterozygous (RyR2p/s) and homozygous (RyR2s/s) RyR2-P2328S hearts, and wild-type (WT) controls, were studied before and after treatment with epinephrine (100?nM and 1 ?M) and propranolol (100?nM). Monophasic action potential recordings demonstrated significantly greater incidences of arrhythmia in RyR2p/s and RyR2s/s hearts as compared to WTs. Arrhythmogenicity in RyR2s/s hearts was associated with alternans, particularly at short baseline cycle lengths. Both phenomena were significantly accentuated by treatment with epinephrine and significantly diminished by treatment with propranolol, in full agreement with clinical expectations. These changes took place, however, despite an absence of changes in mean action potential durations, ventricular effective refractory periods or restitution curve characteristics. Furthermore pooled data from all hearts in which arrhythmia occurred demonstrated significantly greater alternans magnitudes, but similar restitution curve slopes, to hearts that did not demonstrate arrhythmia. These findings thus further validate the RyR2-P2328S murine heart as a model for human CPVT, confirming an alternans phenotype in common with murine genetic models of the Brugada syndrome and the congenital long-QT syndrome type 3. In contrast to these latter similarities, however, this report demonstrates the dissociation of alternans from changes in the properties of restitution curves for the first time in a murine model of a human arrhythmic syndrome.
Sabir, Ian N.; Ma, Nan; Jones, Victoria J.; Goddard, Catharine A.; Zhang, Yanmin; Kalin, Asli; Grace, Andrew A.; Huang, Christopher L.-H.
Using to analysis of hypervariable fragment polymorphism in the control region of mitochondrial DNA(268 bp), the genetic variability\\u000a of Swan goose Anser cygnoides L., included in the first category of endangered species in the Russian Red Book, has been investigated. Samples from the\\u000a two main groups nesting in Russia—the Far Eastern group (Khabarovsk krai, n = 38) and the Dauric
N. D. Poyarkov; A. V. Klenova; M. V. Kholodova
Aim:The inflammatory marker C-reactive protein (CRP) has been strongly correlated with the risk of cardiovascular disease. Some single-nucleotide polymorphisms (SNPs) have been reported to be associated with serum CRP levels. In this study, we assessed the genetic association between SNPs within the CRP gene and ischemic and hemorrhagic stroke in the Han Chinese population.Methods:This study comprises 564 ischemic stroke patients,
Qi Wang; Hu Ding; Jia-rong Tang; Lan Zhang; Yu-jun Xu; Jiang-tao Yan; Wei Wang; Ru-tai Hui; Cong-yi Wang; Dao-wen Wang
AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H pylori) infection occurs in humans. iNOS Ser608Leu allele, a novel genetic polymorphism (C\\/T) occurring within exon 16 of the iNOS reductase domain, may have a dramatic effect on the enzymatic activity. The aim of this study
Jing Shen; Run-Tian Wang; Li-Wei Wang; Yao-Chu Xu; Xin-Ru Wang
The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1
Manzoor Ahmad Malik; Rohit Upadhyay; Rama Devi Mittal; Showket Ali Zargar; Balraj Mittal
Objective: Our objective was to determine the influence of cytochrome P450 (CYP) 2C9 and CYP2C19 genetic polymorphisms on warfarin dose requirement and metabolic clearance.Methods: The study population consisted of 93 Italian outpatients receiving long-term warfarin anticoagulant therapy (international normalized ratio values, 2-3), divided into 3 dose groups: low (43.75 mg\\/wk; n = 24). Steady-state unbound plasma concentrations of S- and
Maria Gabriella Scordo; Vittorio Pengo; Edoardo Spina; Marja Liisa Dahl; Milena Gusella; Roberto Padrini
The objective of this study was to investigate the influence of genetic polymorphisms in the CYP3A and CYP2C19 genes on cilostazol pharmacokinetics, with the drug being administered orally as a 50-mg single dose in healthy subjects. CYP2C19 genotypes in individuals with the CYP3A5*3\\/*3 genotype were associated with statistically significant differences (P < 0.05) in cilostazol pharmacokinetics parameters (apparent oral clearance
H-D Yoo; S-A Park; H-Y Cho; Y-B Lee
Intraspecific genetic polymorphism of a Baikal Lake endemic, little Baikal oilfish (Comephorus dybowski Korotneff, 1905), was evaluated based on microsatellite analysis. Six microsatellite loci designed for the European sculpin, Cottus gobio, were used. Each locus was typed using 25 to 35 individuals from each of the Baikal trenches (southern, middle, and northern). Analysis of genetic differentiation (F(ST) and R(ST)) revealed no statistical significant differences between the samples. The data showed that the target species was represented by a single panmictic stable population. PMID:16152796
Teterina, V I; Sukhanova, L V; Bogdanov, B E; Anoshko, P N; Kirilchik, S V
Molecular analysis encouraged discovery of genetic diversity and relationships of cultivated melon (Cucumis melo L.). We sequenced nine inter- and intra-genic regions of the chloroplast genome, about 5500 bp, using 60 melon accessions and six reference accessions of wild species of Cucumis to show intra-specific variation of the chloroplast genome. Sequence polymorphisms were detected among melon accessions and other Cucumis species, indicating intra-specific diversification of the chloroplast genome. Melon accessions were classified into three subclusters by cytoplasm type and then into 12 subgroups. Geographical origin and seed size also differed between the three subclusters. Subcluster Ia contained small-seed melon from Southern Africa and South and East Asia and subcluster Ib mainly consisted of large-seed melon from northern Africa, Europe and USA. Melon accessions of subcluster Ic were only found in West, Central and Southern Africa. Our results indicated that European melon groups and Asian melon groups diversified independently and shared the same maternal lineage with northern African large-seed melon and Southern African small-seed melon, respectively. Cultivated melon of subcluster Ic may have been domesticated independently in Africa. The presence of 11 cytoplasm types in Africa strongly supported African origin of cultivated melon and indicated the importance of germplasm from Africa.
Tanaka, Katsunori; Akashi, Yukari; Fukunaga, Kenji; Yamamoto, Tatsuya; Aierken, Yasheng; Nishida, Hidetaka; Long, Chun Lin; Yoshino, Hiromichi; Sato, Yo-Ichiro; Kato, Kenji
Aim: To determine the concentration of total plasma homocysteine (tHcy) as well as different genotypes of methylenetetrahydrofolate reductase MTHFR (C677T) in healthy subjects and patients with deep vein thrombosis (DVT). Material and methods: The investigation comprised a total of 160 subjects divided in two main groups: 80 healthy subjects (control group) and 80 patients with deep vein thrombosis. Concentration of tHcy was determined by spectrophotometric cyclic enzymatic method and mutation of MTHFR (C677T) gene was examined by polymerase chain reaction according to Schneider. Results: The results obtained for plasma tHcy in the control group were 11.62±3.43 ?mol/L, while tHcy level was significantly higher in patients with deep vein thrombosis as compared to the control group, 15.19±3.63 ?mol/L (?<0.001). The analysis of the results has shown that MTHFR (C677T) genetic polymorphism was responsible for mild to moderate hyperhomocysteinemia in the majority of subjects. Conclusion: The level of tHcy in the examined patients was significantly higher in comparison with the control group. Multiple regression analysis has shown that tHcy level in CT and TT genotypes of MTHFR (C677T) was statistically higher in comparison with CC genotype of MTHFR (C677T) in both, the control group and the DVT patients.
Brezovska-Kavrakova, Julijana; Krstevska, Marija; Bosilkova, Gordana; Alabakovska, Sonja; Panov, Saso; Orovchanec, Nikola
Mycophenolic acid (MPA), converted from the prodrug mycophenolate mofetil (MMF), is generated by intestinal and hepatic esterases. The role of carboxylesterase (CES) in MMF hydrolysis was examined in vitro using human liver microsomes. V(max) and K(m) values of MMF hydrolysis in pooled human liver microsomes were 1368 +/- 44 nmol min(-1) mg(-1) protein and 1030 +/- 65 microM, respectively. Hydrolytic activity was inhibited by the CES inhibitors phenylmethylsulfonylfluoride, bis-p-nitorophenylphosphate and diisopropylfluorophosphate, with IC(50) values of 77.1, 3.59 and 0.0312 microM, respectively. Eighty Japanese renal transplant recipients that received repeated-doses of MMF, tacrolimus and prednisolone,were evaluated for MPA pharmacokinetics 28 days after transplantation to investigate the relationship between MPA pharmacokinetics and CES2 genetic polymorphisms. No significant differences in MPA pharmacokinetics were observed between CES2 A4595G, C8721T orA-1548G genotype groups. CES2 allelic variants also did not appear to affect plasma MPA concentrations between individuals. In conclusion, the study demonstrated that while CES1 and/or CES2 are involved in the hydrolysis of MMF to MPA, CES2 allelic variants appeared to make only a minor contribution to inter-personal differences in MPA pharmacokinetics. PMID:19274604
Fujiyama, N; Miura, M; Satoh, S; Inoue, K; Kagaya, H; Saito, M; Habuchi, T; Suzuki, T
Molecular analysis encouraged discovery of genetic diversity and relationships of cultivated melon (Cucumis melo L.). We sequenced nine inter- and intra-genic regions of the chloroplast genome, about 5500 bp, using 60 melon accessions and six reference accessions of wild species of Cucumis to show intra-specific variation of the chloroplast genome. Sequence polymorphisms were detected among melon accessions and other Cucumis species, indicating intra-specific diversification of the chloroplast genome. Melon accessions were classified into three subclusters by cytoplasm type and then into 12 subgroups. Geographical origin and seed size also differed between the three subclusters. Subcluster Ia contained small-seed melon from Southern Africa and South and East Asia and subcluster Ib mainly consisted of large-seed melon from northern Africa, Europe and USA. Melon accessions of subcluster Ic were only found in West, Central and Southern Africa. Our results indicated that European melon groups and Asian melon groups diversified independently and shared the same maternal lineage with northern African large-seed melon and Southern African small-seed melon, respectively. Cultivated melon of subcluster Ic may have been domesticated independently in Africa. The presence of 11 cytoplasm types in Africa strongly supported African origin of cultivated melon and indicated the importance of germplasm from Africa. PMID:23853513
Tanaka, Katsunori; Akashi, Yukari; Fukunaga, Kenji; Yamamoto, Tatsuya; Aierken, Yasheng; Nishida, Hidetaka; Long, Chun Lin; Yoshino, Hiromichi; Sato, Yo-Ichiro; Kato, Kenji
Frequencies of kappa-casein gene alleles were determined in 1316 animals from the Brazilian Bos indicus genetic groups (Sindhi cows, Gyr sires, Gyr cows, Guzerat sires, Guzerat cows, Nellore sires, and Gyr x Holstein crossbreds) by means of polymerase chain reaction-restriction fragment length polymorphism analysis using two independent restriction nucleases (Hinf I and HaeIII). The genotyping of kappa-casein alleles (A and B) is of practical importance, since the B allele is found to correlate with commercially valuable parameters of cheese yielding efficiency. The frequencies of the B allele of kappa-casein among breeds ranged from 0.01 to 0.30. The Sindhi breed had the highest frequency for the B allele (0.30), while the frequencies of this allele in other breeds ranged from 0.01 to 0.18. A wide variation in the B allele frequency among B. indicus breeds was found suggesting that molecular selection for animals carrying the B allele could impact breeding programs for dairy production. PMID:18752189
Azevedo, A L S; Nascimento, C S; Steinberg, R S; Carvalho, M R S; Peixoto, M G C D; Teodoro, R L; Verneque, R S; Guimarães, S E F; Machado, M A
The relatedness of several marine Synechococcus spp. was estimated by DNA hybridization. Strains isolated from various geographical locations and representing a diversity of DNA base compositions and phycobiliprotein profiles were compared by restriction fragment length polymorphisms for a number of genes. DNAs from two marine red algae and a cryptomonad alga (which exhibit a phycobiliprotein composition similar to that of the marine Synechococcus spp.) and Synechococcus strain PCC6301 (Anacystis nidulans) were also included in the comparison. Strains WH8008, WH8018, and WH7805 were shown to be very similar to one another, as were strains WH7802 and WH7803. Strains WH8110 and WH5701 were clearly unrelated to any of the other strains, and no marine Synechococcus isolate showed any similarity to the freshwater Synechococcus strain PCC6301 or the eucaryotic algae. The method is relatively straightforward and sensitive and uses a variety of basic molecular biology techniques. Its utility in ascertaining the genetic relatedness and diversity of marine Synechococcus spp. and possible extension to field studies are discussed. PMID:16347797
Douglas, S E; Carr, N
The genetic polymorphisms of Echinococcus spp. in the eastern Tibetan Plateau and the Xinjiang Uyghur Autonomous Region were evaluated by DNA sequencing analyses of genes for mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear elongation factor-1 alpha (ef1a). We collected 68 isolates of Echinococcus granulosus sensu stricto (s.s.) from Xinjiang and 113 isolates of E. granulosus s. s., 49 isolates of Echinococcus multilocularis and 34 isolates of Echinococcus shiquicus from the Tibetan Plateau. The results of molecular identification by mitochondrial and nuclear markers were identical, suggesting the infrequency of introgressive hybridization. A considerable intraspecific variation was detected in mitochondrial cox1 sequences. The parsimonious network of cox1 haplotypes showed star-like features in E. granulosus s. s. and E. multilocularis, but a divergent feature in E. shiquicus. The cox1 neutrality indexes computed by Tajima's D and Fu's Fs tests showed high negative values in E. granulosus s. s. and E. multilocularis, indicating significant deviations from neutrality. In contrast, the low positive values of both tests were obtained in E. shiquicus. These results suggest the following hypotheses: (i) recent founder effects arose in E. granulosus and E. multilocularis after introducing particular individuals into the endemic areas by anthropogenic movement or natural migration of host mammals, and (ii) the ancestor of E. shiquicus was segregated into the Tibetan Plateau by colonizing alpine mammals and its mitochondrial locus has evolved without bottleneck effects.
Nakao, Minoru; Li, Tiaoying; Han, Xiumin; Ma, Xiumin; Xiao, Ning; Qiu, Jiamin; Wang, Hu; Yanagida, Tetsuya; Mamuti, Wulamu; Wen, Hao; Moro, Pedro L.; Giraudoux, Patrick; Craig, Philip S.; Ito, Akira
Thrombophilic mutations increase the tendency toward thromboembolic disease. The aim of this study was to estimate the prevalence of the genetic variants related to thrombophilia among Saudis compared with other populations. Real-time polymerase chain reaction (PCR) genotyping was carried out to determine the polymorphic variants of factor V Leiden 1695G/A, prothrombin 20210G/A, plasmin activator inhibitor 1 4G/5G, methylene tetrahydrofolate reductase (MTHFR) 677C/T, MTHFR 1298A/C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) among a representative sample of healthy Saudi subjects. Carraige rate for each of the mutant variants of factor V Leiden (FVL) and FII genes constituted 2% of the surveyed subjects giving an allele frequency of 0.01, homozygous forms of plasminogen activator inhibitor-1 (PAI-1) gene 4G/4G, MTHFR 677TT, 1298CC, and ACE DD were present among 7.7, 2.55, 7, and 51.8% of subjects with a mutant allele frequency of 0.4, 0.19, 0.29, and 0.73, respectively. This study showed that the Saudi population has a peculiar pattern regarding thrombophilic mutations that might warrant additional considerations for prophylaxis. PMID:22664118
Settin, Ahmad A; Alghasham, Abdullah; Ali, Ahmad; Dowaidar, Moataz; Ismail, Hisham
Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions. PMID:23028912
Su, Guosheng; Christensen, Ole F; Ostersen, Tage; Henryon, Mark; Lund, Mogens S
Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions.
Su, Guosheng; Christensen, Ole F.; Ostersen, Tage; Henryon, Mark; Lund, Mogens S.
Background and purpose Corticosteroid treatment is associated with osteonecrosis of the femoral head (ON) in certain patients. The degree of drug sensitivity in general is governed by genetic variation between individuals. We investigated the relationship between ON and the presence of different alleles of the cytochrome P450 gene (CYP3A4), the product of which metabolizes corticosteroids, and of the P-glycoprotein (P-gp) gene (ABCB1), the product of which modulates cellular uptake of corticosteroids, to determine whether patients with certain alleles may be at higher risk of ON after corticosteroid treatment. Methods We studied 31 patients from Guangdong, China who were both treated with corticosteroid therapy and developed ON, and 17 corticosteroid-therapy patients without ON. Patient DNA was screened for known polymorphisms in the CYP3A4 gene (CYP3A4*4, CYP3A4*5, CYP3A4*6) and the P-gp gene ABCB1 (mutations C3435T, G2677T/A). Results The majority (20/31) of the corticosteroid-treated patients who developed ON were heterozygous for ABCB1, whereas only 3/17 without ON were heterozygous. Statistical significance was observed between the ON and the control groups for the ABCB1 G2677T/A polymorphism. Analysis of haplotypic frequencies indicated significant linkage disequilibrium between the two ABCB1 polymorphisms, C3435T and G2677T/A (D' = 0.034). No CYP3A4 polymorphisms were detected in any of the patients. Interpretation Patients carrying an ABCB1 polymorphism had a higher risk of having corticosteroid-associated ON than those with wild-type genotypes. This statistically significant association conflicts with previous studies, possibly due to different sampling methods. Knowing which genetic backgrounds are most strongly associated with corticosteroid-associated ON provides a method of screening for patients who are most at risk of developing ON.
Speciation involves the establishment of genetic barriers between closely related organisms. The extent of genetic recombination is a key determinant and a measure of genetic isolation. The results reported here reveal that genetic barriers can be established, eliminated, or modified by manipulating two systems which control genetic recombination, SOS and mismatch repair. The extent of genetic isolation between enterobacteria is
Marin Vulic; Francisco Dionisio; Francois Taddei; Miroslav Radman
NRF2 activates several protective genes, such as sulfiredoxin (SRXN1), as a response to oxidative and xenobiotic stress. Defects in NRF2 pathway may increase cancer susceptibility. In tumor cells, activation of NRF2 may lead to chemo- and radioresistance and thus affect patient outcome. Nine single-nucleotide polymorphisms on NRF2 gene and eight on SRXN1 were genotyped in 452 patients with breast cancer and 370 controls. Protein expression of NRF2 and SRXN1 was studied in 373 breast carcinomas by immunohistochemistry. Statistical significance of the associations between genotypes, protein expression, clinicopathologic variables, and survival was assessed. A high level (>25%) of cytoplasmic NRF2 positivity was observed in 237 of 361 (66%) and SRXN1 positivity was observed in 82 of 363 (23%) cases. The NRF2 rs6721961 genotype TT was associated with increased risk of breast cancer [P = 0.008; OR, 4.656; confidence interval (CI), 1.350-16.063] and the T allele was associated with a low extent of NRF2 protein expression (P = 0.0003; OR, 2.420; CI, 1.491-3.926) and negative SRXN1 expression (P = 0.047; OR, 1.867; CI = 1.002-3.478). The NRF2 rs2886162 allele A was associated with low NRF2 expression (P = 0.011; OR, 1.988; CI, 1.162-3.400) and the AA genotype was associated with a worse survival (P = 0.032; HR, 1.687; CI, 1.047-2.748). The NRF2 rs1962142 T allele was associated with a low level of cytoplasmic NRF2 expression (P = 0.036) and negative sulfiredoxin expression (P = 0.042). The NRF2 rs2706110 AA genotype was associated with an increased risk of breast cancer, and the SRXN1 rs6053666 C allele was associated with a decrease in breast cancer risk (P = 0.011 and 0.017). NRF2 and SRXN1 genetic polymorphisms are associated with breast cancer risk and survival, implicating that mechanisms associated with reactive oxygen species and NRF2 pathway are involved in breast cancer initiation and progression. PMID:22964583
Hartikainen, Jaana M; Tengström, Maria; Kosma, Veli-Matti; Kinnula, Vuokko L; Mannermaa, Arto; Soini, Ylermi
The hypothesis of a causal link between inflammation and atherosclerosis would be strengthened if variants of inflammatory\\u000a genes were associated with disease. Polymorphisms of 33 genes encoding inflammatory molecules were tested for association\\u000a with myocardial infarction (MI). Patients with MI and a parental history of MI (n?=?312) and controls from the UK (n?=?317) were genotyped for 162 polymorphisms. Thirteen polymorphisms
Sandrine Barbaux; David-Alexandre Tregouet; Viviane Nicaud; Odette Poirier; Claire Perret; Tiphaine Godefroy; Carole Francomme; Christophe Combadiere; Dominique Arveiler; Gerald Luc; Jean-Bernard Ruidavets; Alun E. Evans; Frank Kee; Caroline Morrison; Laurence Tiret; Stefan Martin Brand-Herrmann; François Cambien
We have applied the technique of random amplification of polymorphic DNA (RAPD) to the analysis of the relationships among\\u000a four species of brine shrimp:Artemia franciscana, A. urmiana, A. sinica, andA. parthenogenetica. Seventy ten-base synthetic oligonucleotides were used to amplify a total of 458 distinct fragments. DNA polymorphisms were\\u000a found in all the species examined; the highest percentage of polymorphic bands
Yi Sun; Yi-Cheng Zhong; Wen-Qin Song; Run-Sheng Zhang; Rui-Yang Chen
Background Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism and the ?-actinin-3 gene (ACTN3) R577X polymorphism have been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis. Methods We systematically reviewed and quantitatively summarized published studies, until October 31, 2012, on relationship between ACE/ACTN3 genetic polymorphisms and sports performance, respectively. Results A total of 366 articles on ACE and 88 articles on ACTN3 were achieved by literature search. A significant association was found for ACE II genotype compared to D allele carriage (DD+ID) with increased possibility of physical performance (OR, 1.23; 95% CI, 1.05–1.45). With respect to sport discipline, the II genotype was found to be associated with performance in endurance athletes (OR, 1.35; 95% CI, 1.17–1.55). On the other hand, no significant association was observed for ACTN3 RR genotype as compared to X allele carriage (XX+RX) (OR, 1.03; 95% CI, 0.92–1.15). However, when restricted the analyses to power events, a significant association was observed (OR, 1.21; 95% CI, 1.03–1.42). Conclusion Our results provide more solid evidence for the associations between ACE II genotype and endurance events and between ACTN3 R allele and power events. The findings suggest that the genetic profiles might influence human physical performance.
Li, Xiangwei; Zhou, Feng; Gao, Cong; Li, Mufei; Gao, Lei
To investigate the genetic polymorphisms of 17 Y-chromosomal short tandem repeats(Y-STR) loci in She ethnic population from Fujian province, and to evaluate their forensic application values and genetic relationship with other 11 populations, 152 unrelated male individuals of She ethnic population in Fujian were used to determine the distribution of allele frequencies and haplotypes by using Y-filerTM System. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations. As a result, 50 haplotypes were found in DYS385a/b loci, and 3?11 alleles were found in the rest 15 Y-STR loci. The GD value was from 0.4037(DYS391) to 0. 9725(DYS385a/b). This study has also revealed "off-ladder" alleles at several Y-loci, namely DYS448, DYS393, DYS458 and DYS635, and several occurrences of duplications at the DYS385a/b, DYS19 and DYS390 loci. One hundred and forty-four haplotypes were found in 17 Y-STR loci, of which 138 were unique, 5 were found in 2 individuals, 1 was found in 4 individuals, and the observed haplotypes diversity value was 0.9990. Comparing with 11 populations, the genetic distance between She ethnic and Han population in Zhejiang was the smallest (0.0042), while it was the largest between She ethnic and Tibet ethnic population (0.2380). Cluster analysis and phylogenetic tree both demonstrated that genetic distance between She ethnic and several south Han populations is closer than between She ethnic and non-Han populations. Multiplex detection of the 17 Y-STR loci revealed a highly polymorphic genetic distribution, which would be very powerful for establishing a Y-STR database, for population genetics and forensic practice. PMID:22917907
Bai, Ru-Feng; Yang, Li-Hai; Yuan, Li; Liang, Quan-Zeng; Lu, Di; Yang, Xue; Shi, Mei-Sen
Background Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. Methods A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24–28, and > 28 kg/m2; respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. Results The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). Conclusions The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.
Most previous studies on genetic fingerprinting and cultivar relatedness in sweet cherry were based on isoenzyme, RAPD, and simple sequence repeat (SSR) markers. This study was carried out to assess the utility of single nucleotide polymorphism (SNP) markers generated from 3? untranslated regions (UTR) for genetic fingerprinting in sweet cherry. A total of 114 sweet cherry germplasm representing advanced selections, commercial cultivars, and old cultivars imported from different parts of the world were screened with seven SSR markers developed from other Prunus species and with 40 SNPs obtained from 3? UTR sequences of Rainier and Bing sweet cherry cultivars. Both types of marker study had 99 accessions in common. The SSR data was used to validate the SNP results. Results showed that the average number of alleles per locus, mean observed heterozygosity, expected heterozygosity, and polymorphic information content values were higher in SSRs than in SNPs although both set of markers were similar in their grouping of the sweet cherry accessions as shown in the dendrogram. SNPs were able to distinguish sport mutants from their wild type germplasm. For example, “Stella” was separated from “Compact Stella.” This demonstrates the greater power of SNPs for discriminating mutants from their original parents than SSRs. In addition, SNP markers confirmed parentage and also determined relationships of the accessions in a manner consistent with their pedigree relationships. We would recommend the use of 3? UTR SNPs for genetic fingerprinting, parentage verification, gene mapping, and study of genetic diversity in sweet cherry.
Fernandez i Marti, Angel; Athanson, Blessing; Koepke, Tyson; Font i Forcada, Carolina; Dhingra, Amit; Oraguzie, Nnadozie
Most previous studies on genetic fingerprinting and cultivar relatedness in sweet cherry were based on isoenzyme, RAPD, and simple sequence repeat (SSR) markers. This study was carried out to assess the utility of single nucleotide polymorphism (SNP) markers generated from 3' untranslated regions (UTR) for genetic fingerprinting in sweet cherry. A total of 114 sweet cherry germplasm representing advanced selections, commercial cultivars, and old cultivars imported from different parts of the world were screened with seven SSR markers developed from other Prunus species and with 40 SNPs obtained from 3' UTR sequences of Rainier and Bing sweet cherry cultivars. Both types of marker study had 99 accessions in common. The SSR data was used to validate the SNP results. Results showed that the average number of alleles per locus, mean observed heterozygosity, expected heterozygosity, and polymorphic information content values were higher in SSRs than in SNPs although both set of markers were similar in their grouping of the sweet cherry accessions as shown in the dendrogram. SNPs were able to distinguish sport mutants from their wild type germplasm. For example, "Stella" was separated from "Compact Stella." This demonstrates the greater power of SNPs for discriminating mutants from their original parents than SSRs. In addition, SNP markers confirmed parentage and also determined relationships of the accessions in a manner consistent with their pedigree relationships. We would recommend the use of 3' UTR SNPs for genetic fingerprinting, parentage verification, gene mapping, and study of genetic diversity in sweet cherry. PMID:22737155
Fernandez I Marti, Angel; Athanson, Blessing; Koepke, Tyson; Font I Forcada, Carolina; Dhingra, Amit; Oraguzie, Nnadozie
Populations of the temperate seagrass, Zostera marina L. (eelgrass), often exist as discontinuous beds in estuaries, harbors, and bays where they can reproduce sexually or vegetatively through clonal propagation. We examined the genetic structure of three geographically and morphologically distinct populations from central California (Elkhorn Slough, Tomales Bay, and Del Monte Beach), using multilocus restriction fragment length polymorphisms (DNA fingerprints).
Randall S. Alberte; Gregory K. Suba; Gabriele Procaccini; Richard C. Zimmerman; Steven R. Fain
Populations of the temperate seagrass, Zostera marina L. (eelgrass), often exist as discontinuous beds in estuaries, harbors, and bays where they can reproduce sexually or vegetatively through clonal propagation. We ex- amined the genetic structure of three geographically and morphologically distinct populations from central California (Elkhorn Slough, Tomales Bay, and Del Monte Beach), using multilocus restriction fragment length polymorphisms (DNA
RANDALL S. ALBERTE; GREGORY K. SUBAt; GABRIELE PROCACCINI; RICHARD C. ZIMMERMANt; STEVEN R. FAIN
In a panel of seven genotypes, 437 expressed sequence tag (EST)-derived DNA fragments were sequenced. Single nucleotide polymorphisms (SNPs) that were polymorphic between the parents of three mapping populations were mapped by heteroduplex analysis and a genome-wide consensus map comprising 216 EST-derived SNPs and 4 InDel (insertion/deletion) markers was constructed. The average frequency of SNPs amounted to 1/130 bp and 1/107.8 bp for a set of randomly selected and a set of mapped ESTs, respectively. The calculated nucleotide diversities (pi) ranged from 0 to 40.0 x 10(-3) (average 3.1 x 10(-3)) and 0.52 x 10(-3) to 39.51 x 10(-3) (average 4.37 x 10(-3)) for random and mapped ESTs, respectively. The polymorphism information content value for mapped SNPs ranged from 0.24 to 0.50 with an average of 0.34. As expected, combination of SNPs present in an amplicon (haplotype) exhibited a higher information content ranging from 0.24 to 0.85 with an average of 0.50. Cleaved amplified polymorphic sequence assays (including InDels) were designed for a total of 87 (39.5%) SNP markers. The high abundance of SNPs in the barley genome provides avenues for the systematic development of saturated genetic maps and their integration with physical maps. PMID:17968603
Kota, R; Varshney, R K; Prasad, M; Zhang, H; Stein, N; Graner, A
Success rate in human pregnancies is believed to be very low and sex-specific mechanisms may operate in prenatal loss. Assuming a sex-differential in prenatal loss exists, we examined genetic markers in biologically plausible targets in the HLA complex, other immune system-related and iron-regulatory genes in 388 healthy newborns from Wales (UK) using one sex as a control group for the other. Genotyping of 333 single nucleotide polymorphisms (SNPs) from 107 genes was achieved mainly by TaqMan assays. Twenty-two of autosomal SNPs showed frequency differences between 187 male and 201 female newborns either individually or as part of a haplotype. Of these, six markers (RXRB rs2076310, HLA complex haplotype HLA-DQA1 rs1142316-HLA-DRA rs7192-HSPA1B rs1061581, HIST1H1T rs198844, IFNG rs2069727, NKG2D rs10772266 and IRF4 heterozygosity) showed statistically robust differences between male and female newborns and multivariable modeling confirmed their independence. There were fewer males homozygote for combined wildtype genotypes of LIF rs929271, TP53 rs1042522 and MDM2 rs2279744 compared with females [OR = 0.3, 95% confidence interval (CI) = 0.1-0.8; P < 0.01] although these SNPs did not show any association individually. It is unlikely that SNPs have clinical utility as single markers in any trait with complex etiology but polygenic predictive models remain a possibility. If their validity is confirmed in larger studies of different populations and functional mechanisms of these preliminary associations are elucidated, these markers from the HLA complex, NKG2D region and cytokines may cumulatively have sufficient predictive value for susceptibility to prenatal selection in each sex. PMID:20587610
Ucisik-Akkaya, Esma; Davis, Charronne F; Do, Thuy N; Morrison, Brittany A; Stemmer, Shlomo M; Amadio, William J; Dorak, M Tevfik
Background- Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10?000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis. Methods and Results- The Exome Sequencing Project database (ESP; n= 6503) was systematically searched for previously published missense and nonsense CPVT-associated variants reported in several comprehensive reviews and in 2 databases: The Human Gene Mutation Database and The Inherited Arrhythmias Database. We used 4 different prediction tools to assess all missense variants previously associated with CPVT and compared the prediction of protein damage between CPVT-associated variants identified in the ESP and those variants not identified in the ESP. We identified 11% of the variants previously associated with CPVT in the ESP population. In the literature, 57% of these variants were reported as novel disease-causing variants absent in the healthy control subjects. These putative CPVT variants were identified in 41 out of 6131 subjects in the ESP population, corresponding to a prevalence of CPVT of up to 1:150. Using an agreement of ?3, in silico prediction tools showed a significantly higher frequency of damaging variants among the CPVT-associated variants not identified in the ESP database (83%) compared with those variants identified in the ESP (50%; P=0.021). Conclusions- We identified a substantial overrepresentation of CPVT-associated variants in a large exome database, suggesting that these variants are not necessarily the monogenic cause of CPVT. PMID:24025405
Jabbari, Javad; Jabbari, Reza; Nielsen, Morten W; Holst, Anders G; Nielsen, Jonas B; Haunsø, Stig; Tfelt-Hansen, Jacob; Svendsen, Jesper H; Olesen, Morten S
Background We previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of the CysLTR2 gene. Methods We measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics having ht1+/+ and ht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively. Results We found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics having ht2+/+ than in those having ht1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines from ht2+/+ asthmatics than those from ht1+/+ asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containing c.-819T than one containing c.-819G. The luciferase activity of the c.-819T type of CysLTR2 promoter was higher than that of the c.-819G type. EGFP expression was higher in the EGFP-c.2078T 3'-UTR fusion construct than in the c.2078C construct. Conclusion The sequence variants of CysLTR2 may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.
Shin, Jeong-Ah; Chang, Hun Soo; Park, Se-Min; Jang, An-Soo; Park, Sung Woo; Park, Jong Sook; Uh, Soo-Taek; Il Lim, Gune; Rhim, Taiyoun; Kim, Mi-Kyeong; Choi, Inseon S; Chung, Il Yup; Park, Byung Lae; Shin, Hyoung Doo; Park, Choon-Sik
alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/Ile1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in Abeta burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway. PMID:9811940
Liao, A; Nitsch, R M; Greenberg, S M; Finckh, U; Blacker, D; Albert, M; Rebeck, G W; Gomez-Isla, T; Clatworthy, A; Binetti, G; Hock, C; Mueller-Thomsen, T; Mann, U; Zuchowski, K; Beisiegel, U; Staehelin, H; Growdon, J H; Tanzi, R E; Hyman, B T
Amplified fragment length polymorphism (AFLP) was evaluated as a method for genotypic characterization and subtyping within the bacterial species Actinobacillus pleuropneumoniae. A total of 155 isolates of A. pleuropneumoniae, representing the serotypic variation described to occur within this species, were analyzed. In order to elucidate the species boundaries, six strains of the phylogenetically closely related species Actinobacillus lignieresii were also included. Furthermore, the ability of AFLP to subtype was studied using 42 isolates of serovar 2 and the performance compared to that obtained by pulsed-field gel electrophoresis (PFGE). AFLP analysis provided a clear separation of A. lignieresii and A. pleuropneumoniae and divided the isolates of A. pleuropneumoniae into 20 clusters. Most of the serovars of A. pleuropneumoniae were represented by single and quite homogeneous clusters. The exceptions were serovars 10, K2:O7, and K1:O7, which were represented by two clusters each. In the cases where the serovars were represented by more than one cluster, the existence of these clusters was supported by additional phenotypic or genotypic properties. Furthermore, AFLP typing was able to allocate serologically nontypeable isolates to appropriate genetic groups within the species. Further investigations are needed to determine whether some of the clusters revealed through AFLP analysis represent additional serovars. When evaluated as a method for subtyping within serovar 2 of A. pleuropneumoniae, AFLP was found to achieve a degree of separation among isolates superior to that obtained by PFGE. However, a higher degree of separation between serovar 2 isolates was obtained by a combination of the two methods. PMID:17959758
Kokotovic, Branko; Angen, Øystein
Amplified fragment length polymorphism (AFLP) was evaluated as a method for genotypic characterization and subtyping within the bacterial species Actinobacillus pleuropneumoniae. A total of 155 isolates of A. pleuropneumoniae, representing the serotypic variation described to occur within this species, were analyzed. In order to elucidate the species boundaries, six strains of the phylogenetically closely related species Actinobacillus lignieresii were also included. Furthermore, the ability of AFLP to subtype was studied using 42 isolates of serovar 2 and the performance compared to that obtained by pulsed-field gel electrophoresis (PFGE). AFLP analysis provided a clear separation of A. lignieresii and A. pleuropneumoniae and divided the isolates of A. pleuropneumoniae into 20 clusters. Most of the serovars of A. pleuropneumoniae were represented by single and quite homogeneous clusters. The exceptions were serovars 10, K2:O7, and K1:O7, which were represented by two clusters each. In the cases where the serovars were represented by more than one cluster, the existence of these clusters was supported by additional phenotypic or genotypic properties. Furthermore, AFLP typing was able to allocate serologically nontypeable isolates to appropriate genetic groups within the species. Further investigations are needed to determine whether some of the clusters revealed through AFLP analysis represent additional serovars. When evaluated as a method for subtyping within serovar 2 of A. pleuropneumoniae, AFLP was found to achieve a degree of separation among isolates superior to that obtained by PFGE. However, a higher degree of separation between serovar 2 isolates was obtained by a combination of the two methods.
Kokotovic, Branko; Angen, ?ystein
We have established a sequencing based typing (SBT) method for detection of genetic polymorphism in the exon 2 to 4 domains of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) and applied it to allele typing of 130 healthy Japanese individuals. A 2.2-kb segment including exons 2, 3 and 4 of the MICA gene was amplified by a pair of generic primers followed by cycle sequencing using exon-specific nested primers. In total, 8 alleles were observed in a Japanese population and the most frequent allele was MICA008 with the gene frequency of 30.8%. MICA009 was the second most frequent (16.5%), while the rarest one was MICA007 (1.2%). MICA alleles displayed strong linkage equilibria with HLA-B antigens (i.e. MICA008 with B7, B48, B60 and B61; MICA009 with B51 and B52; MICA002 with B35, B39, B58 and B67; MICA004 with B44, MICA007 with B13 and B27; MICA010 with B46, B62 and B48, MICA012 with B54, B55, B56 and B59; MICA019 and B70, B71 and B62). Recently, the B48 haplotype has been reported to lack the entire MICA gene by a large-scale deletion in a Japanese population. Among 8 serologically B48 homozygous individuals, 4 were found to represent this MICA null allele as assessed by no polymerase chain reaction (PCR) amplification using MICA-specific primers, while the remaining four possessed the intact MICA gene with MICA008 or MICA010. PMID:10488745
Katsuyama, Y; Ota, M; Ando, H; Saito, S; Mizuki, N; Kera, J; Bahram, S; Nose, Y; Inoko, H
The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn. Images
Carlson, G A; Goodman, P A; Lovett, M; Taylor, B A; Marshall, S T; Peterson-Torchia, M; Westaway, D; Prusiner, S B
We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey') and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917
Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, Yoonkyeong; Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, Kyungho; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E; Crowhurst, Ross N; Chagné, David
We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’×‘Louise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.
Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E.; Crowhurst, Ross N.; Chagne, David
Amplified fragment length polymorphisms (AFLPs) were used to analyze the relationships between sweet cherry (Prunus avium L.) cultivars and selections from the breeding program at the Pacific Agri-Food Research Centre in Summerland, Canada. Six pairs of preselected primers were used for the analysis of a total of 67 cultivars and selections. Scoring the absence and presence of 118 polymorphic DNA
Lili Zhou; Frank Kappel; Cheryl Hampson; Paul A. Wiersma; Guus Bakkeren
We have applied the technique of random amplification of polymorphic DNA (RAPD) to the analysis of the relationships among four species of brine shrimp: Artemia franciscana, A. urmiana, A. sinica, and A. parthenogenetica. Seventy ten-base synthetic oligonucleotides were used to amplify a total of 458 distinct fragments. DNA polymorphisms were found in all the species examined; the highest percentage of
Yi Sun; Yi-Cheng Zhong; Wen-Qin Song; Run-Sheng Zhang; Rui-Yang Chen
Random amplified polymorphic DNA (RAPD) markers were generated from 20 cultivars and accessions representing four agronomically important species of Stylosanthes, S. scabra, S. hamata, S. guianensis, and S. humilis. Approximately 200 fragments generated by 22 primers of arbitrary sequence were used to assess the level of DNA variation. Relatively low levels of polymorphism (0–16% of total bands in pairwise comparisons)
K. Kazan; J. M. Manners; D. F. Cameron
Background: Folate and methionine metabolism is involved in DNA synthesis and methylation. Polymor- phisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In the present study, 2 polymorphisms were evaluated for a folate met- abolic enzyme, methylene-tetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms MTHFR 677 C?T
EMMAD EZZAT HABIB; MONA AZIZ; MAGD KOTB
Population samples from Morocco (El Jadida, south Atlantic coast) and La Alpujarra (Granada mountains, Spain), located on both shores of the western Mediterranean, were typed for 8 erythrocyte genetic markers: ACP1, ESD, PGD, AK1, GLO1, PGM1, SODA, and DIA. Genetic heterogeneity within western Mediterranean groups was investigated on the basis of allele frequencies of these 8 polymorphisms plus ABO and Rh (CDE). Only slight peculiarities for the ACP1, GLO1, and AK1 systems were observed in the 2 samples compared with other Mediterranean data. The new data are consistent with a main north to south genetic differentiation in the Mediterranean region. However, with regard to other European groups, the La Alpujarra population shows a particular affinity with North Africans that may be compatible with both an ancient common substratum and/or a special historical influence during the Muslim domination of the Iberian Peninsula. PMID:10510571
Kandil, M; Moral, P; Esteban, E; Autori, L; Mameli, G E; Zaoui, D; Calo, C; Luna, F; Vacca, L; Vona, G
PICALM might play an important role in AD pathology through participating in altering synaptic vesicle cycling or APP endocytosis. A recent genome-wide study (GWAS) identified a single nucleotide polymorphism (SNP) rs3851179 in the 5' to the PICALM gene strongly associated with Alzheimer's disease (AD) in Caucasians. In order to assess the involvement of the PICALM polymorphism in the risk of developing late-onset AD (LOAD), we analyzed the genotype and allele distributions of these three polymorphisms in 609 Han Chinese subjects. Our data showed no significant association between the PICALM rs3851179 polymorphism and LOAD (genotype distribution: P=0.43; allele frequency: P=0.25, odds ratio=0.87, 95% confidence interval=0.68 to 1.10), even after statistical adjustment for age, gender and apolipoprotein E (APOE) status. Our results suggest that the PICALM polymorphism may not play a major role in the development of LOAD in the Han Chinese population. PMID:20951388
Yu, Jin-Tai; Song, Jing-Hui; Ma, Teng; Zhang, Wei; Yu, Nan-Nan; Xuan, Shi-Ying; Tan, Lan
Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.??
Costa-Mallen, P.; Costa, L.; Smith-Weller, T.; Franklin, G.; Swanson, P.; Checkoway, H.
Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having
S. Sasaki; T. Kondo; F. Sata; Y. Saijo; S. Katoh; S. Nakajima; M. Ishizuka; S. Fujita; R. Kishi
Intraspecific genetic variation in two species of calliphorid blowfly, Lucilia sericata and Lucilia cuprina, was studied by random amplified polymorphic DNA (RAPD) analysis and mitochondrial DNA (mtDNA) sequencing. These species are economically important facultative ectoparasites of sheep. Numerical analysis of RAPD fragment data was used to investigate genetic variation in L. sericata across Europe and in both L. sericata and
Jamie Stevens; Richard Wall
BACKGROUND: Genetic analysis of the human prion protein gene (PRNP) in suspect cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and case classification. Previous publications on the genetic variation at the PRNP locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. It
Matthew T Bishop; Catherine Pennington; Craig A Heath; Robert G Will; Richard SG Knight
Genetic Diversity Among Populations of Red Palm Weevil, Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae), Determined by Random Amplified Polymorphic DNA Polymerase Chain Reaction (RAPD-PCR)
This study reports the genetic variations between populations of the red palm weevil, Rhynchophorus ferrugineus in the UAE area. To test if the red palm weevil population in the UAE belongs to the same genetic group; the randomly amplified polymorphic DNA (RAPD) technique was used to assay seven populations of the insect from different locations. RAPD primer pairs detected a
G. G. GADELHAK; M. R. ENAN
Retinopathy of prematurity (ROP) is a multifactorial disease, that cause visual impairment in premature children. The exact pathogenesis and etiology of ROP is unknown and genetic susceptibility is considered as risk factor. Vascular endothelial growth factor (VEGF) plays a major role in retinal neovascularization and subsequently retinal detachment. VEGF polymorphism is associated with proliferative ROP in some studies. We examined the possible association of the VEGF gene polymorphisms with ROP in preterm infants in south of Iran. A total of 111 preterm infants were examined by ophthalmologist and after that were genotyped. Genotyping of the VEGF +405 (rs2010963) and VEGF +936 (rs3025039) was done by the polymerase chain reaction and restriction fragment length polymorphism methods. The frequency of VEGF alleles, genotypes and haplotype distribution were compared between groups. The patients were divided in three groups: 66 to the normal group (normal fundoscopy), and 45 to the ROP group; 30 infants were not treated with Lasertherapy (Regressive group) and 15 treated with Lasertherapy. The frequency of VEGF +405 and VEGF +936 G/C genotypes as well as allele frequencies was not different between groups. No significant difference was found between ROP with treatment and ROP without lasertherapy. Our report indicate that there is no association between the carrier states of gene polymorphisms VEGF +405, VEGF +936 and progression or spontaneous regression of ROP in preterm infants in Iranian population. However, it should be considered that angiogenesis is a complex process and genetic factors in addition to environmental factors are contributed in this pathway. PMID:23644986
Kalmeh, Zahra Asadi; Azarpira, Negar; Mosallaei, Mahnaz; Hosseini, Hamid; Malekpour, Zahra
Background Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A?>?G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk. Methods The EGF 61A?>?G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China. Results Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR)?=?3.44, 95% confidence interval (CI)?=?0.93–12.76, P?=?0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR?=?3.34, 95% CI?=?1.24-9.03, P?=?0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China. Conclusion Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.
Background The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen. Methods a total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism. Results these studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05). Conclusions these results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.
The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is the causative agent of pine wilt disease and among the most important invasive forest pests in the East-Asian countries, such as Japan and China. Since 1999, it has been found in Europe in the Iberian Peninsula, where it also causes significant damage. In a previous study, 94 pairs of microsatellite primers have been identified in silico in the pinewood nematode genome. In the present study, specific PCR amplifications and polymorphism tests to validate these loci were performed and 17 microsatellite loci that were suitable for routine analysis of B. xylophilus genetic diversity were selected. The polymorphism of these markers was evaluated on nematodes from four field origins and one laboratory collection strain, all originate from the native area. The number of alleles and the expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777, respectively. First insights into the population genetic structure of B. xylophilus were obtained using clustering and multivariate methods on the genotypes obtained from the field samples. The results showed that the pinewood nematode genetic diversity is spatially structured at the scale of the pine tree and probably at larger scales. The role of dispersal by the insect vector versus human activities in shaping this structure is discussed. PMID:23554990
Mallez, Sophie; Castagnone, Chantal; Espada, Margarida; Vieira, Paulo; Eisenback, Jonathan D; Mota, Manuel; Guillemaud, Thomas; Castagnone-Sereno, Philippe
Random amplified polymorphic DNA (RAPD) markers were used to assess genetic relationships and variation among ecotypes of the turfgrass seashore paspalum (Paspalum vaginatum Swartz). Vegetative tissues or seeds of 46 seashore paspalum ecotypes were obtained from various locations in the United States, Argentina, and South Africa. Leaf DNA extracts were screened for RAPD markers using 34 10-mer random primers. A total of 195 reproducible RAPD fragments were observed, with an average of six fragments per primer. One hundred and sixty-nine fragments (87% of the total observed) were polymorphic, among which 27 fragments (16%) were present in three or less ecotypes, indicating the occurrence of a high level of genetic variation among the examined accessions of this species. Cluster analysis (UPGMA) and principal coordinates analysis were performed on the RAPD data set. The results illustrate genetic relationships among the 46 ecotypes, and between ecotypes and their geographical origins. Ecotypes from southern Africa could be differentiated from the U.S. and most of the Argentinean ecotypes. With a few exceptions, ecotypes collected from Argentina, Hawaii, Florida, and Texas were separated into distinct clusters. PMID:18470139
Liu, Z W; Jarret, R L; Duncan, R R; Kresovich, S
A polymorphism in the human serotonin transporter (5-HTT) gene is implicated in susceptibility to anxiety and depression and in enhanced emotion-induced activation in the amygdala. A role for 5-HTT polymorphism in the emotional modulation of human episodic memory has yet to be demonstrated. Here, we demonstrate that whereas emotional memory for aversive events per se is not influenced by 5-HTT polymorphism, an emotion-induced retrograde amnesia is expressed solely in the presence of the short allele. The findings indicate a critical role for the serotonin system in emotion-mediated memory disruption.
Strange, Bryan A.; Kroes, Marijn C. W.; Roiser, Jonathan P.; Tan, Geoffrey C. Y.; Dolan, Raymond J.
An aerial view of Newport Harbor and waterfront in Newport, Rhode Island. Long Wharf, to the right, and Goat Island, the slender island just offshore, are located on the western side of island. The shipping industry has a long history in Newport, beginning as early as the 18th century. The development along the waterfront at the center of the photograph
The restrictions imposed by data protection legislation on the transfer of data outside the European Economic Area (EEA), and particularly to the USA, have been the subject of much comment. A recently introduced ‘Safe Harbor’ arrangement between the EU and the USA is not the panacea that many hoped for, as it currently does not apply to US banking and
The Safe Harbor Water Power Corporation has recently completed the dam and initial section of the power house to develop the fall of the Susquehanna river between the Holtwood project backwater and Columbia, Pennsylvania. This development, when completed, will be one of the largest hydroelectric developments in the United States. In the initial project there will be installed 255,000 turbine
N. B. Higgins
Background Huntington disease (HD) is caused by an expanded CAG repeat in the HD gene. Although the length of the CAG repeat strongly correlates with the age-at-onset (AAO), AAO in HD individuals may differ dramatically in spite of similar expanded CAG repeat lengths. Additional genetic or environmental factors are thought to influence the disease onset. Several modifier genes have been discovered so far but they do not fully explain the variability of AAO in HD. To potentially identify a novel genetic modifier, we analyzed single nucleotide polymorphisms (SNPs) in the kalirin (KALRN) gene. Kalirin is a protein crucially involved in spine plasticity and its interaction with huntingtin-associated protein-1 (HAP-1) and a potential protein dysfunction might contribute to spine pathogenesis in HD. Methods The selected SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and association of SNPs with AAO was investigated with the framework of linear models in an analysis of variance and covariance. Results Eleven SNPs in the kalirin gene were examined in an association study in European HD patients. The ten coding SNPs under investigation were monomorphic, whereas SNP rs10934657 in the promoter region showed a minor allele frequency >1%. An analysis of covariance together with the influence of the expanded HD allele was applied in 680 HD patients. SNP rs10934657 did not affect the AAO of the examined HD population. Conclusions The results did not reveal an association between the analyzed kalirin polymorphisms and the AAO in HD. However, it does not exclude other SNPs of the kalirin gene as susceptible genetic modifiers.
Background The insulin-like growth factor I receptor (IGF1R) has an important effect on growth, carcass, and meat quality traits in many species. However, few studies on associations of the IGF1R gene with growth and carcass traits have been reported in chickens. The objectives of the present study were to study the associations of the IGF1R gene with chicken early growth and carcass traits using a neutral test, variation scan of the gene, genetic diversity, linkage disequilibrium and association analyses. Results The tree generated from the amino acid sequences of 15 species showed that the IGF1R gene was conservative in the whole evolution among the mammalian animals and chickens. In a total of 10,818 bp of sequence, 70 single nucleotide polymorphisms were identified in the chicken IGF1R gene. The allelic and genotypic frequency distribution, genetic diversity and linkage disequilibrium of 18 single nucleotide polymorphisms (SNPs) in the Xinghua and White Recessive Rock chickens showed that six of them were possibly associated with growth traits. Association analyses showed that the A17299834G SNP was significantly associated with chicken carcass body weight, eviscerated weight with giblets, eviscerated weight, body weights at 28, 35, and 56 d of age, leg length at 56 d of age, and daily weight gain at 0–4 weeks. The haplotypes of the A17307750G and A17307494G were associated with early growth traits. The haplotypes of the A17299834G and C17293932T were significantly associated with most of the early growth traits and carcass traits. Conclusion There were rich polymorphisms in the chicken IGF1R gene. Several SNPs associated with chicken early growth traits and carcass traits were identified in the IGF1R gene by genetic diversity, linkage disequilibrium, and association analyses in the present study.
Lei, Mingming; Peng, Xia; Zhou, Min; Luo, Chenglong; Nie, Qinghua; Zhang, Xiquan
Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL1beta genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. IL1beta single nucleotide polymorphisms (SNP) (-1473G > C, -511G > A, -31T > C, 3966C > T, 6054G > A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P = 0.021), and the prevalence of MetS (P = 0.004). Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%CI = 1.49-7.26 for GG and OR = 1.95, 95%CI = 0.85-4.46 for GA, P < 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P = 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL1beta genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake. PMID:17634253
Shen, Jian; Arnett, Donna K; Peacock, James M; Parnell, Laurence D; Kraja, Aldi; Hixson, James E; Tsai, Michael Y; Lai, Chao-Qiang; Kabagambe, Edmond K; Straka, Robert J; Ordovas, Jose M
Objectives To investigate the CYP1A2 genotype-phenotype relationship and to compare CYP1A2 genetic polymorphisms and enzyme activity in terms of the effect of smoking and oral contraceptive (OC) use in Swedes and\\u000a Koreans.\\u000a \\u000a \\u000a \\u000a Methods CYP1A2 enzyme activity was determined in 194 and 150 healthy Swedish and Korean subjects, respectively, on the basis of the\\u000a 4-h plasma paraxanthine\\/caffeine (17X\\/137X) ratio determined using high-performance liquid
Roza Ghotbi; Magnus Christensen; Hyung-Keun Roh; Magnus Ingelman-Sundberg; Eleni Aklillu; Leif Bertilsson
An RT-nested PCR (RT-nPCR)-based restriction fragment length polymorphism (RFLP) analyses of the E2 gene were developed for\\u000a genetic subtyping and differentiation of vaccinated and infected classical swine fever virus (CSFV) strains. RT-nPCR identified\\u000a 96 CSFV-positive samples from 321 clinical specimens from southeastern China during 2003–2008. The PCR products of positive\\u000a samples were further differentiated using MspI digestion, 23 were identified
Ning Chen; Dejiang Li; Xuemei Yuan; Xiaoliang Li; Hongxia Hu; Binglin Zhu; Xiaoyuan Wan; Weihuan Fang
Objective: This study investigates the effect of multiple factors, including exposure to polycyclic aromatic hydrocarbons (PAHs), lifestyle,\\u000a genetic polymorphism of cytochrome P450 (CYP)1A1, glutathione transferase (GST)M1, GSTP1, N-acetyltransferase (NAT)2 and gene p53, as well as any family history of cancer, on DNA adduct levels in coke-oven workers.\\u000a Methods: Sixty-five coke-oven workers employed at the largest iron-steel factory in China were
J. Zhang; M. Ichiba; Y. Feng; G. Pan; T. Hanaoka; Y. Yamano; K. Hara; K. Takahashi; K. Tomokuni
The Han population in Chengdu, China, was investigated for genetic polymorphisms of alpha-2-HS-glycoprotein (A2HS), group-specific component (GC) and orosomucoid (ORM) using isoelectric focusing followed by immunofixation. The allele frequencies were: A2HS*1 ≈ 0.6958, A2HS*2 = 0.3042, GC*1F = 0.4021, GC*1S = 0.3182, GC*2 = 0.2745, GC*1A = 0.0052, ORM1*F1 = 0.7028, ORM1*S = 0.2762, ORM1*F2 = 0.0210, ORM2*A = 0.9965,
Hou Yiping; Gou Qing; Wu Meiyun
Purpose Ulcerative colitis (UC) is a chronic inflammatory condition of the large bowel of unknown etiology, characterized by the presence\\u000a of bloody diarrhea and mucus associated with a negative stool culture for bacteria, ova, or parasites. The aim of this study\\u000a was to investigate the association of p53 codon 72 genetic polymorphism with the risk of UC in northern Iran.\\u000a \\u000a \\u000a \\u000a \\u000a Methods We
Salaheddin Vaji; Zivar Salehi; Keyvan Aminian
Monocarboxylate Transporter 1 (MCT1) mediates the transport of the main fraction of lactate across the sarcolemma. A common polymorphic MCT1 variant has been identified, but its role in high intensity exercise performance has not been defined. We investigated the influence of MCT1 A1470T polymorphism (rs1049434) on lactate accumulation after high intensity circuit training. Ten men aged 20–26 performed three controlled
Rocío Cupeiro; Pedro J. Benito; Nicola Maffulli; F. Javier Calderón; Domingo González-Lamuño
Up to now, many publications have evaluated the correlation between IL-23R polymorphisms and ankylosing spondylitis with conflicting\\u000a results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of\\u000a IL-23R polymorphisms with AS. Relevant published data were retrieved through Medline, PubMed, Embase, Web of Science, CNKI,\\u000a Chinese BioMedical Literature Database on disc,
Zhenhua Duan; Faming Pan; Zhen Zeng; Tianchen Zhang; Sheng Wang; Guixing Li; Shengqian Xu; Jianhua Xu; Li Zhang
Background: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1?). Therefore, we investigated the association of HIF-1? polymorphisms with ischemia\\/hypoxia-related events in hemodialysis patients. Methods: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1? were genotyped.
Zhen Lon Zheng; Young-Hwan Hwang; Seong Kyun Kim; Sejoong Kim; Min Jung Son; Han Ro; Su-Ah Sung; Hyun Hee Lee; Woo Kyung Chung; Kwon Wook Joo; Jaeseok Yang
Background The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility\\u000a to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response
Nizar M Mhaidat; Osama Y Alshogran; Omar F Khabour; Karem H Alzoubi; Ismail I Matalka; William J Haddadin; Ibraheem O Mahasneh; Ahmad N Aldaher
Amplified fragment length polymorphisms (AFLP) were used to rapidly generate a dense linkage map for pinyon pine (Pinus edulis). The map population consisted of 40 megagametophytes derived from one tree at Sunset Crater, Arizona. A total of 78 primer\\u000a combinations, each with three to five selective nucleotides, amplified 542 polymorphic markers. Of these, 33 markers showed\\u000a significant deviation from the
S. E. Travis; K. Ritland; T. G. Whitham; P. Keim
INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T?C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study
Jiun-Horng Chang; Dorota M Gertig; Xiaoqing Chen; Gillian S Dite; Mark A Jenkins; Roger L Milne; Melissa C Southey; Margaret RE McCredie; Graham G Giles; Georgia Chenevix-Trench; John L Hopper; Amanda B Spurdle
The GSH-dependent formaldehyde dehydrogenase (FDH) is the most important enzyme for the metabolic inactivation of formaldehyde. We studied three polymorphisms of this gene with the intention to elucidate their relevance for inter-individual differences in the protection against the (geno-)toxicity of FA. The first polymorphism (rs11568816) was investigated using real-time PCR and restriction fragment analysis in 150 subjects. However, we did
Walter Just; Jasmin Zeller; Clarissa Riegert; Günter Speit
Cyanobacteria have high adaptive potential and occur in the most extreme habitats. The available literature data indicate that the versatility of cyanobacteria is related to their higher polymorphism under stress. The studies of a filamentous cyanobacterium, Nostoc linckia, from the ecological microsite models known as "Evolution Canyons" showed that, among the evolutionary forces maintaining the higher polymorphism and genome diversity under permanent natural stress, the various types of natural selection play a key role. PMID:12648721
Dvornyk, Volodymyr; Nevo, Eviatar
The Pro\\/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro\\/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case–control study in southwestern Taiwan. From
Yen-Ching Chen; Lilian Xu; Yu-Liang Leon Guo; Huey-Jen Jenny Su; Yu-Mei Hsueh; Thomas J. Smith; Louise M. Ryan; Meei-Shyuan Lee; Sheau-Chiou Chaor; Julia Yu-Yun Lee; David C. Christiani
In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4), the G861C polymorphism (rs6296) of the serotonin receptor 1D beta (HTR1B), the T102C (rs6113) and C516T (rs6305) polymorphisms of the serotonin receptor gene subtype 2A (HTR2A), the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3), the Val-158-Met (rs4680) polymorphism of the COMT and the silent mutation G1287A (rs5569) in the norepinephrine transporter gene (SLC6A2). We genotyped 41 obsessive-compulsive disorder (OCD) outpatients, classified as good-responders (n=27) and poor-responders (n=14) to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS). Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample. PMID:21625751
Miguita, Karen; Cordeiro, Quirino; Shavitt, Roseli Gedanke; Miguel, Eurípedes Constantino; Vallada, Homero
Purpose Cyclooxygenase (COX) enzymes, COX1 and COX2, are key in converting arachidonic acid (AA) into prostaglandins that have been associated with colorectal carcinogenesis. The aim of our study was to investigate associations of polymorphisms in COX genes, alone and in interaction with exposures known to be related to inflammation and AA metabolism, with risk of colorectal adenomas. Materials and methods In a community-, colonoscopy-based case–control study with 162 incident, sporadic colorectal adenoma cases and 211 controls, we investigated associations of two promoter polymorphisms (?842 A >G in COX1 and ?765 G>C in COX2) and two polymorphisms in the 3?-UTR of COX2 (8473 T>C and 9850 A>G) with risk of adenomas. Multiple logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma after adjusting for potential confounders. Results Overall, there was no evidence for an association between any of the four polymorphisms and colorectal adenomas. However, we found a statistically significant interaction between the COX2 8473 T>C polymorphism and nonsteroidal anti-inflammatory drug (NSAIDs) use (Pinteraction =0.03): The greatest reduced risk was observed for individuals with the 8473 C variant allele who also regularly used NSAIDs (OR=0.35, 95% CI 0.16–0.75). Conclusion These results suggest that the C allele of COX2 8473 T>C polymorphism may interact with NSAIDs to reduce risk for colorectal adenoma.
Gong, Zhihong; Bostick, Roberd M.; Hurley, Thomas G.; Deng, Zonglin; Dixon, Dan A.; Zhang, Jinhui; Hebert, James R.
OBJECTIVE Multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) susceptibility have been identified in predominantly European-derived populations. These SNPs have not been extensively investigated for individual and cumulative effects on T2D risk in African Americans. RESEARCH DESIGN AND METHODS Seventeen index T2D risk variants were genotyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control subjects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes. RESULTS Frequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs >1, and 5 from ADAMTS9, WFS1, CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P < 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95% CI 1.01–1.08], P = 0.010; weighted 1.06 [1.03–1.10], P = 8.10 × 10?5). When TCF7L2 SNP rs7903146 was included as a covariate, the risk score was no longer associated with T2D in either model (unweighted 1.02 [0.98–1.05], P = 0.33; weighted 1.02 [0.98–1.06], P = 0.40). CONCLUSIONS The trend of increase in risk for T2D with increasing risk allele load is similar to observations in European-derived populations; however, these analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans.
Cooke, Jessica N.; Ng, Maggie C.Y.; Palmer, Nicholette D.; An, S. Sandy; Hester, Jessica M.; Freedman, Barry I.; Langefeld, Carl D.; Bowden, Donald W.
OBJECTIVE: To investigate whether genetic variation at the UCP3 locus contributes to human obesity.SUBJECTS: Ninety-one obese children (BMI>4 standard deviations from age related mean) and 419 Caucasian adults from the Isle of Ely Study.DESIGN: Single strand conformation polymorphism (SSCP) analysis was used to scan the coding region of the UCP3 gene in 91 severely obese children. A common polymorphism identified
DJ Halsall; J Luan; P Saker; S Huxtable; J Keogh; NJ Wareham; S O'Rahilly
Nitric oxide is the primary mediator of vasodilation during mental stress. Since genetic polymorphisms in the nitric oxide\\u000a synthase (eNOS) gene seem to impair the production of NO, this study aimed to evaluate the effect of an exercise bout on hemodynamic\\u000a responses to mental stress in subjects with the 894G>T polymorphism of eNOS. Subjects without (wild-type group; n = 16) or with
Natália Galito Rocha; Fabricia Junqueira Neves; Bruno Moreira Silva; Allan Robson Kluser Sales; Antonio Claudio Nóbrega
BACKGROUND: UGT1A7 is an enzyme involved in the metabolism of (pre)carcinogens present in tobacco smoke. We investigated whether genetic polymorphisms in UGT1A7, with predicted altered enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis. METHODS: Blood samples from 427 patients with oral, pharyngeal, and laryngeal carcinoma and 420 healthy control subjects were investigated for UGT1A7 polymorphisms. Based
Martin Lacko; Hennie M. J. Roelofs; Rene H. M. te Morsche; Adri C. Voogd; Michael B. Oude Ophuis; Wilbert H. M. Peters; Johannes J. Manni
Mutant alleles with the 677C?T and 1298A?C polymorphisms of the MTHFR gene, and consequent lower methylentetrahydro- folate reductase enzyme activity, have been related to higher plasma homocysteine levels, which are associated with cardiovascular diseases. We assessed the genotype frequencies, degrees of fertility and homocysteine levels, and discuss a possible genetic selection for the gene polymorphisms studied. A total of 1777
A. Reyes-Engel; E. Munoz; M. J. Gaitan; E. Fabre; M. Gallo; J. L. Dieguez; M. Ruiz; M. Morell
Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee
The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The
Scott B. Shappell; George V. Thomas; Richard L. Roberts; Ron Herbert; Michael M. Ittmann; Mark A. Rubin; Peter A. Humphrey; John P. Sundberg; Nora Rozengurt; Roberto Barrios; Jerrold M. Ward; Robert D. Cardiff
Fc gamma receptors, and in particular genetic variation in these receptors, are important in disorders of hose defense, immunohematologic disease, and systemic autoimmune diseases. We investigated the His-Arg (CAT/CGT) polymorphism at codon 131 of the Fc gamma receptor IIA gene, which influences ligand binding by the receptor. Previously, individuals had been classified phenotypically on the basis of differential binding of murine immunoglobulin G1, but the Fc gamma receptor IIA genotype distribution has not been reported. We used selective PCR-based sequence analysis of genomic DNA to determine the distribution in healthy individuals. For African-Americans, the genotype distribution was determined to be A/A (14%), A/G (60%), and G/G (26%); for Caucasian Americans, the distribution was A/A (30%), A/G (51%), and G/G (19%). These data correlate well with phenotypic data. We implemented a nonradioactive single-stranded conformational polymorphism analysis to rapidly identify all three genotypes. The PCR-single-stranded conformational polymorphism analysis method will facilitate studies of the genotype distribution in individuals with disorders of immune function. Images
Reilly, A F; Norris, C F; Surrey, S; Bruchak, F J; Rappaport, E F; Schwartz, E; McKenzie, S E
Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed. PMID:23007265
Jackson, Maria D; Tulloch-Reid, Marshall K; McFarlane-Anderson, Norma; Watson, Alexis; Seers, Vestra; Bennett, Franklyn I; Egleston, Brian; Ragin, Camille
An impaired glutathione (GSH) synthesis was observed in several multifactorial diseases, including schizophrenia and myocardial infarction. Genetic studies revealed an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL). Disease-associated genotypes of this polymorphism correlated with a decrease in GCLC protein expression, GCL activity and GSH content. To clarify consequences of a decreased GCL activity at the proteome level, three schizophrenia patients and three controls have been selected based on the GCLC GAG TNR polymorphism. Fibroblast cultures were obtained by skin biopsy and were challenged with tert-butylhydroquinone (t-BHQ), a substance known to induce oxidative stress. Proteome changes were analyzed by two dimensional gel electrophoresis (2-DE) and results revealed 10 spots that were upregulated in patients following t-BHQ treatment, but not in controls. Nine corresponding proteins could be identified by MALDI mass spectrometry and these proteins are involved in various cellular functions, including energy metabolism, oxidative stress response, and cytoskeletal reorganization. In conclusion, skin fibroblasts of subjects with an impaired GSH synthesis showed an altered proteome reaction in response to oxidative stress. Furthermore, the study corroborates the use of fibroblasts as an additional mean to study vulnerability factors of psychiatric diseases. PMID:19041695
Gysin, René; Riederer, Irène M; Cuénod, Michel; Do, Kim Q; Riederer, Beat M
Aims Polymorphisms of the NOSIII gene and of the CYBA gene have been associated with a number of pathological conditions such as arterial hypertension, coronary artery disease, and myocardial infarction. Because endothelium-dependent vasodilation is impaired in these disorders, we hypothesized that polymorphisms of NOSIII or CYBA might modulate endothelial function of venous capacitance vessels already before cardiovascular disease becomes overt. Methods Endothelium-dependent and -independent venodilation was assessed by measuring local vascular responses to bradykinin and sodium nitroprusside in the dorsal hand vein after preconstriction with phenylephrine in 72 healthy male Caucasians after careful exclusion of cardiovascular risk factors. Genotyping was performed for polymorphisms of the NOSIII gene (T-786C, G894T, (CA)n) and the CYBA gene (C242T). Results Genotype distribution for each polymorphism followed the Hardy–Weinberg equilibrium. In all studied single nucleotide polymorphisms no significant difference between the respective genotypes and the venodilator response to either sodium nitroprusside or bradykinin was observed, and the number of CA repeat copies was not related to the venodilator response to bradykinin. Mean venodilation induced by bradykinin 50 ng min?1 (±SEM) for homozygote carriers of the single nucleotide polymorphisms was 48.9 ± 8.5% venodilation (G894T; wild type: 49.8 ± 6.9), 50.3 ± 11.0% venodilation (T-786C; wild type: 42.6 ± 5.2), and 30.4 ± 9.1% venodilation (C242T; wild type: 49.2 ± 6.0), respectively. Conclusions This study suggests that the studied polymorphisms of NOSIII and CYBA do not significantly modulate endothelium-dependent venodilation in individuals without vascular risk factors.
Fricker, Ruth; Hesse, Christiane; Weiss, Johanna; Tayrouz, Yorki; Hoffmann, Michael M; Unnebrink, Kristina; Mansmann, Ulrich; Haefeli, Walter E