Genetic Polymorphism Research Papers - Academia.edu (original) (raw)

n engl j med 360;5 nejm.org january 29, 2009 538 Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal 1. influenza immunization in mothers and infants. N Engl J Med 2008;359:1555-64. Ali HM, Scott R, Toms GL. The effect of foster feeding and 2. bottle feeding expressed breast-milk on the susceptibility of guinea-pig infants to influenza virus. Br J Exp Pathol 1989;70: 183-91. Chantry CJ, Howard CR, Auinger P. Full breastfeeding dura3. tion and associated decrease in respiratory tract infection in US children. Pediatrics 2006;117:425-32.

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- Kidney diseases, Medicine, Hypertension, Mutation

Pollen immigration can offset the effects of genetic drift and inbreeding in small populations. To understand the genetic consequences of forest fragmentation, estimates of pollen flow into remnant fragments are essential. Such estimates are straightforward for plants with singly sired, multiseeded fruits, since the pollen donor genotype for each fruit can be unambiguously reconstructed through full-sib genealogical analyses. Allozyme analyses were used to estimate pollen donor numbers from the progeny of fruits of the tropical dry forest tree Enterolobium cyclocarpum in a small (9.8 ha) fragmented population (N = 11) over three reproductive seasons (1994, 1995, and 1996). These analyses indicate that each tree receives pollen from many pollen donors. When data are pooled for the site, estimated maximum pollen donor pool sizes in all years exceed the number of individuals (56) in the 227 ha study area. Although unidentified pollen donors may be located as close as 250 m to the study...

- by John Nason
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- Genetics, Genetic Drift, Reproduction, Costa Rica

The diversity of local Mediterranean food elements is not known in detail, but offers itself to search for new vegetables, salads, fruits and spices which could be used in to enrich diets outside their region of origin. Most amid those interesting local elements are edible wild plants and weeds. Ethnobotanical research has identified ca. 2,300 different plant and fungi taxa, which are gathered and consumed in the Mediterranean. Among these, 1,000 are only consumed in one single zone, therefore are strictly local. The percentage of local gathered food plant (GFP) taxa (present in 5 samples), is higher in the main centers of diversity at the periphery of the Mediterranean (Sahara, Alps, Caucasus, Canary Islands, the Levant). Islands (Sicily, Sardinia, Crete, Cyprus) also show a high proportion. Endemism of GFP taxa only accounts for a limited number of these ‘ethnobotanical endemics’ (only ca. 350 are endemic/ endangered species). On the other hand, only a few taxa – 30 occurring in...

- by Michael Heinrich
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- History, Geography, Nutrition and Dietetics, Human Genetics
- by Shiva Zargham
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- Geography, Speciation, Molecular Evolution, Australia

Comparative genetic mapping in interspecific pedigrees presents a powerful approach to study genetic differentiation, genome evolution and reproductive isolation in diverging species. We used this approach for genetic analysis of an F 1 hybrid of two Eucalyptus tree species, Eucalyptus grandis (W. Hill ex Maiden.) and Eucalyptus globulus (Labill.). This wide interspecific cross is characterized by hybrid inviability and hybrid abnormality. Approximately 20% of loci in the genome of the F 1 hybrid are expected to be hemizygous due to a difference in genome size between E. grandis (640 Mbp) and E. globulus (530 Mbp). We investigated the extent of colinearity between the two genomes and the distribution of hemizygous loci in the F 1 hybrid using high-throughput, semi-automated AFLP marker analysis. Two pseudobackcross families (backcrosses of an F 1 individual to non-parental individuals of the parental species) were each genotyped with more than 800 AFLP markers. This allowed construction of de novo comparative genetic linkage maps of the F 1 hybrid and the two backcross parents. All shared AFLP marker loci in the three singletree parental maps were found to be colinear and little evidence was found for gross chromosomal rearrangements. Our results suggest that hemizygous AFLP loci are dispersed throughout the E. grandis chromosomes of the F 1 hybrid.

- by A Griffin
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- Technology, Biology, Genome Size, Medicine

Large-insert genomic bacterial artificial chromosome (BAC) libraries of two culturally and economically important oyster species, Crassostrea virginica and C. gigas, have been developed as part of an international effort to develop tools and reagents that will advance our ability to conduct genetic and genomic research. A total of 73,728 C. gigas clones with an average insert size of 152 kb were picked and arrayed representing an 11.8-fold genome coverage. A total of 55,296 clones with an average insert size of 150 kb were picked and arrayed for C. virginica, also representing an 11.8fold genome coverage. The C. gigas and C. virginica libraries were screened with probes derived from selected oyster genes using high-density BAC colony filter arrays. The probes identified 4 to 25 clones per gene for C. virginica and 5 to 50 clones per gene for C. gigas. We conducted a preliminary analysis of genetic polymorphism represented in the C. gigas library. The results suggest that the degree of divergence among similar sequences is highly variable and concentrated in intronic regions. Evidence supporting allelic polymorphism is reported for two genes and allelic and/or locus specific polymorphism for several others. Classical inheritance studies are needed to confirm the nature of these polymorphisms. The oyster BAC libraries are publicly available to the research community on a costrecovery basis at www.genome.clemson.edu.

- by Jeff Tomkins
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- Genetics, Technology, Genomics, Polymorphism

Abstract: RAPD markers were used to measure the genetic diversity of 119 individuals of Ixodes ricinus collected from Lithuania and Norway. The samples were analysed within and also between the populations. We analysed 74 loci in each of 6 populations. Our results show high levels of diversity within the populations. The percentage of polymorphic loci of the six analysed populations: Birzai, Vilnius, Kretinga, Tjore, Kjosvik and Odderoya were 68.9%, 58.1%, 78.38%, 62.2%, 44.6 % and 68.9%, respectively. The percentage of polymorphic loci in the Lithuanian populations was 93.2%, and in the Norwegian populations 81.08%. The genetic distance ranged from 0.019 to 0.079 within Norwegian populations and from 0.005 to 0.0967 within Lithuanian populations and between the countries from 0.022 to 0.146. The genetic variation of I. ricinus among Norwegian populations was lower than among Lithuanian populations. The highest part of genetic variation in I. ricinus ticks depends on variation withi...

- by J. Turcinaviciene
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- Zoology, Polymorphism, Genetic Diversity, DNA

Because polymorphisms in the methyl group metabolism genes methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and cystathione beta-synthetase (CBS) affect plasma homocysteine levels and intracellular concentrations of S-adenosylmethionine (SAM), they modify the susceptibility to cardiovascular diseases and cancer. Specifically, genome-wide decreased DNA methylation ('hypomethylation') in human cancers might be a consequence of decreased SAM levels. Because hypomethylation is particularly prevalent in transitional cell carcinoma of the urinary bladder (TCC), the genotype distributions for the two each most prevalent MTHFR, MS, and CBS alleles were compared between 165 TCC patients and 150 population controls. The distributions of the MTHFR 677A/V and the MS 919G/D alleles were not significantly different between cancer patients and controls, even after stratification according to age, gender, tumor stage or grade. The CBS 844INS68 allele was slightly less...

- by Christine Steinhoff
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- Polymorphism, DNA, Mutation, Methylation

This study looks at novel variants of the TGFb1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176... more

- by Khurshid Andrabi and +1
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- Genetics, Myopia, India, Genotype

1. Frog integumentary mucins (FIM-A.1, FIM-B.1 and FIM-C.1) consist of typical threonine-rich highly O-glycosylated (semi)repetitive domains, and cysteine-rich modules, i.e. the P-domain, the short consensus repeat and a region with high similarity to the C-terminal end of von Willebrand factor (designated here CC29-motif). 2. These modules are thought to be involved in protein-protein interactions and they have been observed in a variety of extracellular proteins. In FIMs, these modules may be involved in oligomerization processes leading to an entangled mucin network. 3. Polydispersities have been detected in FIM-B.1 and FIM-C.1 within single individuals. Multiple transcripts are probably generated by alternative splicing of a huge array of different (semi)repetitive cassettes encoding the threonine-rich domains. 4. Furthermore, genetic polymorphism is observed between different individuals, probably due to allelic variations in the number of (semi)repetitive cassettes.

- by Frank Hauser
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- Physiology, Skin, Glycosylation, Xenopus laevis

As Alzheimer's disease (AD) is a complex disease, we decided to estimate how previously reported genetic polymorphisms interact to increase the risk for the disease. Five candidate genes were chosen: apolipoprotein E (APOE), a2-macroglobulin, cathepsin D, myeloperoxidase and nitric oxide synthase. Genotyping was performed in 100 cases of late-onset AD and 100 healthy controls. We found a highly significant difference in APOE 14 distribution between groups (P , 0:005). However, no evidence of association for other studied loci was found. Cumulative analysis of five genetic polymorphisms was performed, but it also failed to reveal any synergistic effect of candidate genes greater than that caused by APOE itself. Our results suggest that the APOE 14 allele is the only known genetic risk factor for late-onset, sporadic AD. q

- by Dorota Religa
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- Genetics, Neuroscience, Psychology, Cognitive Science

The tumor necrosis factor and TNF receptor (TNF-TNFR) superfamily plays very important roles in the pathogenesis of many immune-mediated diseases. Regulation of TNF-TNFR superfamily gene expression influences many aspects of the pathology associated with these diseases. In order to investigate genetic variations in the regulatory regions of the TNF-TNFR superfamily genes, promoter regions were screened by sequencing DNA samples from 24 unrelated Korean individuals. We identified a total of 68 single-nucleotide polymorphisms (SNPs) in the regulatory regions of the known TNF-TNFR superfamily genes, including 50 SNPs in the promoter regions, 16 SNPs in the 5′-UTR regions, and two SNPs in the coding regions of these genes. Among the 68 SNPs identified in this study, 25 SNPs were novel SNPs. Interestingly, the sequence alteration created by 11 SNPs completely abolished putative transcription factor binding sites in these alleles. These results suggest that these SNP sites can regulate gene expression by controlling the binding of transcription factors. The identification of function-altering SNPs in the promoter regions of the TNF-TNFR superfamily will facilitate efforts to understand the association of TNF-TNFR superfamily genes with several immune-mediated human diseases.

- by Chan Park
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- Immunology, Polymorphism, Biology, Japan
- by Hiroshi Yatsuhashi
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- Japan, Adolescent, Medicine, Hepatitis B

Increasing expression of transforming growth factor-beta 1 (TGF-beta1) from fatty tissue affects the serum level and hence may stimulate expression of the other cytokines. The studies concerning the relation between TGF-beta1 polymorphisms and obesity have been performed in adults, and diverse results have been reported. In this study, we aimed to investigate the association of TGF-beta1 509 C/T, 915 G/C, 869 T/C polymorphisms in childhood obesity and related pathologies. Two hundred and seventy-one children and adolescents were included in the study. One hundred and twenty-one of these cases were in the Obese Group and 150 were in the Control Group. In the Obesity Group, we searched the carbohydrate and lipid metabolism disorders such as insulin resistance, dyslipidemia and hepatosteatosis. The results of this study revealed the lack of an association between TGF-beta1 509 C/T, 915 G/C and 869 T/C polymorphisms and obesity. There were no relations between the polymorphism genotypes...

- by Hasibe Verdi
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- Obesity, Turkey, Adolescent, Medicine

From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (PFJ, AGB, IHR, JS); the NHLBI Family Heart Study, University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City (RRW); the... more

- by Paul Jacques
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- Metabolism, Folic acid, Medicine, Mutation

Background: Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNA Gln T4336C). Case presentation: Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions: The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD.

- by Manuela Lima
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- Cognitive Science, Medicine, Case Report, Mutation

Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics in Czech EOPD patients. A total of 45 EOPD individuals (age at onset <45 years) were phenotyped and screened for parkin mutations. In total, 19 patients (42.2%) were carriers of previously described heterozygous genetic alterations. Parkin mutations (Ex2del, R402C) were identified in two (4.4%) cases, non-pathogenic variant A82E plus polymorphism D394N occurred in one (2.2%) patient and parkin polymorphisms (3x S167N, 1x R334C, 7x V380L, 4x D394N) were found in 15 (34.9%) individuals. Furthermore, the G2019S mutation in the LRRK2 gene was found in one (2.2%) subject. The clinical characteristics of our patients correspond to previous descriptions of EOPD phenotype. This is the first report on EOPD-associated genetic alterations among Czech patient...

- by Pavel Martasek
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- Czech Republic, Mutation, Polymerase Chain Reaction, Phenotype
- by Alan Boobis
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- Genetics, Polymorphism, Experience Design, Pharmacokinetics

Variation in human lifespan is 20 to 30% heritable but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. Genotyped variants (n=845,997) explained 10.2% (SD=1.3%) of combined parental longevity. In GWAS, a locus in the nicotine receptor CHRNA3 - previously associated with increased smoking and lung cancer - was associated with paternal age at death, with each protective allele (rs1051730[G]) being associated with 0.03 years later age at father's death (p=3x10-8). Offspring of longer lived parents had more protective alleles (lower genetic risk scores) for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer&#3...

Ž Ž . Cytogenetic markers chromosomal aberrations, sister chromatid exchanges SCE , cells with high frequency of SCE Ž . Ž . HFC , the heterogeneity index SCE SCE-H and genetic polymorphism of genotypes GSTM1 and NAT2 were evaluated in the peripheral lymphocytes of 64 coke oven workers and 34 control subjects from the same plant. Personal monitors were Ž . w x used to evaluate exposure to eight carcinogenic polycyclic aromatic hydrocarbons PAHs, including B a P, during an 8-h working shift. Smoking habits were checked by urinary cotinine measurement. The exposure among coke oven workers 3 3

- by Radim Šrám
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- Genetic Toxicology, Environmental Biotechnology, High Frequency, Mutation

La mutation G-> A en position 20210 du gène de la prothrombine (facteur II) est en fréquence le second polymorphisme génétique impliqué dans la thrombose veineuse. Nous proposons une étude rétrospective de 38 patients de notre service porteurs à l'état hétérozygote de cette mutation et une discussion avec revue de la littérature. Méthodes.-Nous avons étudié 38 patients porteurs hétérozygotes de la mutation 20210 du gène de la prothrombine, sélectionnés à partir d'une cohorte de 516 patients chez qui ce dosage avait été demandé, issus de notre service sur la période 1997-2002. Le motif de la demande était un événement thrombotique ou obstétrical, une angiopathie ou un dépistage familial. Résultats.-Vingt patients sur trente-huit ont au moins un épisode de thromboses veineuses superficielles et/ou profondes avec ou sans embolie pulmonaire. Un cas de thrombophlébite cérébrale est aussi observé. Des situations à risque de thrombose veineuse sont retrouvées dans 12 cas (soit 60 % des cas). Quatre patients sur trente-huit ont un événement thrombotique artériel de localisation coronaire, carotidienne et iliofémorale et cérébrale. Des facteurs de risque vasculaire artériel sont toujours associés. L'âge moyen de survenue de la première thrombose veineuse est plus précoce que pour la thrombose artérielle (39,11 ans contre 49,25 ans). Conclusion.-Notre étude plaide pour l'intérêt de la recherche de la mutation 20210 du gène de la prothrombine dans l'exploration d'un événement thrombotique veineux (thrombose veineuse profonde et/ou embolie pulmonaire), avec ou sans facteurs de risque acquis de thrombose. L'implication de cette mutation dans la pathologie thrombotique artérielle reste possible mais non démontrée, à ce jour. Il faut poursuivre les études concernant son rôle dans les maladies multisystémiques et les angiopathies (maladie de Léo Buerger, syndrome de Raynaud et migraine). Le mécanisme conduisant à la thrombose serait une augmentation des taux plasmatiques de la prothrombine et une génération accrue de thrombine.

- by S. Cremades
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- Literature Review, Deep Vein Thrombosis, Pulmonary Embolism, Risk factors

OBJECTIVE-Recent studies in European populations have reported a reciprocal association of glucokinase regulatory protein (GCKR) gene with triglyceride versus fasting plasma glucose (FPG) levels and type 2 diabetes risk. GCKR is a rate-limiting factor of glucokinase (GCK), which functions as a key glycolytic enzyme for maintaining glucose homeostasis. We examined the associations of two common genetic polymorphisms of GCKR and GCK with metabolic traits in healthy Chinese adults and adolescents. RESEARCH DESIGN AND METHODS-Two single nucleotide polymorphisms (SNPs), rs780094 at GCKR and rs1799884 at GCK, were genotyped in 600 healthy adults and 986 healthy adolescents. The associations of these SNPs with metabolic traits were assessed by linear regression adjusted for age, sex, and/or BMI. We also tested for the epistasis between these two SNPs and performed a meta-analysis among European and Asian populations. RESULTS-The T-allele of GCKR rs780094 was associated with increased triglycerides (P ϭ 5.4 ϫ 10 Ϫ7), while the A-allele of GCK rs1799884 was associated with higher FPG (P ϭ 3.1 ϫ 10 Ϫ7). A novel interaction effect between the two SNPs on FPG was also observed (P ϭ 0.0025). Meta-analyses strongly supported the additive effects of the two SNPs on FPG and triglycerides, respectively. CONCLUSIONS-In support of the intimate relationship between glucose and lipid metabolisms, GCKR and GCK genetic polymorphisms interact to increase FPG in healthy adults and adolescents. These risk alleles may contribute to increased diabetes risk in subjects who harbor other genetic or environmental/lifestyle risk factors.

- by Mitchell Martin
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- Genetics, Diabetes, Biology, China
- by Bert Gold
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- Genetics, Polymorphism, Intellectual Disability, Mental Retardation

Gender dysphoria, a marked incongruence between one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s experienced gender and biological sex, is commonly believed to arise from discrepant cerebral and genital sexual differentiation. With the discovery that estrogen receptor β is associated with female-to-male (FtM) but not with male-to-female (MtF) gender dysphoria, and given estrogen receptor α involvement in central nervous system masculinization, it was hypothesized that estrogen receptor α, encoded by the ESR1 gene, also might be implicated. To investigate whether ESR1 polymorphisms (TA)n-rs3138774, PvuII-rs2234693, and XbaI-rs9340799 and their haplotypes are associated with gender dysphoria in adults. Molecular analysis was performed in peripheral blood samples from 183 FtM subjects, 184 MtF subjects, and 394 sex- and ethnically-matched controls. Genotype and haplotype analyses of the (TA)n-rs3138774, PvuII-rs2234693, and XbaI-rs9340799 polymorphisms. Allele and genotype frequencies for the polymorphism XbaI were statistically significant only in FtM vs control XX subjects (P = .021 and P = .020). In XX individuals, the A/G genotype was associated with a low risk of gender dysphoria (odds ratio [OR] = 0.34; 95% CI = 0.16-0.74; P = .011); in XY individuals, the A/A genotype implied a low risk of gender dysphoria (OR = 0.39; 95% CI = 0.17-0.89; P = .008). Binary logistic regression showed partial effects for all three polymorphisms in FtM but not in MtF subjects. The three polymorphisms were in linkage disequilibrium: a small number of TA repeats was linked to the presence of PvuII and XbaI restriction sites (haplotype S-T-A), and a large number of TA repeats was linked to the absence of these restriction sites (haplotype L-C-G). In XX individuals, the presence of haplotype L-C-G carried a low risk of gender dysphoria (OR = 0.66; 95% CI = 0.44-0.99; P = .046), whereas the presence of haplotype L-C-A carried a high susceptibility to gender dysphoria (OR = 3.96; 95% CI = 1.04-15.02; P = .044). Global haplotype was associated with FtM gender dysphoria (P = .017) but not with MtF gender dysphoria. XbaI-rs9340799 is involved in FtM gender dysphoria in adults. Our findings suggest different genetic programs for gender dysphoria in men and women. Cortés-Cortés J, Fernández R, Teijeiro N, et al. Genotypes and Haplotypes of the Estrogen Receptor α Gene (ESR1) Are Associated With Female-to-Male Gender Dysphoria. J Sex Med 2017;14:464-472.

- by Rosa Fernandez
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- Psychology, Medicine, Haplotypes, Genotype

Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer. However, pronounced interethnic variations have been described in the frequencies of these polymorphisms, especially between Asians and Caucasians. The present study was set up to establish CYP2E1 (c1, c2 and C, D), CYP1A1 (m1, m2 and Ile, Val) and GSTM1 (null) allelic frequencies in Chileans (n 96) who are an admixture of Native Americans and Caucasians (Spaniards). The rare allele frequencies were found to be 0.15 (c2), 0.21 (C), 0.23 (m2), 0.32 (Val) and 0.21 ('null' genotype). These values are signi®cantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations. q

- by Luis Quiñones
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- Polymorphism, Chile, Native American, France

Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations. Single blood sample was collected after informed consent. Genomic DNA was extracted and genotype analysis for VKORC1 1173C>T and VKORC1-1639G>A polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. A number of samples were also analyzed by direct DNA sequencing for validation of results. Data were analyzed using SPSS version 20. Genotype frequency distributions of VKORC1 1173C>T and VKORC1-1639G>A were found to be different from other populations. Both of these polymorphisms did not demonstrate significant effect on warfarin dose requirement. Although Cytochrome P450 2C9 (CYP2C9) and VKORC1 polymorphisms together attributed only 3.8% variability in warfarin dose but it was statistically significant (p value ¼ .004). It is concluded that there is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome. At the same time, no effect on warfarin dose variation explained by VKORC1 polymorphisms and small variability explained by studied genotypes stresses the need for exploration of more genetic and nongenetic factors in Pakistani population.

- by Ali Kazmi
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- Pakistan, Pharmacogenetics, Young Adult, Aged

To phenotype 200 healthy North Indians for cytochrome P450 3A (CYP3A) activity by measuring urinary ratio of 6β-OH-cortisol/cortisol (6β-OH-CS/CS) and to genotype the subjects demonstrating low and high CYP3A activity for the presence of CYP3 A4*1B, *2, *4, *5, *6 and *10 alleles. Methods: Morning spot urine samples were collected from 200 healthy North Indians. CS and 6β-OH-CS were extracted and quantified by HPLC. Genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Results: Urinary 6β-OH-CS/CS ratio demonstrated a mean of 52.0 ± 46 (1.1-290). North Indians demonstrated unimodal distribution with respect to urinary 6β-OH-CS/CS ratio. On the basis of phenotypes, the subjects were divided into three groups demonstrating low (n=50), intermediate (n=100) and high (n=50) CYP3A activity. These groups demonstrated 6β-OH-CS/CS ratio of 13.4 ± 5.2 (1.1-21.0), 40 ± 11.9 (21.2-63.2) and 114 ± 51.0 (66-290), respectively. One hundred subjects, 50 in the low and 50 in the high activity group, were genotyped for CYP3A4*1B, *2, *4, *5, *6 and *10. Only 2 heterozygotes with genotype CYP3A4*1/*1B were found in the high CYP3A activity group. CYP3A4*2, *4, *5, *6 and *10 were not found in the subjects studied. Conclusion: This is the first investigation establishing CYP3A phenotypes and demonstrating the absence of common CYP3A4 genotypes in North Indians.

- by Naushad Rais
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- India, Cortisol, Pharmacogenetics, Polymerase Chain Reaction

The fungus Mycosphaerella fijiensis is the causative agent of black sigatoka, which is one of the most destructive diseases of banana plants. Infection with this pathogen results in underdeveloped fruit, with no commercial value. We analyzed the distribution of the M. fijiensis mating-type system and its genetic variability using M13 phage DNA markers. We found a 1:1 distribution of mating-type alleles, indicating MAT1-1 and MAT1-2 idiomorphs. A polymorphism analysis using three different primers for M13 markers showed that only the M13 minisatellite primers generated polymorphic products. We then utilized this polymorphism to characterize 40 isolates from various Brazilian states. The largest genetic distances were found between isolates from the ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (1): 443-452 (2013) C.B. Queiroz et al. same location and between isolates from different parts of the country. Therefore, there was no correlation between the genetic similarity and the geographic origin of the isolates. The M13 marker was used to generate genetic fingerprints for five isolates; these fingerprints were compared with the band profiles obtained from inter-simple sequence repeat (UBC861) and inter-retrotransposon amplified polymorphism analyses. We found that the M13 marker was more effective than the other two markers for differentiating these isolates.

- by Casley Queiroz
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- Genetics, Brazil, Molecular Genetics, Molecular Biology and genetics

MicroRNAs (miRNAs) are small, highly conserved, non-coding RNAs that regulate gene expression of target mRNAs through cleavage or translational inhibition. miRNAs are most often identified through computational prediction from genome sequences. The rainbow trout genome sequence is not available yet, which does not allow miRNA prediction for this species which is of great economic interest for aquaculture and sport fisheries, and is a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. To identify miRNAs from rainbow trout, we constructed a miRNA library from a pool of nine somatic tissues. Analysis of the library identified 210 unique sequences representing 54 distinct miRNAs; 50 with conserved sequences matching previously identified miRNAs and four novel miRNAs. In addition, 13 miRNAs were computationally predicted from the rainbow trout transcriptome. Real-time PCR was used to measure miRNA expression patterns in adult somatic tissues and unfertilized eggs. The majority of the miRNAs showed characteristic tissue-specific expression patterns suggesting potential roles in maintaining tissue identity. Potential miRNA-target interactions were computationally predicted and single nucleotide polymorphisms (SNPs) were identified in the miRNAs and their target sites in the rainbow trout transcripts. The rainbow trout miRNAs identified and characterized in this study provide a new tool for functional genome research in salmonids. Tissue-specific miRNAs may serve as molecular markers, predictive of specific functional and diagnostic implications. The data on genetic polymorphisms in miRNA-target interactions is particularly useful for rainbow trout breeding programs.

- by jianbo yao
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- Technology, MicroRNA, Disease ecology, Gene expression

Diabetic retinopathy (DR) may affect 98% of diabetic patients, but its aetiology is poorly understood. Besides glycaemic exposure, genetic factors likely contribute to the onset of DR. The polyol pathway, including aldose reductase and sorbitol dehydrogenase (SDH), can be activated under hyperglycaemic conditions. In our work we searched for an association between the C-1214G and G-888C polymorphisms of the SDH gene promoter and the occurrence and progression of type 2 DR. Two hundred and fifteen unrelated individuals with type 2 diabetes mellitus (T2DM) were divided into three groups: without DR, with non-proliferative diabetic retinopathy (NPDR) and with proliferative diabetic retinopathy (PDR). Genotypes of the C-1214G (rs2055858) and G-888C (rs3759890) polymorphisms of the SDH gene were determined with DNA from the peripheral blood lymphocytes of patients by restriction fragment length polymorphism and allele-specific PCR, respectively. The genotype distributions were contrasted by the chi(2) test and the significance of the polymorphism was assessed by multiple logistic regression producing odds ratios (ORs) and 95% confidence intervals (CIs). We found an association (OR 1.73, 95% CI 1.06-2.83) between NPDR and the G allele of the G-888C polymorphism. There was no association between NPDR and the other polymorphisms of the SDH gene. No differences were found in the distributions of these polymorphisms between patients with PDR and those with NPDR. A weak association (OR 2.0, 95% CI 1.29-3.07) was found between DR and the G allele of the G-888C polymorphism. Analysis of the combined genotypes (haplotypes) of both polymorphisms revealed associations between the C/G-C/G genotype and NPDR (OR 2.95, 95% CI 1.07-8.13) as well as DR in general (OR 2.91, 95% CI 1.15-7.36). The G-888C polymorphism of the SDH gene may be associated with the onset of DR rather than with its progression, and its effect may be strengthened by the interaction with the C-1214G polymorphism, but this association is rather weak and requires further study.

- by Janusz Blasiak and +1
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- Polymorphism, Logistic Regression, Diabetic Retinopathy, Polymerase Chain Reaction

In this study, genetic analyses of diversity and differentiation were performed on five horse breeds raised in Algeria (Barb, Arab-Barb, Arabian, Thoroughbred and French Trotter). All microsatellite markers were highly polymorphic in all the breeds. A total of 123 alleles from 14 microsatellite loci were detected in 201 horses. The average number of alleles per locus was the highest in the Arab-Barb horses (7.86) and lowest in the thoroughbred breed (5.71), whereas the observed and expected heterozygosities per breed ranged from 0.71 (Thoroughbred) to 0.752 (Barb) and 0.71 (Thoroughbred) to 0.77 (Arab-Barb), respectively. The genetic differentiation between the breeds was significant (p < 0.01) based on the infinitesimal model (FST ). Three different approaches for evaluating the genetic relationships were applied. Genetic distances, the factorial correspondence analysis and structure analysis showed that a significant amount of genetic variation is maintained in the native horse...

- by Gregoire Leroy
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- Breeding, Animal Production, Animal breeding and genetics, Algeria
- by George Uhl
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- Pain, Biological Sciences, Mice, Genetic Polymorphism

To examine the genetic diversity in Morocco, the polymorphism at the HLA-DRB1 locus was investigated in two populations: the Metalsa group consisting of Berbers from north Morocco (who speak the Tarifit language and live in the Nador area), and the Chaouya group who are Arabic-speaking people from west Morocco (Atlantic coast) living in the Settat area. The DRB1 alleles of 197 healthy unrelated individuals were identified by direct DNA sequencing of exon 2 using fluorescently-labeled primers. A total of 28 and 29 alleles at DRB1 locus were identified in the Metalsa and Chaouya groups, respectively. The most frequent alleles in the Metalsa group are DRB1*03011 (20.2%), DRB1*0701 (12.12%), and DRB1*1302 (11.11%). In the Chaouya group, DRB1*0701 (16.33%), DRB1*15011 (12.76%), and DRB1*03011 (11.73%) are most common. Each population exhibits some specific variants and some uncommon alleles. The frequency of the DRB1*03011 allele differs significantly between the two populations (p ϭ 0.0311). The DRB1 frequency distributions in the two groups suggest the effects of balancing selection. The interpopulation analysis highlighted a strong relatedness, based on genetic distances, between the two Moroccan groups and the other north Africans (the Moroccans from El Jadida area, Moroccan Souss Berbers, Algerians, and Tunisians), and to a lesser extent with the Iberians, French, and Ethiopians.

- by Rajae Aouad
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- Immunology, Polymorphism, Morocco, Genetic Diversity

DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correl...

- by Radim Šrám
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- Air pollution, Oxidative Stress, DNA damage, DNA

Background Individuals homozygous for the T allele of the MTHFR C677T polymorphism have higher plasma homocysteine concentrations (the phenotype) than those with the CC genotype, which, if pathogenetic, should put them at increased risk of stroke. Since this polymorphism is distributed randomly during gamete formation, its association with stroke should not be biased or confounded. We investigated consistency between the expected odds ratio for stroke among TT homozygotes, extrapolated from genotype-phenotype and phenotype-disease studies, and the observed odds ratio from a meta-analysis of genotype-disease association studies.

- by Leonelo Bautista
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- Causality, Medicine, Stroke, Risk factors

Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment-gene interactions to understand whether folate intake and maternal Pb exposure were associated with smaller newborn size in 474 women with uncomplicated pregnancies delivering term infants in Mexico City. We examined if folate intake modified the negative effects of maternal Pb burden on birth size. We also asked if maternal and infant methylenetetrahydrofolate reductase (MTHFR) genotypes (C677T, A1298C and G1793A) modified the effects of folate intake or Pb exposure on birth size. Women were aged 24·6 (SD 5·1) years; 43·5 % were primiparous. Maternal blood Pb at delivery was 86 (SD 42) μg/l, with 26·7 % having levels ≥100 μg/l. Tibia Pb level was 9·9 (SD 9·8) μg/g. Of the women, 35·3 % had folate intakes <400 μg/d. Birth weight was 3170 (SD 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (β 0·04; P<0·05). Higher bone Pb was associated with lower birth weight (β −4·9; P<0·05). Folate intake did not modify the effects of Pb on birth size, nor did MTHFR modify the association between Pb or folate intake on birth size. Although modest, the relationship between maternal nutrition, Pb burden and birth size does underscore the importance of environmental exposures to child health because patterns of fetal growth may affect health outcomes well into adulthood.

- by Alexandre Pereira
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- Engineering, Genetics, Nutrition and Dietetics, Nutrition

GSTM1, T1 and P1 are important enzymes of glutathione S-transferases (GSTs), involved in the metabolism of many endogenous and exogenous compounds. Individual genetic variation in these metabolizing enzymes may influence the metabolism of their substrates. The present study was designed to determine the genotoxic effects using DNA damage and its association with GSTM1, GSTT1, and GSTP1 (Ile105Val) genetic polymorphisms in workers occupationally exposed to organophosphate pesticides (OPs). We examined 230 subjects including 115 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using individual PCR or PCR–RFLP. Significantly higher DNA tail moment (TM) was observed in workers as compared to control subjects (14.41 ± 2.25 vs. 6.36 ± 1.41 tail % DNA, p < 0.001). The results revealed significantly higher DNA TM in workers with GSTM1 null genotype than those with GSTM1 positive (15.18 vs. 14.15 tail % DNA, p = 0.03). A significantly higher DNA TM was also observed in workers with homozygous Ile–Ile GSTP1 genotype than heterozygous (Ile–Val) and mutant (Val–Val) GSTP1 genotype (p = 0.02). In conclusion, the results show that null deletion of GSTM1 and homozygote wild GSTP1 genotype could be related to inter-individual differences in DNA damage arises from the gene–environment interactions in workers occupationally exposed to OPs.• DNA damage and its association with GSTM1, GSTT1 and GSTP1 genotypes carried out. • Workers with exposure to organophosphate pesticides found increased DNA damage. • DNA damage observed to be associated with GSTM1 null and GSTP1 Ile/Ile genotypes.

- by Shyam GROVER
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- Genetic Toxicology, DNA damage, Environmental Biotechnology, Mutation
- by Claudio Franceschi
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- Genetics, Immune response, Polymorphism, Inflammation

The clinical efficacy of anticancer nucleoside drugs depends on a complex interplay of transporters mediating entry of nucleoside drugs into cells, efflux mechanisms that remove drugs from intracellular compartments and cellular metabolism to active metabolites. Nucleoside transporters (NTs) are important determinants for salvage of preformed nucleosides and mediated uptake of antimetabolite nucleoside drugs into target cells. The focus of this review is the two families of human nucleoside transporters (hENTs, hCNTs) and their role in transport of cytotoxic chemotherapeutic nucleoside drugs. Resistance to anticancer nucleoside drugs is a major clinical problem in which NTs have been implicated. Single nucleotide polymorphisms (SNPs) in drug transporters may contribute to interindividual variation in response to nucleoside drugs. In this review, we give an overview of the functional and molecular characteristics of human NTs and their potential role in resistance to nucleoside drugs and discuss the potential use of genetic polymorphism analyses for NTs to address drug resistance.

- by John Mackey
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- Polymorphism, Cancer, Cell Cycle, Apoptosis

To investigate in a population sample of Portuguese young adults the association of the FTO variant rs9939609 with obesity, BMI, and body-fat and interaction with physical activity (PA) on obesity-susceptibility. SNP rs9939609 A/T was genotyped in 550 subjects (231 males and 319 females; 18-36 years old; mean age 21 years old) by TaqMan assay. PA was assessed with a validated self-reported questionnaire of IPAQ. We replicated the association of rs9939609-A risk allele with BMI (P = 0.04) and fat-mass (P = 0.031), and with overweight (including obesity) under a recessive model (P = 0.034). Stratified analyses showed (i) a significant association with overweight/obesity in inactive individuals (P = 0.02) but not in a group reporting participation in sports (P = 0.97). Spearman's correlation test suggested that the impact of a successive increase in PA was a decrease in the body-fat percentage (r = -0.16; P = 0.0002), which is accentuated for homozygous AA (r = -0.34; P = 0.002), a...

- by Licinio Manco
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- Evolutionary Biology, Nutrition and Dietetics, Anthropology, Obesity

DNA integrity was analyzed in the lymphocytes of 65 non-smoking city policemen during January and September 2004 using the comet assay combined with excision repair enzymes. Information about inhalation exposure was obtained by (1) stationary monitoring of PM2.5 and carcinogenic polycyclic aromatic hydrocarbons (cPAHs) during the sampling periods and (2) personal exposure monitoring of cPAHs 48 h before blood sampling. The data were completed by a lifestyle questionnaire. Regardless of the season of the year, policemen working outdoors (exposed group) exhibited higher levels of DNA damage than those working indoors (controls). Within the exposed group, the levels of both unspecified and oxidative DNA damage detected in January significantly exceeded those found in September. The controls did not show analogous inter-seasonal variability. The winter levels of oxidative DNA damage positively correlated with exposure to cPAHs, probably reflecting increased oxidative stress as a result of high concentrations of PM2.5. In comparison with the wild type genotype, the carriers of at least one mutated allele, CYP1A1*2C (Ile/Val), MTHFR 2656 or MS 2656, and the EPHX1-medium phenotype appeared to be more susceptible specifically to the induction of oxidative DNA damage, while the p53 MspI mutation predisposed the carrier to a higher incidence of both breaks and oxidative lesions in DNA. In contrast, GSTM1-null and vitamin C tended rather to protect DNA integrity.

- by Radim Šrám
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- Police, Environmental Monitoring, Air pollution, Oxidative Stress

We estimated the genetic gains of the 12th cycle of reciprocal recurrent selection for maize traits of agronomic interest. We used 23 ISSR molecular markers in an attempt to maximize genetic variability among and within populations based on selection of S 1 progenies. To this end, 138 full-sib families were evaluated in a randomized block design in two environments (the municipalities of Campos dos Goytacazes and Itaocara, in the State of Rio de Janeiro, Brazil), with replications within sets. Direct selection for grain yield was used for the selection of the families. To assess genetic diversity among and within populations, we examined plants produced from part of the S 1s seeds from the parents that originated the 42 full-sib families that were selected from the agronomic traits. Direct selection for grain yield provided good gains for the traits evaluated, with estimated improvement of-0.87 days for days to flowering, 0.35 plants, 1.79 ears per plot, 0.58 g per 100-grain weight, 308.21 g ear weight per plot, and 261.83 kg/ha grain yield. Application of molecular markers at the stage of superior progeny selection led to increased genetic distance among populations, which is a very important factor for maximizing the ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3398-3408 (2012) Maize reciprocal recurrent selection 3399 utilization of heterosis and providing greater longevity to the reciprocal recurrent selection program.

- by Ana Berilli
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- Genetics, Population Genetics, Principal Component Analysis, Biology

Genomic microsatellite markers are capable of revealing high degree of polymorphism. Sugarcane (Saccharum sp.), having a complex polyploid genome requires more number of such informative markers for various applications in genetics and breeding. With the objective of generating a large set of microsatellite markers designated as Sugarcane Enriched Genomic MicroSatellite (SEGMS), 6,318 clones from genomic libraries of two hybrid sugarcane cultivars enriched with 18 different microsatellite repeat-motifs were sequenced to generate 4.16 Mb high-quality sequences. Microsatellites were identified in 1,261 of the 5,742 non-redundant clones that accounted for 22% enrichment of the libraries. Retrotransposon association was observed for 23.1% of the identified microsatellites. The utility of the microsatellite containing genomic sequences were demonstrated by higher primer designing potential (90%) and PCR amplification efficiency (87.4%). A total of 1,315 markers including 567 class I microsatellite markers were designed and placed in the public domain for unrestricted use. The level of polymorphism detected by these markers among sugarcane species, genera, and varieties was 88.6%, while crosstransferability rate was 93.2% within Saccharum complex and 25% to cereals. Cloning and sequencing of size variant amplicons revealed that the variation in the number of repeat-units was the main source of SEGMS fragment length polymorphism. High level of polymorphism and wide range of genetic diversity (0.16-0.82 with an average of 0.44) assayed with the SEGMS markers suggested their usefulness in various genotyping applications in sugarcane. Communicated by A. Kilian.

- by Nagendra Singh
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- Genetics, Technology, Polymorphism, Public Domain

Prolonged cannabis use has a significant impact on health and well-being. Genetic factors are known to influence cannabis dependence, but few specific genetic markers have been identified. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. The objective of this study is to determine if ABCB1

- by Robert Farinotti and +1
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- Genetics, Addiction, Nonparametric Statistics, Polymorphism

Aim To determine the human Y-chromosome haplogroup backgrounds of non-consensus DYS458.2 short tandem repeat alleles and evaluate their phylogenetic substructure and frequency in representative samples from the Middle East, Europe, and Pakistan. Methods Molecular characterization of lineages was achieved using a combination of Y-chromosome haplogroup defining binary polymorphisms and up to 37 short tandem repeat loci, including DYS388 to construct haplotypes. DNA sequencing of the DYS458 locus and median-joining network analyses were used to evaluate Y-chromosome lineages displaying the DYS458.2 motif. Results We showed that the DYS458.2 allelic innovation arose independently on at least two distinctive binary haplogroup backgrounds and possibly a third as well. The partial allele length pattern was fixed in all haplogroup J1 chromosomes examined, including its known rare sub-haplogroups. Within the alternative R1b3 associated M405 defined sub-haplogroup, both DYS458.0 and DYS458.2 allele classes occurred. A single chromosome also allocated to the R1b3-M269*(xM405) classification. The physical position of the partial insertion/deletion occurrence within the normal tetramer tract differed distinctly in each haplogroup context. Conclusions While unusual DYS458.2 alleles are informative, additional information for other linked polymorphic loci is required when using such non-conforming alleles to infer haplogroup background and common ancestry.

- by Peter Underhill
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- Population Genetics, Pakistan, Turkey, Europe
- by Walter Kaufmann
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- Genetics, Central Nervous System, Fragile X Syndrome, Phenotype

The maintenance of genetic variation in traits under natural selection is a long-standing paradox in evolutionary biology 1-3 . Of the processes capable of maintaining variation, negative frequency-dependent selection (where rare types are favoured by selection) is the most powerful, at least in theory 1 ; however, few experimental studies have confirmed that this process operates in nature. One of the most extreme, unexplained genetic polymorphisms is seen in the colour patterns of male guppies (Poecilia reticulata) 4,5 . Here we manipulated the frequencies of males with different colour patterns in three natural populations to estimate survival rates, and found that rare phenotypes had a highly significant survival advantage compared to common phenotypes. Evidence from humans 6,7 and other species 8,9 implicates frequency-dependent survival in the maintenance of molecular, morphological and health-related polymorphisms. As a controlled manipulation in nature, this study provides unequivocal support for frequency-dependent survival-an evolutionary process capable of maintaining extreme polymorphism.

- by David Reznick
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- Evolutionary Biology, Pigmentation, Polymorphism, Population Dynamics
- by Claudio Franceschi
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- Genetics, Technology, Polymorphism, Multidisciplinary