SNPs In Candidate Genes Research Articles

A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11.

Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P=0.017; 50% vs. 39%, P=0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.

Analysis of nonsynonymous SNPs in candidate genes that influence bovine temperament and evaluation of their effect in Brahman cattle.

Temperament is an important production trait in cattle and multiple strategies had been developed to generate molecular markers to assist animal selection. As nonsynonymous single nucleotide polymorphisms are markers with the potential to affect gene functions, they could be useful to predict phenotypic effects. Genetic selection of less stress-responsive, temperamental animals is desirable from an economic and welfare point of view. Two nonsynonymous single nucleotide polymorphisms identified in HTR1B and SLC18A2 candidate genes for temperament were analyzed in silico to determine their effects on protein structure. Those nsSNPs allowing changes in proteins were selected for a temperament association analysis in a Brahman population. Transversion effects on protein structure were evaluated in silico for each amino acid change model, revealing structural changes in the proteins of the HTR1B and SLC18A2 genes. The selected nsSNPs were genotyped in a Brahman population (n = 138), and their genotypic effects on three temperament traits were analyzed: exit velocity, pen score, and temperament score. Only the SNP rs209984404-HTR1B (C/A) showed a significant association (P = 0.0144) with pen score. The heterozygous genotype showed a pen score value 1.17 points lower than that of the homozygous CC genotype. The results showed that in silico analysis could direct the selection of nsSNPs with the potential to change the protein. Non-synonymous single nucleotide polymorphisms causing structural changes and reduced protein stability were identified. Only rs209984404-HTR1B shows that the allele affecting protein stability was associated with the genotype linked to docility in cattle.

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

SNP discovery and association study for growth, fatness and meat quality traits in Iberian crossbred pigs

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR, ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3, DENND1B, SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10, NLE1, KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits.

Genome wide association study of frost tolerance in wheat

Winter wheat growing areas in the Northern hemisphere are regularly exposed to heavy frost. Due to the negative impact on yield, the identification of genetic factors controlling frost tolerance (FroT) and development of tools for breeding is of prime importance. Here, we detected QTL associated with FroT by genome wide association studies (GWAS) using a diverse panel of 276 winter wheat genotypes that was phenotyped at five locations in Germany and Russia in three years. The panel was genotyped using the 90 K iSelect array and SNPs in FroT candidate genes. In total, 17,566 SNPs were used for GWAS resulting in the identification of 53 markers significantly associated (LOD ≥ 4) to FroT, corresponding to 23 QTL regions located on 11 chromosomes (1A, 1B, 2A, 2B, 2D, 3A, 3D, 4A, 5A, 5B and 7D). The strongest QTL effect confirmed the importance of chromosome 5A for FroT. In addition, to our best knowledge, eight FroT QTLs were discovered for the first time in this study comprising one QTL on chromosomes 3A, 3D, 4A, 7D and two on chromosomes 1B and 2D. Identification of novel FroT candidate genes will help to better understand the FroT mechanism in wheat and to develop more effective combating strategies.

Genetic diversity of meat quality related genes in Argentinean pigs

Genetic influence on pork quality exists between breeds and within a breed. The variation is caused by a large set of genes, and pork quality traits have a multifactorial background. Research into the genetics of meat quality found causative mutations associated with marked effects on pig meat value. This study aimed to investigate the segregation of meat quality-related SNPs and compare their diversity and genetics in commercial and Creole pigs from different farms in the North-West of Argentina. A screen for SNPs in RYR1, PRKAG3, CAST, and SOX6 candidate genes and the differentiation of their genotypes by PCR–RFLP was conducted. All genes were characterized by a high level of polymorphism and heterozygosity, and populations showed no differences in the genetic structure for the analyzed SNPs. These results highlighted the role of pig genotypes as a source of basic variability potentially affecting processed meat products and fresh meat.

Genes Involved in Physiological Dysregulation and Decline in Resilience: Role in Alzheimer’s Disease

Our recent GWAS of a composite measure of physiological dysregulation (PD) in the Long Life Family Study (LLFS) found that the top genes associated with age-related changes in PD are involved in biological pathways relevant to maintaining neural networks and brain resilience. In our prior work, PD itself was linked to resilience-related traits. Alzheimer’s disease (AD) is a heterogeneous trait and it may involve an accelerated decline in resilience with age as a contributing factor. We proposed that genes associated with aging-changes in PD and brain resilience may contribute to AD risk. We investigated interactions between SNPs in such candidate genes with AD in LLFS and Health and Retirement Study (HRS). Our analysis revealed significant interactions between SNPs in UNC5C and other genes with AD, in both LLFS and HRS. These findings support roles of genetic interactions with UNC5C gene (implemented in axon growth and neuronal apoptosis) in AD.

Genes Involved in Physiological Dysregulation and Decline in Resilience: Role in Alzheimer’s Disease

BackgroundUnscheduled emergency department (ED) revisits leading to acute hospital admission (RVA) are tantamount to a failed discharge, associated with physician error, mis-prognosis, and inadequate care planning. Previous research has shown RVA to be associated with adverse outcomes such as ICU admissions, long hospitalizations and mortality. Given the limited impact of pre-existing screening tools for older adults, we developed and validated a machine learning model to predict individual patient risk of RVA within 72 hours and 9 days of index ED visits. Method: A machine learning model was applied to retrospective electronic health record (EHR) data of patients presenting to 2 geographically and demographically divergent urban EDs in 2019. 478 clinically meaningful EHR data variables were included: socio-demographics, ED and comorbidity diagnoses, therapeutics, laboratory test orders and test results, diagnostic imaging test orders, vital signs, and utilization and operational data. Multiple machine learning algorithms were constructed; models were compared against a pre-existing adult ED-RVA risk score as a baseline.ResultsA total of 62,154 patients were included in the analysis, with 508 (0.82%) and 889 (1.4%) having 72-hour and 9-day RVA. The best-performing model, combining deep significance clustering (DICE) and regularized logistic regression, achieved AUC of 0.86 and 0.79 for 72-hour and 9-day ED-RVA for older adult patients, respectively, outperforming the pre-existing RVA risk score (0.704 and 0.694).DiscussionMachine learning models to screen for and predict older adults at high-risk for ED-RVA may be useful in directing interventions to reduce adverse events in older adults discharged from the ED.

Polymorphism of candidate genes associated with reproductive performance in crossbred pigs

This investigation was done to analyze the polymorphism of 5 SNPs in candidate genes associated with reproductive performance in crossbred pig population by PCR-RFLP. The results revealed that out of 5 SNPs genotyped, 2 were polymorphic and 3 were monomorphic. Genotypic frequency of crossbred pigs were CC (100%) for ESR1; GG (21%), GT 65%) and TT (14%) for Prei3; CC (100%) for FSHβ; AA (100%) for OPN and CC (21%), CT (63%) and TT (16%) for CDK20 SNPs, respectively. Allelic frequencies for these SNPs {ESR1 (c.1227C>T), Prei3 (T802G), FSHβ (c.930A>G), OPN (c.425G>A) and CDK20 (T96C)} were 1.00 (C), 0.53 and 0.47 (G/T), 1.00 (C), 1.00 (A) and 0.52 and 0.48 (C/T), respectively. The least squares analysis revealed that both polymorphic SNPs had non-significant effect on litter traits. The values of PIC, heterozygosity and allelic diversity indicated that crossbred population under investigation was of intermediate diversity for both polymorphic SNP loci.

Genome-wide discovery of SNPs in candidate genes related to production and fertility traits in Sahiwal cattle.

The present study was carried out to identify genome-wide genetic markers and variants in candidate genes for production and reproduction traits in Sahiwal cattle using a cost-effective reduced representation sequencing method. A total of 258,231 genome-wide SNPs were identified in Sahiwal cattle with reference to Bos indicus genome, of which 150,231 were novel SNPs. Among the high-confidence SNPs identified, 91.86% and 27.30% were genotyped in 50% and 100% of the samples. Mapping of the identified SNPs revealed 525 SNPs in candidate genes related to production traits while 333 SNPs were mapped to candidate genes related to reproduction traits. The SNPs identified in this study will facilitate further insights on tropical adaptation, domestication history and population structure of indigenous cattle. The variants in candidate genes identified in this study will serve as useful genetic tools, in the quest for phenotype modifying nucleotide change and help in designing appropriate genetic improvement programs.

Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil

BackgroundHost genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. MethodsWe examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. ResultsAmong 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15–12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26–272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). ConclusionsPolymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

Evaluation of genetic association of 40 SNPs in candidate genes with cholesterol gallstone disease in north Indian population

BackgroundIn north Indian population, Gallbladder Stone Disease (GSD) affects 7% of population, with majority of stones containing >50% cholesterol. In general, GSD susceptibility has been suggested to include the combination of predisposing alleles of multiple lithogenic (LITH) genes and environmental factors. Materials and methodsStudy included 610 GSD patients (USG positive) and 315 healthy controls. A panel of 48 SNPs was prepared for candidate genes based on pathobiology of GSD, MAF in Hapmap and 1000 genome database, and Tagger SNPs in Linkage Disequilibrium. Genotyping was carried out by Sequenom Mass ARRAY platform and statistical analyses were performed using SPSS version 16.0, Bonferroni adjustment was applied for multiple testing corrections. Potential functional consequences of the exonic polymorphisms were determined using Polyphen2, SIFT score and interaction networks of associated genes by GENEMANIA. ResultsGenotypes of 40 out of 48 SNPs followed Hardy Weinberg Equilibrium in controls and subjected to present analysis. We observed significant associations of genotypes/alleles of FGFR4, CYP7A1, APOE, TM4SF4, NR1H2, IL10, PLCE1, CYP1A1, SLC10A2, MMP2, CYP8B1, Gab1 with GSD whereas remaining SNPs revealed no association.Analysis after gender stratification and Bonferroni correction revealed that in males SNPs in TM4SF4, PLCE1 and Gab1 were significantly associated with GSD while in females APOE and CYP8B1 polymorphisms were significantly associated with GSD.All but three significantly associated SNPs were intronic. The potential functional consequences of associated exonic SNPs by Polyphen2 predicted probable damaging effects of FGFR4 and APOE variants, while PLCE1 SNP showed benign effect. Further SIFT score predicted probable tolerated effects of FGFR4 and PLCE1, while APOE variant showed deleterious effect. ConclusionsOur study suggests that FGFR4, CYP7A1, APOE, TM4SF4, NR1H2, IL10, PLCE1, CYP1A1, SLC10A2, MMP2, CYP8B1 genetic variants confer significant risk for gallstone disease in North Indian population. The association of many genes with disease risk was found to be sex-specific.

Genetic polymorphisms associated with type 2 diabetes in the Arab world: A systematic review and meta-analysis

AimsT2DM reach epidemic levels in the Arab countries. In this study, we aimed to perform a systematic review and meta-analysis to underline the susceptibility genetic profile of Arab patients with T2DM that result from SNPs. MethodsWe searched four literature databases (PubMed, Scopus, Science Direct and Web of Science) through January 2019. We included all SNPs in candidate genes with an OR > 1 that were associated with T2DM among Arab patients with T2DM. Statistical programs such as software Review Manager (Version 5.02) and STATA (Version 15.1) were used. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random effects model or a fixed effect model depending on the heterogeneity among studies. I2 statistics and Egger’s tests were performed to assess heterogeneity and publication bias. ResultsOut of 2245 studies, 47 were used for meta-analysis. We captured 31,307 cases and 26,464 controls in which we collected 71 SNPs in 32 genes. A pooled meta-analysis demonstrated 24–69% increase in T2DM risk. Among the 57 SNPs (in 32 genes) that were not included in the meta-analysis, the OR for diabetes ranged from 1.02 to 5.10, with a median of 1.38 (interquartile range 1.33–2.09). Ten studies examined the association between the TCF7L2 polymorphism rs7903146 and T2DM, leading to an aggregated OR of 1.34 (95%CI 1.27–1.41). ConclusionThe genetic profile that confer susceptibility to T2DM in Arab patients is diverse. This study may serve as a platform for designing a gene panel for testing the susceptibility to T2DM.

Associations of CYP2C9 and CYP2A6 Polymorphisms with the Concentrations of Valproate and its Hepatotoxin Metabolites and Valproate-Induced Hepatotoxicity.

The aim of this study was to compare genetic polymorphisms and concentrations of hepatotoxic metabolites in patients with epilepsy and liver injury and those with normal liver function receiving valproate monotherapy to identify risk factors for VPA-induced hepatotoxicity. A total of 279 Chinese patients with epilepsy were divided into an abnormal liver function (ANLFT) group (n = 79) and a normal liver function (NLFT) group (n = 200). Polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP and nested PCR were applied to identify the frequency of two SNPs in candidate genes. Serum concentrations of VPA and its major metabolites were determined by Ultra-Performance Liquid Chromatography-tandem mass spectrometry UPLC-MS/MS. Significant differences were found in genotype distributions of CYP2A6 and CYP2C9 between the two groups. The values of 4-ene-VPA and 2,4-diene-VPA in the ANLFT group were significantly higher than in the NLFT group. Only CYP2A6 polymorphisms had associations with the concentrations of 4-ene-VPA and 2,4-diene-VPA. CYP2A6*1/*4 and CYP2A6*4/*4 variant carriers had higher CDR4-ene-VPA and CDR2,4-diene-VPA values than CYP2A6*1/*1 carriers. The logistic regression analysis showed that CYP2C9 and CYP2A6 were significant risk factors for hepatotoxicity by increasing the risk by 7.50 and 5.13 times, respectively. These findings provide preliminary evidence that CYP2A6 and CYP2C9 are associated with hepatotoxicity. However, only the CYP2A6 polymorphism was found to be associated with concentrations of 4-ene-VPA and 2,4-diene-VPA. Potential important risk factors include mutated genotypes of CYP2C9 and CYP2A6 and higher concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA.

A combination test for detection of gene-environment interaction in cohort studies.

Identifying gene-environment (G-E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G-E interaction is the lack of power due to sample size. Studies often restrict the interaction search to the top few hundred hits from a genome-wide association study or focus on potential candidate genes. In this paper, we test interactions between a candidate gene and an environmental factor to improve power by analyzing multiple variants within a gene. We extend recently developed score statistic based genetic association testing approaches to the G-E interaction testing problem. We also propose tests for interaction using gene-based summary measures that pool variants together. Although it has recently been shown that these summary measures can be biased and may lead to inflated type I error, we show that under several realistic scenarios, we can still provide valid tests of interaction. These tests use significantly less degrees of freedom and thus can have much higher power to detect interaction. Additionally, we demonstrate that the iSeq-aSum-min test, which combines a gene-based summary measure test, iSeq-aSum-G, and an interaction-based summary measure test, iSeq-aSum-I, provides a powerful alternative to test G-E interaction. We demonstrate the performance of these approaches using simulation studies and illustrate their performance to study interaction between the SNPs in several candidate genes and family climate environment on alcohol consumption using the Minnesota Center for Twin and Family Research dataset.

Inbreeding and genetic diversity loss of four cattle beef breeds in Slovakia

Received: 2016-02-23  |  Accepted: 2016-04-21  |  Available online: 2016-05-30 dx.doi.org/10.15414/afz.2016.19.02.59-63 The aim of the paper was to evaluate trends in inbreeding and loss of genetic diversity in four beef cattle breeds (Blonde d´Aquitaine-BA, Charolais-CH, Limousine-LI, Simmental-SM). The highest ratio of inbred animals was found in the SM breed (63.6 %) and the lowest in the LI (14.1 %). The highest average inbreeding intensity we found in the SM, the lowest in the BA. The amount of genetic diversity in the reference population accounting for diversity loss due to genetic drift and unequal founder contributions was the highest in the SM (6.2 %), following the BA (3.5 %), LI (1.1 %) and CH (0.9 %). The proportion of genetic diversity lost due to genetic drift was higher in BA, CH, LI than the loss of genetic diversity due to unequal founder contribution. Keywords: beef cattle, pedigree analysis, inbreeding, genetic diversity References Boichard, D., Maignel,L. and Verrier. E. (1997) The value of using probabilities of gene origin to measure genetic variability in a population. Genet. Sel. Evol ., vol.29, no. 5, pp.5-23. doi: http://dx.doi.org/10.1186/1297-9686-29-1-5 Cabalero, A. and Toro, M.A. (2000) Interrelations between effective population size and other tools for management of conserved populations. Genet. Res ., vol. 75, no. 3, pp.331-343. doi: http://dx.doi.org/10.1017/S0016672399004449 Gutiérrez, J.P. and Goyache, F. ( 2005) Note on ENDOG: a computer program for analysis pedigree information. J. Anim.Breed. Genet ., vol.122. pp.172-176. Gutiérrez, J.P., Goyache, F. and Cervantes, F. ( 2009) Endog v 4.6. A computer program for monitoring genetic variability of populations using pedigree information. User guide . Madrid: Universidad Complutense de Madrid. 45 p.. Kadlečík, O. and Pavlík,I. (2012) Genealogical analysis in small populations: The case of four Slovak beef cattle breeds. Slovak J. Anim. Sci., vol. 45, no. 4. pp. 111-117. Kasarda. R. and Kadlečík. O. (2007) An economic impact of inbreeding in the purebred population of Pinzgau cattle in Slovakia on milk production traits. Czech J. Anim. Sci., vol. 52, no. 1, pp. 7-11. Krupa, E., Žáková, E. and Krupová, Z. (2015) Evaluation of inbreeding and genetic variability of five pig breeds in Czech Republic. Asian Australas. J.Anim. Sci.. vol. 28, no. 1, pp. 25-36. doi: http://dx.doi.org/10.5713/ajas.14.0251 Lacy, R.C. (1989) Analysis of founder representation in pedigree: Founder equivalents and founder genome equivalents. Zool.Biol ., vol. 8, no. 2, pp. 111-123. doi: http://dx.doi.org/10.1002/zoo.1430080203 Lacy, R.C. (1995) Classification of genetic terms and their use in the management of captive populations. Zoo. Biol ., vol. 14, no. 6, pp. 565-577. doi: http://dx.doi.org/10.1002/zoo.1430140609 Melka, M.G. et al. (2013) Analyses of genetic diversity in five Canadian dairy breeds using pedigree data. J. Anim. Breed. Genet ., vol. 130, pp. 476–486. doi:http://dx.doi.org/10.1111/jbg.12050 McParland, S. et al. (2007) Inbreeding trends and pedigree analysis of Irish dairy and beef cattle populations. Journal of Animal Science , vol. 85, no. 2, pp.322-331. doi: http://dx.doi.org/10.2527/jas.2006-367 Maignel, L., Boichard, D. and Verrier.E. (1996) Genetic variability of French dairy breeds estimated from pedigree information. Interbul Bulletin , vol. 14, pp.49-54. Meuwissen, T.H.E. and Luo,Z. (1992) Computing in breeding coefficients in large populations. Genet. Sel. Evol., vol. 24. pp. 305-313. doi:http://dx.doi.org/10.1186/1297-9686-24-4-305 Pavlík.I, et al. (2014) Pedigree analysis of Thoroughbred horses in Slovakia. Acta fytotechnica et zootechnica, vol. 17, no. 4, pp. 122-126. doi: http://dx.doi.org/10.15414/afz.2014.17.04.122-126 Stachowic, K. et al. (2011) Schenkel Rates of inbreeding and genetic diversity in Canadian Holstein and Jersey cattle. J. Dairy Sci ., vol. 94, no.  10, pp. 5160–5175. doi: http://dx.doi.org/10.3168/jds.2010-3308 ŠIDLOVÁ, V. et al. (2015) Genomic variability among cattle populations based on runs of homozygosity. Poljoprivreda , vol. 21. no. 1 (Supplement), pp. 44-47. Tang, G. Q. et al. (2013) Inbreeding and genetic Ddversity in three imported swine breeds in China using pedigree data Asian Australas. J. Anim .Sci ., vol.26, no. 6, pp.755-765.  doi: http://dx.doi.org/10.5713/ajas.2012.12645 Trakovická, A. et al.(2015) Impact of SNPs in candidate genes on economically important traits in Pinzgau cattle. Poljoprivreda . vol. 21, no. 1(Supplement), pp. 150-154. doi: http://dx.doi.org/10.18047/poljo.21.1.sup.35

New set of candidate gene SNPs and microsatellites to disentangle selective and neutral processes shaping population responses of European flounder (Platichthys flesus) to anthropogenic stress and contrasted environments

Six candidate gene SNP assays and 12 new microsatellites were developed in the European flounder (Platichthys flesus), in order to provide new tools to (1) further investigate signatures of selection suspected on candidate genes, and (2) better depict the neutral evolutionary background shaping the differentiation of populations. All markers were successfully tested in two populations from contrasted estuaries, and should be helpful to better understand the possible adaptive responses of flounder populations to anthropogenic pressures (e.g. global warming, eutrophication, pollutions), over the whole distribution range of the species.

Impact of SNPs in candidate genes on economically important traits in Pinzgau cattle

Impact of SNPs in candidate genes on economically important traits in Pinzgau cattle

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.

Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.

Correlation Between SNPs in Candidate Genes and VerifyNow-Detected Platelet Responsiveness to Aspirin and Clopidogrel Treatment.

Patients with high on-treatment platelet reactivity (HPR) against aspirin or clopidogrel are at increased risk for adverse cardiovascular events. In this study, we explored the predictive value of common SNPs for the on-treatment platelet reactivity (OPR) against aspirin and clopidogrel assessed by VerifyNow assays. This study recruited 286 Han Chinese individuals undergoing antiplatelet treatment, including 159 cases with aspirin only (100 mg/day) and 127 cases with dual therapy (aspirin 100 mg/day plus clopidogrel 75 mg/day) for at least 2 weeks. The OPR against aspirin and clopidogrel were assessed by VerifyNow Aspirin (ARU) and P2Y12 assays (PRU), respectively. Genotyping for the selected 25 SNPs within 11 genes and 2 GWAS loci was carried out by ABI multiplex SNaPshot method. The results indicated that rs4244285 (CYP2C19) and rs342293 (7q22.3) were significantly associated with PRU value (both P < 0.01). As for the OPR to aspirin, a weak statistical significance was observed in rs5445 (GNB3) (P = 0.049) and rs5758 (TBXA2R) (P = 0.045). After adjusting for the covariates including gender, age and smoking, carriers of allele A of rs4244285 remained as a strong predictor for HPR against clopidogrel. The current study suggests that common SNPs may predict OPR against clopidogrel as assessed by VerifyNow P2Y12, but are less likely to respond against aspirin as assessed by VerifyNow Aspirin.