Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study
Gichohi-Wainaina, W.N. ; Boonstra, A. ; Feskens, E.J.M. ; Demir, A.Y. ; Veenemans, J. ; Verhoef, H. - \ 2015
Malaria Journal 14 (2015). - ISSN 1475-2875 - 11 p.
plasmodium-falciparum malaria - tnf-alpha promoter - cerebral malaria - linkage disequilibrium - rheumatoid-arthritis - diabetes-mellitus - polymorphisms - gene - disease - hla
Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. Methods Data from a placebo-controlled trial in which 612 Tanzanian children aged 6–60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature =37.5°C or whole blood C-reactive protein concentration =8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. Results Genotyping of 94.9% (581/612) children for TNF-1031 (TNF-1031 T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF-308 G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF-1031 CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01¿1.97] and 1.31 [0.97¿1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF-308 AA genotype (corresponding HR: 0.13 [0.02¿0.63] and 0.16 [0.04¿0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF-1031 and TNF-308 affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed.
Common variants and haplotypes in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in a female black South African population
Gichohi-Wainaina, W.N. ; Boonstra, A. ; Swinkels, D.W. ; Zimmermann, M.B. ; Feskens, E.J.M. ; Towers, G.W. - \ 2015
The Journal of Nutrition 145 (2015)5. - ISSN 0022-3166 - p. 945 - 953.
tumor-necrosis-factor - transferrin g277s mutation - deficiency anemia - serum hepcidin - women - risk - disease - hfe - polymorphisms - saturation
Background: It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population. Objectives: We aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from women (n = 686; range, 32–86 y) who were part of the Prospective Urban and Rural Epidemiology study. Thirty-two SNPs in 12 genes were selected based on existing genome-wide association study data. Results: In the transferrin (TF) gene, SF and BI were significantly lower in the heterozygote genotype (AG) of reference SNP (rs) 1799852 (P = 0.01 and 0.03, respectively) and sTfR concentrations were significantly higher (P = 0.004) than the homozygote minor allele genotype (AA), whereas transferrin receptor and BI concentrations were significantly lower in the heterozygote genotype (AG) of rs3811647 (both P = 0.03) than the homozygote wild-type (AA) and minor allele groups (GG). The chromosome 6 allele combination (AAA) consisting of rs1799964 and rs1800629 both in tumor necrosis factor-a (TNF-a) and rs2071592 in nuclear factor ¿B inhibitor–like protein 1 (NFKBIL1) was associated with higher odds for low SF concentrations (SF <15 µg/L; OR: 1.86; 95% CI: 1.23, 2.79) than the allele combinations AGA, GGT, and AGT. The chromosome 22 allele combination (GG) consisting of rs228918 and rs228921 in the transmembrane protease serine 6 (TMPRSS6) gene was associated with lower odds for increased sTfR concentrations (sTfR > 8.3mg/L; OR: 0.79; 95% CI: 0.63, 0.98) than the allele combination AA. Conclusions: Various SNPs and allele combinations in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in black South African women; however, these association patterns are different compared with European ancestry populations. This stresses the need for population-specific genomic data.
Genomic analysis reveals selection for Asian genes in European pigs following human-mediated introgression
Bosse, M. ; Megens, H.J.W.C. ; Frantz, L.A.F. ; Madsen, O. ; Paudel, Y. ; Duijvestein, N. ; Crooijmans, R.P.M.A. ; Groenen, M. - \ 2014
Nature Communications 5 (2014). - ISSN 2041-1723 - 8 p.
hydrocarbon dioxin receptor - recent positive selection - haplotype structure - molecular characterization - reproductive traits - domestic pig - wide snp - evolution - models - polymorphisms
The independent domestication of local wild boar populations in Asia and Europe about 10,000 years ago led to distinct European and Asian pig breeds, each with very different phenotypic characteristics. During the Industrial Revolution, Chinese breeds were imported to Europe to improve commercial traits in European breeds. Here we demonstrate the presence of introgressed Asian haplotypes in European domestic pigs and selection signatures on some loci in these regions, using whole genome sequence data. The introgression signatures are widespread and the Asian haplotypes are rarely fixed. The Asian introgressed haplotypes are associated with regions harbouring genes involved in meat quality, development and fertility. We identify Asian-derived non-synonymous mutations in the ¿AHR gene that associate with increased litter size in multiple European commercial lines. These findings demonstrate that increased fertility was an important breeding goal for early nineteenth century pig farmers, and that Asian variants of genes related to this trait were preferentially selected during the development of modern European pig breeds.
Fine mapping of a quantitative trait locus for bovine milk fat composition on Bos taurus autosome 19
Bouwman, A.C. ; Visker, M.H.P.W. ; Arendonk, J.A.M. van; Bovenhuis, H. - \ 2014
Journal of Dairy Science 97 (2014)2. - ISSN 0022-0302 - p. 1139 - 1149.
genome-wide association - stearoyl-coa desaturase - dairy-cattle - acid-composition - genotype imputation - genetic-parameters - missense mutation - fasn gene - polymorphisms - yield
A major quantitative trait locus (QTL) for milk fat content and fatty acids in both milk and adipose tissue has been detected on Bos taurus autosome 19 (BTA19) in several cattle breeds. The objective of this study was to refine the location of the QTL on BTA19 for bovine milk fat composition using a denser set of markers. Opportunities for fine mapping were provided by imputation from 50,000 genotyped single nucleotide polymorphisms (SNP) toward a high-density SNP panel with up to 777,000 SNP. The QTL region was narrowed down to a linkage disequilibrium block formed by 22 SNP covering 85,007 bp, from 51,303,322 to 51,388,329 bp on BTA19. This linkage disequilibrium block contained 2 genes: coiled-coil domain containing 57 (CCDC57) and fatty acid synthase (FASN). The gene CCDC57 is minimally characterized and has not been associated with bovine milk fat previously, but is expressed in the mammary gland. The gene FASN has been associated with bovine milk fat and fat in adipose tissue before. This gene is a likely candidate for the QTL on BTA19 because of its involvement in de novo fat synthesis. Future studies using sequence data of both CCDC57 and FASN, and eventually functional studies, will have to be pursued to assign the causal variant(s).
A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
Baltar, V.T. ; Xun, W.W. ; Johansson, M. ; Bueno-de-Mesquita, B. ; Boshuizen, H.C. ; Gils, C.H. van; Onland-Moret, C.N. - \ 2013
European Journal of Epidemiology 28 (2013)8. - ISSN 0393-2990 - p. 677 - 688.
one-carbon metabolism - dna methylation - indoleamine 2,3-dioxygenase - colorectal-cancer - system activation - folate - infection - men - polymorphisms - neopterin
The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
Genome-wide association study of insect bite hypersensitivity in Dutch Shetland pony mares
Schurink, A. ; Ducro, B.J. ; Bastiaansen, J.W.M. ; Frankena, K. ; Arendonk, J.A.M. van - \ 2013
Animal Genetics 44 (2013)1. - ISSN 0268-9146 - p. 44 - 52.
icelandic horses - sweet itch - genetic association - complex traits - summer eczema - polymorphisms - netherlands - sequence - diseases - british
Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome-wide association study to identify and quantify genomic regions contributing to IBH in the Dutch Shetland pony population. A total of 97 cases and 91 controls were selected and matched on withers height, coat colour and pedigree to minimise the population stratification. A blood sample was collected from participating Shetland pony mares, their IBH phenotype was scored and the owner filled in a questionnaire. A total of 40 021 single-nucleotide polymorphisms (SNPs) were fitted in a univariable logistic model fitting an additive effect. Analysis revealed no effects of population stratification. Significant associations with IBH were detected for 24 SNPs on 12 chromosomes [log10(P-value) > 2.5]. Odds ratios of allele substitution effects of the unfavourable allele were between 1.94 and 5.95. The most significant SNP was found on chromosome 27, with an odds ratio of 2.31 and with an allele frequency of the unfavourable allele of 0.72 in cases and 0.53 in controls. Genome-wide association studies on additional horse populations are desired to validate the identified associations, to identify the genes involved in IBH and to develop genomic tools to o decrease IBH prevalence.
Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands
Schurink, A. ; Wolc, A. ; Ducro, B.J. ; Frankena, K. ; Garrick, D.J. ; Dekkers, J.C.M. ; Arendonk, J.A.M. van - \ 2012
Genetics, Selection, Evolution 44 (2012)1. - ISSN 0999-193X - 12 p.
icelandic horses - linkage disequilibrium - summer eczema - bayesian-inference - allergic diseases - sequence - polymorphisms - prediction - genetics - vector
Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods: Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results: The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of geneticvariance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions: The genome-wide association study identified several genomic regions associated with insect bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on insect bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease insect bite hypersensitivity prevalence.
Genomic regions associated with bovine milk fatty acids in both summer and winter milk samples
Bouwman, A.C. ; Visker, M.H.P.W. ; Arendonk, J.A.M. van; Bovenhuis, H. - \ 2012
BMC Genetics 13 (2012). - ISSN 1471-2156 - 13 p.
wide association - genetic-parameters - dairy-cattle - bos-taurus - dgat1 - polymorphisms - replication - validation - synthase - cows
Background - In this study we perform a genome-wide association study (GWAS) for bovine milk fatty acids from summer milk samples. This study replicates a previous study where we performed a GWAS for bovine milk fatty acids based on winter milk samples from the same population. Fatty acids from summer and winter milk are genetically similar traits and we therefore compare the regions detected in summer milk to the regions previously detected in winter milk GWAS to discover regions that explain genetic variation in both summer and winter milk. Results - The GWAS of summer milk samples resulted in 51 regions associated with one or more milk fatty acids. Results are in agreement with most associations that were previously detected in a GWAS of fatty acids from winter milk samples, including eight ‘new’ regions that were not considered in the individual studies. The high correlation between the –log10(P-values) and effects of SNPs that were found significant in both GWAS imply that the effects of the SNPs were similar on winter and summer milk fatty acids. Conclusions - The GWAS of fatty acids based on summer milk samples was in agreement with most of the associations detected in the GWAS of fatty acids based on winter milk samples. Associations that were in agreement between both GWAS are more likely to be involved in fatty acid synthesis compared to regions detected in only one GWAS and are therefore worthwhile to pursue in fine-mapping studies.
Empirical evaluation of DArT, SNP, and SSR marker-systems for genotyping, clustering, and assigning sugar beet hybrid varieties into populations
Simko, I. ; Eujayl, I. ; Hintum, T.J.L. van - \ 2012
Plant Science 184 (2012). - ISSN 0168-9452 - p. 54 - 62.
simple sequence repeat - beta-vulgaris l. - genetic diversity - linkage disequilibrium - microsatellite markers - technology dart - genome - inference - map - polymorphisms
Dominant and co-dominant molecular markers are routinely used in plant genetic research. In the present study we assessed the success-rate of three marker-systems for estimating genotypic diversity, clustering varieties into populations, and assigning a single variety into the expected population. A set of 54 diploid sugar beet (Beta vulgaris L. ssp. vulgaris) hybrid varieties from five seed companies was genotyped with 702 Diversity Array-Technology (DArT), 34 Single Nucleotide Polymorphisms (SNP), and 30 Simple Sequence Repeats (SSR) markers. Analysis of the population structure revealed three well-defined populations and clustering of varieties that generally correlates with their seed company origin. Two populations each contained varieties from two different seed companies indicating genetic similarity of this material. The third population was comprised only of varieties from a single seed company. Analysis of the SSR and SNP datasets indicates that some of the hybrid varieties likely have a common (or very closely related) parent. Comparison of the three marker-systems revealed substantial differences in the number of loci needed for analyses. Varietal clustering required approximately 1.8–2 × more SSR, 3–4.5 × more SNP, and 4.8 × more DArT markers than were required for detection of genotypic diversity. When marker-systems were compared across different types of analyses per locus success-rate was the highest for the SSR and the lowest for the DArT markers. Generally, about 1.4–3 × more SNPs, and 4.9–13.3 × more DArTs then SSRs were needed to achieve the 100% success-rate. However, using only DArT markers with a high level of polymorphism decreased the number of DArT loci needed for analyses by 38–61%. Results from the present work provide a premise to selecting the type(s) and number of markers that are needed for genetic diversity analysis of sugar beet hybrid varieties
C-reactive protein haplotypes and dispositional optimism in obese and nonobese elderly subjects
Rius-Ottenheim, N. ; Craen, A.J.M. ; Geleijnse, J.M. ; Slagboom, P.E. ; Westendorp, R.G. ; Giltay, E.J. - \ 2012
Inflammation Research 61 (2012)1. - ISSN 1023-3830 - p. 43 - 51.
nutrition examination survey - coronary-heart-disease - 3rd national-health - crp gene - mendelian randomization - positive affect - inflammatory markers - depression - polymorphisms - women
Background Chronic low-grade inflammation, characterized by elevated plasma levels of C-reactive protein (CRP), has been inversely associated with dispositional optimism. Using a Mendelian randomization design, this study explores whether CRP haplotypes that determine CRP plasma levels are also associated with dispositional optimism. Methods In a sample of 1,084 community-dwelling subjects (aged 60–85 years) from three cohort studies (Arnhem Elderly Study, n = 426; Leiden Longevity Study, n = 355; Zutphen Elderly Study, n = 303), six CRP polymorphisms (rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) coding for five common haplotypes were genotyped. The association of CRP haplotypes with CRP plasma levels and dispositional optimism was analyzed using multivariable linear regression models. Subanalyses were stratified by body mass index (BMI =25 kg/m2). Results CRP haplotypes determined CRP plasma levels (adjusted ß = 0.094, p <0.001). In the whole group, no association was found between CRP haplotypes and dispositional optimism scores (adjusted ß = -0.02, p = 0.45). In BMI strata, CRP haplotypes were associated with increasing levels of plasma CRP levels (adjusted ß = 0.112; p = 0.002) and lower dispositional optimism levels (adjusted ß = -0.068; p = 0.03) in the obese group only. Conclusions These results suggest that genetically increased CRP levels are involved in low dispositional optimism, but only in case of obesity
Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.
Leufkens, A.M. ; Duijnhoven, F.J.B. van; Siersema, P.D. ; Boshuizen, H.C. ; Vrieling, A. ; Agudo, A. ; Gram, I.T. ; Weiderpass, E. ; Dahm, C. ; Overvad, K. ; Tjonneland, A. ; Olsen, A. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Morois, S. ; Palli, D. ; Grioni, S. ; Tumino, R. ; Sacerdote, C. ; Mattiello, A. ; Herman, S. ; Kaaks, R. ; Steffen, A. ; Boeing, H. ; Trichopoulou, A. ; Lagiou, P. ; Trichopoulos, D. ; Peeters, P.H. ; Gils, C.H. van; Kranen, H. van; Lund, E. ; Dumeaux, V. ; Engeset, D. ; Rodriguez, L. ; Sanchez, M.J. ; Chirlaque, M.D. ; Barricarte, A. ; Manjer, J. ; Almquist, M. ; Guelpen, B. ; Hallmans, G. ; Khaw, K.T. ; Wareham, N. ; Tsilidis, K.K. ; Straif, K. ; Leon-Roux, M. ; Vineis, P. ; Norat, T. ; Riboli, E. ; Bueno-de-Mesquita, H.B. - \ 2011
Clinical Gastroenterology and Hepatology 9 (2011)2. - ISSN 1542-3565 - p. 137 - 144.
tumor microsatellite instability - life-style factors - alcohol-consumption - rectal-cancer - colon tumors - cohort - women - polymorphisms - associations - metaanalysis
BACKGROUND & AIMS: There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location. METHODS: We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06-1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08-1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% CI, 0.98-1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04-1.50) and current smokers (HR, 1.31; 95% CI, 1.06-1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P = .45) for former smokers and a significant difference for current smokers (P = .02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers. CONCLUSIONS: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.
Variation in European harbour seal immune response genes and susceptibility to phocine distemper virus (PDV)
McCarthy, A.J. ; Shaw, M. ; Jepson, P.D. ; Brasseur, S.M.J.M. ; Reijnders, P.J.H. ; Goodman, S.J. - \ 2011
Infection, Genetics and Evolution 11 (2011)7. - ISSN 1567-1348 - p. 1616 - 1623.
subacute sclerosing-panencephalitis - measles-virus - conservation genetics - cellular receptor - whole-genome - disease - association - vitulina - polymorphisms - populations
Phocine distemper virus (PDV) has caused two mass mortalities of European harbour seals (Phoca vitulina) in recent decades. Levels of mortality varied considerably among European populations in both the 1988 and 2002 epidemics, with higher mortality in continental European populations in comparison to UK populations. High levels of genetic differentiation at neutral makers among seal populations allow for the possibility that there could be potential genetic differences at functional loci that may account for some of the variation in mortality. Recent genome sequencing of carnivore species and development of genomic tools have now made it possible to explore the possible contribution of variation in candidate genes from harbour seals in relation to the differential mortality patterns. We assessed variation in eight genes (CD46, IFNG, IL4, IL8, IL10, RARa, SLAM and TLR2) encoding key proteins involved in host cellular interactions with Morbilliviruses and the relationship of variants to disease status. This work constitutes the first genetic association study for Morbillivirus disease susceptibility in a non-model organism, and for a natural mortality event. We found no variation in harbour seals from across Europe in the protein coding domains of the viral receptors SLAM and CD46, but SNPs were present in SLAM intron 2. SNPs were also present in IL8 p2 and RARa exon 1. There was no significant association of SLAM or RARa polymorphisms with disease status implying no role of these genes in determining resistance to PDV induced mortality, that could be detected with the available samples and the small number of polymorphisms indentified. However there was significant differentiation of allele frequencies among populations. PDV and other morbilliviruses are important models for wildlife epidemiology, host switches and viral evolution. Despite a negative result in this case, full sequencing of pinniped and other 'non-model' carnivore genomes will help in refining understanding the role of host genetics in disease susceptibility for these viruses
Statistical Techniques for Defining Reference Sets of Accessions and Microsatellite Markers
Odong, T.L. ; Heerwaarden, J. van; Jansen, J. ; Hintum, T.J.L. van; Eeuwijk, F.A. van - \ 2011
Crop Science 51 (2011)6. - ISSN 0011-183X - p. 2401 - 2411.
genetic distances - core collections - polymorphisms - populations - relatedness - diversity - richness - strategy - breeds
Exploitation of the available genetic resources around the world requires information about the relationships and genetic diversity present among genebank collections. These relations can be established by defining for each crop a small but informative set of accessions, together with a small set of reliable molecular markers, that can be used as reference material. In this study, various strategies to arrive at small but informative reference sets are discussed. For selection of accessions, we proposed genetic distance optimization (GDOpt) method, which selects a subset of accessions that optimally represent the accessions not included in the core collection. The performance of GDOpt was compared with Core Hunter, an advanced stochastic local search algorithm for selecting core subsets. For the selection of molecular markers, we evaluated (i) the backward elimination (BE) method and (ii) methods based on principal component analysis (PCA). We examined the performance of the proposed methodologies using five real datasets. Relative to average distance between an accession and the nearest selected accession (representativeness), GDOpt outperformed Core Hunter. However, Core Hunter outperformed GDOpt with respect to allelic richness. The BE performed much better than other methods in selecting subsets of markers. Methods based on PCA showed that, for practical purposes, the inclusion of the first few (two or three) principal components (PCs) was often sufficient. To obtain robust and high-quality reference sets of accessions and markers we advise a combination of GDOpt (for accessions) and BE or methods based on PCA using a few PCs (for subsets of markers).
Association of bovine ß-casein protein variant I with milk production and milk protein composition
Visker, M.H.P.W. ; Dibbits, B.W. ; Kinders, S.M. ; Valenberg, H.J.F. van; Arendonk, J.A.M. van; Bovenhuis, H. - \ 2011
Animal Genetics 42 (2011)2. - ISSN 0268-9146 - p. 212 - 218.
finnish ayrshire cows - production traits - genetic-parameters - polymorphisms - genotypes - holstein - cattle - haplotypes
The aim of this study was to detect new polymorphisms in the bovine ß-casein (ß-CN) gene and to evaluate association of (new) ß-CN protein variants with milk production traits and milk protein composition. Screening of the ß-CN gene in genomic DNA from 72 Holstein Friesian (HF) bulls resulted in detection of 19 polymorphisms and revealed the presence of ß-CN protein variant I in the Dutch HF population. Studies of association of ß-CN protein variants with milk composition usually do not discriminate protein variant I from variant A2. Association of ß-CN protein variants with milk composition was studied in 1857 first-lactation HF cows and showed that associations of protein variants A2 and I were quite different for several traits. ß-CN protein variant I was significantly associated with protein percentage and protein yield, and with as1-casein (as1-CN), as2-casein (as2-CN), ¿-casein (¿-CN), a-lactalbumin (a-LA), ß-lactoglobulin (ß-LG), casein index and casein yield. Inferring ß-¿-CN haplotypes showed that ß-CN protein variant I occurred only with ¿-CN variant B. Consequently, associations of ß-¿-CN haplotype IB with protein percentage, ¿-CN, a-LA, ß-LG and casein index are likely resulting from associations of ¿-CN protein variant B, while associations of ß-¿-CN haplotype IB with as1-CN and as2-CN seem to be resulting from associations of ß-CN variant I.
Age at which dairy cattle become Mycobacterium avium subsp. paratuberculosis faecal culture positive
Weber, M.F. ; Kogut, J. ; Bree, J. de; Schaik, G. van; Nielen, M. van - \ 2010
Preventive Veterinary Medicine 97 (2010)1. - ISSN 0167-5877 - p. 29 - 36.
genetic-variation - johnes-disease - ssp-paratuberculosis - antibody-response - immune-responses - diagnostic-tests - infection - calves - susceptibility - polymorphisms
Age at which cattle become faecal culture positive for Mycobacterium avium subsp. paratuberculosis (Map) can be used as a proxy parameter for age at onset of faecal shedding, which is an important parameter in the control of Map in cattle herds. To investigate the age at becoming faecal culture positive, survival analysis methods were applied. The analyses were carried out on asynchronous interval censored data of faecal culture results of samples collected from 18,979 female Holstein-Frisian cattle in 353 Dutch herds between 1996 and 2002. The data were analysed with a Weibull proportional hazards model. The results indicate that the distribution of age at onset of faecal shedding in Holstein-Frisian dairy cattle in infected herds is associated with the within-herd prevalence. In higher classes of apparent prevalence, cattle started to shed Map at younger age on average. In herds with an apparent prevalence = 0.2, the proportion (95% CI) of cattle with onset of faecal shedding before 2 years of age was estimated at 1% (0.5%; 2%), 4% (3%; 5%), 8% (5%; 10%) and 20% (11%; 32%), respectively. This study indicates that a considerable proportion of young stock is shedding Map, especially in high prevalence herds. Therefore, infectious young stock should be a major concern in the control of paratuberculosis
|Genetic diversity and population structure of Iranian wild Pleurotus eryngii species-complex strains revealed by URP-PCR markers
Behnamian, Mahdi ; Mohammadi, Seyed A. ; Sonnenberg, A.S.M. ; Goltapeh, Ebrahim M. ; Hendrickx, P.M. - \ 2010
Journal of Food, Agriculture & Environment 8 (2010)3&4. - ISSN 1459-0255 - p. 1203 - 1207.
rapd analysis - mushroom - dna - polymorphisms - amplification - primers - fungi
In the present study, a set of 68 P. eryngii wild strains collected from nine locations in northwest and west of Iran along with six commercial strains were studied using universal rice primers (URP). The wild strains were isolated from Ferula ovina, F. haussknechtii, Cachrys ferulacea, Kellusia odoratissima and Smyrniopsis aucheri plant species. Eleven URP primers amplified 188 polymorphic fragments. A total of 3, 2 and 7 bands were specific to the strains collected from F. ovina and C. ferulacea plant species and commercial strains, respectively. The highest and lowest polymorphisms were identified in populations B (66.49%) and F (24.47%), respectively. Genetic distances among populations ranged from 0.027 (between populations A and B) to 0.393 (between populations C and F) with an average of 0.210. The closest and furthest wild populations to commercial strains were populations B (0.102) and F (0.234), respectively. Analysis of molecular variance (AMOVA) revealed significant among regions, among populations within regions and within population diversity, whereas within population variation (61.6%) accounted for most of the total molecular variance.
Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris
Madsen, O. ; Kortum, T.T. ; Hupkes, H. ; Kohlen, W. ; Rheede, T. ; Jong, W.W. de - \ 2010
Journal of Molecular Evolution 71 (2010)5-6. - ISSN 0022-2844 - p. 356 - 363.
creutzfeldt-jakob-disease - protein gene prnp - octapeptide repeats - binding - region - copper - prp - susceptibility - polymorphisms - deletion
The N-terminal region of the mammalian prion protein (PrP) contains an 'octapeptide' repeat which is involved in copper binding. This eight- or nine-residue peptide is repeated four to seven times, depending on the species, and polymorphisms in repeat number do occur. Alleles with three repeats are very rare in humans and goats, and deduced PrP sequences with two repeats have only been reported in two lemur species and in the red squirrel, Sciurus vulgaris. We here describe that the red squirrel two-repeat PrP sequence actually represents a retroposed pseudogene, and that an additional and older processed pseudogene with three repeats also occurs in this species as well as in ground squirrels. We argue that repeat numbers may tend to contract rather than expand in prion retropseudogenes, and that functional prion genes with two repeats may not be viable
Exploring genetic determinants of plasma total cholesterol levels and their predictive value in a longitudinal study
Lu, Y. ; Feskens, E.J.M. ; Boer, J.M.A. ; Imholz, S. ; Verschuren, W.M.M. ; Wijmenga, C. ; Vaarhorst, A. ; Slagboom, E. ; Müller, M.R. ; Dollé, M.E.T. - \ 2010
Atherosclerosis 213 (2010)1. - ISSN 0021-9150 - p. 200 - 205.
density-lipoprotein cholesterol - heart-disease risk - cardiovascular-disease - apolipoprotein-e - lipid-levels - association - women - variants - reclassification - polymorphisms
BACKGROUND: Plasma total cholesterol (TC) levels are highly genetically determined. Although ample evidence of genetic determination of separate lipoprotein cholesterol levels has been reported, using TC level directly as a phenotype in a relatively large broad-gene based association study has not been reported to date. METHODS AND RESULTS: We genotyped 361 single nucleotide polymorphisms (SNPs) across 243 genes based on pathways potentially relevant to cholesterol metabolism in 3575 subjects that were examined thrice over 11 years. Twenty-three SNPs were associated with TC levels after adjustment for multiple testing. We used 12 of them (rs7412 and rs429358 in APOE, rs646776 in CELSR2, rs1367117 in APOB, rs6756629 in ABCG5, rs662799 in APOA5, rs688 in LDLR, rs10889353 in DOCK7, rs2304130 in NCAN, rs3846662 in HMGCR, rs2275543 in ABCA1, rs7275 in SMARCA4) that were confirmed in previous candidate association or genome-wide-association studies to define a gene risk score (GRS). Average TC levels increased from 5.23 ± 0.82 mmol/L for those with 11 or less cholesterol raising alleles to 6.03 ± 1.11 mmol/L for those with 18 or more (P for trend
Relationships between milk protein composition, milk protein variants, and cow fertility traits in Dutch Holstein-Friesian cattle
Demeter, R.M. ; Markiewicz, K. ; Arendonk, J.A.M. van; Bovenhuis, H. - \ 2010
Journal of Dairy Science 93 (2010)11. - ISSN 0022-0302 - p. 5495 - 5502.
dairy-cows - reproductive-performance - bovine-milk - liquid-chromatography - genetic-parameters - yield - quantification - polymorphisms - associations - lactation
Selective breeding can change milk protein composition to improve the manufacturing properties of milk. However, the effects of such breeding strategies on other economically important traits should be investigated before implementation. The objectives of this study were to examine the association between cow fertility traits and (1) milk protein composition and (2) milk protein variants (ß-lactoglobulin, ß-casein, ¿-casein, and ß-¿-casein) in commercial Dutch Holstein-Friesian cattle. Data on 1,644 first-lactation cows were analyzed by fitting linear mixed models. Greater relative concentration of aS1-casein within total milk protein had a positive phenotypic relationship with nonreturn rates and calving rate after first insemination. Furthermore, results showed virtually no significant relationship between cow fertility and concentration of other milk proteins or milk protein variants. Results of this study can be used to assess the correlated effects of breeding for improved milk protein composition on reproduction, thereby allowing for better evaluation of breeding programs before implementation. Our findings suggest that selecting cows based on milk protein composition or milk protein variants for improved manufacturing properties would have no negative influence on reproductive performance.
Novel tools for extraction and validation of disease-related mutations applied to fabry disease
Kuipers, R.K.P. ; Bergh, T. ; Joosten, H.J. ; Lekanne dit Deprez, R.H. ; Mannens, M.M.A.M. ; Schaap, P.J. - \ 2010
Human Mutation 31 (2010)9. - ISSN 1059-7794 - p. 1026 - 1032.
ligand-binding domain - alpha-galactosidase-a - iarc tp53 database - protein - identification - polymorphisms - knowledgebase - residues
Genetic disorders are often caused by nonsynonymous nucleotide changes in one or more genes associated with the disease. Specific amino acid changes, however, can lead to large variability of phenotypic expression. For many genetic disorders this results in an increasing amount of publications describing phenotype-associated mutations in disorder-related genes. Keeping up with this stream of publications is essential for molecular diagnostics and translational research purposes but often impossible due to time constraints: there are simply too many articles to read. To help solve this problem, we have created Mutator, an automated method to extract mutations from full-text articles. Extracted mutations are crossreferenced to sequence data and a scoring method is applied to distinguish false-positives. To analyze stored and new mutation data for their (potential) effect we have developed Validator, a Web-based tool specifically designed for DNA diagnostics. Fabry disease, a monogenetic gene disorder of the GLA gene, was used as a test case. A structure-based sequence alignment of the alpha-amylase superfamily was used to validate results. We have compared our data with existing Fabry mutation data sets obtained from the HGMD and Swiss-Prot databases. Compared to these data sets, Mutator extracted 30% additional mutations from the literature