KMgene: a unified R package for gene-based association analysis for complex traits.

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Yan, Qi; Fang, Zhou; Chen, Wei; Stegle, Oliver

2018-02-09

In this report, we introduce an R package KMgene for performing gene-based association tests for familial, multivariate or longitudinal traits using kernel machine (KM) regression under a generalized linear mixed model (GLMM) framework. Extensive simulations were performed to evaluate the validity of the approaches implemented in KMgene. http://cran.r-project.org/web/packages/KMgene. qi.yan@chp.edu or wei.chen@chp.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2018. Published by Oxford University Press.

Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds.

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Fang, Lingzhao; Sahana, Goutam; Ma, Peipei; Su, Guosheng; Yu, Ying; Zhang, Shengli; Lund, Mogens Sandø; Sørensen, Peter

2017-08-10

A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic regions defined by genes grouped on the basis of "Gene Ontology" (GO), and that incorporating this independent biological information into genomic prediction models might improve their predictive ability. Four complex traits (i.e., milk, fat and protein yields, and mastitis) together with imputed sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased prediction model (GBLUP) to a genomic feature BLUP (GFBLUP) model, including an additional genomic effect quantifying the joint effect of a group of variants located in a genomic feature. The GBLUP model using a single random effect assumes that all genomic variants contribute to the genomic relationship equally, whereas GFBLUP attributes different weights to the individual genomic relationships in the prediction equation based on the estimated genomic parameters. Our results demonstrate that the immune-relevant GO terms were more associated with mastitis than milk production, and several biologically meaningful GO terms improved the prediction accuracy with GFBLUP for the four traits, as compared with GBLUP. The improvement of the genomic prediction between breeds (the average increase across the four traits was 0.161) was more apparent than that it was within the HOL (the average increase across the four traits was 0.020). Our genomic feature modelling approaches provide a framework to simultaneously explore the genetic architecture and genomic prediction of complex traits by taking advantage of

Assessment of Tools for Marker-Assisted Selection in a Marine Commercial Species: Significant Association between MSTN-1 Gene Polymorphism and Growth Traits

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Irma Sánchez-Ramos

2012-01-01

Full Text Available Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata: the growth hormone (GH, insulin-like growth factor-1 (IGF-1, myostatin (MSTN-1, prolactin (PRL, and somatolactin (SL genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny. In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair.

Genetic evaluation with major genes and polygenic inheritance when some animals are not genotyped using gene content multiple-trait BLUP.

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Legarra, Andrés; Vitezica, Zulma G

2015-11-17

In pedigreed populations with a major gene segregating for a quantitative trait, it is not clear how to use pedigree, genotype and phenotype information when some individuals are not genotyped. We propose to consider gene content at the major gene as a second trait correlated to the quantitative trait, in a gene content multiple-trait best linear unbiased prediction (GCMTBLUP) method. The genetic covariance between the trait and gene content at the major gene is a function of the substitution effect of the gene. This genetic covariance can be written in a multiple-trait form that accommodates any pattern of missing values for either genotype or phenotype data. Effects of major gene alleles and the genetic covariance between genotype at the major gene and the phenotype can be estimated using standard EM-REML or Gibbs sampling. Prediction of breeding values with genotypes at the major gene can use multiple-trait BLUP software. Major genes with more than two alleles can be considered by including negative covariances between gene contents at each different allele. We simulated two scenarios: a selected and an unselected trait with heritabilities of 0.05 and 0.5, respectively. In both cases, the major gene explained half the genetic variation. Competing methods used imputed gene contents derived by the method of Gengler et al. or by iterative peeling. Imputed gene contents, in contrast to GCMTBLUP, do not consider information on the quantitative trait for genotype prediction. GCMTBLUP gave unbiased estimates of the gene effect, in contrast to the other methods, with less bias and better or equal accuracy of prediction. GCMTBLUP improved estimation of genotypes in non-genotyped individuals, in particular if these individuals had own phenotype records and the trait had a high heritability. Ignoring the major gene in genetic evaluation led to serious biases and decreased prediction accuracy. CGMTBLUP is the best linear predictor of additive genetic merit including

Positional RNA-Seq identifies candidate genes for phenotypic engineering of sexual traits

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Arbore, Roberto; Sekii, Kiyono; Beisel, Christian; Ladurner, Peter; Berezikov, Eugene; Schaerer, Lukas

2015-01-01

Introduction: RNA interference (RNAi) of trait-specific genes permits the manipulation of specific phenotypic traits ("phenotypic engineering") and thus represents a powerful tool to test trait function in evolutionary studies. The identification of suitable candidate genes, however, often relies on

The Hidden Complexity of Mendelian Traits across Natural Yeast Populations

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Jing Hou

2016-07-01

Full Text Available Mendelian traits are considered to be at the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel’s law, the global landscape of monogenic variants, as well as their effects and inheritance patterns within natural populations, is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey of Mendelian traits across a large population of isolates. We generated offspring from 41 unique parental pairs and analyzed 1,105 cross/trait combinations. We found that 8.9% of the cases were Mendelian. Further tracing of causal variants revealed background-specific expressivity and modified inheritances, gradually transitioning from Mendelian to complex traits in 30% of the cases. In fact, when taking into account the natural population diversity, the hidden complexity of traits could be substantial, confounding phenotypic predictability even for simple Mendelian traits.

Detection of expression quantitative trait Loci in complex mouse crosses: impact and alleviation of data quality and complex population substructure.

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Iancu, Ovidiu D; Darakjian, Priscila; Kawane, Sunita; Bottomly, Daniel; Hitzemann, Robert; McWeeney, Shannon

2012-01-01

Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased resolution for quantitative trait loci detection. However, increased genetic complexity challenges detection methods, with discordant results due to low data quality or complex genetic architecture. We quantified the impact of theses factors across three mouse crosses and two different detection methods, identifying procedures that greatly improve detection quality. Importantly, HS populations have complex genetic architectures not fully captured by the whole genome kinship matrix, calling for incorporating chromosome specific relatedness information. We analyze three increasingly complex crosses, using gene expression levels as quantitative traits. The three crosses were an F(2) intercross, a HS formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the eight lines found in the collaborative cross. Brain (striatum) gene expression and genotype data were obtained using the Illumina platform. We found large disparities between methods, with concordance varying as genetic complexity increased; this problem was more acute for probes with distant regulatory elements (trans). A suite of data filtering steps resulted in substantial increases in reproducibility. Genetic relatedness between samples generated overabundance of detected eQTLs; an adjustment procedure that includes the kinship matrix attenuates this problem. However, we find that relatedness between individuals is not evenly distributed across the genome; information from distinct chromosomes results in relatedness structure different from the whole genome kinship matrix. Shared polymorphisms from distinct chromosomes collectively affect expression levels, confounding eQTL detection. We suggest that considering chromosome specific relatedness can result in improved eQTL detection.

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

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Volkov, Petr; Olsson, Anders H; Gillberg, Linn

2016-01-01

Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, w...... and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dys)metabolic traits associated with the development of obesity and diabetes.......Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men......, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs) in cis and 5...

Epistasis × environment interactions among Arabidopsis thaliana glucosinolate genes impact complex traits and fitness in the field

DEFF Research Database (Denmark)

Kerwin, Rachel E.; Feusier, Julie; Muok, Alise

2017-01-01

(GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation...

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

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Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

2016-11-17

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships between structural complexity, coral traits, and reef fish assemblages

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Darling, Emily S.; Graham, Nicholas A. J.; Januchowski-Hartley, Fraser A.; Nash, Kirsty L.; Pratchett, Morgan S.; Wilson, Shaun K.

2017-06-01

With the ongoing loss of coral cover and the associated flattening of reef architecture, understanding the links between coral habitat and reef fishes is of critical importance. Here, we investigate whether considering coral traits and functional diversity provides new insights into the relationship between structural complexity and reef fish communities, and whether coral traits and community composition can predict structural complexity. Across 157 sites in Seychelles, Maldives, the Chagos Archipelago, and Australia's Great Barrier Reef, we find that structural complexity and reef zone are the strongest and most consistent predictors of reef fish abundance, biomass, species richness, and trophic structure. However, coral traits, diversity, and life histories provided additional predictive power for models of reef fish assemblages, and were key drivers of structural complexity. Our findings highlight that reef complexity relies on living corals—with different traits and life histories—continuing to build carbonate skeletons, and that these nuanced relationships between coral assemblages and habitat complexity can affect the structure of reef fish assemblages. Seascape-level estimates of structural complexity are rapid and cost effective with important implications for the structure and function of fish assemblages, and should be incorporated into monitoring programs.

On the Origin of Complex Adaptive Traits: Progress Since the Darwin Versus Mivart Debate.

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Suzuki, Takao K

2017-06-01

The evolutionary origin of complex adaptive traits has been a controversial topic in the history of evolutionary biology. Although Darwin argued for the gradual origins of complex adaptive traits within the theory of natural selection, Mivart insisted that natural selection could not account for the incipient stages of complex traits. The debate starting from Darwin and Mivart eventually engendered two opposite views: gradualism and saltationism. Although this has been a long-standing debate, the issue remains unresolved. However, recent studies have interrogated classic examples of complex traits, such as the asymmetrical eyes of flatfishes and leaf mimicry of butterfly wings, whose origins were debated by Darwin and Mivart. Here, I review recent findings as a starting point to provide a modern picture of the evolution of complex adaptive traits. First, I summarize the empirical evidence that unveils the evolutionary steps toward complex traits. I then argue that the evolution of complex traits could be understood within the concept of "reducible complexity." Through these discussions, I propose a conceptual framework for the formation of complex traits, named as reducible-composable multicomponent systems, that satisfy two major characteristics: reducibility into a sum of subcomponents and composability to construct traits from various additional and combinatorial arrangements of the subcomponents. This conceptual framework provides an analytical foundation for exploring evolutionary pathways to build up complex traits. This review provides certain essential avenues for deciphering the origin of complex adaptive traits. © 2017 Wiley Periodicals, Inc.

Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships

NARCIS (Netherlands)

Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P.L.; Lund, Mogens Sandø; Sahana, Goutam

2016-01-01

Background: There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map

QTL global meta-analysis: are trait determining genes clustered?

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Adelson David L

2009-04-01

Full Text Available Abstract Background A key open question in biology is if genes are physically clustered with respect to their known functions or phenotypic effects. This is of particular interest for Quantitative Trait Loci (QTL where a QTL region could contain a number of genes that contribute to the trait being measured. Results We observed a significant increase in gene density within QTL regions compared to non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine QTL Viewer database into 8 categories of non-redundant regions, we have been able to analyze gene density and gene function distribution, based on Gene Ontology (GO with relation to their location within QTL regions, outside of QTL regions and across the entire bovine genome. We identified a number of GO terms that were significantly over represented within particular QTL categories. Furthermore, select GO terms expected to be associated with the QTL category based on common biological knowledge have also proved to be significantly over represented in QTL regions. Conclusion Our analysis provides evidence of over represented GO terms in QTL regions. This increased GO term density indicates possible clustering of gene functions within QTL regions of the bovine genome. Genes with similar functions may be grouped in specific locales and could be contributing to QTL traits. Moreover, we have identified over-represented GO terminology that from a biological standpoint, makes sense with respect to QTL category type.

Characterization of Genes for Beef Marbling Based on Applying Gene Coexpression Network

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Dajeong Lim

2014-01-01

Full Text Available Marbling is an important trait in characterization beef quality and a major factor for determining the price of beef in the Korean beef market. In particular, marbling is a complex trait and needs a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with marbling, we used a weighted gene coexpression network analysis from the expression value of bovine genes. Hub genes were identified; they were topologically centered with large degree and BC values in the global network. We performed gene expression analysis to detect candidate genes in M. longissimus with divergent marbling phenotype (marbling scores 2 to 7 using qRT-PCR. The results demonstrate that transmembrane protein 60 (TMEM60 and dihydropyrimidine dehydrogenase (DPYD are associated with increasing marbling fat. We suggest that the network-based approach in livestock may be an important method for analyzing the complex effects of candidate genes associated with complex traits like marbling or tenderness.

Sexual selection and magic traits in speciation with gene flow

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Maria R. SERVEDIO, Michael KOPP

2012-06-01

Full Text Available The extent to which sexual selection is involved in speciation with gene flow remains an open question and the subject of much research. Here, we propose that some insight can be gained from considering the concept of magic traits (i.e., traits involved in both reproductive isolation and ecological divergence. Both magic traits and other, “non-magic”, traits can contribute to speciation via a number of specific mechanisms. We argue that many of these mechanisms are likely to differ widely in the extent to which they involve sexual selection. Furthermore, in some cases where sexual selection is present, it may be prone to inhibit rather than drive speciation. Finally, there are a priori reasons to believe that certain categories of traits are much more effective than others in driving speciation. The combination of these points suggests a classification of traits that may shed light on the broader role of sexual selection in speciation with gene flow. In particular, we suggest that sexual selection can act as a driver of speciation in some scenarios, but may play a negligible role in potentially common categories of magic traits, and may be likely to inhibit speciation in common categories of non-magic traits [Current Zoology 58 (3: 507–513, 2012].

Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic Determinism.

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Ricard, Anne; Robert, Céline; Blouin, Christine; Baste, Fanny; Torquet, Gwendoline; Morgenthaler, Caroline; Rivière, Julie; Mach, Nuria; Mata, Xavier; Schibler, Laurent; Barrey, Eric

2017-01-01

. This lncRNA could be one element of the cardiac rhythm regulation. Our GWAS revealed that equine performance during endurance races is a complex polygenic trait, and is partially governed by at least 5 QTL: two coding genes involved in neuronal tissues and three other loci with many regulatory functions such as slowing down heart rate.

Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic Determinism

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Anne Ricard

2017-06-01

fibroblasts. This lncRNA could be one element of the cardiac rhythm regulation. Our GWAS revealed that equine performance during endurance races is a complex polygenic trait, and is partially governed by at least 5 QTL: two coding genes involved in neuronal tissues and three other loci with many regulatory functions such as slowing down heart rate.

Integrated GWAS and Pathway profiling for feed efficiency traits in pigs leads to novel genes and their molecular pathways

DEFF Research Database (Denmark)

Do, Duy Ngoc; Ostersen, Tage; Strathe, Anders Bjerring

2013-01-01

Genome wide association studies (GWAS) are being extensively used in revealing genetic architecture of complex traits. However, GWAS offer limited understanding of the biological role of significant single nucleotide polymorphisms (SNPs) affecting complex traits. Pathway analysis using GWAS results...... is an important step where we firstly detect genes located near GWAS-detected SNPs and subsequently we detect enrichment of these genes in various biological processes and pathways. The objective of this study was to apply these steps to identify relevant pathways involved in residual feed intake (RFI) in pigs....... Residual feed intake is a feed efficiency measure and is highly economically important in animal production. In our study, a total of 596 Yorkshire boars had phenotypic and genotypic records. After quality control, 37,915 SNPs were available for GWAS which was implemented in the DMU software package...

Regression-based approach for testing the association between multi-region haplotype configuration and complex trait

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Zhao Hongbo

2009-09-01

Full Text Available Abstract Background It is quite common that the genetic architecture of complex traits involves many genes and their interactions. Therefore, dealing with multiple unlinked genomic regions simultaneously is desirable. Results In this paper we develop a regression-based approach to assess the interactions of haplotypes that belong to different unlinked regions, and we use score statistics to test the null hypothesis of non-genetic association. Additionally, multiple marker combinations at each unlinked region are considered. The multiple tests are settled via the minP approach. The P value of the "best" multi-region multi-marker configuration is corrected via Monte-Carlo simulations. Through simulation studies, we assess the performance of the proposed approach and demonstrate its validity and power in testing for haplotype interaction association. Conclusion Our simulations showed that, for binary trait without covariates, our proposed methods prove to be equal and even more powerful than htr and hapcc which are part of the FAMHAP program. Additionally, our model can be applied to a wider variety of traits and allow adjustment for other covariates. To test the validity, our methods are applied to analyze the association between four unlinked candidate genes and pig meat quality.

Correlating single nucleotide polymorphisms in the myostatin gene with performance traits in rabbit

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E.M. Abdel-Kafy

2016-09-01

Full Text Available The Myostatin (MSTN, or Growth and Differentiation Factor 8 (GDF8, gene has been implicated in the double muscling phenomenon, in which a series of mutations render the gene inactive and unable to properly regulate muscle fibre deposition. Single nucleotide polymorphisms (SNPs in the MSTN gene have been correlated to production traits, making it a candidate target gene to enhance livestock and fowl productivity. This study aimed to assess any association of three SNPs in the rabbit MSTN gene (c.713T>A in exon 2, c.747+34C>T in intron 2, and c.*194A>G in 3’-untranslated region and their combinations, with carcass, production and reproductive traits. The investigated traits included individual body weight, daily body weight gain, carcass traits and reproductive traits. The 3 SNPs were screened using PCR-restriction fragment length polymorphism (RFLP-based analysis and the effects of the different SNP genotypes and their combinations were estimated in a rabbit population. Additionally, additive and dominance effects were estimated for significant traits. The results found no significant association between the c.713 T>A SNP and all the examined traits. Allele T at the c.747+34C>T SNP was only significantly associated (PG, allele G was significantly associated (PG SNP also had positive effects on most carcass traits. The estimated additive genetic effect for the c.*194A>G SNP was significant (PA and c.747+34C>T, GG at the c.*194A>G SNP correlated with highest values in body weight and daily weight gain. In conclusion, the ‘G’ allele at the c.*194A>G SNP had positive effects on growth and carcass traits and so could be used as a favourable allele in planning rabbit selection. Further population-wide studies are necessary to test the association of the c.*194A>G SNP with carcass traits. We also recommend evaluation of the potential effects of the c.*194A>G SNP on MSTN gene expression.

Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs.

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Camarinha-Silva, Amelia; Maushammer, Maria; Wellmann, Robin; Vital, Marius; Preuss, Siegfried; Bennewitz, Jörn

2017-07-01

The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology. Eight from 49 investigated bacteria genera showed a significant narrow sense host heritability, ranging from 0.32 to 0.57. Microbial mixed linear models were applied to estimate the microbiota variance for each complex trait. The fraction of phenotypic variance explained by the microbial variance was 0.28, 0.21, and 0.16 for daily gain, feed conversion, and feed intake, respectively. The SNP data and the microbiota composition were used to predict the complex traits using genomic best linear unbiased prediction (G-BLUP) and microbial best linear unbiased prediction (M-BLUP) methods, respectively. The prediction accuracies of G-BLUP were 0.35, 0.23, and 0.20 for daily gain, feed conversion, and feed intake, respectively. The corresponding prediction accuracies of M-BLUP were 0.41, 0.33, and 0.33. Thus, in addition to SNP data, microbiota abundances are an informative source of complex trait predictions. Since the pig is a well-suited animal for modeling the human digestive tract, M-BLUP, in addition to G-BLUP, might be beneficial for predicting human predispositions to some diseases, and, consequently, for preventative and personalized medicine. Copyright © 2017 by the Genetics Society of America.

Quantitative trait loci linked to PRNP gene controlling health and production traits in INRA 401 sheep

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Brunel Jean-Claude

2007-07-01

Full Text Available Abstract In this study, the potential association of PrP genotypes with health and productive traits was investigated. Data were recorded on animals of the INRA 401 breed from the Bourges-La Sapinière INRA experimental farm. The population consisted of 30 rams and 852 ewes, which produced 1310 lambs. The animals were categorized into three PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR allele. Two analyses differing in the approach considered were carried out. Firstly, the potential association of the PrP genotype with disease (Salmonella resistance and production (wool and carcass traits was studied. The data used included 1042, 1043 and 1013 genotyped animals for the Salmonella resistance, wool and carcass traits, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. Association analyses do not indicate any evidence of an effect of PrP genotypes on traits studied in this breed. Secondly, a quantitative trait loci (QTL detection approach using the PRNP gene as a marker was applied on ovine chromosome 13. Interval mapping was used. Evidence for one QTL affecting mean fiber diameter was found at 25 cM from the PRNP gene. However, a linkage between PRNP and this QTL does not imply unfavorable linkage disequilibrium for PRNP selection purposes.

Ubiquitous polygenicity of human complex traits: genome-wide analysis of 49 traits in Koreans.

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Jian Yang

Full Text Available Recent studies in population of European ancestry have shown that 30% ~ 50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05 proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array ([Formula: see text]. On average across 47 of the 49 traits for which the estimate of h(G(2 is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8% of narrow sense heritability. The estimate of h(G(2 is highly correlated with the proportion of SNPs with association P<0.031 (r(2 = 0.92. Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the "missing heritability" is captured by common SNPs.

Characterization, expression profiles, intracellular distribution and association analysis of porcine PNAS-4 gene with production traits

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Wang Heng

2008-06-01

Full Text Available Abstract Background In a previous screen to identify differentially expressed genes associated with embryonic development, the porcine PNAS-4 gene had been found. Considering differentially expressed genes in early stages of muscle development are potential candidate genes to improve meat quality and production efficiency, we determined how porcine PNAS-4 gene regulates meat production. Therefore, this gene has been sequenced, expression analyzed and associated with meat production traits. Results We cloned the full-length cDNA of porcine PNAS-4 gene encoding a protein of 194 amino acids which was expressed in the Golgi complex. This gene was mapped to chromosome 10, q11–16, in a region of conserved synteny with human chromosome 1 where the human homologous gene was localized. Real-time PCR revealed that PNAS-4 mRNA was widely expressed with highest expression levels in skeletal muscle followed by lymph, liver and other tissues, and showed a down-regulated expression pattern during prenatal development while a up-regulated expression pattern after weaning. Association analysis revealed that allele C of SNP A1813C was prevalent in Chinese indigenous breeds whereas A was dominant allele in Landrace and Large White, and the pigs with homozygous CC had a higher fat content than those of the pigs with other genotypes (P Conclusion Porcine PNAS-4 protein tagged with green fluorescent protein accumulated in the Golgi complex, and its mRNA showed a widespread expression across many tissues and organs in pigs. It may be an important factor affecting the meat production efficiency, because its down-regulated expression pattern during early embryogenesis suggests involvement in increase of muscle fiber number. In addition, the SNP A1813C associated with fat traits might be a genetic marker for molecular-assisted selection in animal breeding.

Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds

DEFF Research Database (Denmark)

Fang, Lingzhao; Sahana, Goutam; Ma, Peipei

2017-01-01

sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased......BACKGROUND: A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic...

Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships.

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Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P L; Lund, Mogens Sandø; Sahana, Goutam

2016-08-17

There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map rare variants. Besides, livestock populations have large half-sib families and the occurrence of rare variants may be confounded with family structure, which makes it difficult to disentangle their effects from family mean effects. We compared the power of methods that are commonly applied in human genetics to map rare variants in cattle using whole-genome sequence data and simulated phenotypes. We also studied the power of mapping rare variants using linear mixed models (LMM), which are the method of choice to account for both family relationships and population structure in cattle. We observed that the power of the LMM approach was low for mapping a rare variant (defined as those that have frequencies lower than 0.01) with a moderate effect (5 to 8 % of phenotypic variance explained by multiple rare variants that vary from 5 to 21 in number) contributing to a QTL with a sample size of 1000. In contrast, across the scenarios studied, statistical methods that are specialized for mapping rare variants increased power regardless of whether multiple rare variants or a single rare variant underlie a QTL. Different methods for combining rare variants in the test single nucleotide polymorphism set resulted in similar power irrespective of the proportion of total genetic variance explained by the QTL. However, when the QTL variance is very small (only 0.1 % of the total genetic variance), these specialized methods for mapping rare variants and LMM generally had no power to map the variants within a gene with sample sizes of 1000 or 5000. We observed that the methods that combine multiple rare variants within a gene into a meta-variant generally had greater power to map rare variants compared

Fine mapping and candidate gene prediction of a pleiotropic quantitative trait locus for yield-related trait in Zea mays.

Directory of Open Access Journals (Sweden)

Ruixiang Liu

Full Text Available The yield of maize grain is a highly complex quantitative trait that is controlled by multiple quantitative trait loci (QTLs with small effects, and is frequently influenced by multiple genetic and environmental factors. Thus, it is challenging to clone a QTL for grain yield in the maize genome. Previously, we identified a major QTL, qKNPR6, for kernel number per row (KNPR across multiple environments, and developed two nearly isogenic lines, SL57-6 and Ye478, which differ only in the allelic constitution at the short segment harboring the QTL. Recently, qKNPR6 was re-evaluated in segregating populations derived from SL57-6×Ye478, and was narrowed down to a 2.8 cM interval, which explained 56.3% of the phenotypic variance of KNPR in 201 F(2∶3 families. The QTL simultaneously affected ear length, kernel weight and grain yield. Furthermore, a large F(2 population with more than 12,800 plants, 191 recombinant chromosomes and 10 overlapping recombinant lines placed qKNPR6 into a 0.91 cM interval corresponding to 198Kb of the B73 reference genome. In this region, six genes with expressed sequence tag (EST evidence were annotated. The expression pattern and DNA diversity of the six genes were assayed in Ye478 and SL57-6. The possible candidate gene and the pathway involved in inflorescence development were discussed.

Integrative Genomic Analysis of Complex traits

DEFF Research Database (Denmark)

Ehsani, Ali Reza

In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...

Association of candidate gene polymorphisms with milk technological traits, yield, composition, and somatic cell score in Italian Holstein-Friesian sires.

Science.gov (United States)

Viale, E; Tiezzi, F; Maretto, F; De Marchi, M; Penasa, M; Cassandro, M

2017-09-01

Advances in DNA-based marker technology have enabled the identification of genomic regions underlying complex phenotypic traits in livestock species. The incorporation of detected quantitative trait loci into genetic evaluation provides great potential to enhance selection accuracies, hence expediting the genetic improvement of economically important traits. The objective of the present study was to investigate 96 single nucleotide polymorphisms (SNP) located in 53 candidate genes previously reported to have effects on milk production and quality traits in a population of highly selected Holstein-Friesian bulls. A total of 423 semen samples were used to genotype the bulls through a custom oligo pool assay. Forty-five SNP in 32 genes were found to be associated with at least 1 of the tested traits. Most significant and favorable SNP trait associations were observed for polymorphisms located in CCL3 and AGPAT6 genes for fat yield (0.037 and 0.033 kg/d, respectively), DGKG gene for milk yield (0.698 kg/d), PPARGC1A, CSN1S1, and AGPAT6 genes for fat percentage (0.127, 0.113, and 0.093%, respectively), GHR gene for protein (0.064%) and casein percentage (0.053%), and TLR4 gene for fat (0.090%), protein (0.066%), and casein percentage (0.050%). Somatic cell score was favorably affected by GHR (-0.095) and POU1F1 (-0.137), and interesting SNP-trait associations were observed for polymorphisms located in CSN2, POU1F1, and AGPAT6 genes for rennet coagulation time (-0.592, -0.558, and -0.462 min, respectively), and GHR and CSN2 genes for curd firmness 30 min after rennet addition (1.264 and 1.183 mm, respectively). In addition to the influence of individual SNP, the effects of composite genotypes constructed by grouping SNP according to their individual effects on traits considered in the analysis were also examined. Favorable and significant effects on milk traits were observed for 2 composite genotypes, one including 10 SNP and the other 4 SNP. The former was associated

Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

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Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

2016-10-01

Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

Large-scale in silico mapping of complex quantitative traits in inbred mice.

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Pengyuan Liu

2007-07-01

Full Text Available Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with approximately 40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.

Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken

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Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

2016-01-01

The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

Association of porcine UCP3 gene polymorphisms with fatness traits ...

African Journals Online (AJOL)

Administrator

2011-04-25

Apr 25, 2011 ... ... for fatness traits in pig. Polymorphism in UCP3 gene may change the function ... NM_214049) and human UCP3 gene DNA sequence (GenBank accession No. NC_000011). ..... Sleep, 29: 645-649. Zhao J, Li H, Kong X, ...

Genome Wide Association Analysis Reveals New Production Trait Genes in a Male Duroc Population.

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Kejun Wang

Full Text Available In this study, 796 male Duroc pigs were used to identify genomic regions controlling growth traits. Three production traits were studied: food conversion ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome-wide single nucleotide polymorphism trait associations. The Gene ontology analysis identified 14 candidate genes close to significant single nucleotide polymorphisms, with growth-related functions: six for days to 100 KG (WT1, FBXO3, DOCK7, PPP3CA, AGPAT9, and NKX6-1, seven for food conversion ratio (MAP2, TBX15, IVL, ARL15, CPS1, VWC2L, and VAV3, and one for average daily gain (COL27A1. Gene ontology analysis indicated that most of the candidate genes are involved in muscle, fat, bone or nervous system development, nutrient absorption, and metabolism, which are all either directly or indirectly related to growth traits in pigs. Additionally, we found four haplotype blocks composed of suggestive single nucleotide polymorphisms located in the growth trait-related quantitative trait loci and further narrowed down the ranges, the largest of which decreased by ~60 Mb. Hence, our results could be used to improve pig production traits by increasing the frequency of favorable alleles via artificial selection.

Good genes, complementary genes and human mate preferences.

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Roberts, S Craig; Little, Anthony C

2008-09-01

The past decade has witnessed a rapidly growing interest in the biological basis of human mate choice. Here we review recent studies that demonstrate preferences for traits which might reveal genetic quality to prospective mates, with potential but still largely unknown influence on offspring fitness. These include studies assessing visual, olfactory and auditory preferences for potential good-gene indicator traits, such as dominance or bilateral symmetry. Individual differences in these robust preferences mainly arise through within and between individual variation in condition and reproductive status. Another set of studies have revealed preferences for traits indicating complementary genes, focussing on discrimination of dissimilarity at genes in the major histocompatibility complex (MHC). As in animal studies, we are only just beginning to understand how preferences for specific traits vary and inter-relate, how consideration of good and compatible genes can lead to substantial variability in individual mate choice decisions and how preferences expressed in one sensory modality may reflect those in another. Humans may be an ideal model species in which to explore these interesting complexities.

Mapping of genes for flower-related traits and QTLs for flowering ...

Indian Academy of Sciences (India)

Mapping of genes for flower-related traits and QTLs for flowering time ... which would greatly enhance the use of G. darwinii-specific desirable genes in ... used to determine all linkage groups, the order of groups on the same ... age groups.

Associations between variants of the HAL gene and milk production traits in Chinese Holstein cows.

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Wang, Haifei; Jiang, Li; Wang, Wenwen; Zhang, Shengli; Yin, Zongjun; Zhang, Qin; Liu, Jian-Feng

2014-11-25

The histidine ammonia-lyse gene (HAL) encodes the histidine ammonia-lyase, which catalyzes the first reaction of histidine catabolism. In our previous genome-wide association study in Chinese Holstein cows to identify genetic variants affecting milk production traits, a SNP (rs41647754) located 357 bp upstream of HAL, was found to be significantly associated with milk yield and milk protein yield. In addition, the HAL gene resides within the reported QTLs for milk production traits. The aims of this study were to identify genetic variants in HAL and to test the association between these variants and milk production traits. Fifteen SNPs were identified within the regions under study of the HAL gene, including three coding mutations, seven intronic mutations, one promoter region mutation, and four 3'UTR mutations. Nine of these identified SNPs were chosen for subsequent genotyping and association analyses. Our results showed that five SNP markers (ss974768522, ss974768525, ss974768531, ss974768533 and ss974768534) were significantly associated with one or more milk production traits. Haplotype analysis showed that two haplotype blocks were significantly associated with milk yield and milk protein yield, providing additional support for the association between HAL variants and milk production traits in dairy cows (P HAL gene and milk production traits in Chinese Holstein cows, indicating the potential role of HAL variants in these traits. These identified SNPs may serve as genetic markers used in genomic selection schemes to accelerate the genetic gains of milk production traits in dairy cattle.

Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining

DEFF Research Database (Denmark)

Hulsegge, Ina; Woelders, Henri; Smits, Mari

2013-01-01

Reproduction is of significant economic importance in dairy cattle. Improved understanding of mechanisms that control estrous behavior and other reproduction traits could help in developing strategies to improve and/or monitor these traits. The objective of this study was to predict and rank gene...

Prioritization of Candidate Genes in QTL Regions for Physiological and Biochemical Traits Underlying Drought Response in Barley (Hordeum vulgare L.

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Kornelia Gudys

2018-06-01

Full Text Available Drought is one of the most adverse abiotic factors limiting growth and productivity of crops. Among them is barley, ranked fourth cereal worldwide in terms of harvested acreage and production. Plants have evolved various mechanisms to cope with water deficit at different biological levels, but there is an enormous challenge to decipher genes responsible for particular complex phenotypic traits, in order to develop drought tolerant crops. This work presents a comprehensive approach for elucidation of molecular mechanisms of drought tolerance in barley at the seedling stage of development. The study includes mapping of QTLs for physiological and biochemical traits associated with drought tolerance on a high-density function map, projection of QTL confidence intervals on barley physical map, and the retrievement of positional candidate genes (CGs, followed by their prioritization based on Gene Ontology (GO enrichment analysis. A total of 64 QTLs for 25 physiological and biochemical traits that describe plant water status, photosynthetic efficiency, osmoprotectant and hormone content, as well as antioxidant activity, were positioned on a consensus map, constructed using RIL populations developed from the crosses between European and Syrian genotypes. The map contained a total of 875 SNP, SSR and CGs, spanning 941.86 cM with resolution of 1.1 cM. For the first time, QTLs for ethylene, glucose, sucrose, maltose, raffinose, α-tocopherol, γ-tocotrienol content, and catalase activity, have been mapped in barley. Based on overlapping confidence intervals of QTLs, 11 hotspots were identified that enclosed more than 60% of mapped QTLs. Genetic and physical map integration allowed the identification of 1,101 positional CGs within the confidence intervals of drought response-specific QTLs. Prioritization resulted in the designation of 143 CGs, among them were genes encoding antioxidants, carboxylic acid biosynthesis enzymes, heat shock proteins, small auxin

Impacts of population structure and analytical models in genome-wide association studies of complex traits in forest trees: a case study in Eucalyptus globulus.

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Eduardo P Cappa

Full Text Available The promise of association genetics to identify genes or genomic regions controlling complex traits has generated a flurry of interest. Such phenotype-genotype associations could be useful to accelerate tree breeding cycles, increase precision and selection intensity for late expressing, low heritability traits. However, the prospects of association genetics in highly heterozygous undomesticated forest trees can be severely impacted by the presence of cryptic population and pedigree structure. To investigate how to better account for this, we compared the GLM and five combinations of the Unified Mixed Model ( UMM on data of a low-density genome-wide association study for growth and wood property traits carried out in a Eucalyptus globulus population (n = 303 with 7,680 Diversity Array Technology (DArT markers. Model comparisons were based on the degree of deviation from the uniform distribution and estimates of the mean square differences between the observed and expected p-values of all significant marker-trait associations detected. Our analysis revealed the presence of population and family structure. There was not a single best model for all traits. Striking differences in detection power and accuracy were observed among the different models especially when population structure was not accounted for. The UMM method was the best and produced superior results when compared to GLM for all traits. Following stringent correction for false discoveries, 18 marker-trait associations were detected, 16 for tree diameter growth and two for lignin monomer composition (S:G ratio, a key wood property trait. The two DArT markers associated with S:G ratio on chromosome 10, physically map within 1 Mbp of the ferulate 5-hydroxylase (F5H gene, providing a putative independent validation of this marker-trait association. This study details the merit of collectively integrate population structure and relatedness in association analyses in undomesticated, highly

Impacts of Population Structure and Analytical Models in Genome-Wide Association Studies of Complex Traits in Forest Trees: A Case Study in Eucalyptus globulus

Science.gov (United States)

Garcia, Martín N.; Acuña, Cintia; Borralho, Nuno M. G.; Grattapaglia, Dario; Marcucci Poltri, Susana N.

2013-01-01

The promise of association genetics to identify genes or genomic regions controlling complex traits has generated a flurry of interest. Such phenotype-genotype associations could be useful to accelerate tree breeding cycles, increase precision and selection intensity for late expressing, low heritability traits. However, the prospects of association genetics in highly heterozygous undomesticated forest trees can be severely impacted by the presence of cryptic population and pedigree structure. To investigate how to better account for this, we compared the GLM and five combinations of the Unified Mixed Model (UMM) on data of a low-density genome-wide association study for growth and wood property traits carried out in a Eucalyptus globulus population (n = 303) with 7,680 Diversity Array Technology (DArT) markers. Model comparisons were based on the degree of deviation from the uniform distribution and estimates of the mean square differences between the observed and expected p-values of all significant marker-trait associations detected. Our analysis revealed the presence of population and family structure. There was not a single best model for all traits. Striking differences in detection power and accuracy were observed among the different models especially when population structure was not accounted for. The UMM method was the best and produced superior results when compared to GLM for all traits. Following stringent correction for false discoveries, 18 marker-trait associations were detected, 16 for tree diameter growth and two for lignin monomer composition (S∶G ratio), a key wood property trait. The two DArT markers associated with S∶G ratio on chromosome 10, physically map within 1 Mbp of the ferulate 5-hydroxylase (F5H) gene, providing a putative independent validation of this marker-trait association. This study details the merit of collectively integrate population structure and relatedness in association analyses in undomesticated, highly

Parameters in dynamic models of complex traits are containers of missing heritability.

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Yunpeng Wang

Full Text Available Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation, and improving this situation within the current paradigm appears daunting. Given a well-validated dynamic model of a complex physiological trait, a substantial part of the underlying genetic variation must manifest as variation in model parameters. These parameters are themselves phenotypic traits. By linking whole-cell phenotypic variation to genetic variation in a computational model of a single heart cell, incorporating genotype-to-parameter maps, we show that genome-wide association studies on parameters reveal much more genetic variation than when using higher-level cellular phenotypes. The results suggest that letting such studies be guided by computational physiology may facilitate a causal understanding of the genotype-to-phenotype map of complex traits, with strong implications for the development of phenomics technology.

Statistical power to detect genetic (covariance of complex traits using SNP data in unrelated samples.

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Peter M Visscher

2014-04-01

Full Text Available We have recently developed analysis methods (GREML to estimate the genetic variance of a complex trait/disease and the genetic correlation between two complex traits/diseases using genome-wide single nucleotide polymorphism (SNP data in unrelated individuals. Here we use analytical derivations and simulations to quantify the sampling variance of the estimate of the proportion of phenotypic variance captured by all SNPs for quantitative traits and case-control studies. We also derive the approximate sampling variance of the estimate of a genetic correlation in a bivariate analysis, when two complex traits are either measured on the same or different individuals. We show that the sampling variance is inversely proportional to the number of pairwise contrasts in the analysis and to the variance in SNP-derived genetic relationships. For bivariate analysis, the sampling variance of the genetic correlation additionally depends on the harmonic mean of the proportion of variance explained by the SNPs for the two traits and the genetic correlation between the traits, and depends on the phenotypic correlation when the traits are measured on the same individuals. We provide an online tool for calculating the power of detecting genetic (covariation using genome-wide SNP data. The new theory and online tool will be helpful to plan experimental designs to estimate the missing heritability that has not yet been fully revealed through genome-wide association studies, and to estimate the genetic overlap between complex traits (diseases in particular when the traits (diseases are not measured on the same samples.

Allelic frequencies and association with carcass traits of six genes in local subpopulations of Japanese Black cattle.

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Nishimaki, Takahiro; Ibi, Takayuki; Siqintuya; Kobayashi, Naohiko; Matsuhashi, Tamako; Akiyama, Takayuki; Yoshida, Emi; Imai, Kazumi; Matsui, Mayu; Uemura, Keiichi; Eto, Hisayoshi; Watanabe, Naoto; Fujita, Tatsuo; Saito, Yosuke; Komatsu, Tomohiko; Hoshiba, Hiroshi; Mannen, Hideyuki; Sasazaki, Shinji; Kunieda, Tetsuo

2016-04-01

Marker-assisted selection (MAS) is expected to accelerate the genetic improvement of Japanese Black cattle. However, verification of the effects of the genes for MAS in different subpopulations is required prior to the application of MAS. In this study, we investigated the allelic frequencies and genotypic effects for carcass traits of six genes, which can be used in MAS, in eight local subpopulations. These genes are SCD, FASN and SREBP1, which are associated with the fatty acid composition of meat, and NCAPG, MC1R and F11, which are associated with carcass weight, coat color and blood coagulation abnormality, respectively. The frequencies of desirable alleles of SCD and FASN were relatively high and that of NCAPG was relatively low, and NCAPG was significantly associated with several carcass traits, including carcass weight. The proportions of genotypic variance explained by NCAPG to phenotypic variance were 4.83 for carcass weight. We thus confirmed that NCAPG is a useful marker for selection of carcass traits in these subpopulations. In addition, we found that the desirable alleles of six genes showed no negative effects on carcass traits. Therefore, selection using these genes to improve target traits should not have negative impacts on carcass traits. © 2015 Japanese Society of Animal Science.

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq.

Science.gov (United States)

Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

2017-01-01

Flax ( Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L. Using SLAF-seq

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Dongwei Xie

2018-01-01

Full Text Available Flax (Linum usitatissimum L. is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq was employed to perform a genome-wide association study (GWAS for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM and a mixed linear model (MLM as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

Gene Set Analyses of Genome-Wide Association Studies on 49 Quantitative Traits Measured in a Single Genetic Epidemiology Dataset

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Jihye Kim

2013-09-01

Full Text Available Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr < 0.05. Pairwise comparison of the traits in terms of the semantic similarity in their GO sets revealed surprising cases where phenotypically uncorrelated traits showed high similarity in terms of biological pathways. For example, the pH level was related to 7 other traits that showed low phenotypic correlations with it. A literature survey implies that these traits may be regulated partly by common pathways that involve neuronal or nerve systems.

The sheep growth hormone gene polymorphism and its effects on milk traits.

Science.gov (United States)

Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Paschino, Pietro; Vacca, Giuseppe Massimo

2015-05-01

Growth hormone (GH) is encoded by the GH gene, which may be single copy or duplicate in sheep. The two copies of the sheep GH gene (GH1/GH2-N and GH2-Z) were entirely sequenced in one 106 ewes of Sarda breed, in order to highlight sequence polymorphisms and investigate possible association between genetic variants and milk traits. Milk traits included milk yield, fat, protein, casein and lactose percentage. We evidenced 75 nucleotide changes. Transcription factor binding site prediction revealed two sequences potentially recognised by the pituitary-specific transcription factor POU1FI at the GH1/GH2-N gene, which were lost at the promoter of GH2-Z, which might explain the different tissues of expression of GH1/GH2-N (pituitary) and GH2-Z (placenta). Significant differences in milk traits were observed among genotypes at polymorphic loci only for the GH2-Z gene. Sheep with homozygote genotype ss748770547 CC had higher fat percentage (P < 0.01) than TT. SNP ss748770547 was part of a potential transcription factor binding site for C/EBP alpha (CCAAT/Enhancer Binding Protein), which is involved in the regulation of adipogenesis and adipoblast differentiation. SNP ss748770547, located in the GH2-Z gene 5' flanking region, may be a causal mutation affecting milk fat content. These findings might contribute to the knowledge of the sheep GH locus and might be useful in selection processes in sheep.

A power set-based statistical selection procedure to locate susceptible rare variants associated with complex traits with sequencing data.

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Sun, Hokeun; Wang, Shuang

2014-08-15

Existing association methods for rare variants from sequencing data have focused on aggregating variants in a gene or a genetic region because of the fact that analysing individual rare variants is underpowered. However, these existing rare variant detection methods are not able to identify which rare variants in a gene or a genetic region of all variants are associated with the complex diseases or traits. Once phenotypic associations of a gene or a genetic region are identified, the natural next step in the association study with sequencing data is to locate the susceptible rare variants within the gene or the genetic region. In this article, we propose a power set-based statistical selection procedure that is able to identify the locations of the potentially susceptible rare variants within a disease-related gene or a genetic region. The selection performance of the proposed selection procedure was evaluated through simulation studies, where we demonstrated the feasibility and superior power over several comparable existing methods. In particular, the proposed method is able to handle the mixed effects when both risk and protective variants are present in a gene or a genetic region. The proposed selection procedure was also applied to the sequence data on the ANGPTL gene family from the Dallas Heart Study to identify potentially susceptible rare variants within the trait-related genes. An R package 'rvsel' can be downloaded from http://www.columbia.edu/∼sw2206/ and http://statsun.pusan.ac.kr. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments

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Gifford, Miriam L.; Banta, Joshua A.; Katari, Manpreet S.; Hulsmans, Jo; Chen, Lisa; Ristova, Daniela; Tranchina, Daniel; Purugganan, Michael D.; Coruzzi, Gloria M.; Birnbaum, Kenneth D.

2013-01-01

Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments? When the plant adjusts its development to different environments, related traits can change in a coordinated fashion, such that two traits co-vary across many genotypes. Alternatively, traits can vary independently, such that a change in one trait has little predictive value for the change in a second trait. To characterize such “tunability” in developmental plasticity, we carried out a detailed phenotypic characterization of complex root traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen environments. The results revealed a surprising level of independence in the control of traits to environment – a highly tunable form of plasticity. We mapped genetic architecture of plasticity using genome-wide association studies and further used gene expression analysis to narrow down gene candidates in mapped regions. Mutants in genes implicated by association and expression analysis showed precise defects in the predicted traits in the predicted environment, corroborating the independent control of plasticity traits. The overall results suggest that there is a pool of genetic variability in plants that controls traits in specific environments, with opportunity to tune crop plants to a given environment. PMID:24039603

Complex pedigree analysis to detect quantitative trait loci in dairy cattle

NARCIS (Netherlands)

Bink, M.C.A.M.

1998-01-01

In dairy cattle, many quantitative traits of economic importance show phenotypic variation. For breeding purposes the analysis of this phenotypic variation and uncovering the contribution of genetic factors is very important. Usually, the individual gene effects contributing to the

"Are we there yet?": Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits.

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Page, Grier P; George, Varghese; Go, Rodney C; Page, Patricia Z; Allison, David B

2003-10-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, "Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it." We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what "causation" means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called "causative."

Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model.

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Gerhard Moser

2015-04-01

Full Text Available Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96% had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches.

Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex.

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Kazantseva, A; Gaysina, D; Kutlumbetova, Yu; Kanzafarova, R; Malykh, S; Lobaskova, M; Khusnutdinova, E

2015-01-02

Personality traits are complex phenotypes influenced by interactions of multiple genetic variants of small effect and environmental factors. It has been suggested that the brain derived neurotrophic factor gene (BDNF) is involved in personality traits. Season of birth (SOB) has also been shown to affect personality traits due to its influences on brain development during prenatal and early postnatal periods. The present study aimed to investigate the effects of BDNF on personality traits; and the modifying effects of SOB and sex on associations between BDNF and personality traits. A sample of 1018 young adults (68% women; age range 17-25years) of Caucasian origin from the Russian Federation was assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence) with the Temperament and Character Inventory-125 (TCI-125). Associations between personality traits and 12 BDNF SNPs were tested using linear regression models. The present study demonstrated the effect of rs11030102 on Persistence in females only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB (PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the modifying effect of SOB on the association between BDNF and Harm Avoidance, and for the modifying effect of sex on the association between BDNF and Persistence. Copyright © 2014 Elsevier Inc. All rights reserved.

The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy.

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Wu, Nan; Li, Zhi; Su, Yanjie

2012-05-01

Oxytocin exerts well accepted effects on one of the key social processes: empathy. Previous researches have demonstrated that oxytocin promotes emotional and cognitive aspects of empathy, by exogenous administration as well as on gene level. However, the effect of diverse gene locus haplotypes of oxytocin receptor gene (OXTR) on trait empathy lacks reliable evidence. Participants consisted of 101 genetically unrelated, non-clinical Chinese subjects (46 males and 55 females). Interpersonal Reactivity Index (IRI) was applied to measure the trait empathy from four dimensions: empathy concern, personal distress, perspective taking and fantasy. Fantasy and perspective taking measured cognitive aspect of empathy, while empathy concern and personal distress measured emotional aspect of empathy. Ten single tagging SNPs on OXTR rs2268491, rs1042778, rs53576, rs7632287, rs2254298, rs13316193, rs237897, rs237887, rs4686302, and rs2268493 were tested. Genotype difference in emotional empathy was found on rs237887 and rs4686302 whereas cognitive empathy varied on SNPs rs2268491 and rs2254298 between homozygous and variant carriers. For IRI score, there is a genotype and gender interaction on rs4686302 and rs13316193. The sample sizes from the current study were not so optimal that these results should have to be interpreted with caution when amplified into a larger population. The findings demonstrate that natural variants of OXTR associated with trait empathy; specifically, individuals with certain OXTR genotype did perform better on trait empathy, while others did not. Our findings also provide genetic evidence for gender-related difference on empathy, indicating the popular fact that females who displayed more empathy than males could be likely to trace back to the genetic variants. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic Marker Discovery in Complex Traits: A Field Example on Fat Content and Composition in Pigs

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Ramona Natacha Pena

2016-12-01

Full Text Available Among the large number of attributes that define pork quality, fat content and composition have attracted the attention of breeders in the recent years due to their interaction with human health and technological and sensorial properties of meat. In livestock species, fat accumulates in different depots following a temporal pattern that is also recognized in humans. Intramuscular fat deposition rate and fatty acid composition change with life. Despite indication that it might be possible to select for intramuscular fat without affecting other fat depots, to date only one depot-specific genetic marker (PCK1 c.2456C>A has been reported. In contrast, identification of polymorphisms related to fat composition has been more successful. For instance, our group has described a variant in the stearoyl-coA desaturase (SCD gene that improves the desaturation index of fat without affecting overall fatness or growth. Identification of mutations in candidate genes can be a tedious and costly process. Genome-wide association studies can help in narrowing down the number of candidate genes by highlighting those which contribute most to the genetic variation of the trait. Results from our group and others indicate that fat content and composition are highly polygenic and that very few genes explain more than 5% of the variance of the trait. Moreover, as the complexity of the genome emerges, the role of non-coding genes and regulatory elements cannot be disregarded. Prediction of breeding values from genomic data is discussed in comparison with conventional best linear predictors of breeding values. An example based on real data is given, and the implications in phenotype prediction are discussed in detail. The benefits and limitations of using large SNP sets versus a few very informative markers as predictors of genetic merit of breeding candidates are evaluated using field data as an example.

The dopamine transporter gene may not contribute to susceptibility and the specific personality traits of amphetamine dependence.

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Tzeng, Nian-Sheng; Lu, Ru-Band; Yeh, Hui-Wen; Yeh, Yi-Wei; Huang, Chang-Chih; Yen, Che-Hung; Kuo, Shin-Chang; Chen, Chun-Yen; Chang, Hsin-An; Ho, Pei-Shen; Cheng, Serena; Shih, Mei-Chen; Huang, San-Yuan

2015-04-01

A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene (DAT1, SLC6A3) is associated with development of AD and whether this gene influences personality traits in patients with AD. Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants. A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores. This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Quantitative trait locus (QTL) analysis of pod related traits in different ...

African Journals Online (AJOL)

Administrator

2011-09-26

Sep 26, 2011 ... assistant breeding selection. Key words: Soybean, pod traits, QTL, different environments. INTRODUCTION. Yield related traits in soybean are generally controlled by multiple genes and environmental dependent (Kwon and. Torrie, 1964). Epigenetics of genes controlling these traits also affect the yield.

A power study of bivariate LOD score analysis of a complex trait and fear/discomfort with strangers.

Science.gov (United States)

Ji, Fei; Lee, Dayoung; Mendell, Nancy Role

2005-12-30

Complex diseases are often reported along with disease-related traits (DRT). Sometimes investigators consider both disease and DRT phenotypes separately and sometimes they consider individuals as affected if they have either the disease or the DRT, or both. We propose instead to consider the joint distribution of the disease and the DRT and do a linkage analysis assuming a pleiotropic model. We evaluated our results through analysis of the simulated datasets provided by Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of the simulated disease, Kofendrerd Personality Disorder and one of its simulated associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we considered the bivariate phenotype, which combined the information on Kofendrerd Personality Disorder and fear/discomfort with strangers. We developed a program to perform bivariate linkage analysis using an extension to the Elston-Stewart peeling method of likelihood calculation. Using this program we considered the microsatellites within 30 cM of the gene pleiotropic for this simulated disease and DRT. Based on 100 simulations of 300 families we observed excellent power to detect linkage within 10 cM of the disease locus using the DRT and the bivariate trait.

Genome-wide association study identifies candidate genes for male fertility traits in humans.

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Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

2012-06-08

Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Identification of candidate genes associated with porcine meat color traits by genome-wide transcriptome analysis.

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Li, Bojiang; Dong, Chao; Li, Pinghua; Ren, Zhuqing; Wang, Han; Yu, Fengxiang; Ning, Caibo; Liu, Kaiqing; Wei, Wei; Huang, Ruihua; Chen, Jie; Wu, Wangjun; Liu, Honglin

2016-10-17

Meat color is considered to be the most important indicator of meat quality, however, the molecular mechanisms underlying traits related to meat color remain mostly unknown. In this study, to elucidate the molecular basis of meat color, we constructed six cDNA libraries from biceps femoris (Bf) and soleus (Sol), which exhibit obvious differences in meat color, and analyzed the whole-transcriptome differences between Bf (white muscle) and Sol (red muscle) using high-throughput sequencing technology. Using DEseq2 method, we identified 138 differentially expressed genes (DEGs) between Bf and Sol. Using DEGseq method, we identified 770, 810, and 476 DEGs in comparisons between Bf and Sol in three separate animals. Of these DEGs, 52 were overlapping DEGs. Using these data, we determined the enriched GO terms, metabolic pathways and candidate genes associated with meat color traits. Additionally, we mapped 114 non-redundant DEGs to the meat color QTLs via a comparative analysis with the porcine quantitative trait loci (QTL) database. Overall, our data serve as a valuable resource for identifying genes whose functions are critical for meat color traits and can accelerate studies of the molecular mechanisms of meat color formation.

A Genetic Epidemiological Study of Behavioral Traits

NARCIS (Netherlands)

N. Amin (Najaf)

2011-01-01

textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to

Personality traits in Huntington's disease: An exploratory study of gene expansion carriers and non-carriers.

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Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua; Nielsen, Jørgen Erik; Knudsen, Gitte Moos; Vogel, Asmus

2016-12-01

Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons between HD carriers and HD non-carriers were mostly non-significant but the combined group of HD carriers and non-carriers showed significantly higher scores on the facets: "hostility," "assertiveness," and "activity" and on the trait "Conscientiousness" relative to controls, "Conscientiousness" have been associated with resilience to psychiatric symptoms. Twelve HD carriers and non-carriers were classified as depressed and showed significantly lower scores on "Extraversion" and "Conscientiousness" and significantly higher scores on "Neuroticism," which are associated with vulnerability to psychiatric symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Single Nucleotide Polymorphisms in Growth Hormone Gene and Their Association with Growth Traits in Siniperca chuatsi (Basilewsky

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Changxu Tian

2014-04-01

Full Text Available Growth hormone (GH has been considered as a candidate gene for growth traits in fish. In this study, polymorphisms of the GH gene were evaluated for associations with growth traits in 282 Siniperca chuatsi individuals. Using directly sequencing, four single nucleotide polymorphisms (SNPs were identified in GH gene, with two mutations in intron 4 (g.4940A>C, g.4948A>T, one mutation in exon 5 (g.5045T>C and one in intron 5 (g.5234T>G. Notably, three of them were significantly associated with growth performance, particularly for g.4940A>C which was highly correlated with all the four growth traits. In conclusion, our results demonstrated that these SNPs in GH gene could influence growth performance of S.chuatsi and could be used for marker-assisted selection (MAS in this species.

Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle.

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Mateescu, Raluca G; Garrick, Dorian J; Reecy, James M

2017-01-01

Improvements in eating satisfaction will benefit consumers and should increase beef demand which is of interest to the beef industry. Tenderness, juiciness, and flavor are major determinants of the palatability of beef and are often used to reflect eating satisfaction. Carcass qualities are used as indicator traits for meat quality, with higher quality grade carcasses expected to relate to more tender and palatable meat. However, meat quality is a complex concept determined by many component traits making interpretation of genome-wide association studies (GWAS) on any one component challenging to interpret. Recent approaches combining traditional GWAS with gene network interactions theory could be more efficient in dissecting the genetic architecture of complex traits. Phenotypic measures of 23 traits reflecting carcass characteristics, components of meat quality, along with mineral and peptide concentrations were used along with Illumina 54k bovine SNP genotypes to derive an annotated gene network associated with meat quality in 2,110 Angus beef cattle. The efficient mixed model association (EMMAX) approach in combination with a genomic relationship matrix was used to directly estimate the associations between 54k SNP genotypes and each of the 23 component traits. Genomic correlated regions were identified by partial correlations which were further used along with an information theory algorithm to derive gene network clusters. Correlated SNP across 23 component traits were subjected to network scoring and visualization software to identify significant SNP. Significant pathways implicated in the meat quality complex through GO term enrichment analysis included angiogenesis, inflammation, transmembrane transporter activity, and receptor activity. These results suggest that network analysis using partial correlations and annotation of significant SNP can reveal the genetic architecture of complex traits and provide novel information regarding biological mechanisms

Association Genetics of Wood Physical Traits in the Conifer White Spruce and Relationships With Gene Expression

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Beaulieu, Jean; Doerksen, Trevor; Boyle, Brian; Clément, Sébastien; Deslauriers, Marie; Beauseigle, Stéphanie; Blais, Sylvie; Poulin, Pier-Luc; Lenz, Patrick; Caron, Sébastien; Rigault, Philippe; Bicho, Paul; Bousquet, Jean; MacKay, John

2011-01-01

Marker-assisted selection holds promise for highly influencing tree breeding, especially for wood traits, by considerably reducing breeding cycles and increasing selection accuracy. In this study, we used a candidate gene approach to test for associations between 944 single-nucleotide polymorphism markers from 549 candidate genes and 25 wood quality traits in white spruce. A mixed-linear model approach, including a weak but nonsignificant population structure, was implemented for each marker–trait combination. Relatedness among individuals was controlled using a kinship matrix estimated either from the known half-sib structure or from the markers. Both additive and dominance effect models were tested. Between 8 and 21 single-nucleotide polymorphisms (SNPs) were found to be significantly associated (P ≤ 0.01) with each of earlywood, latewood, or total wood traits. After controlling for multiple testing (Q ≤ 0.10), 13 SNPs were still significant across as many genes belonging to different families, each accounting for between 3 and 5% of the phenotypic variance in 10 wood characters. Transcript accumulation was determined for genes containing SNPs associated with these traits. Significantly different transcript levels (P ≤ 0.05) were found among the SNP genotypes of a 1-aminocyclopropane-1-carboxylate oxidase, a β-tonoplast intrinsic protein, and a long-chain acyl-CoA synthetase 9. These results should contribute toward the development of efficient marker-assisted selection in an economically important tree species. PMID:21385726

Polymorphisms in the GHRL gene and their associations with traits of economic interest in beef cattle.

Science.gov (United States)

Braz, C U; Camargo, G M F; Cardoso, D F; Gil, F M M; Fonseca, P D S; Cyrillo, J N S G; Mercadante, M E Z; Oliveira, H N; Tonhati, H

2015-12-28

The hormone ghrelin is produced in the stomach wall, has an orexigenic function, stimulates growth hormone secretion, and affects the energy balance of the animal. Therefore, the ghrelin gene (GHRL) is considered to be a good candidate marker for the identification of traits of great economic importance in cattle, such as those associated with feed intake, growth, and carcass quality. The use of molecular genetic markers associated with such traits permits the earlier and more accurate identification of superior animals, thus reducing the interval between generations, and increasing the genetic gain. Six SNPs were found in the GHRL gene, located in intron 3, intron 4, and exon 5. The positions of the SNPs on the gene and the substitutions were: g.2184A>G, g.2347T>C, g.4469T>C, g.4548A>G, g.4663T>C, and g.4729T>C (GenBank accession No. JX565585). After analysis of linkage disequilibrium, association tests were performed between four SNPs with the traits year weight for males, yearling weight for females, dry matter intake, loin eye area, and rump fat thickness (P ≤ 0.05). Therefore, GHRL is an important candidate gene that may be used to identify genetic variations that influence traits of economic importance in beef cattle.

Identification of growth trait related genes in a Yorkshire purebred pig population by genome-wide association studies

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Qingli Meng

2017-04-01

Full Text Available Objective The aim of this study is to identify genomic regions or genes controlling growth traits in pigs. Methods Using a panel of 54,148 single nucleotide polymorphisms (SNPs, we performed a genome-wide Association (GWA study in 562 pure Yorshire pigs with four growth traits: average daily gain from 30 kg to 100 kg or 115 kg, and days to 100 kg or 115 kg. Fixed and random model Circulating Probability Unification method was used to identify the associations between 54,148 SNPs and these four traits. SNP annotations were performed through the Sus scrofa data set from Ensembl. Bioinformatics analysis, including gene ontology analysis, pathway analysis and network analysis, was used to identify the candidate genes. Results We detected 6 significant and 12 suggestive SNPs, and identified 9 candidate genes in close proximity to them (suppressor of glucose by autophagy [SOGA1], R-Spondin 2 [RSPO2], mitogen activated protein kinase kinase 6 [MAP2K6], phospholipase C beta 1 [PLCB1], rho GTPASE activating protein 24 [ARHGAP24], cytoplasmic polyadenylation element binding protein 4 [CPEB4], GLI family zinc finger 2 [GLI2], neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 [NYAP2], and zinc finger protein multitype 2 [ZFPM2]. Gene ontology analysis and literature mining indicated that the candidate genes are involved in bone, muscle, fat, and lung development. Pathway analysis revealed that PLCB1 and MAP2K6 participate in the gonadotropin signaling pathway and suggests that these two genes contribute to growth at the onset of puberty. Conclusion Our results provide new clues for understanding the genetic mechanisms underlying growth traits, and may help improve these traits in future breeding programs.

Association between FASN gene polymorphisms ultrasound carcass traits and intramuscular fat in Qinchuan cattle.

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Raza, Sayed Haidar Abbas; Gui, Linsheng; Khan, Rajwali; Schreurs, Nicola M; Xiaoyu, Wang; Wu, Sen; Mei, Chugang; Wang, Li; Ma, Xueyao; Wei, Dawei; Guo, Hongfang; Zhang, Song; Wang, Xingping; Kaleri, Hubdar Ali; Zan, Linsen

2018-03-01

Fatty acid synthase (FASN) is an enzyme involved with fat deposition and fatty acid composition in cattle. This study was conducted to detect single nucleotide polymorphisms (SNPs) of the FASN gene and explore their relationships with ultrasound carcass traits in order to assess the potential use of the FASN gene for the breeding selection of Qinchuan cattle for desirable carcass traits. The frequencies of SNP g.12740C>T, g.13192T>C and g.13232C>T were identified in 525 individual Qinchuan cattle which were also assessed for backfat depth, eye muscle area and intramuscular fat by ultrasound. According to the PIC values, g.13192T>C possessed an intermediate polymorphism (0.25T, g.12740C>T possessed low polymorphism (PICC were in Hardy-Weinberg disequilibrium (c2C was associated with a greater eye muscle area and the TT genotype at g.13232C>T was associated with greater intramuscular fat. When these genotypes were combined there was no difference in eye muscle area and intramuscular fat between the diplotypes. The H 2 H 2 diplotype was associated with carcass traits that are likely to provide economic advantage in Qinchuan cattle. Variations in the FASN genes and their corresponding genotypes may be considered as molecular markers for economic traits in cattle breeding. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between the SPRY1 gene polymorphism and obesity-related traits and osteoporosis in Korean women.

Science.gov (United States)

Jin, Hyun-Seok; Kim, Bo-Young; Kim, Jeonghyun; Hong, Kyung-Won; Jung, Suk-Yul; Lee, Yun-Seok; Huh, Dam; Oh, Bermseok; Chung, Yoon-Sok; Jeong, Seon-Yong

2013-01-01

Emerging evidence has revealed a close relationship between obesity and osteoporosis. It was reported recently that conditional knockout of the Spry1 gene in mice adipocytes causes an increase in body fat and a decrease in bone mass, and that these phenotypes are rescued by Spry1 overexpression in adipose tissue. In this study, we investigated whether genetic variation in the human SPRY1 gene is associated with obesity-related phenotypes and/or osteoporosis in humans. We performed a candidate gene association analysis between the four single nucleotide polymorphisms (SNPs) and 14 imputed SNPs in the SPRY1 gene and obesity-related traits and osteoporosis in a Korean women cohort (3013 subjects). All four SPRY1 gene SNPs were significantly associated with either obesity-related traits or osteoporosis. The TGCC haplotype in the SRPY1 gene showed simultaneous association with an increased risk for obesity-related traits, percentage body fat (p=0.0087) and percentage abdominal fat (p=0.047), and osteoporosis (odds ratio=1.50; p=0.025) in the recessive genetic model. Our results support a previous finding in conditional Spry1 gene knockout mice and suggest that the SPRY1 gene is an important genetic factor for determining the risk of both obesity and osteoporosis in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.

Directory of Open Access Journals (Sweden)

Yi-Hsiang Hsu

2010-06-01

Full Text Available Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD at the lumbar spine (LS and femoral neck (FN, as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW. A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6x10(-8, 2q11.2 (TBC1D8, and 18q11.2 (OSBPL1A, and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6x10(-13; SOX6, p = 6.4x10(-10 associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

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Petr Volkov

Full Text Available Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI, lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL, hemoglobin A1c (HbA1c and homeostatic model assessment of insulin resistance (HOMA-IR via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dysmetabolic traits associated with the development of

Gene interactions and genetics for yield and its attributes in grass ...

Indian Academy of Sciences (India)

A. K. PARIHAR

explaining the manifestation of complex traits such as yield. ... interactions (i, j, l) contributed towards the inheritance of traits in the given crosses. ... Keywords. grass pea; scaling test; gene interactions; gene effects; heritability; Lathyrus sativus.

“Are We There Yet?”: Deciding When One Has Demonstrated Specific Genetic Causation in Complex Diseases and Quantitative Traits

Science.gov (United States)

Page, Grier P.; George, Varghese; Go, Rodney C.; Page, Patricia Z.; Allison, David B.

2003-01-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, “Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it.” We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what “causation” means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called “causative.” PMID:13680525

Early warm-rewarding parenting moderates the genetic contributions to callous-unemotional traits in childhood.

Science.gov (United States)

Henry, Jeffrey; Dionne, Ginette; Viding, Essi; Vitaro, Frank; Brendgen, Mara; Tremblay, Richard E; Boivin, Michel

2018-04-23

Previous gene-environment interaction studies of CU traits have relied on the candidate gene approach, which does not account for the entire genetic load of complex phenotypes. Moreover, these studies have not examined the role of positive environmental factors such as warm/rewarding parenting. The aim of the present study was to determine whether early warm/rewarding parenting moderates the genetic contributions (i.e., heritability) to callous-unemotional (CU) traits at school age. Data were collected in a population sample of 662 twin pairs (Quebec Newborn Twin Study - QNTS). Mothers reported on their warm/rewarding parenting. Teachers assessed children's CU traits. These reports were subjected to twin modeling. Callous-unemotional traits were highly heritable, with the remaining variance accounted for by nonshared environmental factors. Warm/rewarding parenting significantly moderated the role of genes in CU traits; heritability was lower when children received high warm/rewarding parenting than when they were exposed to low warm/rewarding parenting. High warm/rewarding parenting may partly impede the genetic expression of CU traits. Developmental models of CU traits need to account for such gene-environment processes. © 2018 Association for Child and Adolescent Mental Health.

Uncovering the genetic landscape for multiple sleep-wake traits.

Directory of Open Access Journals (Sweden)

Christopher J Winrow

Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

MACROD2 gene associated with autistic-like traits in a general population sample.

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Jones, Rachel M; Cadby, Gemma; Blangero, John; Abraham, Lawrence J; Whitehouse, Andrew J O; Moses, Eric K

2014-12-01

There is now substantial evidence that autistic-like traits in the general population lie on a continuum, with clinical autism spectrum disorders (ASD) representing the extreme end of this distribution. In this study, we sought to evaluate five independently identified genetic associations with ASD with autistic-like traits in the general population. In the study cohort, clinical phenotype and genomewide association genotype data were obtained from the Western Australian Pregnancy Cohort (Raine) Study. The outcome measure used was the Autism Spectrum Quotient (AQ), a quantitative measure of autistic-like traits of individuals in the cohort. Total AQ scores were calculated for each individual, as well as scores for three subscales. Five candidate single nucleotide polymorphism (SNP) associations with ASD, reported in previously published genomewide association studies, were selected using a nominal cutoff value of P less than 1.0×10. We tested whether these five SNPs were associated with total AQ and the subscales, after adjustment for possible confounders. SNP rs4141463 located in the macro domain containing 2 (MACROD2) gene was significantly associated with the Communication/Mindreading subscale. No other SNP was significantly associated with total AQ or the subscales. The MACROD2 gene is a strong positional candidate risk factor for autistic-like traits in the general population.

Characterization of porcine cytokine inducible SH2-containing protein gene and its association with piglet diarrhea traits.

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Niu, Buyue; Guo, Dongchun; Liu, Zhiran; Han, Xiaofei; Wang, Xibiao

2017-12-01

The cytokine inducible SH2-containing protein (CISH), which might play a role in porcine intestine immune responses, was one of the promising candidate genes for piglet anti-disease traits. An experiment was conducted to characterize the porcine CISH (pCISH) gene and to evaluate its genetic effects on pig anti-disease breeding. Both reverse transcription polymerase chain reaction (RT-PCR) and PCR were performed to obtain the sequence of pCISH gene. A pEGFP-C1-CISH vector was constructed and transfected into PK-15 cells to analysis the distribution of pCISH. The sequences of individuals were compared with each other to find the polymorphisms in pCISH gene. The association analysis was performed in Min pigs and Landrace pigs to evaluate the genetic effects on piglet diarrhea traits. In the present research, the coding sequence and genomic sequence of pCISH gene was obtained. Porcine CISH was mainly localized in cytoplasm. TaqI and HaeIII PCR restriction fragment length polymorphism (RFLP) assays were established to detect single nucleotide polymorphisms (SNPs); A-1575G in promoter region and A2497C in Intron1, respectively. Association studies indicated that SNP A-1575G was significantly associated with diarrhea index of Min piglets (p<0.05) and SNP A2497C was significantly associated with the diarrhea trait of both Min pig and Landrace piglets (p<0.05). This study suggested that the pCISH gene might be a novel candidate gene for pig anti-disease traits, and further studies are needed to confirm the results of this preliminary research.

Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

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Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

2018-04-13

Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

Pleiotropic Genes Affecting Carcass Traits in Bos indicus (Nellore Cattle Are Modulators of Growth.

Directory of Open Access Journals (Sweden)

Anirene G T Pereira

Full Text Available Two complementary methods, namely Multi-Trait Meta-Analysis and Versatile Gene-Based Test for Genome-wide Association Studies (VEGAS, were used to identify putative pleiotropic genes affecting carcass traits in Bos indicus (Nellore cattle. The genotypic data comprised over 777,000 single-nucleotide polymorphism markers scored in 995 bulls, and the phenotypic data included deregressed breeding values (dEBV for weight measurements at birth, weaning and yearling, as well visual scores taken at weaning and yearling for carcass finishing precocity, conformation and muscling. Both analyses pointed to the pleomorphic adenoma gene 1 (PLAG1 as a major pleiotropic gene. VEGAS analysis revealed 224 additional candidates. From these, 57 participated, together with PLAG1, in a network involved in the modulation of the function and expression of IGF1 (insulin like growth factor 1, IGF2 (insulin like growth factor 2, GH1 (growth hormone 1, IGF1R (insulin like growth factor 1 receptor and GHR (growth hormone receptor, suggesting that those pleiotropic genes operate as satellite regulators of the growth pathway.

Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress: are there links to gene expression and phenotypic traits?

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Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes; Holmstrup, Martin; Nielsen, Niels Chr.; Loeschcke, Volker

2013-05-01

We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic 1H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led to a general stress selection response at the metabolomic level. Integrative analyses across data sets showed little similarity when general correlations between selection effects at the level of the metabolome and gene expression were compared. This is likely due to the fact that the changes caused by these selection regimes were rather mild and/or that the dominating determinants for gene expression and metabolite levels were different. However, expression of a number of genes was correlated with the metabolite data. Many of the identified genes were general stress response genes that are down-regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level. The results highlight the extreme complexity of environmental stress adaptation and the difficulty of extrapolating and interpreting responses across levels of biological organization.

How powerful are summary-based methods for identifying expression-trait associations under different genetic architectures?

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Veturi, Yogasudha; Ritchie, Marylyn D

2018-01-01

Transcriptome-wide association studies (TWAS) have recently been employed as an approach that can draw upon the advantages of genome-wide association studies (GWAS) and gene expression studies to identify genes associated with complex traits. Unlike standard GWAS, summary level data suffices for TWAS and offers improved statistical power. Two popular TWAS methods include either (a) imputing the cis genetic component of gene expression from smaller sized studies (using multi-SNP prediction or MP) into much larger effective sample sizes afforded by GWAS - TWAS-MP or (b) using summary-based Mendelian randomization - TWAS-SMR. Although these methods have been effective at detecting functional variants, it remains unclear how extensive variability in the genetic architecture of complex traits and diseases impacts TWAS results. Our goal was to investigate the different scenarios under which these methods yielded enough power to detect significant expression-trait associations. In this study, we conducted extensive simulations based on 6000 randomly chosen, unrelated Caucasian males from Geisinger's MyCode population to compare the power to detect cis expression-trait associations (within 500 kb of a gene) using the above-described approaches. To test TWAS across varying genetic backgrounds we simulated gene expression and phenotype using different quantitative trait loci per gene and cis-expression /trait heritability under genetic models that differentiate the effect of causality from that of pleiotropy. For each gene, on a training set ranging from 100 to 1000 individuals, we either (a) estimated regression coefficients with gene expression as the response using five different methods: LASSO, elastic net, Bayesian LASSO, Bayesian spike-slab, and Bayesian ridge regression or (b) performed eQTL analysis. We then sampled with replacement 50,000, 150,000, and 300,000 individuals respectively from the testing set of the remaining 5000 individuals and conducted GWAS on each

Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster.

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Allen, Aaron M; Anreiter, Ina; Neville, Megan C; Sokolowski, Marla B

2017-02-01

Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. Copyright © 2017 by the Genetics Society of America.

Gene stacking of multiple traits for high yield of fermentable sugars in plant biomass

DEFF Research Database (Denmark)

Aznar, Aude; Chalvin, Camille; Shih, Patrick M.

2018-01-01

the ratio of C6 to C5 sugars in the cell wall and decreasing the lignin content are two important targets in engineering of plants that are more suitable for downstream processing for second-generation biofuel production.Results: We have studied the basic mechanisms of cell wall biosynthesis and identified...... genes involved in biosynthesis of pectic galactan, including the GALS1 galactan synthase and the UDP-galactose/UDP-rhamnose transporter URGT1. We have engineered plants with a more suitable biomass composition by applying these findings, in conjunction with synthetic biology and gene stacking tools...... to vessels where this polysaccharide is essential. Finally, the high galactan and low xylan traits were stacked with the low lignin trait obtained by expressing the QsuB gene encoding dehydroshikimate dehydratase in lignifying cells.Conclusion: The results show that approaches to increasing C6 sugar content...

Climatic conditions cause complex patterns of covariation between demographic traits in a long-lived raptor

NARCIS (Netherlands)

Herfindal, Ivar; van de Pol, Martijn; Nielsen, Jan Tøttrup; Sæther, Bernt-Erik; Møller, Anders Pape

2015-01-01

1.Environmental variation can induce life history changes that can last over a large part of the lifetime of an organism. If multiple demographic traits are affected, expected changes in climate may influence environmental covariances among traits in a complex manner. Thus, examining the

Molecular evolution of candidate genes for crop-related traits in sunflower (Helianthus annuus L.).

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Mandel, Jennifer R; McAssey, Edward V; Nambeesan, Savithri; Garcia-Navarro, Elena; Burke, John M

2014-01-01

Evolutionary analyses aimed at detecting the molecular signature of selection during crop domestication and/or improvement can be used to identify genes or genomic regions of likely agronomic importance. Here, we describe the DNA sequence-based characterization of a pool of candidate genes for crop-related traits in sunflower. These genes, which were identified based on homology to genes of known effect in other study systems, were initially sequenced from a panel of improved lines. All genes that exhibited a paucity of sequence diversity, consistent with the possible effects of selection during the evolution of cultivated sunflower, were then sequenced from a panel of wild sunflower accessions an outgroup. These data enabled formal tests for the effects of selection in shaping sequence diversity at these loci. When selection was detected, we further sequenced these genes from a panel of primitive landraces, thereby allowing us to investigate the likely timing of selection (i.e., domestication vs. improvement). We ultimately identified seven genes that exhibited the signature of positive selection during either domestication or improvement. Genetic mapping of a subset of these genes revealed co-localization between candidates for genes involved in the determination of flowering time, seed germination, plant growth/development, and branching and QTL that were previously identified for these traits in cultivated × wild sunflower mapping populations.

Toward Bridging the Mechanistic Gap between Genes and Traits by Emphasizing the Role of Proteins in a Computational Environment

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Haskel-Ittah, Michal; Yarden, Anat

2017-01-01

Previous studies have shown that students often ignore molecular mechanisms when describing genetic phenomena. Specifically, students tend to directly link genes to their encoded traits, ignoring the role of proteins as mediators in this process. We tested the ability of 10th grade students to connect genes to traits through proteins, using…

Characterization of porcine cytokine inducible SH2-containing protein gene and its association with piglet diarrhea traits

Directory of Open Access Journals (Sweden)

Buyue Niu

2017-12-01

Full Text Available Objective The cytokine inducible SH2-containing protein (CISH, which might play a role in porcine intestine immune responses, was one of the promising candidate genes for piglet anti-disease traits. An experiment was conducted to characterize the porcine CISH (pCISH gene and to evaluate its genetic effects on pig anti-disease breeding. Methods Both reverse transcription polymerase chain reaction (RT-PCR and PCR were performed to obtain the sequence of pCISH gene. A pEGFP-C1-CISH vector was constructed and transfected into PK-15 cells to analysis the distribution of pCISH. The sequences of individuals were compared with each other to find the polymorphisms in pCISH gene. The association analysis was performed in Min pigs and Landrace pigs to evaluate the genetic effects on piglet diarrhea traits. Results In the present research, the coding sequence and genomic sequence of pCISH gene was obtained. Porcine CISH was mainly localized in cytoplasm. TaqI and HaeIII PCR restriction fragment length polymorphism (RFLP assays were established to detect single nucleotide polymorphisms (SNPs; A-1575G in promoter region and A2497C in Intron1, respectively. Association studies indicated that SNP A-1575G was significantly associated with diarrhea index of Min piglets (p<0.05 and SNP A2497C was significantly associated with the diarrhea trait of both Min pig and Landrace piglets (p<0.05. Conclusion This study suggested that the pCISH gene might be a novel candidate gene for pig anti-disease traits, and further studies are needed to confirm the results of this preliminary research.

Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat.

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Nazari-Ghadikolaei, Anahit; Mehrabani-Yeganeh, Hassan; Miarei-Aashtiani, Seyed R; Staiger, Elizabeth A; Rashidi, Amir; Huson, Heather J

2018-01-01

The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS). This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair) traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY , and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic causality and

Mapping of genes for flower-related traits and QTLs for flowering ...

Indian Academy of Sciences (India)

Mapping of genes for flower-related traits and QTLs for flowering time in an interspecific population of Gossypium hirsutum × G. darwinii. Shuwen Zhang, Qianqian Lan, Xiang Gao, Biao Yang, Caiping Cai, Tianzhen Zhang and Baoliang Zhou. J. Genet. 95, 197–201. Table 1. Loci composition and recombination distances of ...

Integrating Nonadditive Genomic Relationship Matrices into the Study of Genetic Architecture of Complex Traits.

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Nazarian, Alireza; Gezan, Salvador A

2016-03-01

The study of genetic architecture of complex traits has been dramatically influenced by implementing genome-wide analytical approaches during recent years. Of particular interest are genomic prediction strategies which make use of genomic information for predicting phenotypic responses instead of detecting trait-associated loci. In this work, we present the results of a simulation study to improve our understanding of the statistical properties of estimation of genetic variance components of complex traits, and of additive, dominance, and genetic effects through best linear unbiased prediction methodology. Simulated dense marker information was used to construct genomic additive and dominance matrices, and multiple alternative pedigree- and marker-based models were compared to determine if including a dominance term into the analysis may improve the genetic analysis of complex traits. Our results showed that a model containing a pedigree- or marker-based additive relationship matrix along with a pedigree-based dominance matrix provided the best partitioning of genetic variance into its components, especially when some degree of true dominance effects was expected to exist. Also, we noted that the use of a marker-based additive relationship matrix along with a pedigree-based dominance matrix had the best performance in terms of accuracy of correlations between true and estimated additive, dominance, and genetic effects. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of the porcine APOA2 gene expression in liver, polymorphism identification and association with fatty acid composition traits

NARCIS (Netherlands)

Ballester, M.; Revilla, M.; Puig-Oliveras, A.; Marchesi, J.A.; Castello, A.; Corominas, J.; Fernandez, A.I.; Folch, J.M.

2016-01-01

APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

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Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

2017-11-02

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genomic prediction of complex human traits: relatedness, trait architecture and predictive meta-models

Science.gov (United States)

Spiliopoulou, Athina; Nagy, Reka; Bermingham, Mairead L.; Huffman, Jennifer E.; Hayward, Caroline; Vitart, Veronique; Rudan, Igor; Campbell, Harry; Wright, Alan F.; Wilson, James F.; Pong-Wong, Ricardo; Agakov, Felix; Navarro, Pau; Haley, Chris S.

2015-01-01

We explore the prediction of individuals' phenotypes for complex traits using genomic data. We compare several widely used prediction models, including Ridge Regression, LASSO and Elastic Nets estimated from cohort data, and polygenic risk scores constructed using published summary statistics from genome-wide association meta-analyses (GWAMA). We evaluate the interplay between relatedness, trait architecture and optimal marker density, by predicting height, body mass index (BMI) and high-density lipoprotein level (HDL) in two data cohorts, originating from Croatia and Scotland. We empirically demonstrate that dense models are better when all genetic effects are small (height and BMI) and target individuals are related to the training samples, while sparse models predict better in unrelated individuals and when some effects have moderate size (HDL). For HDL sparse models achieved good across-cohort prediction, performing similarly to the GWAMA risk score and to models trained within the same cohort, which indicates that, for predicting traits with moderately sized effects, large sample sizes and familial structure become less important, though still potentially useful. Finally, we propose a novel ensemble of whole-genome predictors with GWAMA risk scores and demonstrate that the resulting meta-model achieves higher prediction accuracy than either model on its own. We conclude that although current genomic predictors are not accurate enough for diagnostic purposes, performance can be improved without requiring access to large-scale individual-level data. Our methodologically simple meta-model is a means of performing predictive meta-analysis for optimizing genomic predictions and can be easily extended to incorporate multiple population-level summary statistics or other domain knowledge. PMID:25918167

Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

Science.gov (United States)

Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

2017-08-01

Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

ThMYC4E, candidate Blue aleurone 1 gene controlling the associated trait in Triticum aestivum.

Directory of Open Access Journals (Sweden)

Na Li

Full Text Available Blue aleurone is a useful and interesting trait in common wheat that was derived from related species. Here, transcriptomes of blue and white aleurone were compared for isolating Blue aleurone 1 (Ba1 transferred from Thinopyrum ponticum. In the genes involved in anthocyanin biosynthesis, only a basic helix-loop-helix (bHLH transcription factor, ThMYC4E, had a higher transcript level in blue aleurone phenotype, and was homologous to the genes on chromosome 4 of Triticum aestivum. ThMYC4E carried the characteristic domains (bHLH-MYC_N, HLH and ACT-like of a bHLH transcription factor, and clustered with genes regulating anthocyanin biosynthesis upon phylogenetic analysis. The over-expression of ThMYC4E regulated anthocyanin biosynthesis with the coexpression of the MYB transcription factor ZmC1 from maize. ThMYC4E existed in the genomes of the addition, substitution and near isogenic lines with the blue aleurone trait derived from Th. ponticum, and could not be detected in any germplasm of T. urartu, T. monococcum, T. turgidum, Aegilops tauschii or T. aestivum, with white aleurone. These results suggested that ThMYC4E was candidate Ba1 gene controlling the blue aleurone trait in T. aestivum genotypes carrying Th. ponticum introgression. The ThMYC4E isolation aids in better understanding the genetic mechanisms of the blue aleurone trait and in its more effective use during wheat breeding.

Longevity Candidate Genes and Their Association With Personality Traits in the Elderly

NARCIS (Netherlands)

Luciano, M.; Lopez, L.M.; de Moor, M.H.M.; Harris, S.E.; Davies, G.; Nutile, T.; Krueger, R.F.; Esko, T.; Schlessinger, D.; Toshiko, T.; Derringer, J.; Realo, A.; Hansell, N.K.; Pergadia, M.L.; Pesonen, A.-K.; Sanna, S.; Terracciano, A.; Madden, P.A.F.; Penninx, B.W.J.H.; Spinhoven, Ph.D.; Hartman, C.A.; Oostra, B.A.; Janssens, A.C.J.W.; Eriksson, J.G.; Starr, J.M.; Cannas, A.; Ferrucci, L.; Metspalu, A.; Wright, M.J.; Heath, A.C.; van Duijn, C.M.; Bierut, L.J.; Raikkonen, K.; Martin, N.G.; Ciullo, M.; Rujescu, D.; Boomsma, D.I.; Deary, I.J.

2012-01-01

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

Longevity candidate genes and their association with personality traits in the elderly

NARCIS (Netherlands)

Luciano, Michelle; Lopez, Lorna M.; de Moor, Marleen H. M.; Harris, Sarah E.; Davies, Gail; Nutile, Teresa; Krueger, Robert F.; Esko, Tonu; Schlessinger, David; Toshiko, Tanaka; Derringer, Jaime L.; Realo, Anu; Hansell, Narelle K.; Pergadia, Michele L.; Pesonen, Anu-Katriina; Sanna, Serena; Terracciano, Antonio; Madden, Pamela A. F.; Penninx, Brenda; Spinhoven, Philip; Hartman, Catherina A.; Oostra, Ben A.; Janssens, A. Cecile J. W.; Eriksson, Johan G.; Starr, John M.; Cannas, Alessandra; Ferrucci, Luigi; Metspalu, Andres; Wright, Margeret J.; Heath, Andrew C.; van Duijn, Cornelia M.; Bierut, Laura J.; Raikkonen, Katri; Martin, Nicholas G.; Ciullo, Marina; Rujescu, Dan; Boomsma, Dorret I.; Deary, Ian J.

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

Adrenal cortex expression quantitative trait loci in a German Holstein × Charolais cross.

Science.gov (United States)

Brand, Bodo; Scheinhardt, Markus O; Friedrich, Juliane; Zimmer, Daisy; Reinsch, Norbert; Ponsuksili, Siriluck; Schwerin, Manfred; Ziegler, Andreas

2016-10-06

The importance of the adrenal gland in regard to lactation and reproduction in cattle has been recognized early. Caused by interest in animal welfare and the impact of stress on economically important traits in farm animals the adrenal gland and its function within the stress response is of increasing interest. However, the molecular mechanisms and pathways involved in stress-related effects on economically important traits in farm animals are not fully understood. Gene expression is an important mechanism underlying complex traits, and genetic variants affecting the transcript abundance are thought to influence the manifestation of an expressed phenotype. We therefore investigated the genetic background of adrenocortical gene expression by applying an adaptive linear rank test to identify genome-wide expression quantitative trait loci (eQTL) for adrenal cortex transcripts in cattle. A total of 10,986 adrenal cortex transcripts and 37,204 single nucleotide polymorphisms (SNPs) were analysed in 145 F2 cows of a Charolais × German Holstein cross. We identified 505 SNPs that were associated with the abundance of 129 transcripts, comprising 482 cis effects and 17 trans effects. These SNPs were located on all chromosomes but X, 16, 24 and 28. Associated genes are mainly involved in molecular and cellular functions comprising free radical scavenging, cellular compromise, cell morphology and lipid metabolism, including genes such as CYP27A1 and LHCGR that have been shown to affect economically important traits in cattle. In this study we showed that adrenocortical eQTL affect the expression of genes known to contribute to the phenotypic manifestation in cattle. Furthermore, some of the identified genes and related molecular pathways were previously shown to contribute to the phenotypic variation of behaviour, temperament and growth at the onset of puberty in the same population investigated here. We conclude that eQTL analysis appears to be a useful approach providing

Association of MYF5 and KLF15 gene polymorphisms with carcass traits in domestic pigeons (Columba livia).

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Yin, Z Z; Dong, X Y; Dong, D J; Ma, Y Z

2016-10-01

Single nucleotide polymorphisms (SNPs) in the exons of the myogenic factor 5 (MYF5) and Kruppel-like factor 15 (KLF15) genes were identified and analysed by using DNA sequencing methods in 60 female domestic pigeons (Columba livia). Five SNPs (T5067A, C5084T, C5101T, T5127A and C5154G) were detected in exon 3 of MYF5 and 6 SNPs (C1398T, C1464T, G1542A, C1929T, G1965A and A2355G) were found in exon 2 of KLF15, respectively. The analysis revealed three genotypes, in which the AA genotype was dominant and the A allele showed a dominant advantage. For the MYF5 gene, the C5084T and T5127A SNP genotypes were significantly associated with carcass traits of pigeons. Within those two SNPs, the BB genotype showed relatively higher trait association values than those of AA or AB genotypes. No significant association was observed between the KLF15 SNP genotypes and carcass traits. These results indicated that the MYF5 gene is a potential major gene affecting carcass traits in domestic pigeons. The BB genotype of the C5084T and T5127A SNPs could be a potential candidate genetic marker for marker-assisted selection in pigeon.

Functional mapping imprinted quantitative trait loci underlying developmental characteristics

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Li Gengxin

2008-03-01

Full Text Available Abstract Background Genomic imprinting, a phenomenon referring to nonequivalent expression of alleles depending on their parental origins, has been widely observed in nature. It has been shown recently that the epigenetic modification of an imprinted gene can be detected through a genetic mapping approach. Such an approach is developed based on traditional quantitative trait loci (QTL mapping focusing on single trait analysis. Recent studies have shown that most imprinted genes in mammals play an important role in controlling embryonic growth and post-natal development. For a developmental character such as growth, current approach is less efficient in dissecting the dynamic genetic effect of imprinted genes during individual ontology. Results Functional mapping has been emerging as a powerful framework for mapping quantitative trait loci underlying complex traits showing developmental characteristics. To understand the genetic architecture of dynamic imprinted traits, we propose a mapping strategy by integrating the functional mapping approach with genomic imprinting. We demonstrate the approach through mapping imprinted QTL controlling growth trajectories in an inbred F2 population. The statistical behavior of the approach is shown through simulation studies, in which the parameters can be estimated with reasonable precision under different simulation scenarios. The utility of the approach is illustrated through real data analysis in an F2 family derived from LG/J and SM/J mouse stains. Three maternally imprinted QTLs are identified as regulating the growth trajectory of mouse body weight. Conclusion The functional iQTL mapping approach developed here provides a quantitative and testable framework for assessing the interplay between imprinted genes and a developmental process, and will have important implications for elucidating the genetic architecture of imprinted traits.

Four linked genes participate in controlling sporulation efficiency in budding yeast.

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Giora Ben-Ari

2006-11-01

Full Text Available Quantitative traits are conditioned by several genetic determinants. Since such genes influence many important complex traits in various organisms, the identification of quantitative trait loci (QTLs is of major interest, but still encounters serious difficulties. We detected four linked genes within one QTL, which participate in controlling sporulation efficiency in Saccharomyces cerevisiae. Following the identification of single nucleotide polymorphisms by comparing the sequences of 145 genes between the parental strains SK1 and S288c, we analyzed the segregating progeny of the cross between them. Through reciprocal hemizygosity analysis, four genes, RAS2, PMS1, SWS2, and FKH2, located in a region of 60 kilobases on Chromosome 14, were found to be associated with sporulation efficiency. Three of the four "high" sporulation alleles are derived from the "low" sporulating strain. Two of these sporulation-related genes were verified through allele replacements. For RAS2, the causative variation was suggested to be a single nucleotide difference in the upstream region of the gene. This quantitative trait nucleotide accounts for sporulation variability among a set of ten closely related winery yeast strains. Our results provide a detailed view of genetic complexity in one "QTL region" that controls a quantitative trait and reports a single nucleotide polymorphism-trait association in wild strains. Moreover, these findings have implications on QTL identification in higher eukaryotes.

Variation of gene effects of six agronomic traits with water regimes in ...

African Journals Online (AJOL)

Separate generations mean analyses revealed that gene effects were dependent upon water regime. Under irrigated regime, only additive and dominance effects were implicated in inheritance of all traits, except plant height in the two crosses and grains per spike in the cross Razzek × Chili. However, under rainfed ...

Similar traits, different genes? Examining convergent evolution in related weedy rice populations.

Science.gov (United States)

Thurber, Carrie S; Jia, Melissa H; Jia, Yulin; Caicedo, Ana L

2013-02-01

Convergent phenotypic evolution may or may not be associated with convergent genotypic evolution. Agricultural weeds have repeatedly been selected for weed-adaptive traits such as rapid growth, increased seed dispersal and dormancy, thus providing an ideal system for the study of convergent evolution. Here, we identify QTL underlying weedy traits and compare their genetic architecture to assess the potential for convergent genetic evolution in two distinct populations of weedy rice. F(2) offspring from crosses between an indica cultivar and two individuals from genetically differentiated U.S. weedy rice populations were used to map QTL for four quantitative (heading date, seed shattering, plant height and growth rate) and two qualitative traits. We identified QTL on nine of the twelve rice chromosomes, yet most QTL locations do not overlap between the two populations. Shared QTL among weed groups were only seen for heading date, a trait for which weedy groups have diverged from their cultivated ancestors and from each other. Sharing of some QTL with wild rice also suggests a possible role in weed evolution for genes under selection during domestication. The lack of overlapping QTL for the remaining traits suggests that, despite a close evolutionary relationship, weedy rice groups have adapted to the same agricultural environment through different genetic mechanisms. © 2012 Blackwell Publishing Ltd.

Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat

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Anahit Nazari-Ghadikolaei

2018-04-01

Full Text Available The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS. This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY, and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic

Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.

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Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong

2015-05-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.

Age of Onset of Mood Disorders and Complexity of Personality Traits

OpenAIRE

Ostacoli, L.; Zuffranieri, M.; Cavallo, M.; Zennaro, A.; Rainero, I.; Pinessi, L.; Pacchiana Parravicini, M. V.; Ladisa, E.; Furlan, P. M.; Picci, R. L.

2013-01-01

Objective. The aim of the present study is to evaluate the link between the age of onset of mood disorders and the complexity of the personality traits. Methods. 209 patients with major depressive or manic/hypomanic episodes were assessed using the Structured Clinical Interview for DSM Axis I diagnoses and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Results. 17.2% of the patients had no elevated MCMI-III scores, 45.9% had one peak, and 36.9% had a complex personality disorder wit...

A novel approach to simulate gene-environment interactions in complex diseases

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Nicodemi Mario

2010-01-01

Full Text Available Abstract Background Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.. Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS, a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte

POLYMORPHISM OF PROLACTIN RECEPTOR GENE (PRLR IN THE POLISH LANDRACE AND POLISH LARGE WHITE SWINE POPULATION AND REPRODUCTIVE TRAITS

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AGATA ZIÓŁKOWSKA

2011-01-01

Full Text Available Prolactin receptor gene was found in pig chromosome 16, and it is one of the genes with a significant effect on reproduction traits in sows. The objective of the research was to determine polymorphism of the prolactin receptor gene in pigs of two maternal breeds: Polish Landrace and Polish Large White, as well as analyse relations between particular allelomorphic variants, and reproduction traits of examined sows. Two PRLR gene alleles, A and B, were isolated, they were obtained after AluI restriction gene digestion of the PCR product with the length of 163 bp; furthermore, three genotypes were identified: PRLRAA – 85, 59, 19 bp; PRLRAB – 104, 85, 59, 19 bp; PRLRBB – 104, 59 bp. We assessed 122 sows, in terms of their age at the first farrowing, as well as the sizes of the two subsequent litters. No statistically significant differences were found in the examined reproduction traits in sows with different allelomorphic relations, both within each breed and between breeds. Obtained results indicate that it is necessary to conduct further research on a larger animal group.

Directional selection can drive the evolution of modularity in complex traits.

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Melo, Diogo; Marroig, Gabriel

2015-01-13

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

MAGMA: Generalized Gene-Set Analysis of GWAS Data

NARCIS (Netherlands)

de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

2015-01-01

By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

MAGMA: generalized gene-set analysis of GWAS data.

NARCIS (Netherlands)

de Leeuw, C.A.; Mooij, J.M.; Heskes, T.; Posthuma, D.

2015-01-01

By aggregating data for complex traits in a biologically meaningful way, gene and gene-set analysis constitute a valuable addition to single-marker analysis. However, although various methods for gene and gene-set analysis currently exist, they generally suffer from a number of issues. Statistical

Functional validation of candidate genes detected by genomic feature models

DEFF Research Database (Denmark)

Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

2018-01-01

Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated...

Polymorphisms of the myostatin gene and its relationship with reproduction traits in the Bian chicken.

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Zhang, Genxi; Zhang, Li; Wei, Yue; Wang, Jinyu; Ding, Fuxiang; Dai, Guojun; Xie, Kaizhou

2012-01-01

Myostatin, or growth and differentiation factor 8, is a member of the transforming growth factor-β superfamily; it functions as a negative regulator of skeletal muscle development and growth in mammals. In this study, single nucleotide polymorphisms in the 5' regulatory region and exon 1 of the myostatin gene were detected by PCR-SSCP in the Bian, Jinghai, Youxi, and Arbor Acre chickens, and the associations of the polymorphisms with reproduction traits were analyzed. Seven SNPs (A326G, C334G, C1346T, G1375A, A1473G, G1491A, and G2283A) were found in the myostatin gene. Association analysis showed that the G2283A were significantly associated with reproduction traits. Bian chickens of the GG genotype had a greater age at first egg than those of the GA and AA genotypes (Pchickens of the GA and AA genotypes had larger egg number at 300 days than those of the GG genotype (Pchickens of the AA genotype had significantly higher body weight at 300 days than those of the GG genotype (P<0.05). These results suggested that the myostatin gene may have certain effects on reproduction traits other than merely as a negative regulator of skeletal muscle development and growth in mammals previously reported.

Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability

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Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

2015-01-01

Abstract In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. PMID:26484978

The genetic basis of natural variation in oenological traits in Saccharomyces cerevisiae.

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Francisco Salinas

Full Text Available Saccharomyces cerevisiae is the main microorganism responsible for wine alcoholic fermentation. The oenological phenotypes resulting from fermentation, such as the production of acetic acid, glycerol, and residual sugar concentration are regulated by multiple genes and vary quantitatively between different strain backgrounds. With the aim of identifying the quantitative trait loci (QTLs that regulate oenological phenotypes, we performed linkage analysis using three crosses between highly diverged S. cerevisiae strains. Segregants from each cross were used as starter cultures for 20-day fermentations, in synthetic wine must, to simulate actual winemaking conditions. Linkage analysis on phenotypes of primary industrial importance resulted in the mapping of 18 QTLs. We tested 18 candidate genes, by reciprocal hemizygosity, for their contribution to the observed phenotypic variation, and validated five genes and the chromosome II right subtelomeric region. We observed that genes involved in mitochondrial metabolism, sugar transport, nitrogen metabolism, and the uncharacterized ORF YJR030W explained most of the phenotypic variation in oenological traits. Furthermore, we experimentally validated an exceptionally strong epistatic interaction resulting in high level of succinic acid between the Sake FLX1 allele and the Wine/European MDH2 allele. Overall, our work demonstrates the complex genetic basis underlying wine traits, including natural allelic variation, antagonistic linked QTLs and complex epistatic interactions between alleles from strains with different evolutionary histories.

Quantitative Trait Locus (QTL meta-analysis and comparative genomics for candidate gene prediction in perennial ryegrass (Lolium perenne L.

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Shinozuka Hiroshi

2012-11-01

Full Text Available Abstract Background In crop species, QTL analysis is commonly used for identification of factors contributing to variation of agronomically important traits. As an important pasture species, a large number of QTLs have been reported for perennial ryegrass based on analysis of biparental mapping populations. Further characterisation of those QTLs is, however, essential for utilisation in varietal improvement programs. Results A bibliographic survey of perennial ryegrass trait-dissection studies identified a total of 560 QTLs from previously published papers, of which 189, 270 and 101 were classified as morphology-, physiology- and resistance/tolerance-related loci, respectively. The collected dataset permitted a subsequent meta-QTL study and implementation of a cross-species candidate gene identification approach. A meta-QTL analysis based on use of the BioMercator software was performed to identify two consensus regions for pathogen resistance traits. Genes that are candidates for causal polymorphism underpinning perennial ryegrass QTLs were identified through in silico comparative mapping using rice databases, and 7 genes were assigned to the p150/112 reference map. Markers linked to the LpDGL1, LpPh1 and LpPIPK1 genes were located close to plant size, leaf extension time and heading date-related QTLs, respectively, suggesting that these genes may be functionally associated with important agronomic traits in perennial ryegrass. Conclusions Functional markers are valuable for QTL meta-analysis and comparative genomics. Enrichment of such genetic markers may permit further detailed characterisation of QTLs. The outcomes of QTL meta-analysis and comparative genomics studies may be useful for accelerated development of novel perennial ryegrass cultivars with desirable traits.

Comparative genomics and transcriptomics of trait-gene association

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Pierlé Sebastián

2012-11-01

Full Text Available Abstract Background The Order Rickettsiales includes important tick-borne pathogens, from Rickettsia rickettsii, which causes Rocky Mountain spotted fever, to Anaplasma marginale, the most prevalent vector-borne pathogen of cattle. Although most pathogens in this Order are transmitted by arthropod vectors, little is known about the microbial determinants of transmission. A. marginale provides unique tools for studying the determinants of transmission, with multiple strain sequences available that display distinct and reproducible transmission phenotypes. The closed core A. marginale genome suggests that any phenotypic differences are due to single nucleotide polymorphisms (SNPs. We combined DNA/RNA comparative genomic approaches using strains with different tick transmission phenotypes and identified genes that segregate with transmissibility. Results Comparison of seven strains with different transmission phenotypes generated a list of SNPs affecting 18 genes and nine promoters. Transcriptional analysis found two candidate genes downstream from promoter SNPs that were differentially transcribed. To corroborate the comparative genomics approach we used three RNA-seq platforms to analyze the transcriptomes from two A. marginale strains with different transmission phenotypes. RNA-seq analysis confirmed the comparative genomics data and found 10 additional genes whose transcription between strains with distinct transmission efficiencies was significantly different. Six regions of the genome that contained no annotation were found to be transcriptionally active, and two of these newly identified transcripts were differentially transcribed. Conclusions This approach identified 30 genes and two novel transcripts potentially involved in tick transmission. We describe the transcriptome of an obligate intracellular bacterium in depth, while employing massive parallel sequencing to dissect an important trait in bacterial pathogenesis.

QTLs for seedling traits under salinity stress in hexaploid wheat

OpenAIRE

Ren, Yongzhe; Xu, Yanhua; Teng, Wan; Li, Bin; Lin, Tongbao

2018-01-01

ABSTRACT: Soil salinity limits agricultural production and is a major obstacle for increasing crop yield. Common wheat is one of the most important crops with allohexaploid characteristic and a highly complex genome. QTL mapping is a useful way to identify genes for quantitative traits such as salinity tolerance in hexaploid wheat. In the present study, a hydroponic trial was carried out to identify quantitative trait loci (QTLs) associated with salinity tolerance of wheat under 150mM NaCl co...

Genetic Characterization of Dog Personality Traits.

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Ilska, Joanna; Haskell, Marie J; Blott, Sarah C; Sánchez-Molano, Enrique; Polgar, Zita; Lofgren, Sarah E; Clements, Dylan N; Wiener, Pamela

2017-06-01

The genetic architecture of behavioral traits in dogs is of great interest to owners, breeders, and professionals involved in animal welfare, as well as to scientists studying the genetics of animal (including human) behavior. The genetic component of dog behavior is supported by between-breed differences and some evidence of within-breed variation. However, it is a challenge to gather sufficiently large datasets to dissect the genetic basis of complex traits such as behavior, which are both time-consuming and logistically difficult to measure, and known to be influenced by nongenetic factors. In this study, we exploited the knowledge that owners have of their dogs to generate a large dataset of personality traits in Labrador Retrievers. While accounting for key environmental factors, we demonstrate that genetic variance can be detected for dog personality traits assessed using questionnaire data. We identified substantial genetic variance for several traits, including fetching tendency and fear of loud noises, while other traits revealed negligibly small heritabilities. Genetic correlations were also estimated between traits; however, due to fairly large SEs, only a handful of trait pairs yielded statistically significant estimates. Genomic analyses indicated that these traits are mainly polygenic, such that individual genomic regions have small effects, and suggested chromosomal associations for six of the traits. The polygenic nature of these traits is consistent with previous behavioral genetics studies in other species, for example in mouse, and confirms that large datasets are required to quantify the genetic variance and to identify the individual genes that influence behavioral traits. Copyright © 2017 by the Genetics Society of America.

Contribution of Large Region Joint Associations to Complex Traits Genetics

Science.gov (United States)

Paré, Guillaume; Asma, Senay; Deng, Wei Q.

2015-01-01

A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

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Wangler, Michael F.; Hu, Yanhui

2017-01-01

ABSTRACT Human genome-wide association studies (GWAS) have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease. PMID:28151408

Missing heritability : Is the gap closing? An analysis of 32 complex traits in the Lifelines Cohort Study

NARCIS (Netherlands)

Nolte, Ilja M.; van der Most, Peter J.; Alizadeh, Behrooz Z.; de Bakker, Paul I. W.; Boezen, H. Marike; Bruinenberg, Marcel; Franke, Lude; van der Harst, Pim; Navis, Gerjan; Postma, Dirkje S.; Rots, Marianne G.; Stolk, Ronald P.; Swertz, Morris A.; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Snieder, Harold

Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this 'heritability gap' is

The NSL Complex Regulates Housekeeping Genes in Drosophila

Science.gov (United States)

Raja, Sunil Jayaramaiah; Holz, Herbert; Luscombe, Nicholas M.; Manke, Thomas; Akhtar, Asifa

2012-01-01

MOF is the major histone H4 lysine 16-specific (H4K16) acetyltransferase in mammals and Drosophila. In flies, it is involved in the regulation of X-chromosomal and autosomal genes as part of the MSL and the NSL complexes, respectively. While the function of the MSL complex as a dosage compensation regulator is fairly well understood, the role of the NSL complex in gene regulation is still poorly characterized. Here we report a comprehensive ChIP–seq analysis of four NSL complex members (NSL1, NSL3, MBD-R2, and MCRS2) throughout the Drosophila melanogaster genome. Strikingly, the majority (85.5%) of NSL-bound genes are constitutively expressed across different cell types. We find that an increased abundance of the histone modifications H4K16ac, H3K4me2, H3K4me3, and H3K9ac in gene promoter regions is characteristic of NSL-targeted genes. Furthermore, we show that these genes have a well-defined nucleosome free region and broad transcription initiation patterns. Finally, by performing ChIP–seq analyses of RNA polymerase II (Pol II) in NSL1- and NSL3-depleted cells, we demonstrate that both NSL proteins are required for efficient recruitment of Pol II to NSL target gene promoters. The observed Pol II reduction coincides with compromised binding of TBP and TFIIB to target promoters, indicating that the NSL complex is required for optimal recruitment of the pre-initiation complex on target genes. Moreover, genes that undergo the most dramatic loss of Pol II upon NSL knockdowns tend to be enriched in DNA Replication–related Element (DRE). Taken together, our findings show that the MOF-containing NSL complex acts as a major regulator of housekeeping genes in flies by modulating initiation of Pol II transcription. PMID:22723752

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

Science.gov (United States)

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data

Single nucleotide polymorphisms in BMPR-IB and STAT5B genes and their association with growth and reproductive traits in chicken

Directory of Open Access Journals (Sweden)

Shahram Niknafs

2014-04-01

Full Text Available The aim of the current study was to investigate the association of G4533815A SNP in STAT5B and A287G SNP in BMPR-IB genes with growth and reproduction related traits in chicken. A sample of 205 individuals from breeding station of Mazandaran native chicken population was selected randomly. All of the individuals were genotyped for both SNPs using PCR-RFLP technique. Marker-trait association analyses were performed using estimated breeding value of the traits as dependent variable in GLM procedure of SAS 9.1. Results suggested that breeding value least square means for genotypes of G4533815A SNP is significantly differed from each other for traits of body weight at 8 and 12 weeks (P<0.01. In the case of BMPR-IB gene, no significant difference was found. In conclusion, STAT5B gene may be associated with body growth in chicken and may be considered in Marker Assisted Selection program to improve chicken growth performance.

Association of a missense mutation in the positional candidate gene glutamate receptor-interacting protein 1 with backfat thickness traits in pigs

Directory of Open Access Journals (Sweden)

Jae-Bong Lee

2017-08-01

Full Text Available Objective Previously, we reported quantitative trait loci (QTLs affecting backfat thickness (BFT traits on pig chromosome 5 (SW1482–SW963 in an F2 intercross population between Landrace and Korean native pigs. The aim of this study was to evaluate glutamate receptor-interacting protein 1 (GRIP1 as a positional candidate gene underlying the QTL affecting BFT traits. Methods Genotype and phenotype analyses were performed using the 1,105 F2 progeny. A mixed-effect linear model was used to access association between these single nucleotide polymorphism (SNP markers and the BFT traits in the F2 intercross population. Results Highly significant associations of two informative SNPs (c.2442 T>C, c.3316 C>G [R1106G] in GRIP1 with BFT traits were detected. In addition, the two SNPs were used to construct haplotypes that were also highly associated with the BFT traits. Conclusion The SNPs and haplotypes of the GRIP1 gene determined in this study can contribute to understand the genetic structure of BFT traits in pigs.

Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton.

Science.gov (United States)

Su, Junji; Li, Libei; Zhang, Chi; Wang, Caixiang; Gu, Lijiao; Wang, Hantao; Wei, Hengling; Liu, Qibao; Huang, Long; Yu, Shuxun

2018-06-01

Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton. A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation

Using a system of differential equations that models cattle growth to uncover the genetic basis of complex traits.

Science.gov (United States)

Freua, Mateus Castelani; Santana, Miguel Henrique de Almeida; Ventura, Ricardo Vieira; Tedeschi, Luis Orlindo; Ferraz, José Bento Sterman

2017-08-01

The interplay between dynamic models of biological systems and genomics is based on the assumption that genetic variation of the complex trait (i.e., outcome of model behavior) arises from component traits (i.e., model parameters) in lower hierarchical levels. In order to provide a proof of concept of this statement for a cattle growth model, we ask whether model parameters map genomic regions that harbor quantitative trait loci (QTLs) already described for the complex trait. We conducted a genome-wide association study (GWAS) with a Bayesian hierarchical LASSO method in two parameters of the Davis Growth Model, a system of three ordinary differential equations describing DNA accretion, protein synthesis and degradation, and fat synthesis. Phenotypic and genotypic data were available for 893 Nellore (Bos indicus) cattle. Computed values for parameter k 1 (DNA accretion rate) ranged from 0.005 ± 0.003 and for α (constant for energy for maintenance requirement) 0.134 ± 0.024. The expected biological interpretation of the parameters is confirmed by QTLs mapped for k 1 and α. QTLs within genomic regions mapped for k 1 are expected to be correlated with the DNA pool: body size and weight. Single nucleotide polymorphisms (SNPs) which were significant for α mapped QTLs that had already been associated with residual feed intake, feed conversion ratio, average daily gain (ADG), body weight, and also dry matter intake. SNPs identified for k 1 were able to additionally explain 2.2% of the phenotypic variability of the complex ADG, even when SNPs for k 1 did not match the genomic regions associated with ADG. Although improvements are needed, our findings suggest that genomic analysis on component traits may help to uncover the genetic basis of more complex traits, particularly when lower biological hierarchies are mechanistically described by mathematical simulation models.

Personality Traits in Huntington's Disease

DEFF Research Database (Denmark)

Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua

2016-01-01

Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene......-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons...... symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms....

Simulating the yield impacts of organ-level quantitative trait loci associated with drought response in maize: a "gene-to-phenotype" modeling approach.

Science.gov (United States)

Chenu, Karine; Chapman, Scott C; Tardieu, François; McLean, Greg; Welcker, Claude; Hammer, Graeme L

2009-12-01

Under drought, substantial genotype-environment (G x E) interactions impede breeding progress for yield. Identifying genetic controls associated with yield response is confounded by poor genetic correlations across testing environments. Part of this problem is related to our inability to account for the interplay of genetic controls, physiological traits, and environmental conditions throughout the crop cycle. We propose a modeling approach to bridge this "gene-to-phenotype" gap. For maize under drought, we simulated the impact of quantitative trait loci (QTL) controlling two key processes (leaf and silk elongation) that influence crop growth, water use, and grain yield. Substantial G x E interaction for yield was simulated for hypothetical recombinant inbred lines (RILs) across different seasonal patterns of drought. QTL that accelerated leaf elongation caused an increase in crop leaf area and yield in well-watered or preflowering water deficit conditions, but a reduction in yield under terminal stresses (as such "leafy" genotypes prematurely exhausted the water supply). The QTL impact on yield was substantially enhanced by including pleiotropic effects of these QTL on silk elongation and on consequent grain set. The simulations obtained illustrated the difficulty of interpreting the genetic control of yield for genotypes influenced only by the additive effects of QTL associated with leaf and silk growth. The results highlight the potential of integrative simulation modeling for gene-to-phenotype prediction and for exploiting G x E interactions for complex traits such as drought tolerance.

Identifying the genes underlying quantitative traits: a rationale for the QTN programme.

Science.gov (United States)

Lee, Young Wha; Gould, Billie A; Stinchcombe, John R

2014-01-01

The goal of identifying the genes or even nucleotides underlying quantitative and adaptive traits has been characterized as the 'QTN programme' and has recently come under severe criticism. Part of the reason for this criticism is that much of the QTN programme has asserted that finding the genes and nucleotides for adaptive and quantitative traits is a fundamental goal, without explaining why it is such a hallowed goal. Here we outline motivations for the QTN programme that offer general insight, regardless of whether QTNs are of large or small effect, and that aid our understanding of the mechanistic dynamics of adaptive evolution. We focus on five areas: (i) vertical integration of insight across different levels of biological organization, (ii) genetic parallelism and the role of pleiotropy in shaping evolutionary dynamics, (iii) understanding the forces maintaining genetic variation in populations, (iv) distinguishing between adaptation from standing variation and new mutation, and (v) the role of genomic architecture in facilitating adaptation. We argue that rather than abandoning the QTN programme, we should refocus our efforts on topics where molecular data will be the most effective for testing hypotheses about phenotypic evolution.

Identifying the genes underlying quantitative traits: a rationale for the QTN programme

Science.gov (United States)

Lee, Young Wha; Gould, Billie A.; Stinchcombe, John R.

2014-01-01

The goal of identifying the genes or even nucleotides underlying quantitative and adaptive traits has been characterized as the ‘QTN programme’ and has recently come under severe criticism. Part of the reason for this criticism is that much of the QTN programme has asserted that finding the genes and nucleotides for adaptive and quantitative traits is a fundamental goal, without explaining why it is such a hallowed goal. Here we outline motivations for the QTN programme that offer general insight, regardless of whether QTNs are of large or small effect, and that aid our understanding of the mechanistic dynamics of adaptive evolution. We focus on five areas: (i) vertical integration of insight across different levels of biological organization, (ii) genetic parallelism and the role of pleiotropy in shaping evolutionary dynamics, (iii) understanding the forces maintaining genetic variation in populations, (iv) distinguishing between adaptation from standing variation and new mutation, and (v) the role of genomic architecture in facilitating adaptation. We argue that rather than abandoning the QTN programme, we should refocus our efforts on topics where molecular data will be the most effective for testing hypotheses about phenotypic evolution. PMID:24790125

A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape trait in peach.

Science.gov (United States)

López-Girona, Elena; Zhang, Yu; Eduardo, Iban; Mora, José Ramón Hernández; Alexiou, Konstantinos G; Arús, Pere; Aranzana, María José

2017-07-27

In peach, the flat phenotype is caused by a partially dominant allele in heterozygosis (Ss), fruits from homozygous trees (SS) abort a few weeks after fruit setting. Previous research has identified a SSR marker (UDP98-412) highly associated with the trait, found suitable for marker assisted selection (MAS). Here we report a ∼10 Kb deletion affecting the gene PRUPE.6G281100, 400 Kb upstream of UDP98-412, co-segregating with the trait. This gene is a leucine-rich repeat receptor-like kinase (LRR-RLK) orthologous to the Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) group. PCR markers suitable for MAS confirmed its strong association with the trait in a collection of 246 cultivars. They were used to evaluate the DNA from a round fruit derived from a somatic mutation of the flat variety 'UFO-4', revealing that the mutation affected the flat associated allele (S). Protein BLAST alignment identified significant hits with genes involved in different biological processes. Best protein hit occurred with AtRLP12, which may functionally complement CLAVATA2, a key regulator that controls the stem cell population size. RT-PCR analysis revealed the absence of transcription of the partially deleted allele. The data support PRUPE.6G281100 as a candidate gene for flat shape in peach.

Evaluation of novel SNPs and haplotypes within the ATBF1 gene and their effects on economically important production traits in cattle

Directory of Open Access Journals (Sweden)

H. Xu

2017-08-01

Full Text Available AT motif binding factor 1 (ATBF1 gene can promote the expression level of the growth hormone 1 (GH1 gene by binding to the enhancers of the POU1F1 and PROP1 genes; thus, it affects the growth and development of livestock. Considering that the ATBF1 gene also has a close relationship with the Janus kinase–signal transductor and activator of transcription (JAK–STAT pathway, the objective of this work was to identify novel single-nucleotide polymorphism (SNP variations and their association with growth traits in native Chinese cattle breeds. Five novel SNPs within the ATBF1 gene were found in 644 Qinchuan and Jinnan cattle for first time using 25 pairs of screening and genotyping primers. The five novel SNPs were named as AC_000175:g.140344C>G (SNP1, g.146573T>C (SNP2, g.205468C>T (SNP3, g.205575A>G (SNP4 and g.297690Ctraits in Jinnan cattle. SNP3 was found to have significant associations with four growth traits in Qinchuan cattle. Moreover, the different combined genotypes, SNP1–SNP3, SNP1–SNP4 and SNP2–SNP5 were significantly associated with the growth traits in cattle. These findings indicated that the bovine ATBF1 gene had marked effects on growth traits, and the growth-trait-related loci can be used as DNA markers for maker-assisted selection (MAS breeding programs in cattle.

The Ghrelin Receptor (Ghsr) Gene Polymorphism in Indonesian Local Chicken and Crossbreed is Associated with Carcass Traits

OpenAIRE

Khaerunnisa, Isyana; Jakaria, Jakaria; Arief, Irma Isnafia; Budiman, Cahyo; Sumantri, Cece

2017-01-01

Ghrelin receptor (GHSR) gene is candidate gene for growth performance in chicken by modulating growth hormone release from the pituitary by binding to its ligand of ghrelin. Ghrelin gene, or growth hormone secretagogue (GHS) gene, is well known as feed intake and energy homeostasis regulator in mammals and birds. The objectives of this study were to identify the polymorphism of the T1857C GHSR locus in Indonesian local chicken and to evaluate its effects on carcass traits. The gene polymorphi...

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

NARCIS (Netherlands)

Astle, William J.; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L.; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A.; Lambourne, John J.; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R.; Daugherty, Louise C.; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F.; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M.; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H. A.; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M.; Staley, James R.; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P.; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G.; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W.; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S.; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J.; Ouwehand, Willem H.; Butterworth, Adam S.; Soranzo, Nicole

2016-01-01

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell,

Comparison of statistical tests for association between rare variants and binary traits.

OpenAIRE

Bacanu, SA; Nelson, MR; Whittaker, JC

2012-01-01

: Genome-wide association studies have found thousands of common genetic variants associated with a wide variety of diseases and other complex traits. However, a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some of the missing variation is due to the effects of rare variants. Nonetheless, the statistical analysis of rare variants is challenging. A commonly used method is to contrast, within the same region (gene), the fr...

Flexible metabolic pathway construction using modular and divisible selection gene regulators

DEFF Research Database (Denmark)

Rugbjerg, Peter; Myling-Petersen, Nils; Sommer, Morten Otto Alexander

2015-01-01

Genetic selections are important to biological engineering. Although selectable traits are limited,currently each trait only permits simultaneous introduction of a single DNA fragment. Complex pathwayand strain construction however depends on rapid, combinatorial introduction of many genes thaten...

The search for Pleiades in trait constellations: functional integration and phenotypic selection in the complex flowers of Morrenia brachystephana (Apocynaceae).

Science.gov (United States)

Baranzelli, M C; Sérsic, A N; Cocucci, A A

2014-04-01

Pollinator-mediated natural selection on single traits, such as corolla tube or spur length, has been well documented. However, flower phenotypes are usually complex, and selection is expected to act on several traits that functionally interact rather than on a single isolated trait. Despite the fact that selection on complex phenotypes is expectedly widespread, multivariate selection modelling on such phenotypes still remains under-explored in plants. Species of the subfamily Asclepiadoideae (Apocynaceae) provide an opportunity to study such complex flower contrivances integrated by fine-scaled organs from disparate developmental origin. We studied the correlation structure among linear floral traits (i) by testing a priori morphological, functional or developmental hypotheses among traits and (ii) by exploring the organization of flower covariation, considering alternative expectations of modular organization or whole flower integration through conditional dependence analysis (CDA) and integration matrices. The phenotypic selection approach was applied to determine whether floral traits involved in the functioning of the pollination mechanism were affected by natural selection. Floral integration was low, suggesting that flowers are organized in more than just one correlation pleiad; our hypothetical functional correlation matrix was significantly correlated with the empirical matrix, and the CDA revealed three putative modules. Analyses of phenotypic selection showed significant linear and correlational gradients, lending support to expectations of functional interactions between floral traits. Significant correlational selection gradients found involved traits of different floral whorls, providing evidence for the existence of functional integration across developmental domains. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Sex differences in genetic architecture of complex phenotypes?

Directory of Open Access Journals (Sweden)

Jacqueline M Vink

Full Text Available We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.

A Bayesian Framework for Multiple Trait Colo-calization from Summary Association Statistics.

Science.gov (United States)

Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen; Hauberg, Mads; Shi, Huwenbo; Boocock, James; Pickrell, Joe; Jaffe, Andrew E; Pasaniuc, Bogdan; Roussos, Panos

2018-03-19

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. moloc is available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest. claudia.giambartolomei@gmail.com. Supplementary data are available at Bioinformatics online.

Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean.

Science.gov (United States)

Fang, Chao; Ma, Yanming; Wu, Shiwen; Liu, Zhi; Wang, Zheng; Yang, Rui; Hu, Guanghui; Zhou, Zhengkui; Yu, Hong; Zhang, Min; Pan, Yi; Zhou, Guoan; Ren, Haixiang; Du, Weiguang; Yan, Hongrui; Wang, Yanping; Han, Dezhi; Shen, Yanting; Liu, Shulin; Liu, Tengfei; Zhang, Jixiang; Qin, Hao; Yuan, Jia; Yuan, Xiaohui; Kong, Fanjiang; Liu, Baohui; Li, Jiayang; Zhang, Zhiwu; Wang, Guodong; Zhu, Baoge; Tian, Zhixi

2017-08-24

Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.

A Bayesian variable selection procedure for ranking overlapping gene sets

DEFF Research Database (Denmark)

Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

2012-01-01

Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been de...

Gene-trait matching across the Bifidobacterium longum pan-genome reveals considerable diversity in carbohydrate catabolism among human infant strains.

LENUS (Irish Health Repository)

Arboleya, Silvia

2018-01-08

Bifidobacterium longum is a common member of the human gut microbiota and is frequently present at high numbers in the gut microbiota of humans throughout life, thus indicative of a close symbiotic host-microbe relationship. Different mechanisms may be responsible for the high competitiveness of this taxon in its human host to allow stable establishment in the complex and dynamic intestinal microbiota environment. The objective of this study was to assess the genetic and metabolic diversity in a set of 20 B. longum strains, most of which had previously been isolated from infants, by performing whole genome sequencing and comparative analysis, and to analyse their carbohydrate utilization abilities using a gene-trait matching approach.

Genetic architecture of complex traits and accuracy of genomic prediction: coat colour, milk-fat percentage, and type in Holstein cattle as contrasting model traits.

Directory of Open Access Journals (Sweden)

Ben J Hayes

2010-09-01

Full Text Available Prediction of genetic merit using dense SNP genotypes can be used for estimation of breeding values for selection of livestock, crops, and forage species; for prediction of disease risk; and for forensics. The accuracy of these genomic predictions depends in part on the genetic architecture of the trait, in particular number of loci affecting the trait and distribution of their effects. Here we investigate the difference among three traits in distribution of effects and the consequences for the accuracy of genomic predictions. Proportion of black coat colour in Holstein cattle was used as one model complex trait. Three loci, KIT, MITF, and a locus on chromosome 8, together explain 24% of the variation of proportion of black. However, a surprisingly large number of loci of small effect are necessary to capture the remaining variation. A second trait, fat concentration in milk, had one locus of large effect and a host of loci with very small effects. Both these distributions of effects were in contrast to that for a third trait, an index of scores for a number of aspects of cow confirmation ("overall type", which had only loci of small effect. The differences in distribution of effects among the three traits were quantified by estimating the distribution of variance explained by chromosome segments containing 50 SNPs. This approach was taken to account for the imperfect linkage disequilibrium between the SNPs and the QTL affecting the traits. We also show that the accuracy of predicting genetic values is higher for traits with a proportion of large effects (proportion black and fat percentage than for a trait with no loci of large effect (overall type, provided the method of analysis takes advantage of the distribution of loci effects.

Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

Science.gov (United States)

Torday, John S.; Rehan, V. K.

2009-01-01

an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cell–cell signaling and extrinsic factors is the reverse of the “top-down” conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a “middle-out” cell–cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cell–cell communication as the basis for complex physiologic traits, from sponges to man. PMID:20607136

Basal host resistance of barley to powdery mildew: connecting quantitative trait loci and candidate genes

NARCIS (Netherlands)

Aghnoum, R.; Marcel, T.C.; Johrde, A.; Pecchioni, N.; Schweizer, P.; Niks, R.E.

2010-01-01

The basal resistance of barley to powdery mildew (Blumeria graminis f. sp. hordei) is a quantitatively inherited trait that is based on nonhypersensitive mechanisms of defense. A functional genomic approach indicates that many plant candidate genes are involved in the defense against formation of

Trait specific expression profiling of salt stress responsive genes in diverse rice genotypes as determined by modified Significance Analysis of Microarrays

Directory of Open Access Journals (Sweden)

Mohammad Rashed Hossain

2016-05-01

Full Text Available Stress responsive gene expression is commonly profiled in a comparative manner involving different stress conditions or genotypes with contrasting reputation of tolerance/resistance. In contrast, this research exploited a wide natural variation in terms of taxonomy, origin and salt sensitivity in eight genotypes of rice to identify the trait specific patterns of gene expression under salt stress. Genome wide transcptomic responses were interrogated by the weighted continuous morpho-physiological trait responses using modified Significance Analysis of Microarrays. More number of genes was found to be differentially expressed under salt stressed compared to that of under unstressed conditions. Higher numbers of genes were observed to be differentially expressed for the traits shoot Na+/K+, shoot Na+, root K+, biomass and shoot Cl-, respectively. The results identified around sixty genes to be involved in Na+, K+ and anion homeostasis, transport and transmembrane activity under stressed conditions. Gene Ontology (GO enrichment analysis identified 1.36% (578 genes of the entire transcriptome to be involved in the major molecular functions such as signal transduction (>150 genes, transcription factor (81 genes and translation factor activity (62 genes etc. under salt stress. Chromosomal mapping of the genes suggests that majority of the genes are located on chromosomes 1, 2, 3, 6 & 7. The gene network analysis showed that the transcription factors and translation initiation factors formed the major gene networks and are mostly active in nucleus, cytoplasm and mitochondria whereas the membrane and vesicle bound proteins formed a secondary network active in plasma membrane and vacuoles. The novel genes and the genes with unknown functions thus identified provide picture of a synergistic salinity response representing the potentially fundamental mechanisms that are active in the wide natural genetic background of rice and will be of greater use once

Characterization of gene expression associated with drought avoidance and tolerance traits in a perennial grass species.

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Peng Zhou

Full Text Available To understand molecular mechanisms of perennial grass adaptation to drought stress, genes associated with drought avoidance or tolerance traits were identified and their expression patterns were characterized in C4 hybrid bermudagrass [Cynodon dactylon (L. Pers.×C. transvaalensis Burtt Davy, cv. Tifway] and common bermudagrass (C. dactylon, cv. C299. Plants of drought-tolerant 'Tifway' and drought-sensitive 'C299' were exposed to drought for 5 d (mild stress and 10 d (severe stress by withholding irrigation in a growth chamber. 'Tifway' maintained significantly lower electrolyte leakage and higher relative water content than 'C299' at both 5 and 10 d of drought stress. Four cDNA libraries via suppression subtractive hybridization analysis were constructed and identified 277 drought-responsive genes in the two genotypes at 5 and 10 d of drought stress, which were mainly classified into the functional categories of stress defense, metabolism, osmoregulation, membrane system, signal and regulator, structural protein, protein synthesis and degradation, and energy metabolism. Quantitative-PCR analysis confirmed the expression of 36 drought up-regulated genes that were more highly expressed in drought-tolerant 'Tifway' than drought-sensitive 'C299', including those for drought avoidance traits, such as cuticle wax formation (CER1 and sterol desaturase, for drought tolerance traits, such as dehydration-protective proteins (dehydrins, HVA-22-like protein and oxidative stress defense (superoxide dismutase, dehydroascorbate reductase, 2-Cys peroxiredoxins, and for stress signaling (EREBP-4 like protein and WRKY transcription factor. The results suggest that the expression of genes for stress signaling, cuticle wax accumulation, antioxidant defense, and dehydration-protective protein accumulation could be critically important for warm-season perennial grass adaptation to long-term drought stress.

A Chromosome Segment Substitution Library of Weedy Rice for Genetic Dissection of Complex Agronomic and Domestication Traits.

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Prasanta K Subudhi

Full Text Available Chromosome segment substitution lines (CSSLs are a powerful alternative for locating quantitative trait loci (QTL, analyzing gene interactions, and providing starting materials for map-based cloning projects. We report the development and characterization of a CSSL library of a U.S. weedy rice accession 'PSRR-1' with genome-wide coverage in an adapted rice cultivar 'Bengal' background. The majority of the CSSLs carried a single defined weedy rice segment with an average introgression segment of 2.8 % of the donor genome. QTL mapping results for several agronomic and domestication traits from the CSSL population were compared with those obtained from two recombinant inbred line (RIL populations involving the same weedy rice accession. There was congruence of major effect QTLs between both types of populations, but new and additional QTLs were detected in the CSSL population. Although, three major effect QTLs for plant height were detected on chromosomes 1, 4, and 8 in the CSSL population, the latter two escaped detection in both RIL populations. Since this was observed for many traits, epistasis may play a major role for the phenotypic variation observed in weedy rice. High levels of shattering and seed dormancy in weedy rice might result from an accumulation of many small effect QTLs. Several CSSLs with desirable agronomic traits (e.g. longer panicles, longer grains, and higher seed weight identified in this study could be useful for rice breeding. Since weedy rice is a reservoir of genes for many weedy and agronomic attributes, the CSSL library will serve as a valuable resource to discover latent genetic diversity for improving crop productivity and understanding the plant domestication process through cloning and characterization of the underlying genes.

Exploring the potential relevance of human-specific genes to complex disease

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Cooper David N

2011-01-01

Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

Quantitative genetic methods depending on the nature of the phenotypic trait.

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de Villemereuil, Pierre

2018-01-24

A consequence of the assumptions of the infinitesimal model, one of the most important theoretical foundations of quantitative genetics, is that phenotypic traits are predicted to be most often normally distributed (so-called Gaussian traits). But phenotypic traits, especially those interesting for evolutionary biology, might be shaped according to very diverse distributions. Here, I show how quantitative genetics tools have been extended to account for a wider diversity of phenotypic traits using first the threshold model and then more recently using generalized linear mixed models. I explore the assumptions behind these models and how they can be used to study the genetics of non-Gaussian complex traits. I also comment on three recent methodological advances in quantitative genetics that widen our ability to study new kinds of traits: the use of "modular" hierarchical modeling (e.g., to study survival in the context of capture-recapture approaches for wild populations); the use of aster models to study a set of traits with conditional relationships (e.g., life-history traits); and, finally, the study of high-dimensional traits, such as gene expression. © 2018 New York Academy of Sciences.

Genotype-dependent participation of coat color gene loci in the behavioral traits of laboratory mice.

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Yamamuro, Yutaka; Shiraishi, Aya

2011-10-01

To evaluate if loci responsible for coat color phenotypes contribute to behavioral characteristics, we specified novel gene loci associated with social exploratory behavior and examined the effects of the frequency of each allele at distinct loci on behavioral expression. We used the F2 generation, which arose from the mating of F1 mice obtained by interbreeding DBA/2 and ICR mice. Phenotypic analysis indicated that the agouti and albino loci affect behavioral traits. A genotype-based analysis revealed that novel exploratory activity was suppressed in a manner dependent on the frequency of the dominant wild-type allele at the agouti, but not albino, locus. The allele-dependent suppression was restricted to colored mice and was not seen in albino mice. The present results suggest that the agouti locus contributes to a particular behavioral trait in the presence of a wild-type allele at the albino locus, which encodes a structural gene for tyrosinase. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of Variants in and Genes on Growth, Carcass, and Meat Quality Traits in Rabbits

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Wen-Chao Liu

2014-05-01

Full Text Available Appetite-related neuropeptides proopiomelanocortin (POMC and Neuropeptide Y (NPY are essential for regulating feeding behavior and energy homeostasis. The objective of this study was to evaluate the effects of variants in POMC and NPY genes on growth, carcass and meat quality traits in rabbits. A total of six SNPs were identified for POMC (n = 2 and NPY (n = 4 genes by direct sequencing. Three SNPs were subsequently genotyped by using MassArray system (Sequenom iPLEXassay in 235 individuals, which belong to three meat rabbit breeds, including 93 Ira rabbits; 81 Champagne rabbits and 61 Tianfu black rabbits. The SNP c.112-12G>T was in intron-exon boundaries (intron 1 of POMC gene, and the association analysis showed that individuals with TT genotype had a greater 84 d body weight (BW84, eviscerated weight and semi-eviscerated weight than those with GT genotype (pC SNP, which was in complete linkage with other three SNPs (g.1491G>A, g.1525G>T and g.1530C>T in intron 1 of NPY gene, was significantly correlated with eviscerated slaughter percentage and semi-eviscerated slaughter percentage in rabbits, and the individuals with CC genotype had a better performance than CG genotype (p<0.05. These findings would provide primary clues for the biological roles of POMC and NPY underlying the rabbit growth-related traits.

Association of DGAT2 gene polymorphisms with carcass and meat quality traits in domestic pigeons (Columba livia).

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Mao, H G; Dong, X Y; Cao, H Y; Xu, N Y; Yin, Z Z

2018-04-01

1. Diacylglycerol acyltransferase (DGAT) plays an important role in the synthesis of triacylglycerol, but its effects on meat quality and carcass composition in pigeons are unclear. In this study, single-nucleotide polymorphisms (SNPs) in the exons of the DGAT2 gene were identified and analysed by using DNA sequencing methods in 200 domestic pigeons (Columba livia). The associations between DGAT2 polymorphisms and carcass and meat quality traits were also analysed. 2. Sequencing results showed that 5 nucleotide mutations were detected in exons 3, 4, 5 and 6 of the DGAT2 gene. The analysis revealed three genotypes (AA, AB and BB) in G18398T and G22484C, in which the AA genotype and A allele had the highest frequency. 3. In the SNP of G18398T located in exon 5, individuals with genotype BB had significantly higher meat quality and lower abdominal fat content than those with AA or AB genotype. In the SNP of G22484C located in exon 6, the genotype AA showed highest carcass trait values, while the genotype BB represented better meat quality, compared to AA and AB genotypes. 4. The results imply that DGAT2 gene has a close relationship with carcass and meat quality traits in pigeons, and the SNPs of G18398T and G22484C can be used as genetic markers for marker-assisted breeding in pigeon.

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle

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Mullen Michael P

2010-10-01

Full Text Available Abstract Background Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215 that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep. Results Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01 were observed at four loci. Phenotypic associations (P ≤ 0.05 were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3 gene cluster were associated (P ≤ 0.05 with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215 was associated with milk protein percentage (P ≤ 0.05, progeny carcass weight (P ≤ 0.05, culled cow carcass weight (P ≤ 0

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle

Science.gov (United States)

2010-01-01

Background Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215) that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep). Results Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01) were observed at four loci. Phenotypic associations (P ≤ 0.05) were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3) gene cluster were associated (P ≤ 0.05) with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215) was associated with milk protein percentage (P ≤ 0.05), progeny carcass weight (P ≤ 0.05), culled cow carcass weight (P ≤ 0.01), angularity (P �

Sensory response system of social behavior tied to female reproductive traits.

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Jennifer M Tsuruda

Full Text Available Honey bees display a complex set of anatomical, physiological, and behavioral traits that correlate with the colony storage of surplus pollen (pollen hoarding. We hypothesize that the association of these traits is a result of pleiotropy in a gene signaling network that was co-opted by natural selection to function in worker division of labor and foraging specialization. By acting on the gene network, selection can change a suite of traits, including stimulus/response relationships that affect individual foraging behavior and alter the colony level trait of pollen hoarding. The 'pollen-hoarding syndrome' of honey bees is the best documented syndrome of insect social organization. It can be exemplified as a link between reproductive anatomy (ovary size, physiology (yolk protein level, and foraging behavior in honey bee strains selected for pollen hoarding, a colony level trait. The syndrome gave rise to the forager-Reproductive Ground Plan Hypothesis (RGPH, which proposes that the regulatory control of foraging onset and foraging preference toward nectar or pollen was derived from a reproductive signaling network. This view was recently challenged. To resolve the controversy, we tested the associations between reproductive anatomy, physiology, and stimulus/response relationships of behavior in wild-type honey bees.Central to the stimulus/response relationships of honey bee foraging behavior and pollen hoarding is the behavioral trait of sensory sensitivity to sucrose (an important sugar in nectar. To test the linkage of reproductive traits and sensory response systems of social behavior, we measured sucrose responsiveness with the proboscis extension response (PER assay and quantified ovary size and vitellogenin (yolk precursor gene expression in 6-7-day-old bees by counting ovarioles (ovary filaments and by using semiquantitative real time RT-PCR. We show that bees with larger ovaries (more ovarioles are characterized by higher levels of

Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor ( Gene

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Xiaoyan Zhang

2015-10-01

Full Text Available The AT motif-binding factor (ATBF1 not only interacts with protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3 (PIAS3 to suppress STAT3 signaling regulating embryo early development and cell differentiation, but is required for early activation of the pituitary specific transcription factor 1 (Pit1 gene (also known as POU1F1 critically affecting mammalian growth and development. The goal of this study was to detect novel nucleotide variations and haplotypes structure of the ATBF1 gene, as well as to test their associations with growth-related traits in goats. Herein, a total of seven novel single nucleotide polymorphisms (SNPs (SNP 1-7 within this gene were found in two well-known Chinese native goat breeds. Haplotypes structure analysis demonstrated that there were four haplotypes in Hainan black goat while seventeen haplotypes in Xinong Saanen dairy goat, and both breeds only shared one haplotype (hap1. Association testing revealed that the SNP2, SNP5, SNP6, and SNP7 loci were also found to significantly associate with growth-related traits in goats, respectively. Moreover, one diplotype in Xinong Saanen dairy goats significantly linked to growth related traits. These preliminary findings not only would extend the spectrum of genetic variations of the goat ATBF1 gene, but also would contribute to implementing marker-assisted selection in genetics and breeding in goats.

High-resolution mapping of a fruit firmness-related quantitative trait locus in tomato reveals epistatic interactions associated with a complex combinatorial locus.

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Chapman, Natalie H; Bonnet, Julien; Grivet, Laurent; Lynn, James; Graham, Neil; Smith, Rebecca; Sun, Guiping; Walley, Peter G; Poole, Mervin; Causse, Mathilde; King, Graham J; Baxter, Charles; Seymour, Graham B

2012-08-01

Fruit firmness in tomato (Solanum lycopersicum) is determined by a number of factors including cell wall structure, turgor, and cuticle properties. Firmness is a complex polygenic trait involving the coregulation of many genes and has proved especially challenging to unravel. In this study, a quantitative trait locus (QTL) for fruit firmness was mapped to tomato chromosome 2 using the Zamir Solanum pennellii interspecific introgression lines (ILs) and fine-mapped in a population consisting of 7,500 F2 and F3 lines from IL 2-3 and IL 2-4. This firmness QTL contained five distinct subpeaks, Fir(s.p.)QTL2.1 to Fir(s.p.)QTL2.5, and an effect on a distal region of IL 2-4 that was nonoverlapping with IL 2-3. All these effects were located within an 8.6-Mb region. Using genetic markers, each subpeak within this combinatorial locus was mapped to a physical location within the genome, and an ethylene response factor (ERF) underlying Fir(s.p.)QTL2.2 and a region containing three pectin methylesterase (PME) genes underlying Fir(s.p.)QTL2.5 were nominated as QTL candidate genes. Statistical models used to explain the observed variability between lines indicated that these candidates and the nonoverlapping portion of IL 2-4 were sufficient to account for the majority of the fruit firmness effects. Quantitative reverse transcription-polymerase chain reaction was used to quantify the expression of each candidate gene. ERF showed increased expression associated with soft fruit texture in the mapping population. In contrast, PME expression was tightly linked with firm fruit texture. Analysis of a range of recombinant lines revealed evidence for an epistatic interaction that was associated with this combinatorial locus.

Gene-based testing of interactions in association studies of quantitative traits.

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Li Ma

Full Text Available Various methods have been developed for identifying gene-gene interactions in genome-wide association studies (GWAS. However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene-gene interaction (GGG tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein-protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.

Fine mapping and candidate gene search of quantitative trait loci for growth and obesity using mouse intersubspecific subcongenic intercrosses and exome sequencing.

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Akira Ishikawa

Full Text Available Although growth and body composition traits are quantitative traits of medical and agricultural importance, the genetic and molecular basis of those traits remains elusive. Our previous genome-wide quantitative trait locus (QTL analyses in an intersubspecific backcross population between C57BL/6JJcl (B6 and wild Mus musculus castaneus mice revealed a major growth QTL (named Pbwg1 on a proximal region of mouse chromosome 2. Using the B6.Cg-Pbwg1 intersubspecific congenic strain created, we revealed 12 closely linked QTLs for body weight and body composition traits on an approximately 44.1-Mb wild-derived congenic region. In this study, we narrowed down genomic regions harboring three (Pbwg1.12, Pbwg1.3 and Pbwg1.5 of the 12 linked QTLs and searched for possible candidate genes for the QTLs. By phenotypic analyses of F2 intercross populations between B6 and each of four B6.Cg-Pbwg1 subcongenic strains with overlapping and non-overlapping introgressed regions, we physically defined Pbwg1.12 affecting body weight to a 3.8-Mb interval (61.5-65.3 Mb on chromosome 2. We fine-mapped Pbwg1.3 for body length to an 8.0-Mb interval (57.3-65.3 and Pbwg1.5 for abdominal white fat weight to a 2.1-Mb interval (59.4-61.5. The wild-derived allele at Pbwg1.12 and Pbwg1.3 uniquely increased body weight and length despite the fact that the wild mouse has a smaller body size than that of B6, whereas it decreased fat weight at Pbwg1.5. Exome sequencing and candidate gene prioritization suggested that Gcg and Grb14 are putative candidate genes for Pbwg1.12 and that Ly75 and Itgb6 are putative candidate genes for Pbwg1.5. These genes had nonsynonymous SNPs, but the SNPs were predicted to be not harmful to protein functions. These results provide information helpful to identify wild-derived quantitative trait genes causing enhanced growth and resistance to obesity.

Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

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Min Kyung Sung

2014-12-01

Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

Polymorphisms of POU1F1 and STAT5A genes and their associate on with milk production traits in cattle

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Sonia Zakizadeh

2015-04-01

Full Text Available Specific trait candidate genes are sequenced genes with known biological activity. The effects of POU1F1 and STAT5A on milk production traits have been studied in several studies. POU1F1 affects on transcription of prolactin and growth hormone gene, as well as, STAT5A is known as a main mediator of growth hormone action on target genes and intracellular mediator of prolactin signaling. Since these genes are essential for development of mammary system, the aim of this study was to determine association of their polymorphism with milk production breeding values in Brown Swiss cattle. Blood of ninety milking cow were randomly obtained. DNA was extracted from whole blood using modified salting out method, then the desired fragments were PCR amplified and digested by specific restriction endonuclease enzymes. Gene and genotype frequencies, heterozygosity indexes, the real and effective allele number were calculated by PopGene software; and the breeding values of production traits were estimated by DFREML. SAS software was used to analyze association between genotypes and breeding values. The frequency of 'A' and 'C' alleles of POU1F1 and STAT5A were 0.455 and 0.489, respectively. This population was in hardy-weinburg equilibrium for both loci. There was no significant association between genotypes and breeding values, although POU1F1*B tended to produce higher milk and POU1F1*A showed higher fat and protein percent.

Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans.

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Franzen, Julia; Menzel, Ralph; Höss, Sebastian; Claus, Evelyn; Steinberg, Christian E W

2012-03-01

River water quality is strongly influenced by their sediments and their associated pollutants. To assess the toxic potential of sediments, sediment toxicity tests require reliable control sediments, potentially including formulated control sediments as one major option. Although some standardization has been carried out, one critical issue still remains the quality of sediment organic matter (SOM). Organic carbon not only binds hydrophobic contaminants, but may be a source of mild toxicity, even if the SOM is essentially uncontaminated. We tested two different sources of organic carbon and the mixture of both (Sphagnum peat (P) and one commercial humic substances preparation-HuminFeed(®), HF) in terms of life trait variables and expression profiles of selected life performance and stress genes of the nematode Caenorhabditis elegans. In synchronous cultures, gene expression profiling was done after 6 and 48 h, respectively. The uncontaminated Sphagnum P reduced growth, but increased numbers of offspring, whereas HF did not significantly alter life trait variables. The 6 h expression profile showed most of the studied stress genes repressed, except for slight to strong induction in cyp-35B1 (all exposures), gst-38 (only mixture), and small hsp-16 genes (all exposures). After 48 h, the expression of almost all studied genes increased, particularly genes coding for antioxidative defense, multiple xenobiotic resistance, vitellogenin-like proteins, and genes regulating lifespan. Overall, even essentially uncontaminated SOM may induce several modes of action on the molecular level in C. elegans which may lead to false results if testing synthetic xenobiotics. This contribution is a plea for a strict standardization of the SOM quality in formulated sediments and to check for corresponding effects in other model sediment organisms, especially if using molecular toxicity endpoints.

Novel SNPs in HSPB8 gene and their association with heat tolerance traits in Sahiwal indigenous cattle.

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Verma, Nishant; Gupta, Ishwar Dayal; Verma, Archana; Kumar, Rakesh; Das, Ramendra; Vineeth, M R

2016-01-01

Heat shock proteins (HSPs) are expressed in response to heat stress, and the polymorphism in HSP genes at single-nucleotide level has been reported to be associated with heat tolerance and production performance traits in cattle. HSPB8 gene has been mapped on Bos taurus autosome 17 (BTA-17) spanning nearly 13,252 bp and comprising three exons and two introns. The present study was conducted in Sahiwal cows (n = 108) reared in subtropical climate with the objectives to identify SNPs in all three exons and part of intron 1 of HSPB8 gene and to analyze their association with heat tolerance traits in Sahiwal cows. Respiration rate (RR) and rectal temperature (RT) were recorded once during probable extreme hours in different seasons or Temperature-Humidity Index (THI), i.e., winter, spring, and summer. Heat tolerance coefficient (HTC) was also calculated to check the adaptability of the animals during the period of heat stress. The comparative sequence analysis revealed a total two single-nucleotide polymorphisms (SNPs), i.e., g.507G>A in exon 1 and g.881T>C in intron 1 of HSPB8 gene. Out of these two identified SNPs, only one SNP, i.e., g.507G>A, was found to be significantly associated with heat tolerance indicator traits (RR, RT, and HTC) in Sahiwal cows. The perusal of results across different seasons showed the significant (P A SNP of HSPB8 gene. However, in case of another SNP, i.e., g.881T>C, located on intron 1, the RR, RT, and HTC were having non-significant association with the different genotypes, i.e., TT and TC. These findings may partly suggest that GA genotype of SNP g.507G>A of HSPB8 gene has a probable role in heat tolerance in Sahiwal cattle and can therefore be utilized as a marker in propagation of thermo-tolerance cattle in hot tropical and subtropical climate. Nevertheless, the involvement of other regulatory mechanisms cannot be overruled.

Evolutionary history of the recruitment of conserved developmental genes in association to the formation and diversification of a novel trait

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Shirai Leila T

2012-02-01

Full Text Available Abstract Background The origin and modification of novel traits are important aspects of biological diversification. Studies combining concepts and approaches of developmental genetics and evolutionary biology have uncovered many examples of the recruitment, or co-option, of genes conserved across lineages for the formation of novel, lineage-restricted traits. However, little is known about the evolutionary history of the recruitment of those genes, and of the relationship between them -for example, whether the co-option involves whole or parts of existing networks, or whether it occurs by redeployment of individual genes with de novo rewiring. We use a model novel trait, color pattern elements on butterfly wings called eyespots, to explore these questions. Eyespots have greatly diversified under natural and sexual selection, and their formation involves genetic circuitries shared across insects. Results We investigated the evolutionary history of the recruitment and co-recruitment of four conserved transcription regulators to the larval wing disc region where circular pattern elements develop. The co-localization of Antennapedia, Notch, Distal-less, and Spalt with presumptive (eyespot organizers was examined in 13 butterfly species, providing the largest comparative dataset available for the system. We found variation between families, between subfamilies, and between tribes. Phylogenetic reconstructions by parsimony and maximum likelihood methods revealed an unambiguous evolutionary history only for Antennapedia, with a resolved single origin of eyespot-associated expression, and many homoplastic events for Notch, Distal-less, and Spalt. The flexibility in the (co-recruitment of the targeted genes includes cases where different gene combinations are associated with morphologically similar eyespots, as well as cases where identical protein combinations are associated with very different phenotypes. Conclusions The evolutionary history of gene

Association between perilipin gene polymorphisms and body weight traits in Jinmao Hua chickens

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T. Li

2017-09-01

Full Text Available The perilipin gene (PLIN plays a crucial role in lipid metabolism and fat deposition. In order to reveal the genetic effects of PLIN polymorphisms on body weight (BW traits in chickens, PLIN gene polymorphisms in 322 Jinmao Hua chickens were detected by PCR-SSCP and DNA sequencing methods. For PLIN primer pair 1, five genotypes (AA, AB, BB, JJ and JL were detected in the Jinmao Hua chicken population and three mutations (g.1889C > T, g.1904T > C and g.1922C > T were revealed by gene sequencing. For PLIN primer pair 2, three genotypes (CC, CD and DD were detected in the same population and two mutations (g.2014A > G and g.2020C > T were revealed by gene sequencing. Least squares analysis showed that individuals with the JJ and CD genotypes performed better than the other Jinmao Hua chicken genotypes. Based on the five SNPs, the frequency distributions of the eight haplotypes were estimated with PHASE2.1 software. C-T-C-G-T was the major haplotype with a frequency of 58.6957 %, while the frequency of C-C-C-A-C was less than 1 %. Fourteen diplotypes were obtained from the eight haplotypes. H1H1 was the dominant diplotype with a frequency of 47.205 %. Least squares analysis indicated that BW with the H3H3 diplotype was the lowest, while the H2H2 diplotype was the highest, suggesting that selecting for the H3H3 diplotype improved the BW traits of Jinmao Hua chickens. The findings of this study should be useful to expand the theoretical basis of the role the PLIN in poultry molecular breeding of poultry.

Genes, psychological traits and civic engagement

Science.gov (United States)

Dawes, Christopher T.; Settle, Jaime E.; Loewen, Peter John; McGue, Matt; Iacono, William G.

2015-01-01

Civic engagement is a classic example of a collective action problem: while civic participation improves life in the community as a whole, it is individually costly and thus there is an incentive to free ride on the actions of others. Yet, we observe significant inter-individual variation in the degree to which people are in fact civically engaged. Early accounts reconciling the theoretical prediction with empirical reality focused either on variation in individuals’ material resources or their attitudes, but recent work has turned to genetic differences between individuals. We show an underlying genetic contribution to an index of civic engagement (0.41), as well as for the individual acts of engagement of volunteering for community or public service activities (0.33), regularly contributing to charitable causes (0.28) and voting in elections (0.27). There are closer genetic relationships between donating and the other two activities; volunteering and voting are not genetically correlated. Further, we show that most of the correlation between civic engagement and both positive emotionality and verbal IQ can be attributed to genes that affect both traits. These results enrich our understanding of the way in which genetic variation may influence the wide range of collective action problems that individuals face in modern community life. PMID:26503688

Monoamine Oxidase A (MAOA Gene and Personality Traits from Late Adolescence through Early Adulthood: A Latent Variable Investigation

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Man K. Xu

2017-10-01

Full Text Available Very few molecular genetic studies of personality traits have used longitudinal phenotypic data, therefore molecular basis for developmental change and stability of personality remains to be explored. We examined the role of the monoamine oxidase A gene (MAOA on extraversion and neuroticism from adolescence to adulthood, using modern latent variable methods. A sample of 1,160 male and 1,180 female participants with complete genotyping data was drawn from a British national birth cohort, the MRC National Survey of Health and Development (NSHD. The predictor variable was based on a latent variable representing genetic variations of the MAOA gene measured by three SNPs (rs3788862, rs5906957, and rs979606. Latent phenotype variables were constructed using psychometric methods to represent cross-sectional and longitudinal phenotypes of extraversion and neuroticism measured at ages 16 and 26. In males, the MAOA genetic latent variable (AAG was associated with lower extraversion score at age 16 (β = −0.167; CI: −0.289, −0.045; p = 0.007, FDRp = 0.042, as well as greater increase in extraversion score from 16 to 26 years (β = 0.197; CI: 0.067, 0.328; p = 0.003, FDRp = 0.036. No genetic association was found for neuroticism after adjustment for multiple testing. Although, we did not find statistically significant associations after multiple testing correction in females, this result needs to be interpreted with caution due to issues related to x-inactivation in females. The latent variable method is an effective way of modeling phenotype- and genetic-based variances and may therefore improve the methodology of molecular genetic studies of complex psychological traits.

Sensory trait variation in an echolocating bat suggests roles for both selection and plasticity

Science.gov (United States)

2014-01-01

Background Across heterogeneous environments selection and gene flow interact to influence the rate and extent of adaptive trait evolution. This complex relationship is further influenced by the rarely considered role of phenotypic plasticity in the evolution of adaptive population variation. Plasticity can be adaptive if it promotes colonization and survival in novel environments and in doing so may increase the potential for future population differentiation via selection. Gene flow between selectively divergent environments may favour the evolution of phenotypic plasticity or conversely, plasticity itself may promote gene flow, leading to a pattern of trait differentiation in the presence of gene flow. Variation in sensory traits is particularly informative in testing the role of environment in trait and population differentiation. Here we test the hypothesis of ‘adaptive differentiation with minimal gene flow’ in resting echolocation frequencies (RF) of Cape horseshoe bats (Rhinolophus capensis) across a gradient of increasingly cluttered habitats. Results Our analysis reveals a geographically structured pattern of increasing RF from open to highly cluttered habitats in R. capensis; however genetic drift appears to be a minor player in the processes influencing this pattern. Although Bayesian analysis of population structure uncovered a number of spatially defined mitochondrial groups and coalescent methods revealed regional-scale gene flow, phylogenetic analysis of mitochondrial sequences did not correlate with RF differentiation. Instead, habitat discontinuities between biomes, and not genetic and geographic distances, best explained echolocation variation in this species. We argue that both selection for increased detection distance in relatively less cluttered habitats and adaptive phenotypic plasticity may have influenced the evolution of matched echolocation frequencies and habitats across different populations. Conclusions Our study reveals

Using Gene Ontology to describe the role of the neurexin-neuroligin-SHANK complex in human, mouse and rat and its relevance to autism.

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Patel, Sejal; Roncaglia, Paola; Lovering, Ruth C

2015-06-06

People with an autistic spectrum disorder (ASD) display a variety of characteristic behavioral traits, including impaired social interaction, communication difficulties and repetitive behavior. This complex neurodevelopment disorder is known to be associated with a combination of genetic and environmental factors. Neurexins and neuroligins play a key role in synaptogenesis and neurexin-neuroligin adhesion is one of several processes that have been implicated in autism spectrum disorders. In this report we describe the manual annotation of a selection of gene products known to be associated with autism and/or the neurexin-neuroligin-SHANK complex and demonstrate how a focused annotation approach leads to the creation of more descriptive Gene Ontology (GO) terms, as well as an increase in both the number of gene product annotations and their granularity, thus improving the data available in the GO database. The manual annotations we describe will impact on the functional analysis of a variety of future autism-relevant datasets. Comprehensive gene annotation is an essential aspect of genomic and proteomic studies, as the quality of gene annotations incorporated into statistical analysis tools affects the effective interpretation of data obtained through genome wide association studies, next generation sequencing, proteomic and transcriptomic datasets.

Functional validation of candidate genes detected by genomic feature models

DEFF Research Database (Denmark)

Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

2018-01-01

to investigate locomotor activity, and applied genomic feature prediction models to identify gene ontology (GO) cate- gories predictive of this phenotype. Next, we applied the covariance association test to partition the genomic variance of the predictive GO terms to the genes within these terms. We...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated......Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...

Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population.

Science.gov (United States)

Vojinovic, Dina; Brison, Nathalie; Ahmad, Shahzad; Noens, Ilse; Pappa, Irene; Karssen, Lennart C; Tiemeier, Henning; van Duijn, Cornelia M; Peeters, Hilde; Amin, Najaf

2017-08-01

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 × 10 -7 ) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-value meta =1.5 × 10 -8 ). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.

Studies on fluctuating asymmetry (FA for certain morphological traits in four species of the Drosophila bipectinata complex

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Banerjee Parul

2015-01-01

Full Text Available Fluctuating asymmetry (FA is defined as subtle deviations from perfect bilateral symmetry, evident in differences between the right and the left sides of any given trait. It is a pattern of variation between sides and measures developmental instability. Differences in the level of FA may be used for comparing developmental precision among closely related species and thus may give an idea whether developmental stability was affected during the divergence and separation of populations into distinct species. Keeping this in view, FA was studied in four species of the Drosophila bipectinata complex i.e. D. bipectinata, D. parabipectinata, D. malerkotliana and D. pseudoananassae. In females of all the four species, FA values did not vary significantly for any of the traits considered. However, in case of males, they varied significantly for Wing length (WL and sex comb tooth number (SCTN. Also, while in females Composite fluctuating asymmetry (CFA did not exhibit significant variation, in males it was found to vary significantly across the four species. However, Bonferroni t-tests did not reveal any consistent difference in FA levels between any two species. The magnitude of FA was found to differ significantly among traits and CFA values were found to be higher for males than females in all the four species. Therefore, it may be concluded that the level of FA shows trait specific variations and males are more prone to developmental perturbations. However, the FA levels are more or less similar in all the four species of this complex. Thus, developmental precision remains nearly same in all the four species of this complex irrespective of the degree of evolutionary divergence reached.

SNP variation in the promoter of the PRKAG3 gene and association with meat quality traits in pig.

Science.gov (United States)

Ryan, Marion T; Hamill, Ruth M; O'Halloran, Aisling M; Davey, Grace C; McBryan, Jean; Mullen, Anne M; McGee, Chris; Gispert, Marina; Southwood, Olwen I; Sweeney, Torres

2012-07-25

The PRKAG3 gene encodes the γ3 subunit of adenosine monophosphate activated protein kinase (AMPK), a protein that plays a key role in energy metabolism in skeletal muscle. Non-synonymous single nucleotide polymorphisms (SNPs) in this gene such as I199V are associated with important pork quality traits. The objective of this study was to investigate the relationship between gene expression of the PRKAG3 gene, SNP variation in the PRKAG3 promoter and meat quality phenotypes in pork. PRKAG3 gene expression was found to correlate with a number of traits relating to glycolytic potential (GP) and intramuscular fat (IMF) in three phenotypically diverse F1 crosses comprising of 31 Large White, 23 Duroc and 32 Pietrain sire breeds. The majority of associations were observed in the Large White cross. There was a significant association between genotype at the g.-311A>G locus and PRKAG3 gene expression in the Large White cross. In the same population, ten novel SNPs were identified within a 1.3 kb region spanning the promoter and from this three major haplotypes were inferred. Two tagging SNPs (g.-995A>G and g.-311A>G) characterised the haplotypes within the promoter region being studied. These two SNPs were subsequently genotyped in larger populations consisting of Large White (n = 98), Duroc (n = 99) and Pietrain (n = 98) purebreds. Four major haplotypes including promoter SNP's g.-995A>G and g.-311A>G and I199V were inferred. In the Large White breed, HAP1 was associated with IMF% in the M. longissmus thoracis et lumborum (LTL) and driploss%. HAP2 was associated with IMFL% GP-influenced traits pH at 24 hr in LTL (pHULT), pH at 45 min in LTL (pH(45)LT) and pH at 45 min in the M. semimembranosus muscle (pH(45)SM). HAP3 was associated with driploss%, pHULT pH(45)LT and b* Minolta. In the Duroc breed, associations were observed between HAP1 and driploss% and pHUSM. No associations were observed with the remaining haplotypes (HAP2, HAP3 and HAP4) in the Duroc breed. The

SNP variation in the promoter of the PRKAG3 gene and association with meat quality traits in pig

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Ryan Marion T

2012-07-01

Full Text Available Abstract Background The PRKAG3 gene encodes the γ3 subunit of adenosine monophosphate activated protein kinase (AMPK, a protein that plays a key role in energy metabolism in skeletal muscle. Non-synonymous single nucleotide polymorphisms (SNPs in this gene such as I199V are associated with important pork quality traits. The objective of this study was to investigate the relationship between gene expression of the PRKAG3 gene, SNP variation in the PRKAG3 promoter and meat quality phenotypes in pork. Results PRKAG3 gene expression was found to correlate with a number of traits relating to glycolytic potential (GP and intramuscular fat (IMF in three phenotypically diverse F1 crosses comprising of 31 Large White, 23 Duroc and 32 Pietrain sire breeds. The majority of associations were observed in the Large White cross. There was a significant association between genotype at the g.-311A>G locus and PRKAG3 gene expression in the Large White cross. In the same population, ten novel SNPs were identified within a 1.3 kb region spanning the promoter and from this three major haplotypes were inferred. Two tagging SNPs (g.-995A>G and g.-311A>G characterised the haplotypes within the promoter region being studied. These two SNPs were subsequently genotyped in larger populations consisting of Large White (n = 98, Duroc (n = 99 and Pietrain (n = 98 purebreds. Four major haplotypes including promoter SNP’s g.-995A>G and g.-311A>G and I199V were inferred. In the Large White breed, HAP1 was associated with IMF% in the M. longissmus thoracis et lumborum (LTL and driploss%. HAP2 was associated with IMFL% GP-influenced traits pH at 24 hr in LTL (pHULT, pH at 45 min in LTL (pH45LT and pH at 45 min in the M. semimembranosus muscle (pH45SM. HAP3 was associated with driploss%, pHULT pH45LT and b* Minolta. In the Duroc breed, associations were observed between HAP1 and driploss% and pHUSM. No associations were observed with the remaining haplotypes (HAP2

Candidate Gene Identification of Feed Efficiency and Coat Color Traits in a C57BL/6J × Kunming F2 Mice Population Using Genome-Wide Association Study.

Science.gov (United States)

Miao, Yuanxin; Soudy, Fathia; Xu, Zhong; Liao, Mingxing; Zhao, Shuhong; Li, Xinyun

2017-01-01

Feed efficiency (FE) is a very important trait in livestock industry. Identification of the candidate genes could be of benefit for the improvement of FE trait. Mouse is used as the model for many studies in mammals. In this study, the candidate genes related to FE and coat color were identified using C57BL/6J (C57) × Kunming (KM) F2 mouse population. GWAS results showed that 61 and 2 SNPs were genome-wise suggestive significantly associated with feed conversion ratio (FCR) and feed intake (FI) traits, respectively. Moreover, the Erbin, Msrb2, Ptf1a, and Fgf10 were considered as the candidate genes of FE. The Lpl was considered as the candidate gene of FI. Further, the coat color trait was studied. KM mice are white and C57 ones are black. The GWAS results showed that the most significant SNP was located at chromosome 7, and the closely linked gene was Tyr. Therefore, our study offered useful target genes related to FE in mice; these genes may play similar roles in FE of livestock. Also, we identified the major gene of coat color in mice, which would be useful for better understanding of natural mutation of the coat color in mice.

Candidate Gene Identification of Feed Efficiency and Coat Color Traits in a C57BL/6J × Kunming F2 Mice Population Using Genome-Wide Association Study

Directory of Open Access Journals (Sweden)

Yuanxin Miao

2017-01-01

Full Text Available Feed efficiency (FE is a very important trait in livestock industry. Identification of the candidate genes could be of benefit for the improvement of FE trait. Mouse is used as the model for many studies in mammals. In this study, the candidate genes related to FE and coat color were identified using C57BL/6J (C57 × Kunming (KM F2 mouse population. GWAS results showed that 61 and 2 SNPs were genome-wise suggestive significantly associated with feed conversion ratio (FCR and feed intake (FI traits, respectively. Moreover, the Erbin, Msrb2, Ptf1a, and Fgf10 were considered as the candidate genes of FE. The Lpl was considered as the candidate gene of FI. Further, the coat color trait was studied. KM mice are white and C57 ones are black. The GWAS results showed that the most significant SNP was located at chromosome 7, and the closely linked gene was Tyr. Therefore, our study offered useful target genes related to FE in mice; these genes may play similar roles in FE of livestock. Also, we identified the major gene of coat color in mice, which would be useful for better understanding of natural mutation of the coat color in mice.

Molecular Characterization of Bovine SMO Gene and Effects of Its Genetic Variations on Body Size Traits in Qinchuan Cattle (Bos taurus)

Science.gov (United States)

Zhang, Ya-Ran; Gui, Lin-Sheng; Li, Yao-Kun; Jiang, Bi-Jie; Wang, Hong-Cheng; Zhang, Ying-Ying; Zan, Lin-Sen

2015-01-01

Smoothened (Smo)-mediated Hedgehog (Hh) signaling pathway governs the patterning, morphogenesis and growth of many different regions within animal body plans. This study evaluated the effects of genetic variations of the bovine SMO gene on economically important body size traits in Chinese Qinchuan cattle. Altogether, eight single nucleotide polymorphisms (SNPs: 1–8) were identified and genotyped via direct sequencing covering most of the coding region and 3ʹUTR of the bovine SMO gene. Both the p.698Ser.>Ser. synonymous mutation resulted from SNP1 and the p.700Ser.>Pro. non-synonymous mutation caused by SNP2 mapped to the intracellular C-terminal tail of bovine Smo protein; the other six SNPs were non-coding variants located in the 3ʹUTR. The linkage disequilibrium was analyzed, and five haplotypes were discovered in 520 Qinchuan cattle. Association analyses showed that SNP2, SNP3/5, SNP4 and SNP6/7 were significantly associated with some body size traits (p 0.05). Meanwhile, cattle with wild-type combined haplotype Hap1/Hap1 had significantly (p < 0.05) greater body length than those with Hap2/Hap2. Our results indicate that variations in the SMO gene could affect body size traits of Qinchuan cattle, and the wild-type haplotype Hap1 together with the wild-type alleles of these detected SNPs in the SMO gene could be used to breed cattle with superior body size traits. Therefore, our results could be helpful for marker-assisted selection in beef cattle breeding programs. PMID:26225956

Genome-wide scans for delineation of candidate genes regulating seed-protein content in chickpea

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Hari Deo eUpadhyaya

2016-03-01

Full Text Available Identification of potential genes/alleles governing complex seed-protein content (SPC trait is essential in marker-assisted breeding for quality trait improvement of chickpea. Henceforth, the present study utilized an integrated genomics-assisted breeding strategy encompassing trait association analysis, selective genotyping in traditional bi-parental mapping population and differential expression profiling for the first-time to understand the complex genetic architecture of quantitative SPC trait in chickpea. For GWAS (genome-wide association study, high-throughput genotyping information of 16376 genome-based SNPs (single nucleotide polymorphism discovered from a structured population of 336 sequenced desi and kabuli accessions [with 150-200 kb LD (linkage disequilibrium decay] was utilized. This led to identification of seven most effective genomic loci (genes associated [10 to 20% with 41% combined PVE (phenotypic variation explained] with SPC trait in chickpea. Regardless of the diverse desi and kabuli genetic backgrounds, a comparable level of association potential of the identified seven genomic loci with SPC trait was observed. Five SPC-associated genes were validated successfully in parental accessions and homozygous individuals of an intra-specific desi RIL (recombinant inbred line mapping population (ICC 12299 x ICC 4958 by selective genotyping. The seed-specific expression, including differential up-regulation (> 4-fold of six SPC-associated genes particularly in accessions, parents and homozygous individuals of the aforementioned mapping population with high level of contrasting seed-protein content (21-22% was evident. Collectively, the integrated genomic approach delineated diverse naturally occurring novel functional SNP allelic variants in six potential candidate genes regulating SPC trait in chickpea. Of these, a non-synonymous SNP allele-carrying zinc finger transcription factor gene exhibiting strong association with SPC trait

Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

Energy Technology Data Exchange (ETDEWEB)

Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

1996-09-01

Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

Science.gov (United States)

Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

2016-08-01

Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

A family-based joint test for mean and variance heterogeneity for quantitative traits.

Science.gov (United States)

Cao, Ying; Maxwell, Taylor J; Wei, Peng

2015-01-01

Traditional quantitative trait locus (QTL) analysis focuses on identifying loci associated with mean heterogeneity. Recent research has discovered loci associated with phenotype variance heterogeneity (vQTL), which is important in studying genetic association with complex traits, especially for identifying gene-gene and gene-environment interactions. While several tests have been proposed to detect vQTL for unrelated individuals, there are no tests for related individuals, commonly seen in family-based genetic studies. Here we introduce a likelihood ratio test (LRT) for identifying mean and variance heterogeneity simultaneously or for either effect alone, adjusting for covariates and family relatedness using a linear mixed effect model approach. The LRT test statistic for normally distributed quantitative traits approximately follows χ(2)-distributions. To correct for inflated Type I error for non-normally distributed quantitative traits, we propose a parametric bootstrap-based LRT that removes the best linear unbiased prediction (BLUP) of family random effect. Simulation studies show that our family-based test controls Type I error and has good power, while Type I error inflation is observed when family relatedness is ignored. We demonstrate the utility and efficiency gains of the proposed method using data from the Framingham Heart Study to detect loci associated with body mass index (BMI) variability. © 2014 John Wiley & Sons Ltd/University College London.

Integrating modelling and phenotyping approaches to identify and screen complex traits - Illustration for transpiration efficiency in cereals.

Science.gov (United States)

Chenu, K; van Oosterom, E J; McLean, G; Deifel, K S; Fletcher, A; Geetika, G; Tirfessa, A; Mace, E S; Jordan, D R; Sulman, R; Hammer, G L

2018-02-21

Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plants and with their environments, and to target traits of most relevance for the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to identify traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their values in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding program. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programs for improving yield gains in target populations of environments.

Candidate genes affecting fat deposition, carcass composition and meat quality traits in pigs

OpenAIRE

Gandolfi, Greta

2011-01-01

Pig meat quality is determined by several parameters, such as lipid content, tenderness, water-holding capacity, pH, color and flavor, that affect consumers’ acceptance and technological properties of meat. Carcass quality parameters are important for the production of fresh and dry-cure high-quality products, in particular the fat deposition and the lean cut yield. The identification of genes and markers associated with meat and carcass quality traits is of prime interest, for the possibilit...

Effects of vertebral number variations on carcass traits and genotyping of Vertnin candidate gene in Kazakh sheep

Directory of Open Access Journals (Sweden)

Zhifeng Zhang

2017-09-01

Full Text Available Objective The vertebral number is associated with body length and carcass traits, which represents an economically important trait in farm animals. The variation of vertebral number has been observed in a few mammalian species. However, the variation of vertebral number and quantitative trait loci in sheep breeds have not been well addressed. Methods In our investigation, the information including gender, age, carcass weight, carcass length and the number of thoracic and lumbar vertebrae from 624 China Kazakh sheep was collected. The effect of vertebral number variation on carcass weight and carcass length was estimated by general linear model. Further, the polymorphic sites of Vertnin (VRTN gene were identified by sequencing, and the association of the genotype and vertebral number variation was analyzed by the one-way analysis of variance model. Results The variation of thoracolumbar vertebrae number in Kazakh sheep (18 to 20 was smaller than that in Texel sheep (17 to 21. The individuals with 19 thoracolumbar vertebrae (T13L6 were dominant in Kazakh sheep (79.2%. The association study showed that the numbers of thoracolumbar vertebrae were positively correlated with the carcass length and carcass weight, statistically significant with carcass length. To investigate the association of thoracolumbar vertebrae number with VRTN gene, we genotyped the VRTN gene. A total of 9 polymorphic sites were detected and only a single nucleotide polymorphism (SNP (rs426367238 was suggested to associate with thoracic vertebral number statistically. Conclusion The variation of thoracolumbar vertebrae number positively associated with the carcass length and carcass weight, especially with the carcass length. VRTN gene polymorphism of the SNP (rs426367238 with significant effect on thoracic vertebral number could be as a candidate marker to further evaluate its role in influence of thoracolumbar vertebral number.

Effects of vertebral number variations on carcass traits and genotyping of Vertnin candidate gene in Kazakh sheep.

Science.gov (United States)

Zhang, Zhifeng; Sun, Yawei; Du, Wei; He, Sangang; Liu, Mingjun; Tian, Changyan

2017-09-01

The vertebral number is associated with body length and carcass traits, which represents an economically important trait in farm animals. The variation of vertebral number has been observed in a few mammalian species. However, the variation of vertebral number and quantitative trait loci in sheep breeds have not been well addressed. In our investigation, the information including gender, age, carcass weight, carcass length and the number of thoracic and lumbar vertebrae from 624 China Kazakh sheep was collected. The effect of vertebral number variation on carcass weight and carcass length was estimated by general linear model. Further, the polymorphic sites of Vertnin ( VRTN ) gene were identified by sequencing, and the association of the genotype and vertebral number variation was analyzed by the one-way analysis of variance model. The variation of thoracolumbar vertebrae number in Kazakh sheep (18 to 20) was smaller than that in Texel sheep (17 to 21). The individuals with 19 thoracolumbar vertebrae (T13L6) were dominant in Kazakh sheep (79.2%). The association study showed that the numbers of thoracolumbar vertebrae were positively correlated with the carcass length and carcass weight, statistically significant with carcass length. To investigate the association of thoracolumbar vertebrae number with VRTN gene, we genotyped the VRTN gene. A total of 9 polymorphic sites were detected and only a single nucleotide polymorphism (SNP) (rs426367238) was suggested to associate with thoracic vertebral number statistically. The variation of thoracolumbar vertebrae number positively associated with the carcass length and carcass weight, especially with the carcass length. VRTN gene polymorphism of the SNP (rs426367238) with significant effect on thoracic vertebral number could be as a candidate marker to further evaluate its role in influence of thoracolumbar vertebral number.

Complex nature of SNP genotype effects on gene expression in primary human leucocytes

Directory of Open Access Journals (Sweden)

Dinesen Lotte C

2009-01-01

Full Text Available Abstract Background Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown. Methods We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110 from individuals with celiac disease – a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90, and performed a meta-analysis to increase power to detect non-tissue specific effects. Results In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (cis expression quantitative trait loci, eQTLs. 135 of the detected SNP-probe effects (reflecting 51 unique probes were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed cis-eQTLs. Celiac associated risk variants from two regions, containing genes IL18RAP and CCR3, showed significant cis genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected. Conclusion In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.

Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and carcass traits in Nelore cattle

Science.gov (United States)

Fonseca, Patrícia D. da S.; de Souza, Fábio R.P.; de Camargo, Gregório M.F.; Gil, Fernanda M.M.; Cardoso, Diercles F.; Zetouni, Larissa; Braz, Camila U.; Boligon, Arione A.; Branco, Renata H.; de Albuquerque, Lucia G.; Mercadante, Maria E.Z.; Tonhati, Humberto

2015-01-01

In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight. PMID:25853056

Number of genes controlling a quantitative trait in a hybrid zone of the aposematic frog Ranitomeya imitator

DEFF Research Database (Denmark)

Vestergaard, Jacob Schack; Twomey, Evan; Larsen, Rasmus

2015-01-01

The number of genes controlling mimetic traits has been a topic of much research and discussion. In this paper, we examine a mimetic, dendrobatid frog Ranitomeya imitator, which harbours extensive phenotypic variation with multiple mimetic morphs, not unlike the celebrated Heliconius system...... and apply it to the R. imitator system. We show that probably one or two, or at most three genes, control the mimetic phenotype segregating in a R. imitator hybrid zone identified using image analyses....

Genome-wide association mapping of growth dynamics detects time-specific and general quantitative trait loci

NARCIS (Netherlands)

Bac-Molenaar, J.A.; Vreugdenhil, D.; Granier, C.; Keurentjes, J.J.B.

2015-01-01

Growth is a complex trait determined by the interplay between many genes, some of which play a role at a specific moment during development whereas others play a more general role. To identify the genetic basis of growth, natural variation in Arabidopsis rosette growth was followed in 324 accessions

Beta-thalassaemia trait: haematological parameters

International Nuclear Information System (INIS)

Yousafzai, Y.M.; Khan, S.; Raziq, F.

2010-01-01

Thalassaemia syndromes are a group of hereditary disorders characterised by a genetic deficiency in the synthesis of --globin genes. The objective of this study was to determine the haematological features -thalassaemia trait (BTT), and to determine the sensitivity of Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and -thalassaemia trait. Methods: A descriptive study was conducted in Hayatabad Medical Complex, Peshawar from May 2009 to May 2010 with 203 subjects having BTT. Blood samples were collected in EDTA anti-coagulated tubes. RBC indices were taken as part of complete blood count (CBC) by haematology analyser, and Haemoglobin (Hb) electrophoresis was done to determine the HbA2 percentage. The data was collected and analyzed on statistical software for demographic details, RBC indices and HBA2 levels. Results: Out of 203 patients, 92 (45%) were males and 111 (55%) were females. Most patients tested were in the 15-45 year age group. One-hundred-sixty (79%) patients had anaemia. MCV was lower than 76 fl in all the cases. Mean MCV was 59.1 fl. MCH was low, the mean MCH being 19.3 g/dl. MCH <26 gave sensitivity of 99% in detecting BTT. We calculated MI for these cases and found out that it was <12 in 75% of cases and <15 in 197 (97%). Conclusion: Beta-thalassaemia traits present with a microcytic hypochromic blood picture, detected on simple haematology analysers as low MCV and MCH and MI which provide a beta- thalassaemia trait. (author)

Single Nucleotide Polymorphisms in the Leptin-a Gene and Associations with Growth Traits in the Orange-Spotted Grouper (Epinephelus coioides

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Haoran Lin

2013-04-01

Full Text Available Leptin is a multifunctional protein involved in processes such as body weight regulation, energy expenditure, fat metabolism, food intake, and appetite regulation. Duplicate leptin genes, leptin-a and leptin-b, were previously detected in the orange-spotted grouper. In this study, we cloned the full-length open reading frame (ORF of the leptin-a gene in the orange-spotted grouper, searched for polymorphisms, and performed association analyses between these polymorphisms and seven growth traits. Six polymorphisms, consisting of 2 SNPs in intron 1 (c.182T > G, c.183G > T and 4 SNPs in exon 2 (c.339C > G, c.345C > T, c.447G > A, c.531C > T, were identified and genotyped in 200 individuals. The c.182T > G and c.183G > T polymorphisms showed complete linkage and were analyzed together. Association analyses revealed that the c.182 + 183TG > GT polymorphism was significantly associated with body weight (BWT and body width (BWH, with the AB (TG/GT genotype showing positive effects on growth traits. Additionally, the SNP c.447G > A was significantly associated with BWT, BWH, overall length (OL, trunk width (TW, and head length (HL, with the GA genotype displaying positive effects on growth traits. The c.531C > T SNP showed a close association between the TT genotype and decreased growth. Our results demonstrate that several polymorphisms in the leptin-a gene are associated with growth traits and can be used for marker-assisted selection (MAS in orange-spotted grouper populations.

Identification of Quantitative Trait Loci (QTL) and Candidate Genes for Cadmium Tolerance in Populus

Energy Technology Data Exchange (ETDEWEB)

Induri, Brahma R [West Virginia University; Ellis, Danielle R [West Virginia University; Slavov, Gancho [West Virginia University; Yin, Tongming [ORNL; Muchero, Wellington [ORNL; Tuskan, Gerald A [ORNL; DiFazio, Stephen P [West Virginia University

2012-01-01

Knowledge of genetic variation in response of Populus to heavy metals like cadmium (Cd) is an important step in understanding the underlying mechanisms of tolerance. In this study, a pseudo-backcross pedigree of Populus trichocarpa and Populus deltoides was characterized for Cd exposure. The pedigree showed significant variation for Cd tolerance thus enabling the identification of relatively tolerant and susceptible genotypes for intensive characterization. A total of 16 QTLs at logarithm of odds (LOD) ratio > 2.5, were found to be associated with total dry weight, its components, and root volume. Four major QTLs for total dry weight were mapped to different linkage groups in control (LG III) and Cd conditions (LG XVI) and had opposite allelic effects on Cd tolerance, suggesting that these genomic regions were differentially controlled. The phenotypic variation explained by Cd QTL for all traits under study varied from 5.9% to 11.6% and averaged 8.2% across all QTL. Leaf Cd contents also showed significant variation suggesting the phytoextraction potential of Populus genotypes, though heritability of this trait was low (0.22). A whole-genome microarray study was conducted by using two genotypes with extreme responses for Cd tolerance in the above study and differentially expressed genes were identified. Candidate genes including CAD2 (CADMIUM SENSITIVE 2), HMA5 (HEAVY METAL ATPase5), ATGTST1 (Arabidopsis thaliana Glutathione S-Transferase1), ATGPX6 (Glutathione peroxidase 6), and ATMRP 14 (Arabidopsis thaliana Multidrug Resistance associated Protein 14) were identified from QTL intervals and microarray study. Functional characterization of these candidate genes could enhance phytoremediation capabilities of Populus.

The nucleoside diphosphate kinase gene Nme3 acts as quantitative trait locus promoting non-Mendelian inheritance.

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Hermann Bauer

Full Text Available The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (> 95% from heterozygous (t/+ males to their offspring. This phenotype is termed transmission ratio distortion (TRD and is caused by the interaction of the t-complex responder (Tcr with several quantitative trait loci (QTL, the t-complex distorters (Tcd1 to Tcd4, all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas (+-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOK(Tcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and

Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow.

Science.gov (United States)

Sachdeva, Himani; Barton, Nicholas H

2017-06-01

Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Complex single gene disorders and epilepsy.

LENUS (Irish Health Repository)

Merwick, Aine

2012-09-01

Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation.

The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits.

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Josine L Min

Full Text Available The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs from 299 twins and correlated these with 44 quantitative traits (QTs. For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs. We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01 but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.

Discovering genes underlying QTL

Energy Technology Data Exchange (ETDEWEB)

Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

2002-02-01

A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction.

Science.gov (United States)

Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M; Worrall, Bradford B; Williams, Stephen R; Hsu, Fang-Chi; Tzeng, Jung-Ying

2015-09-01

Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level. © 2015 WILEY PERIODICALS, INC.

Full genotyping of a highly polymorphic human gene trait by time-resolved fluorescence resonance energy transfer.

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Edoardo Totè

Full Text Available The ability of detecting the subtle variations occurring, among different individuals, within specific DNA sequences encompassed in highly polymorphic genes discloses new applications in genomics and diagnostics. DQB1 is a gene of the HLA-II DQ locus of the Human Leukocyte Antigens (HLA system. The polymorphisms of the trait of the DQB1 gene including codons 52-57 modulate the susceptibility to a number of severe pathologies. Moreover, the donor-receiver tissue compatibility in bone marrow transplantations is routinely assessed through crossed genotyping of DQB and DQA. For the above reasons, the development of rapid, reliable and cost-effective typing technologies of DQB1 in general, and more specifically of the codons 52-57, is a relevant although challenging task. Quantitative assessment of the fluorescence resonance energy transfer (FRET efficiency between chromophores labelling the opposite ends of gene-specific oligonucleotide probes has proven to be a powerful tool to type DNA polymorphisms with single-nucleotide resolution. The FRET efficiency can be most conveniently quantified by applying a time-resolved fluorescence analysis methodology, i.e. time-correlated single-photon counting, which allows working on very diluted template specimens and in the presence of fluorescent contaminants. Here we present a full in-vitro characterization of the fluorescence responses of two probes when hybridized to oligonucleotide mixtures mimicking all the possible genotypes of the codons 52-57 trait of DQB1 (8 homozygous and 28 heterozygous. We show that each genotype can be effectively tagged by the combination of the fluorescence decay constants extrapolated from the data obtained with such probes.

Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus)

Science.gov (United States)

Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

2015-01-01

An intraspecific genetic map for watermelon was constructed using an F2 population derived from ‘Arka Manik’ × ‘TS34’ and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits. PMID:26700647

Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus).

Science.gov (United States)

Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

2015-01-01

An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

Determination of gene action for some biometrical traits in Lens ...

Indian Academy of Sciences (India)

RESEARCH NOTE. Determination ... limitation of this design is that if the testers do not differ at all loci for ... the traits under study indicating the presence of epistasis for these traits ... Quantitative genetic analysis for yield traits in lentil. Table 1.

Adapting APSIM to model the physiology and genetics of complex adaptive traits in field crops.

Science.gov (United States)

Hammer, Graeme L; van Oosterom, Erik; McLean, Greg; Chapman, Scott C; Broad, Ian; Harland, Peter; Muchow, Russell C

2010-05-01

Progress in molecular plant breeding is limited by the ability to predict plant phenotype based on its genotype, especially for complex adaptive traits. Suitably constructed crop growth and development models have the potential to bridge this predictability gap. A generic cereal crop growth and development model is outlined here. It is designed to exhibit reliable predictive skill at the crop level while also introducing sufficient physiological rigour for complex phenotypic responses to become emergent properties of the model dynamics. The approach quantifies capture and use of radiation, water, and nitrogen within a framework that predicts the realized growth of major organs based on their potential and whether the supply of carbohydrate and nitrogen can satisfy that potential. The model builds on existing approaches within the APSIM software platform. Experiments on diverse genotypes of sorghum that underpin the development and testing of the adapted crop model are detailed. Genotypes differing in height were found to differ in biomass partitioning among organs and a tall hybrid had significantly increased radiation use efficiency: a novel finding in sorghum. Introducing these genetic effects associated with plant height into the model generated emergent simulated phenotypic differences in green leaf area retention during grain filling via effects associated with nitrogen dynamics. The relevance to plant breeding of this capability in complex trait dissection and simulation is discussed.

Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.

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Angelo Scuteri

2007-07-01

Full Text Available The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7, hip circumference (p = 3.4 x 10(-8, and weight (p = 9.1 x 10(-7. In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46 were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6. Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12 were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496 and in Hispanic Americans (N = 839, we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001, weight (p = 0.001, and hip circumference (p = 0.0005. We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for

Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

Directory of Open Access Journals (Sweden)

Sungyoung Lee

2012-12-01

Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

Network graph analysis of gene-gene interactions in genome-wide association study data.

Science.gov (United States)

Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

2012-12-01

Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.

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Markus Drag

Full Text Available Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS were slaughtered at ~100 kg. Gene expression profiles were obtained by RNA-Seq, and genotype data were obtained by an Illumina 60K Porcine SNP chip. Following quality control and filtering, 10,545 and 12,731 genes from liver and testis were included in the eQTL analysis, together with 20,827 SNP variants. A total of 205 and 109 single-tissue eQTLs associated with 102 and 58 unique genes were identified in liver and testis, respectively. By employing a multivariate Bayesian hierarchical model, 26 eQTLs were identified as significant multi-tissue eQTLs. The highest densities of eQTLs were found on pig chromosomes SSC12, SSC1, SSC13, SSC9 and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits curated by the Animal Genome PigQTL database to be significantly overlapped by the genomic coordinates of cis-acting eQTLs. Finally, a subset of 35 cis-acting eQTLs overlapped with known boar taint QTL traits. These eQTLs could be useful in the development of a DNA test for boar taint but careful monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection.

Operon Gene Order Is Optimized for Ordered Protein Complex Assembly

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Wells, Jonathan N.; Bergendahl, L. Therese; Marsh, Joseph A.

2016-01-01

Summary The assembly of heteromeric protein complexes is an inherently stochastic process in which multiple genes are expressed separately into proteins, which must then somehow find each other within the cell. Here, we considered one of the ways by which prokaryotic organisms have attempted to maximize the efficiency of protein complex assembly: the organization of subunit-encoding genes into operons. Using structure-based assembly predictions, we show that operon gene order has been optimized to match the order in which protein subunits assemble. Exceptions to this are almost entirely highly expressed proteins for which assembly is less stochastic and for which precisely ordered translation offers less benefit. Overall, these results show that ordered protein complex assembly pathways are of significant biological importance and represent a major evolutionary constraint on operon gene organization. PMID:26804901

Functional Gene Discovery and Characterization of Genes and Alleles Affecting Wood Biomass Yield and Quality in Populus

Energy Technology Data Exchange (ETDEWEB)

Busov, Victor [Michigan Technological Univ., Houghton, MI (United States)

2017-02-12

Adoption of biofuels as economically and environmentally viable alternative to fossil fuels would require development of specialized bioenergy varieties. A major goal in the breeding of such varieties is the improvement of lignocellulosic biomass yield and quality. These are complex traits and understanding the underpinning molecular mechanism can assist and accelerate their improvement. This is particularly important for tree bioenergy crops like poplars (species and hybrids from the genus Populus), for which breeding progress is extremely slow due to long generation cycles. A variety of approaches have been already undertaken to better understand the molecular bases of biomass yield and quality in poplar. An obvious void in these undertakings has been the application of mutagenesis. Mutagenesis has been instrumental in the discovery and characterization of many plant traits including such that affect biomass yield and quality. In this proposal we use activation tagging to discover genes that can significantly affect biomass associated traits directly in poplar, a premier bioenergy crop. We screened a population of 5,000 independent poplar activation tagging lines under greenhouse conditions for a battery of biomass yield traits. These same plants were then analyzed for changes in wood chemistry using pyMBMS. As a result of these screens we have identified nearly 800 mutants, which are significantly (P<0.05) different when compared to wild type. Of these majority (~700) are affected in one of ten different biomass yield traits and 100 in biomass quality traits (e.g., lignin, S/G ration and C6/C5 sugars). We successfully recovered the position of the tag in approximately 130 lines, showed activation in nearly half of them and performed recapitulation experiments with 20 genes prioritized by the significance of the phenotype. Recapitulation experiments are still ongoing for many of the genes but the results are encouraging. For example, we have shown successful

The genetic architecture of a complex ecological trait: host plant use in the specialist moth, HELIOTHIS SUBFLEXA

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The study of the genetic basis of ecological adaptation remains in its infancy, and most studies have focused on phenotypically simple traits. Host plant use by herbivorous insects is phenotypically complex. While research has illuminated the evolutionary determinants of host use, knowledge of its...

Association of SNP variants of MHC Class II DRB gene with thermo-physiological traits in tropical goats.

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Yakubu, Abdulmojeed; Salako, Adebowale E; De Donato, Marcos; Peters, Sunday O; Takeet, Michael I; Wheto, Mathew; Okpeku, Moses; Imumorin, Ikhide G

2017-02-01

Host defense in vertebrates depend on many secreted regulatory proteins such as major histocompatibility complex (MHC) class II which provide important regulatory and effector functions of T cells. Gene polymorphism in the second exon of Capra-DRB gene in three major Nigerian goat breeds [West African Dwarf (WAD), Red Sokoto (RS), and Sahel (SH)] was analyzed by restriction fragment length polymorphisms (RFLP). Four restriction enzymes, BsaHI, AluI, HaeIII, and SacII, were utilized. The association between the polymorphic sites and some heat tolerance traits were also investigated in a total of 70 WAD, 90 RS, and 50 SH goats. Fourteen different types of alleles identified in the Nigerian goats, four of which were found in the peptide coding region (A57G, Q89R, G104D, and T112I), indicate a high degree of polymorphism at the DRB locus in this species. An obvious excess (P  0.05), except AluI in RS goats and HaeIII in WAD goats (P goat populations, ranged from 0.16 to 0.50. Genotypes AA (BsaHI), GG, GC and CC (AluI) and GG, GA, AA (HaeIII) appeared better in terms of heat tolerance. The heat-tolerant ability of SH and RS goats to the hot and humid tropical environment of Nigeria seemed better than that of the WAD goats. Sex effect (P tropics.

Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

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Raguideau, Sébastien; Plancade, Sandra; Pons, Nicolas; Leclerc, Marion; Laroche, Béatrice

2016-12-01

Whole Genome Shotgun (WGS) metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs) accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF) problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other metabolic processes in

Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

Directory of Open Access Journals (Sweden)

Sébastien Raguideau

2016-12-01

Full Text Available Whole Genome Shotgun (WGS metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other

Kernel-based whole-genome prediction of complex traits: a review.

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Morota, Gota; Gianola, Daniel

2014-01-01

Prediction of genetic values has been a focus of applied quantitative genetics since the beginning of the 20th century, with renewed interest following the advent of the era of whole genome-enabled prediction. Opportunities offered by the emergence of high-dimensional genomic data fueled by post-Sanger sequencing technologies, especially molecular markers, have driven researchers to extend Ronald Fisher and Sewall Wright's models to confront new challenges. In particular, kernel methods are gaining consideration as a regression method of choice for genome-enabled prediction. Complex traits are presumably influenced by many genomic regions working in concert with others (clearly so when considering pathways), thus generating interactions. Motivated by this view, a growing number of statistical approaches based on kernels attempt to capture non-additive effects, either parametrically or non-parametrically. This review centers on whole-genome regression using kernel methods applied to a wide range of quantitative traits of agricultural importance in animals and plants. We discuss various kernel-based approaches tailored to capturing total genetic variation, with the aim of arriving at an enhanced predictive performance in the light of available genome annotation information. Connections between prediction machines born in animal breeding, statistics, and machine learning are revisited, and their empirical prediction performance is discussed. Overall, while some encouraging results have been obtained with non-parametric kernels, recovering non-additive genetic variation in a validation dataset remains a challenge in quantitative genetics.

Kernel-based whole-genome prediction of complex traits: a review

Directory of Open Access Journals (Sweden)

Gota eMorota

2014-10-01

Full Text Available Prediction of genetic values has been a focus of applied quantitative genetics since the beginning of the 20th century, with renewed interest following the advent of the era of whole genome-enabled prediction. Opportunities offered by the emergence of high-dimensional genomic data fueled by post-Sanger sequencing technologies, especially molecular markers, have driven researchers to extend Ronald Fisher and Sewall Wright's models to confront new challenges. In particular, kernel methods are gaining consideration as a regression method of choice for genome-enabled prediction. Complex traits are presumably influenced by many genomic regions working in concert with others (clearly so when considering pathways, thus generating interactions. Motivated by this view, a growing number of statistical approaches based on kernels attempt to capture non-additive effects, either parametrically or non-parametrically. This review centers on whole-genome regression using kernel methods applied to a wide range of quantitative traits of agricultural importance in animals and plants. We discuss various kernel-based approaches tailored to capturing total genetic variation, with the aim of arriving at an enhanced predictive performance in the light of available genome annotation information. Connections between prediction machines born in animal breeding, statistics, and machine learning are revisited, and their empirical prediction performance is discussed. Overall, while some encouraging results have been obtained with non-parametric kernels, recovering non-additive genetic variation in a validation dataset remains a challenge in quantitative genetics.

Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

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Winham, Stacey J.; Biernacka, Joanna M.

2013-01-01

Background: Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized…

QTLs for seedling traits under salinity stress in hexaploid wheat

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Yongzhe Ren

2018-03-01

Full Text Available ABSTRACT: Soil salinity limits agricultural production and is a major obstacle for increasing crop yield. Common wheat is one of the most important crops with allohexaploid characteristic and a highly complex genome. QTL mapping is a useful way to identify genes for quantitative traits such as salinity tolerance in hexaploid wheat. In the present study, a hydroponic trial was carried out to identify quantitative trait loci (QTLs associated with salinity tolerance of wheat under 150mM NaCl concentration using a recombinant inbred line population (Xiaoyan 54×Jing 411. Values of wheat seedling traits including maximum root length (MRL, root dry weight (RDW, shoot dry weight (SDW, total dry weight (TDW and the ratio of TDW of wheat plants between salt stress and control (TDWR were evaluated or calculated. A total of 19QTLs for five traits were detected through composite interval mapping method by using QTL Cartographer version 2.5 under normal and salt stress conditions. These QTLs distributed on 12 chromosomes explained the percentage of phenotypic variation by individual QTL varying from 7.9% to 19.0%. Among them, 11 and six QTLs were detected under normal and salt stress conditions, respectively and two QTLs were detected for TDWR. Some salt tolerance related loci may be pleiotropic. Chromosome 1A, 3A and 7A may harbor crucial candidate genes associated with wheat salt tolerance. Our results would be helpful for the marker assisted selection to breed wheat varieties with improved salt tolerance.

Simple versus complex models of trait evolution and stasis as a response to environmental change

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Hunt, Gene; Hopkins, Melanie J.; Lidgard, Scott

2015-04-01

Previous analyses of evolutionary patterns, or modes, in fossil lineages have focused overwhelmingly on three simple models: stasis, random walks, and directional evolution. Here we use likelihood methods to fit an expanded set of evolutionary models to a large compilation of ancestor-descendant series of populations from the fossil record. In addition to the standard three models, we assess more complex models with punctuations and shifts from one evolutionary mode to another. As in previous studies, we find that stasis is common in the fossil record, as is a strict version of stasis that entails no real evolutionary changes. Incidence of directional evolution is relatively low (13%), but higher than in previous studies because our analytical approach can more sensitively detect noisy trends. Complex evolutionary models are often favored, overwhelmingly so for sequences comprising many samples. This finding is consistent with evolutionary dynamics that are, in reality, more complex than any of the models we consider. Furthermore, the timing of shifts in evolutionary dynamics varies among traits measured from the same series. Finally, we use our empirical collection of evolutionary sequences and a long and highly resolved proxy for global climate to inform simulations in which traits adaptively track temperature changes over time. When realistically calibrated, we find that this simple model can reproduce important aspects of our paleontological results. We conclude that observed paleontological patterns, including the prevalence of stasis, need not be inconsistent with adaptive evolution, even in the face of unstable physical environments.

Molecular Characterization of Bovine SMO Gene and Effects of Its Genetic Variations on Body Size Traits in Qinchuan Cattle (Bos taurus).

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Zhang, Ya-Ran; Gui, Lin-Sheng; Li, Yao-Kun; Jiang, Bi-Jie; Wang, Hong-Cheng; Zhang, Ying-Ying; Zan, Lin-Sen

2015-07-27

Smoothened (Smo)-mediated Hedgehog (Hh) signaling pathway governs the patterning, morphogenesis and growth of many different regions within animal body plans. This study evaluated the effects of genetic variations of the bovine SMO gene on economically important body size traits in Chinese Qinchuan cattle. Altogether, eight single nucleotide polymorphisms (SNPs: 1-8) were identified and genotyped via direct sequencing covering most of the coding region and 3'UTR of the bovine SMO gene. Both the p.698Ser.>Ser. synonymous mutation resulted from SNP1 and the p.700Ser.>Pro. non-synonymous mutation caused by SNP2 mapped to the intracellular C-terminal tail of bovine Smo protein; the other six SNPs were non-coding variants located in the 3'UTR. The linkage disequilibrium was analyzed, and five haplotypes were discovered in 520 Qinchuan cattle. Association analyses showed that SNP2, SNP3/5, SNP4 and SNP6/7 were significantly associated with some body size traits (p 0.05). Meanwhile, cattle with wild-type combined haplotype Hap1/Hap1 had significantly (p cattle, and the wild-type haplotype Hap1 together with the wild-type alleles of these detected SNPs in the SMO gene could be used to breed cattle with superior body size traits. Therefore, our results could be helpful for marker-assisted selection in beef cattle breeding programs.

Association study of molecular polymorphisms in candidate genes related to stress responses with production and meat quality traits in pigs.

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Terenina, E; Babigumira, B M; Le Mignon, G; Bazovkina, D; Rousseau, S; Salin, F; Bendixen, C; Mormede, P

2013-02-01

The hypothalamic-pituitary-adrenal (HPA) axis exerts a large range of effects on metabolism, the immune system, inflammatory processes, and brain functions. Together with the sympathetic nervous system, it is also the most important stress-responsive neuroendocrine system. Both systems influence production traits, carcass composition, and meat quality. The HPA axis may be a critical target for genetic selection of more robust animals. Indeed, numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and genetic polymorphism can be found at each level of the axis, including hormone production by the adrenal cortices under stimulation by adrenocorticotropic hormone (ACTH), hormone bioavailability, or receptor and postreceptor mechanisms. The aim of the present experiment was to extend these findings to the brain neurochemical systems involved in stress responses. To this end, a number of candidate genes were sequenced for molecular polymorphisms and their association was studied with stress neuroendocrine and production traits in a genetically diverse population consisting of 100 female pigs from an advanced intercross (F10-F12) between 2 highly divergent breeds, Large White (LW) and Meishan (MS). The LW breed has a high production potential for lean meat and a low HPA axis activity, and the MS breed has low growth rate, fat carcasses-but large litters of highly viable piglets-and a high HPA axis activity. Candidate genes were chosen in the catecholaminergic and serotonergic pathways, in the pituitary control of cortisol production, among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs, and in cortisol receptors. Sixty new polymorphisms were found. The association study with carcass and meat quality traits and with endocrine traits showed a number of significant results, such as monoamine oxidase (MAOA) polymorphisms with

DNA Polymorphism of Insulin-like Growth Factor-binding Protein-3 Gene and Its Association with Cashmere Traits in Cashmere Goats

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Haiying Liu

2012-11-01

Full Text Available Insulin-like growth factor binding protein-3 (IGFBP-3 gene is important for regulation of growth and development in mammals. The present investigation was carried out to study DNA polymorphism by PCR-RFLP of IGFBP-3 gene and its effect on fibre traits of Chinese Inner Mongolian cashmere goats. The fibre traits data investigated were cashmere fibre diameter, combed cashmere weight, cashmere fibre length and guard hair length. Four hundred and forty-four animals were used to detect polymorphisms in the hircine IGFBP-3 gene. A 316-bp fragment of the IGFBP-3 gene in exon 2 was amplified and digested with HaeIII restriction enzyme. Three patterns of restriction fragments were observed in the populations. The frequency of AA, AB and BB genotypes was 0.58, 0.33 and 0.09 respectively. The allelic frequency of the A and B allele was 0.75 and 0.25 respectively. Nucleotide sequencing revealed a C>G transition in the exon 2 region of the IGFBP-3 gene resulting in R158G change which caused the polymorphism. Least squares analysis revealed a significant effect of genotypes on cashmere weight (p0.05. The animals of AB and BB genotypes showed higher cashmere weight, cashmere fibre length and hair length than the animals possessing AA genotype. These results suggested that polymorphisms in the hircine IGFBP-3 gene might be a potential molecular marker for cashmere weight in cashmere goats.

Genetic and QTL analyses of yield and a set of physiological traits in pepper

NARCIS (Netherlands)

Alimi, N.A.; Bink, M.C.A.M.; Dieleman, J.A.; Nicolaï, M.; Wubs, M.; Heuvelink, E.; Magan, J.; Voorrips, R.E.; Jansen, J.; Rodrigues, P.C.; Heijden, van der G.W.A.M.; Vercauteren, A.; Vuylsteke, M.; Song, Y.; Glasbey, C.; Barocsi, A.; Lefebvre, V.; Palloix, A.; Eeuwijk, van F.A.

2013-01-01

An interesting strategy for improvement of a complex trait dissects the complex trait in a number of physiological component traits, with the latter having hopefully a simple genetic basis. The complex trait is then improved via improvement of its component traits. As first part of such a strategy

Studying the Complex Expression Dependences between Sets of Coexpressed Genes

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Mario Huerta

2014-01-01

Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

Identification of Marker-Trait Associations for Lint Traits in Cotton

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Iqbal, Muhammad A.; Rahman, Mehboob-ur-

2017-01-01

Harvesting high quality lint, a long-awaited breeding goal—accomplished partly, can be achieved by identifying DNA markers which could be used for diagnosing cotton plants containing the desired traits. In the present studies, a total of 185 cotton genotypes exhibiting diversity for lint traits were selected from a set of 546 genotypes evaluated for fiber traits in 2009. These genotypes were extensively studied for three consecutive years (2011–2013) at three different locations. Significant genetic variations were found for average boll weight, ginning out turn (GOT), micronaire value, staple length, fiber bundle strength, and uniformity index. IR-NIBGE-3701 showed maximum GOT (43.63%). Clustering of genotypes using Ward's method was found more informative than that of the clusters generated by principal component analysis. A total of 382 SSRs were surveyed on 10 Gossypium hirsutum genotypes exhibiting contrasting fiber traits. Out of these, 95 polymorphic SSR primer pairs were then surveyed on 185 genotypes. The gene diversity averaged 0.191 and the polymorphic information content (PIC) averaged 0.175. Unweighted pair group method with arithmetic mean (UPGMA), principal coordinate analysis (PCoA), and STRUCTURE software grouped these genotypes into four major clusters each. Genetic distance within the clusters ranged from 0.0587 to 0.1030. A total of 47 (25.41%) genotypes exhibited shared ancestry. In total 6.8% (r2 ≥ 0.05) and 4.4% (r2 ≥ 0.1) of the marker pairs showed significant linkage disequilibrium (LD). A number of marker-trait associations (in total 75) including 13 for average boll weight, 18 for GOT percentage, eight for micronaire value, 18 for staple length, three for fiber bundle strength, and 15 for uniformity index were calculated. Out of these, MGHES-51 was associated with all the traits. Most of the marker-trait associations were novel while few validated the associations reported in the previous studies. High frequency of favorable

Six quantitative trait loci influence task thresholds for hygienic behaviour in honeybees (Apis mellifera).

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Oxley, Peter R; Spivak, Marla; Oldroyd, Benjamin P

2010-04-01

Honeybee hygienic behaviour provides colonies with protection from many pathogens and is an important model system of the genetics of a complex behaviour. It is a textbook example of complex behaviour under simple genetic control: hygienic behaviour consists of two components--uncapping a diseased brood cell, followed by removal of the contents--each of which are thought to be modulated independently by a few loci of medium to large effect. A worker's genetic propensity to engage in hygienic tasks affects the intensity of the stimulus required before she initiates the behaviour. Genetic diversity within colonies leads to task specialization among workers, with a minority of workers performing the majority of nest-cleaning tasks. We identify three quantitative trait loci that influence the likelihood that workers will engage in hygienic behaviour and account for up to 30% of the phenotypic variability in hygienic behaviour in our population. Furthermore, we identify two loci that influence the likelihood that a worker will perform uncapping behaviour only, and one locus that influences removal behaviour. We report the first candidate genes associated with engaging in hygienic behaviour, including four genes involved in olfaction, learning and social behaviour, and one gene involved in circadian locomotion. These candidates will allow molecular characterization of this distinctive behavioural mode of disease resistance, as well as providing the opportunity for marker-assisted selection for this commercially significant trait.

Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

NARCIS (Netherlands)

Brown, Sara J.; Asai, Yuka; Cordell, Heather J.; Campbell, Linda E.; Zhao, Yiwei; Liao, Haihui; Northstone, Kate; Henderson, John; Alizadehfar, Reza; Ben-Shoshan, Moshe; Morgan, Kenneth; Roberts, Graham; Masthoff, Laury J. N.; Pasmans, Suzanne G. M. A.; van den Akker, Peter C.; Wijmenga, Cisca; Hourihane, Jonathan O'B.; Palmer, Colin N. A.; Lack, Gideon; Clarke, Ann; Hull, Peter R.; Irvine, Alan D.; McLean, W. H. Irwin

Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the

Common Variants of Homocysteine Metabolism Pathway Genes and Risk of Type 2 Diabetes and Related Traits in Indians

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Ganesh Chauhan

2012-01-01

Full Text Available Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects and replicated top signals in an independent sample set (2.085 subjects. The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78 (95%  CI=0.67–0.92, P=0.003 and was also associated with 2 h postload plasma glucose (P=0.04, high-density lipoprotein cholesterol (P=0.004, and total cholesterol (P=0.01 in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.

Environmental heterogeneity generates opposite gene-by-environment interactions for two fitness-related traits within a population.

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Culumber, Zachary W; Schumer, Molly; Monks, Scott; Tobler, Michael

2015-02-01

Theory predicts that environmental heterogeneity offers a potential solution to the maintenance of genetic variation within populations, but empirical evidence remains sparse. The live-bearing fish Xiphophorus variatus exhibits polymorphism at a single locus, with different alleles resulting in up to five distinct melanistic "tailspot" patterns within populations. We investigated the effects of heterogeneity in two ubiquitous environmental variables (temperature and food availability) on two fitness-related traits (upper thermal limits and body condition) in two different tailspot types (wild-type and upper cut crescent). We found gene-by-environment (G × E) interactions between tailspot type and food level affecting upper thermal limits (UTL), as well as between tailspot type and thermal environment affecting body condition. Exploring mechanistic bases underlying these G × E patterns, we found no differences between tailspot types in hsp70 gene expression despite significant overall increases in expression under both thermal and food stress. Similarly, there was no difference in routine metabolic rates between the tailspot types. The reversal of relative performance of the two tailspot types under different environmental conditions revealed a mechanism by which environmental heterogeneity can balance polymorphism within populations through selection on different fitness-related traits. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes.

NARCIS (Netherlands)

Rijn, M.J. van; Schut, A.F.; Aulchenko, Y.S.; Deinum, J.; Sayed-Tabatabaei, F.A.; Yazdanpanah, M.; Isaacs, A.; Axenovich, T.I.; Zorkoltseva, I.V.; Zillikens, M.C.; Pols, H.A.; Witteman, J.C.; Oostra, B.A.; Duijn, C.M. van

2007-01-01

OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of

Detecting Genetic Interactions for Quantitative Traits Using m-Spacing Entropy Measure

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Jaeyong Yee

2015-01-01

Full Text Available A number of statistical methods for detecting gene-gene interactions have been developed in genetic association studies with binary traits. However, many phenotype measures are intrinsically quantitative and categorizing continuous traits may not always be straightforward and meaningful. Association of gene-gene interactions with an observed distribution of such phenotypes needs to be investigated directly without categorization. Information gain based on entropy measure has previously been successful in identifying genetic associations with binary traits. We extend the usefulness of this information gain by proposing a nonparametric evaluation method of conditional entropy of a quantitative phenotype associated with a given genotype. Hence, the information gain can be obtained for any phenotype distribution. Because any functional form, such as Gaussian, is not assumed for the entire distribution of a trait or a given genotype, this method is expected to be robust enough to be applied to any phenotypic association data. Here, we show its use to successfully identify the main effect, as well as the genetic interactions, associated with a quantitative trait.

"Touching Triton": Building Student Understanding of Complex Disease Risk.

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Loftin, Madelene; East, Kelly; Hott, Adam; Lamb, Neil

2016-01-01

Life science classrooms often emphasize the exception to the rule when it comes to teaching genetics, focusing heavily on rare single-gene and Mendelian traits. By contrast, the vast majority of human traits and diseases are caused by more complicated interactions between genetic and environmental factors. Research indicates that students have a deterministic view of genetics, generalize Mendelian inheritance patterns to all traits, and have unrealistic expectations of genetic technologies. The challenge lies in how to help students analyze complex disease risk with a lack of curriculum materials. Providing open access to both content resources and an engaging storyline can be achieved using a "serious game" model. "Touching Triton" was developed as a serious game in which students are asked to analyze data from a medical record, family history, and genomic report in order to develop an overall lifetime risk estimate of six common, complex diseases. Evaluation of student performance shows significant learning gains in key content areas along with a high level of engagement.

Genes and quality trait loci (QTLs) associated with firmness in Malus x domestica

KAUST Repository

Marondedze, Claudius

2013-03-31

Fruit firmness, a quality quantitative trait, has long been established as a key textural property and one of the essential parameters for estimating ripening and shelf life of apples. Loss of firmness, also referred to as fruit softening, is undesirable in apples and represents a serious problem for growers in many countries. This results in the reduction of apple shelf life and in turn influences its commercialization. Low firmness impacts negatively on the sensory values of juiciness, crunchiness and crispness. Fruit firmness is affected by the inheritance of alleles at multiple loci and their possible interactions with the environment. Identification of these loci is key for the determination of genetic candidate markers that can be implemented in marker assisted selection and breeding for trees and/or cultivars that can yield firmer fruits with economic value. In turn, this technique can help reduce the time needed to evaluate plants and new cultivars could become available faster. This review provides an overview of quantitative trait loci (QTL), including additional putative QTLs that we have identified, and genes associated with firmness and their importance to biotechnology, the breeding industry and eventually the consumers.

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs

DEFF Research Database (Denmark)

Drag, Markus; Hansen, Mathias B.; Kadarmideen, Haja N.

2018-01-01

Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed...... to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at similar to 100 kg. Gene...... monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection....

Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery

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Teerapong Yata

2014-01-01

Full Text Available Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage, viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage.

A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

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Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

2015-05-05

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Genotype distribution and allele frequencies of the genes associated with body composition and locomotion traits in Myanmar native horses.

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Okuda, Yu; Moe, Hla Hla; Moe, Kyaw Kyaw; Shimizu, Yuki; Nishioka, Kenji; Shimogiri, Takeshi; Mannen, Hideyuki; Kanemaki, Misao; Kunieda, Tetsuo

2017-08-01

Myanmar native horses are small horses used mainly for drafting carts or carriages in rural areas and packing loads in mountainy areas. In the present study, we investigated genotype distributions and allele frequencies of the LCORL/NCAPG, MSTN and DMRT3 genes, which are associated with body composition and locomotion traits of horses, in seven local populations of Myanmar native horses. The genotyping result of LCORL/NCAPG showed that allele frequencies of C allele associated with higher withers height ranged from 0.08 to 0.27, and 0.13 in average. For MSTN, allele frequencies of C allele associated with higher proportion of Type 2B muscular fiber ranged from 0.05 to 0.23, and 0.09 in average. For DMRT3, allele frequencies of A allele associated with ambling gait ranged from 0 to 0.04, and 0.01 in average. The presences of the minor alleles of these genes at low frequencies suggest a possibility that these horse populations have not been under strong selection pressure for particular locomotion traits and body composition. Our findings of the presence of these minor alleles in Southeast Asian native horses are also informative for considering the origins of these minor alleles associated with body composition and locomotion traits in horse populations. © 2016 Japanese Society of Animal Science.

Polymorphism of Insulin-like growth factor-I (IGF-I gene and their effect on growth traits in Indonesia native chicken

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M.A Mu'in

2009-12-01

Full Text Available The research was aimed is to detect Insulin-like growth factor-I (IGF-I gene polymorphism and their effect on growth traits in Indonesia natives chicken. Seventy two Indonesian native chicken are going to be used in this research. The polymorphism of IGF-I gene was detected by PCR-RFLP/Pst-I. Four growth traits (body weight at 1, 2, 3, and 4 months were recorded for analyzing the association between IGF-I gene polymorphism and growth performance.The results showed that allele A (621 bp and allele B (364 and 257 bp were found in this research. It was found that Indonesian native chicken carried high frequencies of allele A (0.82, and frequencies of IGF-I genotypes (AA, AB, BB were 68.0, 27.8, and 4,2%, respectively. When compared to the IGF-I genotypes, the BB genotype had the highest body weight at 1, 2, 3, and 4 month (P<0.05. The results showed that the B allele was positive of associated to a higher growth rate. Therefore, these results suggest that there is a possibility of IGF-I genotypes acting as a molecular marker for growth rate of Indonesia native.

Single nucleotide polymorphism in the STAT5b gene is associated with body weight and reproductive traits of the Jinghai Yellow chicken.

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Zhao, X H; Wang, J Y; Zhang, G X; Wei, Y; Gu, Y P; Yu, Y B

2012-04-01

In our research, signal transducer and activator of transcription 5b (STAT5b) gene was studied as candidate gene associated with body weight and reproductive traits of Jinghai Yellow chicken. Single nucleotide polymorphisms (SNPs) of STAT5b gene were examined in both Jinghai Yellow chicken and three reference chicken populations including the Bian, Youxi and Arbor Acre chickens. Two SNPs (C-1591T and G-250A) were detected in the 5' flanking region of STAT5b gene. Association indicated that the C-1591T mutation is significantly associated with age at fist egg, The G-250A mutation is significantly related with hatch weight and body weight at 300 days. Additionally four STAT5b haplotypes (H1, CG; H2, TG; H3, AC and H4, TA) and their frequency distributions were estimated using the phase program. Diplotype H3H4 is dominant for 8, 16 week-age-weight and body weight at first egg. Thus STAT5b gene may be served as a potential genetic marker for growth and reproduction traits evaluation of the Jinghai Yellow chicken. This study will provide valuable information for the protection and breeding of Jinghai Yellow chicken.

PDK1 and HR46 gene homologs tie social behavior to ovary signals.

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Ying Wang

Full Text Available The genetic basis of division of labor in social insects is a central question in evolutionary and behavioral biology. The honey bee is a model for studying evolutionary behavioral genetics because of its well characterized age-correlated division of labor. After an initial period of within-nest tasks, 2-3 week-old worker bees begin foraging outside the nest. Individuals often specialize by biasing their foraging efforts toward collecting pollen or nectar. Efforts to explain the origins of foraging specialization suggest that division of labor between nectar and pollen foraging specialists is influenced by genes with effects on reproductive physiology. Quantitative trait loci (QTL mapping of foraging behavior also reveals candidate genes for reproductive traits. Here, we address the linkage of reproductive anatomy to behavior, using backcross QTL analysis, behavioral and anatomical phenotyping, candidate gene expression studies, and backcross confirmation of gene-to-anatomical trait associations. Our data show for the first time that the activity of two positional candidate genes for behavior, PDK1 and HR46, have direct genetic relationships to ovary size, a central reproductive trait that correlates with the nectar and pollen foraging bias of workers. These findings implicate two genes that were not known previously to influence complex social behavior. Also, they outline how selection may have acted on gene networks that affect reproductive resource allocation and behavior to facilitate the evolution of social foraging in honey bees.

On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

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Waliszewski, P; Molski, M; Konarski, J

1998-06-01

A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self

Detecting coordinated regulation of multi-protein complexes using logic analysis of gene expression

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Yeates Todd O

2009-12-01

Full Text Available Abstract Background Many of the functional units in cells are multi-protein complexes such as RNA polymerase, the ribosome, and the proteasome. For such units to work together, one might expect a high level of regulation to enable co-appearance or repression of sets of complexes at the required time. However, this type of coordinated regulation between whole complexes is difficult to detect by existing methods for analyzing mRNA co-expression. We propose a new methodology that is able to detect such higher order relationships. Results We detect coordinated regulation of multiple protein complexes using logic analysis of gene expression data. Specifically, we identify gene triplets composed of genes whose expression profiles are found to be related by various types of logic functions. In order to focus on complexes, we associate the members of a gene triplet with the distinct protein complexes to which they belong. In this way, we identify complexes related by specific kinds of regulatory relationships. For example, we may find that the transcription of complex C is increased only if the transcription of both complex A AND complex B is repressed. We identify hundreds of examples of coordinated regulation among complexes under various stress conditions. Many of these examples involve the ribosome. Some of our examples have been previously identified in the literature, while others are novel. One notable example is the relationship between the transcription of the ribosome, RNA polymerase and mannosyltransferase II, which is involved in N-linked glycan processing in the Golgi. Conclusions The analysis proposed here focuses on relationships among triplets of genes that are not evident when genes are examined in a pairwise fashion as in typical clustering methods. By grouping gene triplets, we are able to decipher coordinated regulation among sets of three complexes. Moreover, using all triplets that involve coordinated regulation with the ribosome

A kernel regression approach to gene-gene interaction detection for case-control studies.

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Larson, Nicholas B; Schaid, Daniel J

2013-11-01

Gene-gene interactions are increasingly being addressed as a potentially important contributor to the variability of complex traits. Consequently, attentions have moved beyond single locus analysis of association to more complex genetic models. Although several single-marker approaches toward interaction analysis have been developed, such methods suffer from very high testing dimensionality and do not take advantage of existing information, notably the definition of genes as functional units. Here, we propose a comprehensive family of gene-level score tests for identifying genetic elements of disease risk, in particular pairwise gene-gene interactions. Using kernel machine methods, we devise score-based variance component tests under a generalized linear mixed model framework. We conducted simulations based upon coalescent genetic models to evaluate the performance of our approach under a variety of disease models. These simulations indicate that our methods are generally higher powered than alternative gene-level approaches and at worst competitive with exhaustive SNP-level (where SNP is single-nucleotide polymorphism) analyses. Furthermore, we observe that simulated epistatic effects resulted in significant marginal testing results for the involved genes regardless of whether or not true main effects were present. We detail the benefits of our methods and discuss potential genome-wide analysis strategies for gene-gene interaction analysis in a case-control study design. © 2013 WILEY PERIODICALS, INC.

Gene expression patterns of oxidative phosphorylation complex I subunits are organized in clusters.

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Yael Garbian

Full Text Available After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I, was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were retained in the genome of the mitochondrion, the ancient symbiote of eukaryotes. This division, in combination with the three-fold increase in subunit number from bacteria (N = approximately 14 to man (N = 45, renders the transcription regulation of OXPHOS complex I a challenge. Recently bioinformatics analysis of the promoter regions of all OXPHOS genes in mammals supported patterns of co-regulation, suggesting that natural selection favored a mechanism facilitating the transcriptional regulatory control of genes encoding subunits of these large protein complexes. Here, using real time PCR of mitochondrial (mtDNA- and nuclear DNA (nDNA-encoded transcripts in a panel of 13 different human tissues, we show that the expression pattern of OXPHOS complex I genes is regulated in several clusters. Firstly, all mtDNA-encoded complex I subunits (N = 7 share a similar expression pattern, distinct from all tested nDNA-encoded subunits (N = 10. Secondly, two sub-clusters of nDNA-encoded transcripts with significantly different expression patterns were observed. Thirdly, the expression patterns of two nDNA-encoded genes, NDUFA4 and NDUFA5, notably diverged from the rest of the nDNA-encoded subunits, suggesting a certain degree of tissue specificity. Finally, the expression pattern of the mtDNA-encoded ND4L gene diverged from the rest of the tested mtDNA-encoded transcripts that are regulated by the same promoter, consistent with post-transcriptional regulation. These findings suggest, for the first time, that the regulation of complex I subunits expression in humans is complex rather than reflecting global co-regulation.

Simulating evolution of protein complexes through gene duplication and co-option.

Science.gov (United States)

Haarsma, Loren; Nelesen, Serita; VanAndel, Ethan; Lamine, James; VandeHaar, Peter

2016-06-21

We present a model of the evolution of protein complexes with novel functions through gene duplication, mutation, and co-option. Under a wide variety of input parameters, digital organisms evolve complexes of 2-5 bound proteins which have novel functions but whose component proteins are not independently functional. Evolution of complexes with novel functions happens more quickly as gene duplication rates increase, point mutation rates increase, protein complex functional probability increases, protein complex functional strength increases, and protein family size decreases. Evolution of complexity is inhibited when the metabolic costs of making proteins exceeds the fitness gain of having functional proteins, or when point mutation rates get so large the functional proteins undergo deleterious mutations faster than new functional complexes can evolve. Copyright © 2016 Elsevier Ltd. All rights reserved.

In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

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Wargo, Andrew R.; Kurath, Gael

2011-01-01

The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

Mapping epistasis and environment × QTX interaction based on four -omics genotypes for the detected QTX loci controlling complex traits in tobacco

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Liyuan Zhou

2013-12-01

Full Text Available Using newly developed methods and software, association mapping was conducted for chromium content and total sugar in tobacco leaf, based on four -omics datasets. Our objective was to collect data on genotype and phenotype for 60 leaf samples at four developmental stages, from three plant architectural positions and for three cultivars that were grown in two locations. Association mapping was conducted to detect genetic variants at quantitative trait SNP (QTS loci, quantitative trait transcript (QTT differences, quantitative trait protein (QTP variability, and quantitative trait metabolite (QTM changes, which can be summarized as QTX locus variation. The total heritabilities of the four -omics loci for both traits tested were 23.60% for epistasis and 15.26% for treatment interaction. Epistasis and environment × treatment interaction had important impacts on complex traits at all -omics levels. For decreasing chromium content and increasing total sugar in tobacco leaf, six methylated loci can be directly used for marker-assisted selection, and expression of ten QTTs, seven QTPs and six QTMs can be modified by selection or cultivation.

Genetic control of functional traits related to photosynthesis and water use efficiency in Pinus pinaster Ait. drought response: integration of genome annotation, allele association and QTL detection for candidate gene identification.

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de Miguel, Marina; Cabezas, José-Antonio; de María, Nuria; Sánchez-Gómez, David; Guevara, María-Ángeles; Vélez, María-Dolores; Sáez-Laguna, Enrique; Díaz, Luis-Manuel; Mancha, Jose-Antonio; Barbero, María-Carmen; Collada, Carmen; Díaz-Sala, Carmen; Aranda, Ismael; Cervera, María-Teresa

2014-06-12

Understanding molecular mechanisms that control photosynthesis and water use efficiency in response to drought is crucial for plant species from dry areas. This study aimed to identify QTL for these traits in a Mediterranean conifer and tested their stability under drought. High density linkage maps for Pinus pinaster were used in the detection of QTL for photosynthesis and water use efficiency at three water irrigation regimes. A total of 28 significant and 27 suggestive QTL were found. QTL detected for photochemical traits accounted for the higher percentage of phenotypic variance. Functional annotation of genes within the QTL suggested 58 candidate genes for the analyzed traits. Allele association analysis in selected candidate genes showed three SNPs located in a MYB transcription factor that were significantly associated with efficiency of energy capture by open PSII reaction centers and specific leaf area. The integration of QTL mapping of functional traits, genome annotation and allele association yielded several candidate genes involved with molecular control of photosynthesis and water use efficiency in response to drought in a conifer species. The results obtained highlight the importance of maintaining the integrity of the photochemical machinery in P. pinaster drought response.

Plants with useful traits and related methods

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Mackenzie, Sally Ann; De la Rosa Santamaria, Roberto

2016-10-25

The present invention provides methods for obtaining plants that exhibit useful traits by transient suppression of the MSH1 gene of the plants. Methods for identifying genetic loci that provide for useful traits in plants and plants produced with those loci are also provided. In addition, plants that exhibit the useful traits, parts of the plants including seeds, and products of the plants are provided as well as methods of using the plants.

Interaction between the RGS6 gene and psychosocial stress on obesity-related traits.

Science.gov (United States)

Kim, Hyun-Jin; Min, Jin-Young; Min, Kyoung-Bok

2017-03-31

Obesity is a major risk factor for chronic diseases and arises from the interactions between environmental factors and multiple genes. Psychosocial stress may affect the risk for obesity, modifying food intake and choice. A recent study suggested regulator of G-protein signaling 6 (RGS6) as a novel candidate gene for obesity in terms of reward-related feeding under stress. In this study, we tried to verify the unidentified connection between RGS6 and human obesity with psychosocial stress in a Korean population. A total of 1,462 adult subjects, who participated in the Korean Association Resource cohort project, were included for this analysis. Obesity-related traits including waist circumference, body mass index, and visceral adipose tissue were recorded. A total of 4 intronic SNPs for the RGS6 gene were used for this study. We found that interactions between SNP rs2239219 and psychosocial stress are significantly associated with abdominal obesity (p = 0.007). As risk allele of this SNP increased, prevalence of abdominal obesity under high-stress conditions gradually increased (p = 0.013). However, we found no SNPs-by-stress interaction effect on other adiposity phenotypes. This study suggests that RGS6 is closely linked to stress-induced abdominal obesity in Korean adults.

Discovery of Gene Sources for Economic Traits in Hanwoo by Whole-genome Resequencing

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Younhee Shin

2016-09-01

Full Text Available Hanwoo, a Korean native cattle (Bos taurus coreana, has great economic value due to high meat quality. Also, the breed has genetic variations that are associated with production traits such as health, disease resistance, reproduction, growth as well as carcass quality. In this study, next generation sequencing technologies and the availability of an appropriate reference genome were applied to discover a large amount of single nucleotide polymorphisms (SNPs in ten Hanwoo bulls. Analysis of whole-genome resequencing generated a total of 26.5 Gb data, of which 594,716,859 and 592,990,750 reads covered 98.73% and 93.79% of the bovine reference genomes of UMD 3.1 and Btau 4.6.1, respectively. In total, 2,473,884 and 2,402,997 putative SNPs were discovered, of which 1,095,922 (44.3% and 982,674 (40.9% novel SNPs were discovered against UMD3.1 and Btau 4.6.1, respectively. Among the SNPs, the 46,301 (UMD 3.1 and 28,613 SNPs (Btau 4.6.1 that were identified as Hanwoo-specific SNPs were included in the functional genes that may be involved in the mechanisms of milk production, tenderness, juiciness, marbling of Hanwoo beef and yellow hair. Most of the Hanwoo-specific SNPs were identified in the promoter region, suggesting that the SNPs influence differential expression of the regulated genes relative to the relevant traits. In particular, the non-synonymous (ns SNPs found in CORIN, which is a negative regulator of Agouti, might be a causal variant to determine yellow hair of Hanwoo. Our results will provide abundant genetic sources of variation to characterize Hanwoo genetics and for subsequent breeding.

Association of genetic variants of the incretin-related genes with quantitative traits and occurrence of type 2 diabetes in Japanese

OpenAIRE

Mayumi Enya; Yukio Horikawa; Katsumi Iizuka; Jun Takeda

2014-01-01

Background: None of the high frequency variants of the incretin-related genes has been found by genome-wide association study (GWAS) for association with occurrence of type 2 diabetes in Japanese. However, low frequency and rare and/or high frequency variants affecting glucose metabolic traits remain to be investigated. Method: We screened all exons of the incretin-related genes (GCG, GLP1R, DPP4, PCSK1, GIP, and GIPR) in 96 patients with type 2 diabetes and investigated for association of...

Major-histocompatibility-complex-associated variation in secondary sexual traits of white-tailed deer (Odocoileus virginianus): evidence for good-genes advertisement.

Science.gov (United States)

Ditchkoff, S S; Lochmiller, R L; Masters, R E; Hoofer, S R; Van Den Bussche, R A

2001-03-01

Good-genes hypotheses predict that development of secondary sexual characters can be an honest advertisement of heritable male quality. We explored this hypothesis using a cervid model (adult, male white-tailed deer, Odocoileus virginianus) to determine whether antler development could provide an honest signal of a male's genetic quality and condition to adversaries. We compared antler, morphometric, hormonal, and parasitic data collected from hunter-harvested deer to characteristics of the Mhc-DRB (Odvi), the most widely studied gene of the major histocompatibility complex (MHC) in Artiodactyla. We detected associations between genetic characteristics at Odvi-DRB and antler development and body mass, suggesting that antler development and body mass may be associated with pathogen resistance in deer and thus may be an honest signal of genetic quality. We also detected associations between Odvi-DRB characteristics and serum testosterone during the breeding season, suggesting that certain MHC characteristics may help deer cope with stresses related to breeding activity. In addition, we observed a negative relationship between degree of antler development and overall abundance of abomasal helminths. Our observations provide support for the hypothesis that antler development in white-tailed deer is an honest signal of quality.

Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age.

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Krishnan, Mohanraj; Thompson, John M D; Mitchell, Edwin A; Murphy, Rinki; McCowan, Lesley M E; Shelling, Andrew N; On Behalf Of The Children Of Scope Study Group, G

2017-07-25

Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality. Several gene variants have previously been identified that have provided novel insights into biological factors that contribute to the development of obesity. As obesity tracks through childhood into adulthood, identification of the genetic factors for obesity in early life is important. The objective of this study was to identify putative associations between genetic variants and obesity traits in children at 6 years of age. We recruited 1208 children of mothers from the New Zealand centre of the international Screening for Pregnancy Endpoints (SCOPE) study. Eighty common genetic variants associated with obesity traits were evaluated by the Sequenom assay. Body mass index standardised scores (BMI z-scores) and percentage body fat (PBF; measured by bio-impedance assay (BIA)) were used as anthropometric measures of obesity. A positive correlation was found between BMI z-scores and PBF (p obesity and obesity traits in New Zealand European children.

Interaction Effects of Season of Birth and Cytokine Genes on Schizotypal Traits in the General Population

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Margarita V. Alfimova

2017-01-01

Full Text Available Literature suggests that the effect of winter birth on vulnerability to schizophrenia might be mediated by increased expression of proinflammatory cytokines due to prenatal infection and its inadequate regulation by anti-inflammatory factors. As the response of the immune system depends on genotype, this study assessed the interaction effects of cytokine genes and season of birth (SOB on schizotypy measured with the Schizotypal Personality Questionnaire (SPQ-74. We searched for associations of IL1B rs16944, IL4 rs2243250, and IL-1RN VNTR polymorphisms, SOB, and their interactions with the SPQ-74 total score in a sample of 278 healthy individuals. A significant effect of the IL4 X SOB interaction was found, p=0.007 and η2=0.028. We confirmed this effect using an extended sample of 373 individuals. Homozygotes CC born in winter showed the highest SPQ total score and differed significantly from winter-born T allele carriers, p=0.049. This difference was demonstrated for cognitive-perceptual and disorganized but not interpersonal dimensions. The findings are consistent with the hypothesis that the cytokine genes by SOB interaction can influence variability of schizotypal traits in the general population. The IL4 T allele appeared to have a protective effect against the development of positive and disorganized schizotypal traits in winter-born individuals.

Interaction Effects of Season of Birth and Cytokine Genes on Schizotypal Traits in the General Population.

Science.gov (United States)

Alfimova, Margarita V; Korovaitseva, Galina I; Lezheiko, Tatyana V; Golimbet, Vera E

2017-01-01

Literature suggests that the effect of winter birth on vulnerability to schizophrenia might be mediated by increased expression of proinflammatory cytokines due to prenatal infection and its inadequate regulation by anti-inflammatory factors. As the response of the immune system depends on genotype, this study assessed the interaction effects of cytokine genes and season of birth (SOB) on schizotypy measured with the Schizotypal Personality Questionnaire (SPQ-74). We searched for associations of IL1B rs16944, IL4 rs2243250, and IL-1RN VNTR polymorphisms, SOB, and their interactions with the SPQ-74 total score in a sample of 278 healthy individuals. A significant effect of the IL4 X SOB interaction was found, p = 0.007 and η 2 = 0.028. We confirmed this effect using an extended sample of 373 individuals. Homozygotes CC born in winter showed the highest SPQ total score and differed significantly from winter-born T allele carriers, p = 0.049. This difference was demonstrated for cognitive-perceptual and disorganized but not interpersonal dimensions. The findings are consistent with the hypothesis that the cytokine genes by SOB interaction can influence variability of schizotypal traits in the general population. The IL4 T allele appeared to have a protective effect against the development of positive and disorganized schizotypal traits in winter-born individuals.

Ancestral genes can control the ability of horizontally acquired loci to confer new traits.

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H Deborah Chen

2011-07-01

Full Text Available Horizontally acquired genes typically function as autonomous units conferring new abilities when introduced into different species. However, we reasoned that proteins preexisting in an organism might constrain the functionality of a horizontally acquired gene product if it operates on an ancestral pathway. Here, we determine how the horizontally acquired pmrD gene product activates the ancestral PmrA/PmrB two-component system in Salmonella enterica but not in the closely related bacterium Escherichia coli. The Salmonella PmrD protein binds to the phosphorylated PmrA protein (PmrA-P, protecting it from dephosphorylation by the PmrB protein. This results in transcription of PmrA-dependent genes, including those conferring polymyxin B resistance. We now report that the E. coli PmrD protein can activate the PmrA/PmrB system in Salmonella even though it cannot do it in E. coli, suggesting that these two species differ in an additional component controlling PmrA-P levels. We establish that the E. coli PmrB displays higher phosphatase activity towards PmrA-P than the Salmonella PmrB, and we identified a PmrB subdomain responsible for this property. Replacement of the E. coli pmrB gene with the Salmonella homolog was sufficient to render E. coli resistant to polymyxin B under PmrD-inducing conditions. Our findings provide a singular example whereby quantitative differences in the biochemical activities of orthologous ancestral proteins dictate the ability of a horizontally acquired gene product to confer species-specific traits. And they suggest that horizontally acquired genes can potentiate selection at ancestral loci.

A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL

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Bidanel Jean P

2009-12-01

Full Text Available Abstract Background Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA and total number of piglets born (TNB in a three generation Iberian by Meishan F2 intercross. Results The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P SSC17 (P P P P P Conclusions The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17, dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.

Identification of loci governing eight agronomic traits using a GBS-GWAS approach and validation by QTL mapping in soya bean.

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Sonah, Humira; O'Donoughue, Louise; Cober, Elroy; Rajcan, Istvan; Belzile, François

2015-02-01

Soya bean is a major source of edible oil and protein for human consumption as well as animal feed. Understanding the genetic basis of different traits in soya bean will provide important insights for improving breeding strategies for this crop. A genome-wide association study (GWAS) was conducted to accelerate molecular breeding for the improvement of agronomic traits in soya bean. A genotyping-by-sequencing (GBS) approach was used to provide dense genome-wide marker coverage (>47,000 SNPs) for a panel of 304 short-season soya bean lines. A subset of 139 lines, representative of the diversity among these, was characterized phenotypically for eight traits under six environments (3 sites × 2 years). Marker coverage proved sufficient to ensure highly significant associations between the genes known to control simple traits (flower, hilum and pubescence colour) and flanking SNPs. Between one and eight genomic loci associated with more complex traits (maturity, plant height, seed weight, seed oil and protein) were also identified. Importantly, most of these GWAS loci were located within genomic regions identified by previously reported quantitative trait locus (QTL) for these traits. In some cases, the reported QTLs were also successfully validated by additional QTL mapping in a biparental population. This study demonstrates that integrating GBS and GWAS can be used as a powerful complementary approach to classical biparental mapping for dissecting complex traits in soya bean. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Adaptive traits are maintained on steep selective gradients despite gene flow and hybridization in the intertidal zone.

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Gerardo I Zardi

Full Text Available Gene flow among hybridizing species with incomplete reproductive barriers blurs species boundaries, while selection under heterogeneous local ecological conditions or along strong gradients may counteract this tendency. Congeneric, externally-fertilizing fucoid brown algae occur as distinct morphotypes along intertidal exposure gradients despite gene flow. Combining analyses of genetic and phenotypic traits, we investigate the potential for physiological resilience to emersion stressors to act as an isolating mechanism in the face of gene flow. Along vertical exposure gradients in the intertidal zone of Northern Portugal and Northwest France, the mid-low shore species Fucus vesiculosus, the upper shore species Fucus spiralis, and an intermediate distinctive morphotype of F. spiralis var. platycarpus were morphologically characterized. Two diagnostic microsatellite loci recovered 3 genetic clusters consistent with prior morphological assignment. Phylogenetic analysis based on single nucleotide polymorphisms in 14 protein coding regions unambiguously resolved 3 clades; sympatric F. vesiculosus, F. spiralis, and the allopatric (in southern Iberia population of F. spiralis var. platycarpus. In contrast, the sympatric F. spiralis var. platycarpus (from Northern Portugal was distributed across the 3 clades, strongly suggesting hybridization/introgression with both other entities. Common garden experiments showed that physiological resilience following exposure to desiccation/heat stress differed significantly between the 3 sympatric genetic taxa; consistent with their respective vertical distribution on steep environmental clines in exposure time. Phylogenetic analyses indicate that F. spiralis var. platycarpus is a distinct entity in allopatry, but that extensive gene flow occurs with both higher and lower shore species in sympatry. Experimental results suggest that strong selection on physiological traits across steep intertidal exposure gradients

Selection on a Subunit of the NURF Chromatin Remodeler Modifies Life History Traits in a Domesticated Strain of Caenorhabditis elegans.

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Edward E Large

2016-07-01

Full Text Available Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual's resources to competing life functions. Although life-history traits evolve rapidly, little is known about the genetic and cellular mechanisms that control and couple these tradeoffs. Here, we find that two laboratory-adapted strains of C. elegans descended from a single common ancestor that lived in the 1950s have differences in a number of life-history traits, including reproductive timing, lifespan, dauer formation, growth rate, and offspring number. We identified a quantitative trait locus (QTL of large effect that controls 24%-75% of the total trait variance in reproductive timing at various timepoints. Using CRISPR/Cas9-induced genome editing, we show this QTL is due in part to a 60 bp deletion in the 3' end of the nurf-1 gene, which is orthologous to the human gene encoding the BPTF component of the NURF chromatin remodeling complex. Besides reproduction, nurf-1 also regulates growth rate, lifespan, and dauer formation. The fitness consequences of this deletion are environment specific-it increases fitness in the growth conditions where it was fixed but decreases fitness in alternative laboratory growth conditions. We propose that chromatin remodeling, acting through nurf-1, is a pleiotropic regulator of life history trade-offs underlying the evolution of multiple traits across different species.

A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

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Steinberg, M H; Coleman, M B; Adams, J G; Hartmann, R C; Saba, H; Anagnou, N P

1986-02-01

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

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Loos, Maarten; Verhage, Matthijs; Spijker, Sabine; Smit, August B

2017-01-01

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

'Omics' approaches in tomato aimed at identifying candidate genes ...

African Journals Online (AJOL)

adriana

2013-12-04

Dec 4, 2013 ... approaches could be combined in order to identify candidate genes for the genetic control of ascorbic ..... applied to other traits under the complex control of many ... Engineering increased vitamin C levels in ... Chem. Biol. 13:532–538. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC (2002). A.

Mapping genomic features to functional traits through microbial whole genome sequences.

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Zhang, Wei; Zeng, Erliang; Liu, Dan; Jones, Stuart E; Emrich, Scott

2014-01-01

Recently, the utility of trait-based approaches for microbial communities has been identified. Increasing availability of whole genome sequences provide the opportunity to explore the genetic foundations of a variety of functional traits. We proposed a machine learning framework to quantitatively link the genomic features with functional traits. Genes from bacteria genomes belonging to different functional traits were grouped to Cluster of Orthologs (COGs), and were used as features. Then, TF-IDF technique from the text mining domain was applied to transform the data to accommodate the abundance and importance of each COG. After TF-IDF processing, COGs were ranked using feature selection methods to identify their relevance to the functional trait of interest. Extensive experimental results demonstrated that functional trait related genes can be detected using our method. Further, the method has the potential to provide novel biological insights.

Differential expression of six genes and correlation with fatness traits in a unique broiler population

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Pengcheng Jin

2017-05-01

Full Text Available Previous results from genome wide association studies (GWASs in chickens divergently selected for abdominal fat content of Northeast Agricultural University (NEAUHLF showed that many single nucleotide polymorphism (SNP variants were associated with abdominal fat content. Of them, six top significant SNPs at the genome level were located within SRD5A3, SGCZ, DLC1, GBE1, GALNT9 and DNAJB6 genes. Here, expression levels of these six candidate genes were investigated in abdominal fat and liver tissue between fat and lean broilers from the 14th generation population of NEAUHLF. The results showed that expression levels of SRD5A3, SGCZ and DNAJB6 in the abdominal fat and SRD5A3, DLC1, GALNT9, DNAJB6 and GBE1 in the liver tissue differed significantly between the fat and lean birds, and were correlated with abdominal fat traits. The findings will provide important references for further function investigation of the six candidate genes involved in abdominal fat deposition in chickens.

Genetic polymorphisms within exon 3 of heat shock protein 90AA1 gene and its association with heat tolerance traits in Sahiwal cows

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Kumar, Rakesh; Gupta, I. D.; Verma, Archana; Verma, Nishant; Vineeth, M. R.

2015-01-01

Aim: The present study was undertaken to identify novel single nucleotide polymorphism (SNP) in Exon 3 of HSP90AA1 gene and to analyze their association with respiration rate (RR) and rectal temperature (RT) in Sahiwal cows. Materials and Methods: The present study was carried out in Sahiwal cows (n=100) with the objectives to identify novel SNP in exon 3 of HSP90AA1 gene and to explore the association with heat tolerance traits. CLUSTAL-W multiple sequence analysis was used to identify novel SNPs in exon 3 of HSP90AA1 gene in Sahiwal cows. Gene and genotype frequencies of different genotypes were estimated by standard procedure POPGENE version 1.32 (University of Alberta, Canada). The significant effect of SNP variants on physiological parameters, e.g. RR and RT were analyzed using the General Linear model procedure of SAS Version 9.2. Results: The polymerase chain reaction product with the amplicon size of 450 bp was successfully amplified, covering exon 3 region of HSP90AA1 gene in Sahiwal cows. On the basis of comparative sequence analysis of Sahiwal samples (n=100), transitional mutations were detected at locus A1209G as compared to Bos taurus (NCBI GenBank AC_000178.1). After chromatogram analysis, three genotypes AA, AG, and GG with respective frequencies of 0.23, 0.50, and 0.27 ascertained. RR and RT were recorded once during probable extreme hours in winter, spring, and summer seasons. It was revealed that significant difference (pheat tolerance trait was found in Sahiwal cattle. The homozygotic animals with AA genotype had lower heat tolerance coefficient (HTC) (1.78±0.04a), as compared to both AG and GG genotypes (1.85±0.03b and 1.91±0.02c), respectively. The gene and genotype frequencies for the locus A1209G were ascertained. Conclusions: Novel SNP was found at the A1209G position showed all possible three genotypes (homozygous and heterozygous). Temperature humidity index has a highly significant association with RR, RT, and HTC in all the seasons

β-Cyclodextrin-curcumin complex inhibit telomerase gene ...

African Journals Online (AJOL)

Yomi

2011-12-21

Dec 21, 2011 ... have various applications in cancer therapy. But, its low water solubility and bioavailability is possible for poor drug delivery of curcumin. In this study, we prepared β-cyclodextrin-curcumin complex to determine the inhibitory effect of this drug on telomerase gene expression. Curcumin was encapsulated.

The genetic basis of traits regulating sperm competition and polyandry: can selection favour the evolution of good- and sexy-sperm?

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Evans, Jonathan P; Simmons, Leigh W

2008-09-01

The good-sperm and sexy-sperm (GS-SS) hypotheses predict that female multiple mating (polyandry) can fuel sexual selection for heritable male traits that promote success in sperm competition. A major prediction generated by these models, therefore, is that polyandry will benefit females indirectly via their sons' enhanced fertilization success. Furthermore, like classic 'good genes' and 'sexy son' models for the evolution of female preferences, GS-SS processes predict a genetic correlation between genes for female mating frequency (analogous to the female preference) and those for traits influencing fertilization success (the sexually selected traits). We examine the premise for these predictions by exploring the genetic basis of traits thought to influence fertilization success and female mating frequency. We also highlight recent debates that stress the possible genetic constraints to evolution of traits influencing fertilization success via GS-SS processes, including sex-linked inheritance, nonadditive effects, interacting parental genotypes, and trade-offs between integrated ejaculate components. Despite these possible constraints, the available data suggest that male traits involved in sperm competition typically exhibit substantial additive genetic variance and rapid evolutionary responses to selection. Nevertheless, the limited data on the genetic variation in female mating frequency implicate strong genetic maternal effects, including X-linkage, which is inconsistent with GS-SS processes. Although the relative paucity of studies on the genetic basis of polyandry does not allow us to draw firm conclusions about the evolutionary origins of this trait, the emerging pattern of sex linkage in genes for polyandry is more consistent with an evolutionary history of antagonistic selection over mating frequency. We advocate further development of GS-SS theory to take account of the complex evolutionary dynamics imposed by sexual conflict over mating frequency.

Quantitative trait loci (QTL mapping for growth traits on bovine chromosome 14

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Marcelo Miyata

2007-03-01

Full Text Available Quantitative trait loci (QTL mapping in livestock allows the identification of genes that determine the genetic variation affecting traits of economic interest. We analyzed the birth weight and weight at 60 days QTL segregating on bovine chromosome BTA14 in a F2 resource population using genotypes produced from seven microsatellite markers. Phenotypes were derived from 346 F2 progeny produced from crossing Bos indicus Gyr x Holstein Bos taurus F1 parents. Interval analysis to detect QTL for birth weight revealed the presence of a QTL (p < 0.05 at 1 centimorgan (cM from the centromere with an additive effect of 1.210 ± 0.438 kg. Interval analysis for weight at 60 days revealed the presence of a QTL (p < 0.05 at 0 cM from the centromere with an additive effect of 2.122 ± 0.735 kg. The region to which the QTL were assigned is described in the literature as responsible for some growth traits, milk yield, milk composition, fat deposition and has also been related to reproductive traits such as daughter pregnancy rate and ovulation rate. The effects of the QTL described on other traits were not investigated.

Using genetic markers to orient the edges in quantitative trait networks: the NEO software.

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Aten, Jason E; Fuller, Tova F; Lusis, Aldons J; Horvath, Steve

2008-04-15

Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene expression traits and/or clinical traits can be used to define undirected trait networks. Several authors have argued that genetic markers (e.g expression quantitative trait loci, eQTLs) can serve as causal anchors for orienting the edges of a trait network. The availability of hundreds of thousands of genetic markers poses new challenges: how to relate (anchor) traits to multiple genetic markers, how to score the genetic evidence in favor of an edge orientation, and how to weigh the information from multiple markers. We develop and implement Network Edge Orienting (NEO) methods and software that address the challenges of inferring unconfounded and directed gene networks from microarray-derived gene expression data by integrating mRNA levels with genetic marker data and Structural Equation Model (SEM) comparisons. The NEO software implements several manual and automatic methods for incorporating genetic information to anchor traits. The networks are oriented by considering each edge separately, thus reducing error propagation. To summarize the genetic evidence in favor of a given edge orientation, we propose Local SEM-based Edge Orienting (LEO) scores that compare the fit of several competing causal graphs. SEM fitting indices allow the user to assess local and overall model fit. The NEO software allows the user to carry out a robustness analysis with regard to genetic marker selection. We demonstrate the utility of NEO by recovering known causal relationships in the sterol homeostasis pathway using liver gene expression data from an F2 mouse cross. Further, we use NEO to study the relationship between a disease gene and a biologically important gene co-expression module in liver tissue. The NEO software can be used to orient the edges of gene co-expression networks or quantitative trait

A fruit quality gene map of Prunus

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Bliss Fredrick A

2009-12-01

Full Text Available Abstract Background Prunus fruit development, growth, ripening, and senescence includes major biochemical and sensory changes in texture, color, and flavor. The genetic dissection of these complex processes has important applications in crop improvement, to facilitate maximizing and maintaining stone fruit quality from production and processing through to marketing and consumption. Here we present an integrated fruit quality gene map of Prunus containing 133 genes putatively involved in the determination of fruit texture, pigmentation, flavor, and chilling injury resistance. Results A genetic linkage map of 211 markers was constructed for an intraspecific peach (Prunus persica progeny population, Pop-DG, derived from a canning peach cultivar 'Dr. Davis' and a fresh market cultivar 'Georgia Belle'. The Pop-DG map covered 818 cM of the peach genome and included three morphological markers, 11 ripening candidate genes, 13 cold-responsive genes, 21 novel EST-SSRs from the ChillPeach database, 58 previously reported SSRs, 40 RAFs, 23 SRAPs, 14 IMAs, and 28 accessory markers from candidate gene amplification. The Pop-DG map was co-linear with the Prunus reference T × E map, with 39 SSR markers in common to align the maps. A further 158 markers were bin-mapped to the reference map: 59 ripening candidate genes, 50 cold-responsive genes, and 50 novel EST-SSRs from ChillPeach, with deduced locations in Pop-DG via comparative mapping. Several candidate genes and EST-SSRs co-located with previously reported major trait loci and quantitative trait loci for chilling injury symptoms in Pop-DG. Conclusion The candidate gene approach combined with bin-mapping and availability of a community-recognized reference genetic map provides an efficient means of locating genes of interest in a target genome. We highlight the co-localization of fruit quality candidate genes with previously reported fruit quality QTLs. The fruit quality gene map developed here is a

Segregation of genes controlling seed colour in sesame ( Sesamum ...

African Journals Online (AJOL)

In the sixth cross, involving white and black parents, an array of white, black, brownish white and brown colours were observed in the F2. The variation in gene systems controlling seed colour expression observed in this study revealed the complex nature of the expression of this trait. Results also indicated that plants with ...

Genome-wide association mapping of leaf metabolic profiles for dissecting complex traits in maize.

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Riedelsheimer, Christian; Lisec, Jan; Czedik-Eysenberg, Angelika; Sulpice, Ronan; Flis, Anna; Grieder, Christoph; Altmann, Thomas; Stitt, Mark; Willmitzer, Lothar; Melchinger, Albrecht E

2012-06-05

The diversity of metabolites found in plants is by far greater than in most other organisms. Metabolic profiling techniques, which measure many of these compounds simultaneously, enabled investigating the regulation of metabolic networks and proved to be useful for predicting important agronomic traits. However, little is known about the genetic basis of metabolites in crops such as maize. Here, a set of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for 118 biochemical compounds in the leaves of young plants, as well as for agronomic traits of mature plants in field trials. Metabolite concentrations had on average a repeatability of 0.73 and showed a correlation pattern that largely reflected their functional grouping. Genome-wide association mapping with correction for population structure and cryptic relatedness identified for 26 distinct metabolites strong associations with SNPs, explaining up to 32.0% of the observed genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite associations, each of which explained more then 15% of the genetic variance. For lignin precursors, including p-coumaric acid and caffeic acid, we found strong associations (P values to ) with a region on chromosome 9 harboring cinnamoyl-CoA reductase, a key enzyme in monolignol synthesis and a target for improving the quality of lignocellulosic biomass by genetic engineering approaches. Moreover, lignin precursors correlated significantly with lignin content, plant height, and dry matter yield, suggesting that metabolites represent promising connecting links for narrowing the genotype-phenotype gap of complex agronomic traits.

Gene set-based analysis of polymorphisms: finding pathways or biological processes associated to traits in genome-wide association studies

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Medina, Ignacio; Montaner, David; Bonifaci, Nuria; Pujana, Miguel Angel; Carbonell, José; Tarraga, Joaquin; Al-Shahrour, Fatima; Dopazo, Joaquin

2009-01-01

Genome-wide association studies have become a popular strategy to find associations of genes to traits of interest. Despite the high-resolution available today to carry out genotyping studies, the success of its application in real studies has been limited by the testing strategy used. As an alternative to brute force solutions involving the use of very large cohorts, we propose the use of the Gene Set Analysis (GSA), a different analysis strategy based on testing the association of modules of functionally related genes. We show here how the Gene Set-based Analysis of Polymorphisms (GeSBAP), which is a simple implementation of the GSA strategy for the analysis of genome-wide association studies, provides a significant increase in the power testing for this type of studies. GeSBAP is freely available at http://bioinfo.cipf.es/gesbap/ PMID:19502494

A combined coalescence gene-dropping tool for evaluating genomic selection in complex scenarios (ms2gs).

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Pérez-Enciso, M; Legarra, A

2016-04-01

We present ms2gs, a combined coalescence - gene dropping (i.e. backward-forward) simulator for complex traits. It therefore aims at combining the advantages of both approaches. It is primarily conceived for very short term, recent scenarios such as those that are of interest in animal and plant breeding. It is very flexible in terms of defining QTL architecture and SNP ascertainment bias, and it allows for easy modelling of alternative markers such as RADs. It can use real sequence or chip data or generate molecular polymorphisms via the coalescence. It can generate QTL conditional on extant molecular information, such as low-density genotyping. It models (simplistically) sequence, imputation or genotyping errors. It requires as input both genotypic data in plink or ms formats, and a pedigree that is used to perform the gene dropping. By default, it compares accuracy for BLUP, SNP ascertained data, sequence, and causal SNPs. It employs VanRaden's linear (GBLUP) and nonlinear method for incorporating molecular information. To illustrate the program, we present a small application in a half-sib population and a multiparental (MAGIC) cross. The program, manual and examples are available at https://github.com/mperezenciso/ms2gs. © 2016 Blackwell Verlag GmbH.

Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus.

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Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon; Lee, Jae-Seong

2017-03-01

To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (Pcopepods through the predicted AhR-mediated up-regulation of CYP genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-wide Association Study of Personality Traits in the Long Life Family Study

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Harold T Bae

2013-05-01

Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes

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Syahril Abdullah

2010-01-01

Full Text Available A novel cationic polymer, dextran-spermine (D-SPM, has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range.

Genetic analysis for grain quality traits in pakistani wheat varieties

International Nuclear Information System (INIS)

Minhas, N.M.; Ajmal, S.U.; Iqbal, Z.; Munir, M.

2014-01-01

A set of eight parental diallel involving seven commercial wheat cultivars and one breeding line was made to investigate the nature of gene action determining inheritance pattern of grain quality characters. Highly significant differences were observed among the genotypes for 1000 grain weight, protein content, wet gluten and lysine content. Adequacy tests were employed to estimate the fitness of data sets to additive dominance model. Both the tests i.e. analysis of uniformity of Wr, Vr and joint regression analysis validated the data of these traits for genetic analysis. Gene actions for grain quality traits were ascertained following Hayman's analysis of variance. Results of the genetic analysis revealed that both additive and dominance genetic components were involved in the manifestation of characters under study. However, additive gene effects were more pronounced in the genetic control of these traits. Non significance of b1, b2 and b3 values revealed the absence of directional dominance, symmetrical distribution of genes among the parental lines and absence of specific genes action respectively in all the traits. Maternal effects were also noted in 1000 grain weight, protein content and wet gluten percentage. It is concluded that additive effects are crucial in the expression of grain quality characters of wheat in germplasm under study and single plant selection may be recommended in segregating generations for effective improvement in these characters. (author)

The Birth of a Black Rice Gene and Its Local Spread by Introgression.

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Oikawa, Tetsuo; Maeda, Hiroaki; Oguchi, Taichi; Yamaguchi, Takuya; Tanabe, Noriko; Ebana, Kaworu; Yano, Masahiro; Ebitani, Takeshi; Izawa, Takeshi

2015-09-01

The origin and spread of novel agronomic traits during crop domestication are complex events in plant evolution. Wild rice (Oryza rufipogon) has red grains due to the accumulation of proanthocyanidins, whereas most cultivated rice (Oryza sativa) varieties have white grains induced by a defective allele in the Rc basic helix-loop-helix (bHLH) gene. Although the events surrounding the origin and spread of black rice traits remain unknown, varieties with black grains due to anthocyanin accumulation are distributed in various locations throughout Asia. Here, we show that the black grain trait originated from ectopic expression of the Kala4 bHLH gene due to rearrangement in the promoter region. Both the Rc and Kala4 genes activate upstream flavonol biosynthesis genes, such as chalcone synthase and dihydroflavonol-4-reductase, and downstream genes, such as leucoanthocyanidin reductase and leucoanthocyanidin dioxygenase, to produce the respective specific pigments. Genome analysis of 21 black rice varieties as well as red- and white-grained landraces demonstrated that black rice arose in tropical japonica and its subsequent spread to the indica subspecies can be attributed to the causal alleles of Kala4. The relatively small size of genomic fragments of tropical japonica origin in some indica varieties indicates that refined introgression must have occurred by natural crossbreeding in the course of evolution of the black trait in rice. © 2015 American Society of Plant Biologists. All rights reserved.

Evaluation of bovine chemerin (RARRES2 gene variation on beef cattle production traits

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Amanda K Lindholm-Perry

2012-03-01

Full Text Available A previous study in cattle based on >48,000 markers identified markers on chromosome 4 near the chemerin gene associated with average daily feed intake (ADFI in steers (P<0.008. Chemerin is an adipokine associated with obesity and metabolic syndrome in humans, representing a strong candidate gene potentially underlying the observed association. To evaluate whether the bovine chemerin gene is involved in feed intake, 16 markers within and around the gene were tested for association in the same resource population. Eleven were nominally significant for ADFI (P<0.05 and two were significant after Bonferroni correction. Two and five SNP in this region were nominally significant for the related traits of average daily gain (ADG and residual feed intake (RFI, respectively. All markers were evaluated for effects on meat quality and carcass phenotypes. Many of the markers associated with ADFI were associated with hot carcass weight (HCW, adjusted fat thickness (AFT, and marbling (P<0.05. Marker alleles that were associated with lower ADFI were also associated with lower HCW, AFT, and marbling. Markers associated with ADFI were genotyped in a validation population of steers representing 14 breeds to determine predictive merit across populations. No consistent relationships for ADFI were detected. To determine whether cattle feed intake or growth phenotypes might be related to chemerin transcript abundance, the expression of chemerin was evaluated in adipose of 114 heifers that were siblings of the steers in the discovery population. Relative chemerin transcript abundance was not correlated with ADFI, ADG, or RFI, but associations with body condition score and yearling weight were observed. We conclude that variation in the chemerin gene may underlie observed association in the resource population, but that additional research is required to determine if this variation is widespread among breeds and to develop robust markers with predictive merit across

Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

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Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; Walhout, Albertha J. M.

2014-01-01

SUMMARY Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here we used an interspecies systems biology approach with Caenorhabditis elegans and two if its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal’s gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development and reduces fertility, but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. PMID:24529378

Genome wide association studies for body conformation traits in the Chinese Holstein cattle population

DEFF Research Database (Denmark)

Wu, Xiaoping; Fang, Ming; Liu, Lin

2013-01-01

.Results: The Illumina BovineSNP50 BeadChip was used to identify single nucleotide polymorphisms (SNPs) that are associated with body conformation traits. A least absolute shrinkage and selection operator (LASSO) was applied to detect multiple SNPs simultaneously for 29 body conformation traits with 1,314 Chinese...... Holstein cattle and 52,166 SNPs. Totally, 59 genome-wide significant SNPs associated with 26 conformation traits were detected by genome-wide association analysis; five SNPs were within previously reported QTL regions (Animal Quantitative Trait Loci (QTL) database) and 11 were very close to the reported...... SNPs. Twenty-two SNPs were located within annotated gene regions, while the remainder were 0.6-826 kb away from known genes. Some of the genes had clear biological functions related to conformation traits. By combining information about the previously reported QTL regions and the biological functions...

GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS.

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Anselm S Hoppmann

Full Text Available Genome-wide association studies (GWAS evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses. GWAS require stringent correction for multiple testing, with genome-wide significance typically defined as association p-value <5*10-8. This study presents a new tool that uses external information about genes to prioritize SNP associations (GenToS. For a given list of candidate genes, GenToS calculates an appropriate statistical significance threshold and then searches for trait-associated variants in summary statistics from human GWAS. It thereby allows for identifying trait-associated genetic variants that do not meet genome-wide significance. The program additionally tests for enrichment of significant candidate gene associations in the human GWAS data compared to the number expected by chance. As proof of principle, this report used external information from a comprehensive resource of genetically manipulated and systematically phenotyped mice. Based on selected murine phenotypes for which human GWAS data for corresponding traits were publicly available, several candidate gene input lists were derived. Using GenToS for the investigation of candidate genes underlying murine skeletal phenotypes in data from a large human discovery GWAS meta-analysis of bone mineral density resulted in the identification of significantly associated variants in 29 genes. Index variants in 28 of these loci were subsequently replicated in an independent GWAS replication step, highlighting that they are true positive associations. One signal, COL11A1, has not been discovered through GWAS so far and represents a novel human candidate gene for altered bone mineral density. The number of observed genes that contained significant SNP associations in human GWAS based on murine candidate gene input lists was much greater than the number expected by chance across several complex human traits (enrichment p-value as

Cultural traits as units of analysis.

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O'Brien, Michael J; Lyman, R Lee; Mesoudi, Alex; VanPool, Todd L

2010-12-12

Cultural traits have long been used in anthropology as units of transmission that ostensibly reflect behavioural characteristics of the individuals or groups exhibiting the traits. After they are transmitted, cultural traits serve as units of replication in that they can be modified as part of an individual's cultural repertoire through processes such as recombination, loss or partial alteration within an individual's mind. Cultural traits are analogous to genes in that organisms replicate them, but they are also replicators in their own right. No one has ever seen a unit of transmission, either behavioural or genetic, although we can observe the effects of transmission. Fortunately, such units are manifest in artefacts, features and other components of the archaeological record, and they serve as proxies for studying the transmission (and modification) of cultural traits, provided there is analytical clarity over how to define and measure the units that underlie this inheritance process.

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs

DEFF Research Database (Denmark)

Drag, Markus; Hansen, Mathias B.; Kadarmideen, Haja N.

2018-01-01

Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed...... to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at similar to 100 kg. Gene...... and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits...

Quantitative trait loci and metabolic pathways

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McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

1998-01-01

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

Complexity and Entropy Analysis of DNMT1 Gene

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Background: The application of complexity information on DNA sequence and protein in biological processes are well established in this study. Available sequences for DNMT1 gene, which is a maintenance methyltransferase is responsible for copying DNA methylation patterns to the daughter strands durin...

PLEIOTROPIC EFFECT OF Rht3 DWARFING GENE ON SOME TRAITS OF WHEAT (Tr. aestivum L. em Thell

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M. Jošt

2001-06-01

Full Text Available True-isogenic lines, differing only in the semi-dominant Rht3 dwarfing gene, were developed from the cross 'Tom Thumb x Bankuty 1201' during 17 years of continuous selection on heterozygous semi-dwarf plant. The effect of double (Rht3 Rht3 = full-dwarf, single (Rht3 rht3 =semi-dwarf, or no dwarfing gene (rht3 rht3 = tall dosage on some plant, seed, and flour quality traits were observed in the isogenic lines during two years field experiment, planted by 'honey-comb design' at Kri`evci, Croatia. Significant main effect of Rht3 gene was in shortening of plant height by 54% and 28% in double and single gene dosage respectively. Full-dwarf genotype (Rht3 Rht3 had by 12% more heads/plant, but the other yield components as number of grains/head, and grain weight/head were lower by 25 and 28% respectively, resulting in significantly lower grain yield/plant (-27%. However, this also could be a secondary side effect of prolonged vegetation influenced by doubled Rht3 gene. There was no significant effect on flour protein content. Double gene effect was strong and significant for maximum dough viscosity measured by amylograph in BU (101%. In our environment full dwarf (Rht3 Rht3 has no agronomic value, but single gene dosage could be of commercial interest in hybrid wheat breeding.

Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster

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Kim Man-Sun

2012-05-01

Full Text Available Abstract Background Network motifs provided a “conceptual tool” for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a “spatiotemporal network motif,” a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts. Results On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns. Conclusions Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.

Induced mutations for quantitative traits in rice

International Nuclear Information System (INIS)

Chakrabarti, B.N.

1974-01-01

The characteristics and frequency of micro-mutations induced in quantitative traits by radiation treatment and the extent of heterozygotic effects of different recessive chlorophyll-mutant-genes on quantitative trait has been presented. Mutagenic treatments increased the variance for quantitative traits in all cases although the magnitude of increase varied depending on the treatment and the selection procedure adopted. The overall superiority of the chlorophyll-mutant heterozygotes over the corresponding wild homozygotes, as noted in consecutive two seasons, was not observed when these were grown at a high level of nitrogen fertiliser. (author)

Quantitative trait loci analysis of swine meat quality traits

DEFF Research Database (Denmark)

Li, H D; Lund, M S; Christensen, O F

2010-01-01

loss, and the Minolta color measurements L*, a*, and b* representing meat lightness, redness, and yellowness, respectively. The families consist of 3,883 progenies of 12 Duroc boars that were evaluated to identify the QTL. The linkage map consists of 462 SNP markers on 18 porcine autosomes...... were estimated from a posterior distribution of the QTL position. In total, 31 QTL for the 6 meat quality traits were found to be significant at the 5% chromosome-wide level, among which 11 QTL were significant at the 5% genome-wide level and 5 of these were significant at the 0.1% genome-wide level...... will be helpful for fine mapping and identifying genes affecting meat quality traits, and tightly linked markers may be incorporated into marker-assisted selection programs...

Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

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Meier, Daniel; Schindler, Detlev

2011-01-01

The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

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Daniel Meier

Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

Novel genetic markers of the carbonic anhydrase II gene associated with egg production and reproduction traits in Tsaiya ducks.

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Chang, M-T; Cheng, Y-S; Huang, M-C

2013-02-01

In our previous cDNA microarray study, we found that the carbonic anhydrase II (CA2) gene is one of the differentially expressed transcripts in the duck isthmus epithelium during egg formation period. The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in the CA2 gene of Tsaiya ducks. The relationship of SNP genotype with egg production and reproduction traits was also investigated. A total of 317 ducks from two lines, a control line with no selection and a selected line, were employed for testing. Three SNPs (C37T, A62G and A65G) in the 3'-untranslated region of the CA2 gene were found. SNP-trait association analysis showed that SNP C37T and A62G were associated with duck egg weight besides fertility. The ducks with the CT and AG genotypes had a 1.46 and 1.62 g/egg lower egg weight as compared with ducks with the CC and AA genotypes, respectively (p ducks with CT and AG genotypes had 5.20% and 4.22% higher fertility than those with CC and AA genotypes, respectively (p duck fertility, and the diplotype H1H4 was dominant for duck fertility. These findings might provide the basis for balanced selection and may be used in marker-assisted selection to improve egg weight and fertility simultaneously in the Tsaiya ducks. © 2012 Blackwell Verlag GmbH.

Medea genes, handedness and other traits

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Hatfield, Jeffrey

2015-01-01

Medea factors or genes are maternal-effects mechanisms, found in many species, in which the mother's body selectively kills embryos of a certain genotype.Humans have a similar genetic mechanism, the gene RHD which produces Rh-factor involved in blood type.Recently I proposed that RHD acts as a maternal-effects gene that determines handedness (i.e., right handed or non-right handed) in individuals of our species. Here, I argue that RHD functions as a Medea gene as well.The handedness gene (and also RHD itself in some cases) has been implicated in autism spectrum disorders (ASD), bipolar disorder, cerebral laterality (i.e., right-brained or left-brained speech laterality), hair-whorl rotation, schizophrenia, sexual orientation, and speech dyslexia.Identifying the gene or genes that determine handedness or cerebral laterality may help uncover the mechanisms underlying these behavioral phenotypes in our species.A relatively simple test of the handedness hypothesis has been proposed:In a sample of humans for whom handedness has been evaluated, we would need to genotype for RHD by determining whether Rh+ individuals have one or two copies of the dominant allele. If RHD and perhaps also an interaction with RHCE are involved in sexual orientation, it explains how selection could favor a gene or genes which cause some people to become non-heterosexual.The literature on Medea genes provides the explanation:A Medea allele must increase in frequency, sometimes to fixation (i.e., 100% frequency) even if it reduces fecundity (e.g., birth rate).In addition, treatment for RHD maternal-fetal genotype incompatibility, which allows more fetuses to survive to term now, may be one explanation for why ASD appears to be increasing in frequency in some populations, if RHD is indeed the handedness gene, although many other mechanisms have also been suggested. One wonders if bipolar disorder and the other alternative phenotypes are also increasing in frequency.

The power of gene-based rare variant methods to detect disease-associated variation and test hypotheses about complex disease.

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Loukas Moutsianas

2015-04-01

Full Text Available Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases. Success in this endeavor, however, requires investigators to test a diverse array of genetic hypotheses which differ in the number, frequency and effect sizes of underlying causal variants. In this study, we evaluated the power of gene-based association methods to interrogate such hypotheses, and examined the implications for study design. We developed a flexible simulation approach, using 1000 Genomes data, to (a generate sequence variation at human genes in up to 10K case-control samples, and (b quantify the statistical power of a panel of widely used gene-based association tests under a variety of allelic architectures, locus effect sizes, and significance thresholds. For loci explaining ~1% of phenotypic variance underlying a common dichotomous trait, we find that all methods have low absolute power to achieve exome-wide significance (~5-20% power at α = 2.5 × 10(-6 in 3K individuals; even in 10K samples, power is modest (~60%. The combined application of multiple methods increases sensitivity, but does so at the expense of a higher false positive rate. MiST, SKAT-O, and KBAC have the highest individual mean power across simulated datasets, but we observe wide architecture-dependent variability in the individual loci detected by each test, suggesting that inferences about disease architecture from analysis of sequencing studies can differ depending on which methods are used. Our results imply that tens of thousands of individuals, extensive functional annotation, or highly targeted hypothesis testing will be required to confidently detect or exclude rare variant signals at complex disease loci.

Using the candidate gene approach for detecting genes underlying seed oil concentration and yield in soybean.

Science.gov (United States)

Eskandari, Mehrzad; Cober, Elroy R; Rajcan, Istvan

2013-07-01

Increasing the oil concentration in soybean seeds has been given more attention in recent years because of demand for both edible oil and biodiesel production. Oil concentration in soybean is a complex quantitative trait regulated by many genes as well as environmental conditions. To identify genes governing seed oil concentration in soybean, 16 putative candidate genes of three important gene families (GPAT: acyl-CoA:sn-glycerol-3-phosphate acyltransferase, DGAT: acyl-CoA:diacylglycerol acyltransferase, and PDAT: phospholipid:diacylglycerol acyltransferase) involved in triacylglycerol (TAG) biosynthesis pathways were selected and their sequences retrieved from the soybean database ( http://www.phytozome.net/soybean ). Three sequence mutations were discovered in either coding or noncoding regions of three DGAT soybean isoforms when comparing the parents of a 203 recombinant inbreed line (RIL) population; OAC Wallace and OAC Glencoe. The RIL population was used to study the effects of these mutations on seed oil concentration and other important agronomic and seed composition traits, including seed yield and protein concentration across three field locations in Ontario, Canada, in 2009 and 2010. An insertion/deletion (indel) mutation in the GmDGAT2B gene in OAC Wallace was significantly associated with reduced seed oil concentration across three environments and reduced seed yield at Woodstock in 2010. A mutation in the 3' untranslated (3'UTR) region of GmDGAT2C was associated with seed yield at Woodstock in 2009. A mutation in the intronic region of GmDGAR1B was associated with seed yield and protein concentration at Ottawa in 2010. The genes identified in this study had minor effects on either seed yield or oil concentration, which was in agreement with the quantitative nature of the traits. However, the novel gene-specific markers designed in the present study can be used in soybean breeding for marker-assisted selection aimed at increasing seed yield and oil

Construction of chromosome segment substitution lines enables QTL mapping for flowering and morphological traits in Brassica rapa

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Xiaonan eLi

2015-06-01

Full Text Available Chromosome segment substitution lines (CSSLs represent a powerful method for precise quantitative trait loci (QTL detection of complex agronomical traits in plants. In this study, we used a marker-assisted backcrossing strategy to develop a population consisting of 63 CSSLs, derived from backcrossing of the F1 generated from a cross between two Brassica rapa subspecies: ‘Chiifu’ (ssp. pekinensis, the Brassica A genome-represented line used as the donor, and ‘49caixin’ (ssp. parachinensis, a non-heading cultivar used as the recipient. The 63 CSSLs covered 87.95% of the B. rapa genome. Among them, 39 lines carried a single segment; 15 lines, two segments; and nine lines, three or more segments of the donor parent chromosomes. To verify the potential advantage of these CSSL lines, we used them to locate QTL for six morphology-related traits. A total of 58 QTL were located on eight chromosomes for all six traits: 17 for flowering time, 14 each for bolting time and plant height, 6 for plant diameter, 2 for leaf width, and 5 for flowering stalk diameter. Co-localized QTL were mainly distributed on eight genomic regions in A01, A02, A05, A06, A08, A09, and A10, present in the corresponding CSSLs. Moreover, new chromosomal fragments that harbored QTL were identified using the findings of previous studies. The CSSL population constructed in our study paves the way for fine mapping and cloning of candidate genes involved in late bolting, flowering, and plant architecture-related traits in B. rapa. Furthermore, it has great potential for future marker-aided gene/QTL pyramiding of other interesting traits in B. rapa breeding.

Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor

DEFF Research Database (Denmark)

de los Campos, Gustavo; Vazquez, Ana I; Fernando, Rohan

2013-01-01

Despite important advances from Genome Wide Association Studies (GWAS), for most complex human traits and diseases, a sizable proportion of genetic variance remains unexplained and prediction accuracy (PA) is usually low. Evidence suggests that PA can be improved using Whole-Genome Regression (WGR......) models where phenotypes are regressed on hundreds of thousands of variants simultaneously. The Genomic Best Linear Unbiased Prediction G-BLUP, a ridge-regression type method) is a commonly used WGR method and has shown good predictive performance when applied to plant and animal breeding populations....... However, breeding and human populations differ greatly in a number of factors that can affect the predictive performance of G-BLUP. Using theory, simulations, and real data analysis, we study the erformance of G-BLUP when applied to data from related and unrelated human subjects. Under perfect linkage...

Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

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Vijee Mohan

Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

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Jingjing Liang

2017-05-01

Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

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Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

2017-11-01

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The association between glutamine repeats in the androgen receptor gene and personality traits in dromedary camel (Camelus dromedarius).

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Ramadan, Sherif; Nowier, Amira M; Hori, Yusuke; Inoue-Murayama, Miho

2018-01-01

Temperament traits such as fearfulness are important as they define an animal's responses to its environment and handling. The increasing automation of daily tasks and growing population limits contact between camels and humans. Such limitations contribute to fear of humans and changes in physical environment. Monoamine oxidase A (MAOA) and androgen receptor (AR) genes are important candidates associated with mammal personality. In our analysis, MAOA exon 15 showed no polymorphism but a novel polymorphism was seen in the camel AR exon 1; 16, 17, 18, and 19 glutamine repeats were detected. We genotyped 138 camels belonging to four Egyptian breeds: Maghrabi (n = 90), Sudani (n = 15), Somali (n = 23), and Baladi (n = 10) for AR. Out of the 90 genotyped Maghrabi camels, we evaluated responses of 33 and 32 mature females to a novel object and exposure to an unfamiliar person, respectively. AR gene showed a significant association based on the principal component (PC) score, which indicated the fear of human touch, and the PC score indicates fear during interaction with novel objects. Individuals carrying a shorter genotype in homozygote (S/S) were found to be more fearful. Furthermore, we found that Sudani and Somali breeds had a higher frequency of shorter genotype (S/S), which was associated with increased fearfulness. These findings reflect the behavioral tendency and consequently, affect the use of this breed. This is the first report showing the role of AR glutamine repeats influencing a behavioral trait in dromedary camels and leading to inter-breed differences. Fear-related traits reported here are important because camels cope with various types of stresses and fear, resulting from the demands of intensive production systems and racing events. However, further studies, employing functional genomics and linkage analysis are necessary for confirming the relationship between fearfulness and genetic variation.

The association between glutamine repeats in the androgen receptor gene and personality traits in dromedary camel (Camelus dromedarius.

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Sherif Ramadan

Full Text Available Temperament traits such as fearfulness are important as they define an animal's responses to its environment and handling. The increasing automation of daily tasks and growing population limits contact between camels and humans. Such limitations contribute to fear of humans and changes in physical environment. Monoamine oxidase A (MAOA and androgen receptor (AR genes are important candidates associated with mammal personality. In our analysis, MAOA exon 15 showed no polymorphism but a novel polymorphism was seen in the camel AR exon 1; 16, 17, 18, and 19 glutamine repeats were detected. We genotyped 138 camels belonging to four Egyptian breeds: Maghrabi (n = 90, Sudani (n = 15, Somali (n = 23, and Baladi (n = 10 for AR. Out of the 90 genotyped Maghrabi camels, we evaluated responses of 33 and 32 mature females to a novel object and exposure to an unfamiliar person, respectively. AR gene showed a significant association based on the principal component (PC score, which indicated the fear of human touch, and the PC score indicates fear during interaction with novel objects. Individuals carrying a shorter genotype in homozygote (S/S were found to be more fearful. Furthermore, we found that Sudani and Somali breeds had a higher frequency of shorter genotype (S/S, which was associated with increased fearfulness. These findings reflect the behavioral tendency and consequently, affect the use of this breed. This is the first report showing the role of AR glutamine repeats influencing a behavioral trait in dromedary camels and leading to inter-breed differences. Fear-related traits reported here are important because camels cope with various types of stresses and fear, resulting from the demands of intensive production systems and racing events. However, further studies, employing functional genomics and linkage analysis are necessary for confirming the relationship between fearfulness and genetic variation.

Social traits, social networks and evolutionary biology.

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Fisher, D N; McAdam, A G

2017-12-01

The social environment is both an important agent of selection for most organisms, and an emergent property of their interactions. As an aggregation of interactions among members of a population, the social environment is a product of many sets of relationships and so can be represented as a network or matrix. Social network analysis in animals has focused on why these networks possess the structure they do, and whether individuals' network traits, representing some aspect of their social phenotype, relate to their fitness. Meanwhile, quantitative geneticists have demonstrated that traits expressed in a social context can depend on the phenotypes and genotypes of interacting partners, leading to influences of the social environment on the traits and fitness of individuals and the evolutionary trajectories of populations. Therefore, both fields are investigating similar topics, yet have arrived at these points relatively independently. We review how these approaches are diverged, and yet how they retain clear parallelism and so strong potential for complementarity. This demonstrates that, despite separate bodies of theory, advances in one might inform the other. Techniques in network analysis for quantifying social phenotypes, and for identifying community structure, should be useful for those studying the relationship between individual behaviour and group-level phenotypes. Entering social association matrices into quantitative genetic models may also reduce bias in heritability estimates, and allow the estimation of the influence of social connectedness on trait expression. Current methods for measuring natural selection in a social context explicitly account for the fact that a trait is not necessarily the property of a single individual, something the network approaches have not yet considered when relating network metrics to individual fitness. Harnessing evolutionary models that consider traits affected by genes in other individuals (i.e. indirect genetic

Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.

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Watson, Emma; MacNeil, Lesley T; Ritter, Ashlyn D; Yilmaz, L Safak; Rosebrock, Adam P; Caudy, Amy A; Walhout, Albertha J M

2014-02-13

Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. Copyright © 2014 Elsevier Inc. All rights reserved.

Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle.

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Jiang, Jicai; Shen, Botong; O'Connell, Jeffrey R; VanRaden, Paul M; Cole, John B; Ma, Li

2017-05-30

Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and whether QTL acting in a non-additive manner can be detected in genetic association studies remain controversial. To empirically answer these questions, we analyzed a large cattle dataset that consisted of 42,701 genotyped Holstein cows with genotyped parents and phenotypic records for eight production and reproduction traits. SNP genotypes were phased in pedigree to determine the parent-of-origin of alleles, and a three-component GREML was applied to obtain variance decomposition for additive, dominance, and imprinting effects. The results showed a significant non-zero contribution from dominance to production traits but not to reproduction traits. Imprinting effects significantly contributed to both production and reproduction traits. Interestingly, imprinting effects contributed more to reproduction traits than to production traits. Using GWAS and imputation-based fine-mapping analyses, we identified and validated a dominance association signal with milk yield near RUNX2, a candidate gene that has been associated with milk production in mice. When adding non-additive effects into the prediction models, however, we observed little or no increase in prediction accuracy for the eight traits analyzed. Collectively, our results suggested that non-additive effects contributed a non-negligible amount (more for reproduction traits) to the total genetic variance of complex traits in cattle, and detection of QTLs with non-additive effect is possible in GWAS using a large dataset.

The challenges of commercializing second-generation transgenic crop traits necessitate the development of international public sector research infrastructure.

Science.gov (United States)

Rothstein, Steven J; Bi, Yong-Mei; Coneva, Viktoriya; Han, Mei; Good, Allen

2014-10-01

It has been 30 years since the first transformation of a gene into a plant species, and since that time a number of biotechnology products have been developed, with the most important being insect- and herbicide-resistant crops. The development of second-generation products, including nutrient use efficiency and tolerance to important environmental stressors such as drought, has, up to this time, been less successful. This is in part due to the inherent complexities of these traits and in part due to limitations in research infrastructure necessary for public sector researchers to test their best ideas. Here we discuss lessons from previous work in the generation of the first-generation traits, as well as work from our labs and others on identifying genes for nitrogen use efficiency. We then describe some of the issues that have impeded rapid progress in this area. Finally, we propose the type of public sector organization that we feel is necessary to make advances in important second-generation traits such as nitrogen use efficiency. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A novel synonymous SNP (A47A of the TMEM95 gene is significantly associated with the reproductive traits related to testis in male piglets

Directory of Open Access Journals (Sweden)

L. Liu

2017-07-01

Full Text Available Transmembrane protein 95 (TMEM95 is located on the acrosomal membrane of the sperm head involved in the acrosome reaction; thus, it is regarded as affecting spermatogenesis and reproduction traits. The aim of this study was to explore the novel single nucleotide polymorphisms (SNPs within the pig TMEM95 gene as well as to evaluate their associations with the testicular sizes in male Landrace (LD and Large White (LW breeds. After pool sequencing and bioinformatics analysis, only one novel coding SNP was found in exon 1, namely NC_010454.3: g.341T > C, resulting in a synonymous mutation (A47A. This SNP could be genotyped using the StuI polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP assay. The minor allelic frequencies (MAFs were 0.259 and 0.480 in the LD and LW breeds. Their polymorphism information content (PIC values were 0.310 and 0.375. The LW population was at the Hardy–Weinberg equilibrium (HWE (p > 0.05, whereas the LD population was not (p < 0.05. Association analyses demonstrated that a significant relationship was found between this A47A polymorphism and testis weight at 40 days of age in the LW population (p  =  0.047, and the heterozygote individuals showed lower testis weight than those with other genotypes. Moreover, this SNP was significantly associated with three testis measurement traits at 15 days of age in the LW population (p < 0.05; the individuals with genotypes TT and TC showed consistently superior testis measurement traits than those with genotype CC. These findings demonstrate that the A47A polymorphism had a significant effect on testis measurement traits, suggesting that the TMEM95 gene could be a candidate gene associated with reproductive traits. These results could contribute to breeding and genetics programs in the pig industry via DNA marker-assisted selection (MAS.

Design of magnetic gene complexes as effective and serum resistant gene delivery systems for mesenchymal stem cells.

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Zhang, Tian-Yuan; Wu, Jia-He; Xu, Qian-Hao; Wang, Xia-Rong; Lu, Jingxiong; Hu, Ying; Jo, Jun-Ichiro; Yamamoto, Masaya; Ling, Daishun; Tabata, Yasuhiko; Gao, Jian-Qing

2017-03-30

Gene engineered mesenchymal stem cells (MSCs) have been proposed as promising tools for their various applications in biomedicine. Nevertheless, the lack of an effective and safe way to genetically modify these stem cells is still a major obstacle in the current studies. Herein, we designed novel magnetic complexes by assembling cationized pullulan derivatives with magnetic iron oxide nanoparticles for delivering target genes to MSCs. Results showed that this complexes achieved effective gene expression with the assistance of external magnetic field, and resisted the adverse effect induced by serum proteins on the gene delivery. Moreover, neither significant cytotoxicity nor the interference on the osteogenic differentiation to MSCs were observed after magnetofection. Further studies revealed that this effective and serum resistant gene transfection was partly due to the accelerated and enhanced intracellular uptake process driven by external magnetic field. To conclude, the current study presented a novel option for genetic modification of MSCs in an effective, relatively safe and serum compatible way. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic variations in insulin-like growth factor binding protein acid labile subunit gene associated with growth traits in beef cattle (Bos taurus) in China.

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Liu, Yu; Duan, Xiaoyan; Liu, Xiaolin; Guo, Jiazhong; Wang, Hongliang; Li, Zhixiong; Yang, Jing

2014-05-01

The insulin-like growth factor binding protein acid labile subunit (IGFALS) gene encodes a serum protein that binds to IGFs and regulates growth, development, and other physiological processes. We have found that sequencing of the IGFALS gene in Chinese Qinchuan beef cattle (n=300) revealed four SNP loci in exon two of the gene (g1219: T>C, g1893: T>C, g2612: G>A, and g2696: A>G). The SNP g2696: A>G resulted in a change from asparagine to aspartic acid (p. N574D) in the leucine-rich repeat region in the carboxyl-terminal domain of IGFALS. Four SNPs were in low linkage disequilibrium, and 12 different haplotypes were identified in the population. Association analysis suggested that SNP g1219: T>C had a significant association with hip width (PG displayed a significant association with stature (Pgrowth traits of bovine, and may serve as a genetic marker for selection of beef cattle for growth traits, including stature. Copyright © 2014 Elsevier B.V. All rights reserved.

A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

DEFF Research Database (Denmark)

Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

2008-01-01

to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action.

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Inês Barroso

2003-10-01

Full Text Available Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenotypes in 2,134 Caucasians in a case-control study and an independent quantitative trait (QT cohort in the United Kingdom. Polymorphisms in five of 15 genes (33% encoding molecules known to primarily influence pancreatic beta-cell function-ABCC8 (sulphonylurea receptor, KCNJ11 (KIR6.2, SLC2A2 (GLUT2, HNF4A (HNF4alpha, and INS (insulin-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. We examined 35 genes predicted to have their major influence on insulin action, and three (9%-INSR, PIK3R1, and SOS1-showed significant associations with diabetes. These results confirm the genetic complexity of Type 2 diabetes and provide evidence that common variants in genes influencing pancreatic beta-cell function may make a significant contribution to the inherited component of this disease. This study additionally demonstrates that the systematic examination of panels of biological candidate genes in large, well-characterised populations can be an effective complement to positional cloning approaches. The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to reliably identify the size of effect we now expect for complex diseases.

Non-electrostatic complexes with DNA: towards novel synthetic gene delivery systems.

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Soto, J; Bessodes, M; Pitard, B; Mailhe, P; Scherman, D; Byk, G

2000-05-01

We have developed new DNA complexing amphiphile based on Hoechst 33258 interaction with DNA grooves. The synthesis and physicochemical characterisation of lipid/DNA complexes, as compared to that of classical lipopolyamine for gene delivery, are described and discussed.

Polymorphism in promoter of SIX4 gene shows association with its transcription and body measurement traits in Qinchuan cattle.

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Wei, Dawei; Raza, Sayed Haidar Abbas; Zhang, Jiupan; Gui, Linsheng; Rahman, Siddiq Ur; Khan, Rajwali; Hosseini, Seyed Mahdi; Kaleri, Hubdar Ali; Zan, Linsen

2018-05-20

The sine oculis homeobox homolog 4 (SIX4) gene belongs to the SIX gene family, which plays a critical role in muscle regeneration and early stages of ontogeny. This study aimed to detect promoter variations of bovine SIX4 genes in Qinchuan cattle, and to evaluate the effect of transcription regulations and body measurement traits. Quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of SIX4 gene were found significantly highest in longissimus thoracis tissue and individual before attaining the stage of physiological maturity. Using sequencing technology on a total of 428 Qinchuan cattle, seven single nucleotide polymorphisms (SNPs) were identified in the promoter region of SIX4, and seven haplotypes representing 18 potential transcription factor compositions of polymorphic potential cis-acting elements. Association analysis indicated that the H 3 -H 3 diplotype performed greater withers height, chest depth, chest circumference, back fat thickness and ultrasound loin muscle area (P cattle. Copyright © 2018 Elsevier B.V. All rights reserved.

Associations of GBP2 gene copy number variations with growth traits and transcriptional expression in Chinese cattle.

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Zhang, Gui-Min; Zheng, Li; He, Hua; Song, Cheng-Chuang; Zhang, Zi-Jing; Cao, Xiu-Kai; Lei, Chu-Zhao; Lan, Xian-Yong; Qi, Xing-Lei; Chen, Hong; Huang, Yong-Zhen

2018-03-20

Copy number variations (CNVs) recently have been recognized as another important genetic variability followed single nucleotide polymorphisms (SNPs). The guanylate binding protein 2 (GBP2) gene plays an important role in cell proliferation. This study was performed to determine the presence of GBP2 CNV (relative to Angus cattle) in 466 individuals representing six main cattle breeds from China, identify its relationship with growth, and explore the biological effects of gene expression. There were two CNV regions in the GBP2 gene, for three types, CNV1 loss type (relative to Angus cattle) was more frequent in XN than other breeds, and CNV2 loss type (relative to Angus cattle) was more frequent in XN and CDM than other breeds. Though the GBP2 gene copy number presented no correlation with the transcriptional expression of JX (P > .05), but the transcriptional expression in heart is higher than other tissues, and the copy number in muscles and fat of JX is higher than others breeds. Statistical analysis revealed that the GBP2 gene CNV1 and CNV2 were significantly associated with growth traits (P cattle breeds, and our results suggested that the CNVs in GBP2 gene may be considered markers for the molecular breeding of Chinese beef cattle. Copyright © 2018. Published by Elsevier B.V.

Genomic prediction in contrast to a genome-wide association study in explaining heritable variation of complex growth traits in breeding populations of Eucalyptus.

Science.gov (United States)

Müller, Bárbara S F; Neves, Leandro G; de Almeida Filho, Janeo E; Resende, Márcio F R; Muñoz, Patricio R; Dos Santos, Paulo E T; Filho, Estefano Paludzyszyn; Kirst, Matias; Grattapaglia, Dario

2017-07-11

The advent of high-throughput genotyping technologies coupled to genomic prediction methods established a new paradigm to integrate genomics and breeding. We carried out whole-genome prediction and contrasted it to a genome-wide association study (GWAS) for growth traits in breeding populations of Eucalyptus benthamii (n =505) and Eucalyptus pellita (n =732). Both species are of increasing commercial interest for the development of germplasm adapted to environmental stresses. Predictive ability reached 0.16 in E. benthamii and 0.44 in E. pellita for diameter growth. Predictive abilities using either Genomic BLUP or different Bayesian methods were similar, suggesting that growth adequately fits the infinitesimal model. Genomic prediction models using ~5000-10,000 SNPs provided predictive abilities equivalent to using all 13,787 and 19,506 SNPs genotyped in the E. benthamii and E. pellita populations, respectively. No difference was detected in predictive ability when different sets of SNPs were utilized, based on position (equidistantly genome-wide, inside genes, linkage disequilibrium pruned or on single chromosomes), as long as the total number of SNPs used was above ~5000. Predictive abilities obtained by removing relatedness between training and validation sets fell near zero for E. benthamii and were halved for E. pellita. These results corroborate the current view that relatedness is the main driver of genomic prediction, although some short-range historical linkage disequilibrium (LD) was likely captured for E. pellita. A GWAS identified only one significant association for volume growth in E. pellita, illustrating the fact that while genome-wide regression is able to account for large proportions of the heritability, very little or none of it is captured into significant associations using GWAS in breeding populations of the size evaluated in this study. This study provides further experimental data supporting positive prospects of using genome-wide data to

Mapping in an apple (Malus x domestica) F1 segregating population based on physical clustering of differentially expressed genes.

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Jensen, Philip J; Fazio, Gennaro; Altman, Naomi; Praul, Craig; McNellis, Timothy W

2014-04-04

Apple tree breeding is slow and difficult due to long generation times, self-incompatibility, and complex genetics. The identification of molecular markers linked to traits of interest is a way to expedite the breeding process. In the present study, we aimed to identify genes whose steady-state transcript abundance was associated with inheritance of specific traits segregating in an apple (Malus × domestica) rootstock F1 breeding population, including resistance to powdery mildew (Podosphaera leucotricha) disease and woolly apple aphid (Eriosoma lanigerum). Transcription profiling was performed for 48 individual F1 apple trees from a cross of two highly heterozygous parents, using RNA isolated from healthy, actively-growing shoot tips and a custom apple DNA oligonucleotide microarray representing 26,000 unique transcripts. Genome-wide expression profiles were not clear indicators of powdery mildew or woolly apple aphid resistance phenotype. However, standard differential gene expression analysis between phenotypic groups of trees revealed relatively small sets of genes with trait-associated expression levels. For example, thirty genes were identified that were differentially expressed between trees resistant and susceptible to powdery mildew. Interestingly, the genes encoding twenty-four of these transcripts were physically clustered on chromosome 12. Similarly, seven genes were identified that were differentially expressed between trees resistant and susceptible to woolly apple aphid, and the genes encoding five of these transcripts were also clustered, this time on chromosome 17. In each case, the gene clusters were in the vicinity of previously identified major quantitative trait loci for the corresponding trait. Similar results were obtained for a series of molecular traits. Several of the differentially expressed genes were used to develop DNA polymorphism markers linked to powdery mildew disease and woolly apple aphid resistance. Gene expression profiling

Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

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Colovati Mileny ES

2012-01-01

Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq.

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Wang, Jun; Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet.

Selection for components of complex characteristics - indirect selection

International Nuclear Information System (INIS)

Haensel, H.

1984-01-01

A hierarchy of complexity exists in plant characteristics. The efficiency of indirect selection for a complex characteristic by a sub-trait depends on the heritability of the complex characteristic (hsub(c)), the heritability of the sub-trait (hsub(s)), and the genotypic correlation between sub-trait and complex characteristic (rsub(s.c)). In 1961 hsub(s)Xrsub(s.c)>hsub(c) was postulated, when indirect selection becomes more efficient than direct selection. Numerical examples for this relationship are given and a table for indirect selection for yield in wheat is elaborated. Efficiency ranking of sub-traits in indirect selection may change with climate, conditions of cultivation, the level of other sub-traits, the level of the complex characteristic already reached by breeding, and the breeding material. An example shows that regression analysis for different sub-traits on the same complex characteristic, and an estimation of the differences of the within - and the between - variety slopes, may help to select the more efficient sub-trait. In another example, where simultaneous selection was made for two polygenic characteristics, one directly and the other indirectly by two sub-traits, less than half the F 5 -lines had to be continued, when using the more efficient sub-trait. (author)

QTL analyses on genotype-specific component traits in a crop simulation model for capsicum annuum L.

NARCIS (Netherlands)

Wubs, A.M.; Heuvelink, E.; Dieleman, J.A.; Magan, J.J.; Palloix, A.; Eeuwijk, van F.A.

2012-01-01

Abstract: QTL for a complex trait like yield tend to be unstable across environments and show QTL by environment interaction. Direct improvement of complex traits by selecting on QTL is therefore difficult. For improvement of complex traits, crop growth models can be useful, as such models can

Brassinosteroid and gibberellin control of seedling traits in maize (Zea mays L.).

Science.gov (United States)

Hu, Songlin; Sanchez, Darlene L; Wang, Cuiling; Lipka, Alexander E; Yin, Yanhai; Gardner, Candice A C; Lübberstedt, Thomas

2017-10-01

In this study, we established two doubled haploid (DH) libraries with a total of 207 DH lines. We applied BR and GA inhibitors to all DH lines at seedling stage and measured seedling BR and GA inhibitor responses. Moreover, we evaluated field traits for each DH line (untreated). We conducted genome-wide association studies (GWAS) with 62,049 genome wide SNPs to explore the genetic control of seedling traits by BR and GA. In addition, we correlate seedling stage hormone inhibitor response with field traits. Large variation for BR and GA inhibitor response and field traits was observed across these DH lines. Seedling stage BR and GA inhibitor response was significantly correlate with yield and flowering time. Using three different GWAS approaches to balance false positive/negatives, multiple SNPs were discovered to be significantly associated with BR/GA inhibitor responses with some localized within gene models. SNPs from gene model GRMZM2G013391 were associated with GA inhibitor response across all three GWAS models. This gene is expressed in roots and shoots and was shown to regulate GA signaling. These results show that BRs and GAs have a great impact for controlling seedling growth. Gene models from GWAS results could be targets for seeding traits improvement. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of reference genes for real-time quantitative PCR normalisation in non-heading Chinese cabbage

NARCIS (Netherlands)

Xiao, D.; Zhang, N.; Jianjun Zhao, Jianjun; Bonnema, A.B.; Hou, X.L.

2012-01-01

Non-heading Chinese cabbage is an important vegetable crop that includes pak choi, caixin and several Japanese vegetables like mizuna, mibuna and komatsuna. Gene expression studies are frequently used to unravel the genetics of complex traits and in such studies the proper selection of reference

Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

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Frank P Diekstra

Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls. These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls. Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51 withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible

Mapping fusiform rust resistance genes within a complex mating design of loblolly pine

Science.gov (United States)

Tania Quesada; Marcio F.R. Resende Jr.; Patricio Munoz; Jill L. Wegrzyn; David B. Neale; Matias Kirst; Gary F. Peter; Salvador A. Gezan; C.Dana Nelson; John M. Davis

2014-01-01

Fusiform rust resistance can involve gene-for-gene interactions where resistance (Fr) genes in the host interact with corresponding avirulence genes in the pathogen, Cronartium quercuum f.sp. fusiforme (Cqf). Here, we identify trees with Fr genes in a loblolly pine population derived from a complex mating design challenged with two Cqf inocula (one gall and 10 gall...

Replication of linkage to quantitative trait loci: variation in location and magnitude of the lod score.

Science.gov (United States)

Hsueh, W C; Göring, H H; Blangero, J; Mitchell, B D

2001-01-01

Replication of linkage signals from independent samples is considered an important step toward verifying the significance of linkage signals in studies of complex traits. The purpose of this empirical investigation was to examine the variability in the precision of localizing a quantitative trait locus (QTL) by analyzing multiple replicates of a simulated data set with the use of variance components-based methods. Specifically, we evaluated across replicates the variation in both the magnitude and the location of the peak lod scores. We analyzed QTLs whose effects accounted for 10-37% of the phenotypic variance in the quantitative traits. Our analyses revealed that the precision of QTL localization was directly related to the magnitude of the QTL effect. For a QTL with effect accounting for > 20% of total phenotypic variation, > 90% of the linkage peaks fall within 10 cM from the true gene location. We found no evidence that, for a given magnitude of the lod score, the presence of interaction influenced the precision of QTL localization.

Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

Science.gov (United States)

Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

2016-06-21

QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line.

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Valdecy Aparecida Rocha da Cruz

Full Text Available Apolipoprotein B (APOB and Adiponectin Receptor 1 (ADIPOR1 are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs g.102A>T (APOB and g.729C>T (ADIPOR1 with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML and Generalized Quasi-Likelihood Score (GQLS methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

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Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

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Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

2015-11-01

The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Cross-Lagged Analysis of Interplay Between Differential Traits in Sibling Pairs: Validation and Application to Parenting Behavior and ADHD Symptomatology.

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Moscati, Arden; Verhulst, Brad; McKee, Kevin; Silberg, Judy; Eaves, Lindon

2018-01-01

Understanding the factors that contribute to behavioral traits is a complex task, and partitioning variance into latent genetic and environmental components is a useful beginning, but it should not also be the end. Many constructs are influenced by their contextual milieu, and accounting for background effects (such as gene-environment correlation) is necessary to avoid bias. This study introduces a method for examining the interplay between traits, in a longitudinal design using differential items in sibling pairs. The model is validated via simulation and power analysis, and we conclude with an application to paternal praise and ADHD symptoms in a twin sample. The model can help identify what type of genetic and environmental interplay may contribute to the dynamic relationship between traits using a cross-lagged panel framework. Overall, it presents a way to estimate and explicate the developmental interplay between a set of traits, free from many common sources of bias.

A model of gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype

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Wallace Helen M

2006-10-01

Full Text Available Abstract Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis, gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. Method A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918 assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. Conclusion The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis

Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

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Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

2014-01-01

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

Nannochloropsis genomes reveal evolution of microalgal oleaginous traits.

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Dongmei Wang

2014-01-01

Full Text Available Oleaginous microalgae are promising feedstock for biofuels, yet the genetic diversity, origin and evolution of oleaginous traits remain largely unknown. Here we present a detailed phylogenomic analysis of five oleaginous Nannochloropsis species (a total of six strains and one time-series transcriptome dataset for triacylglycerol (TAG synthesis on one representative strain. Despite small genome sizes, high coding potential and relative paucity of mobile elements, the genomes feature small cores of ca. 2,700 protein-coding genes and a large pan-genome of >38,000 genes. The six genomes share key oleaginous traits, such as the enrichment of selected lipid biosynthesis genes and certain glycoside hydrolase genes that potentially shift carbon flux from chrysolaminaran to TAG synthesis. The eleven type II diacylglycerol acyltransferase genes (DGAT-2 in every strain, each expressed during TAG synthesis, likely originated from three ancient genomes, including the secondary endosymbiosis host and the engulfed green and red algae. Horizontal gene transfers were inferred in most lipid synthesis nodes with expanded gene doses and many glycoside hydrolase genes. Thus multiple genome pooling and horizontal genetic exchange, together with selective inheritance of lipid synthesis genes and species-specific gene loss, have led to the enormous genetic apparatus for oleaginousness and the wide genomic divergence among present-day Nannochloropsis. These findings have important implications in the screening and genetic engineering of microalgae for biofuels.

Restricted pleiotropy facilitates mutational erosion of major life-history traits.

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Marek, Agnieszka; Korona, Ryszard

2013-11-01

Radical shifts to new natural and human made niches can make some functions unneeded and thus exposed to genetic degeneration. Here we ask not about highly specialized and rarely used functions but those relating to major life-history traits, rate of growth, and resistance to prolonged starvation. We found that in yeast each of the two traits was visibly impaired by at least several hundred individual gene deletions. There were relatively few deletions affecting negatively both traits and likely none harming one but improving the other. Functional profiles of gene deletions affecting either growth or survival were strikingly different: the first related chiefly to synthesis of macromolecules whereas the second to maintenance and recycling of cellular structures. The observed pattern of gene indispensability corresponds to that of gene induction, providing a rather rare example of agreement between the results of deletion and expression studies. We conclude that transitions to new environments in which the ability to grow at possibly fastest rate or survive under very long starvation become practically unnecessary can result in rapid erosion of these vital functions because they are coded by many genes constituting large mutational targets and because restricted pleiotropy is unlikely to constrain this process. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Precise regulation of gene expression dynamics favors complex promoter architectures.

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Dirk Müller

2009-01-01

Full Text Available Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure.

Effects of Drought on Morphological Traits in Some Cowpea Genotypes by Evaluating Their Combining Abilities

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Amos Afolarin Olajide

2017-01-01

Full Text Available An evaluation was conducted to understand the genetic effects of combining ability for four different morphological traits, on 42 hybrids in randomized complete block design with three replications in water-stressed and well-watered environments. The significance of the additive variance (D and dominance variance (H1 indicated the presence of both additive and nonadditive gene actions in both environments. Among the parents, there was asymmetrical distribution of positive and negative dominant genes and the preponderance of overdominance gene action for all the traits in both environments. This study also indicated a minimum of ten genes for plant height in water-stressed environment and minimum of three and eight genes for terminal leaflet area and number of leaves per plant in both environments, respectively. Estimates of narrow-sense heritability ranged from 13.0% for number of branches per plant in water-stressed to 95.0% in well-watered environment for terminal leaflet area. The study revealed that Danilla, IT93K-432-1, and IT97K-499-35 were the best general combiners for all traits, Danilla × IT97K-499-35, and Danilla × IT93K-432-1 were found to be the best specific combiners for all traits in water-stressed environment. Genetic interactions, additive × additive and additive × dominance, were more pronounced in the inheritance of the traits. This indicated that the selection for these traits should be delayed till advanced generations.

A predictive coexpression network identifies novel genes controlling the seed-to-seedling phase transition in arabidopsis Thaliana

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Silva, Anderson Tadeu; Ribone, Pamela A.; Chan, Raquel L.; Ligterink, Wilco; Hilhorst, Henk W.M.

2016-01-01

The transition from a quiescent dry seed to an actively growing photoautotrophic seedling is a complex and crucial trait for plant propagation. This study provides a detailed description of global gene expression in seven successive developmental stages of seedling establishment in Arabidopsis

Variation Analysis of Physiological Traits in Betula platyphylla Overexpressing TaLEA-ThbZIP Gene under Salt Stress.

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Xiyang Zhao

Full Text Available The aim of this study was to determine whether transgenic birch (Betula platyphylla ectopic overexpressing a late embryogenesis abundant (LEA gene and a basic leucine zipper (bZIP gene from the salt-tolerant genus Tamarix (salt cedar show increased tolerance to salt (NaCl stress. Co-transfer of TaLEA and ThbZIP in birch under the control of two independent CaMV 35S promoters significantly enhanced salt stress. PCR and northern blot analyses indicated that the two genes were ectopically overexpressed in several dual-gene transgenic birch lines. We compared the effects of salt stress among three transgenic birch lines (L-4, L-5, and L-8 and wild type (WT. In all lines, the net photosynthesis values were higher before salt stress treatment than afterwards. After the salt stress treatment, the transgenic lines L-4 and L-8 showed higher values for photosynthetic traits, chlorophyll fluorescence, peroxidase and superoxide dismutase activities, and lower malondialdehyde and Na+ contents, compared with those in WT and L-5. These different responses to salt stress suggested that the transcriptional level of the TaLEA and ThbZIP genes differed among the transgenic lines, resulting in a variety of genetic and phenotypic effects. The results of this research can provide a theoretical basis for the genetic engineering of salt-tolerant trees.

Quantitative Trait Locus Mapping of Salt Tolerance and Identification of Salt-Tolerant Genes in Brassica napus L

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Lina Lang

2017-06-01

Full Text Available Salinity stress is one of typical abiotic stresses that seriously limit crop production. In this study, a genetic linkage map based on 532 molecular markers covering 1341.1 cM was constructed to identify the loci associated with salt tolerance in Brassica napus. Up to 45 quantitative trait loci (QTLs for 10 indicators were identified in the F2:3 populations. These QTLs can account for 4.80–51.14% of the phenotypic variation. A major QTL, qSPAD5 on LG5 associated with chlorophyll can be detected in three replicates. Two intron polymorphic (IP markers in this QTL region were developed successfully to narrow down the QTL location to a region of 390 kb. A salt tolerance related gene Bra003640 was primary identified as the candidate gene in this region. The full length of the candidate gene was 1,063 bp containing three exons and two introns in B. napus L. The open reading frame (ORF is 867 bp and encodes 287 amino acids. Three amino acid differences (34, 54, and 83 in the conserved domain (B-box were identified. RT-qPCR analysis showed that the gene expression had significant difference between the two parents. The study laid great foundation for salt tolerance related gene mapping and cloning in B. napus L.

Partitioning of genetic variation between regulatory and coding gene segments: the predominance of software variation in genes encoding introvert proteins.

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Mitchison, A

1997-01-01

In considering genetic variation in eukaryotes, a fundamental distinction can be made between variation in regulatory (software) and coding (hardware) gene segments. For quantitative traits the bulk of variation, particularly that near the population mean, appears to reside in regulatory segments. The main exceptions to this rule concern proteins which handle extrinsic substances, here termed extrovert proteins. The immune system includes an unusually large proportion of this exceptional category, but even so its chief source of variation may well be polymorphism in regulatory gene segments. The main evidence for this view emerges from genome scanning for quantitative trait loci (QTL), which in the case of the immune system points to a major contribution of pro-inflammatory cytokine genes. Further support comes from sequencing of major histocompatibility complex (Mhc) class II promoters, where a high level of polymorphism has been detected. These Mhc promoters appear to act, in part at least, by gating the back-signal from T cells into antigen-presenting cells. Both these forms of polymorphism are likely to be sustained by the need for flexibility in the immune response. Future work on promoter polymorphism is likely to benefit from the input from genome informatics.

RiceFOX: a database of Arabidopsis mutant lines overexpressing rice full-length cDNA that contains a wide range of trait information to facilitate analysis of gene function.

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Sakurai, Tetsuya; Kondou, Youichi; Akiyama, Kenji; Kurotani, Atsushi; Higuchi, Mieko; Ichikawa, Takanari; Kuroda, Hirofumi; Kusano, Miyako; Mori, Masaki; Saitou, Tsutomu; Sakakibara, Hitoshi; Sugano, Shoji; Suzuki, Makoto; Takahashi, Hideki; Takahashi, Shinya; Takatsuji, Hiroshi; Yokotani, Naoki; Yoshizumi, Takeshi; Saito, Kazuki; Shinozaki, Kazuo; Oda, Kenji; Hirochika, Hirohiko; Matsui, Minami

2011-02-01

Identification of gene function is important not only for basic research but also for applied science, especially with regard to improvements in crop production. For rapid and efficient elucidation of useful traits, we developed a system named FOX hunting (Full-length cDNA Over-eXpressor gene hunting) using full-length cDNAs (fl-cDNAs). A heterologous expression approach provides a solution for the high-throughput characterization of gene functions in agricultural plant species. Since fl-cDNAs contain all the information of functional mRNAs and proteins, we introduced rice fl-cDNAs into Arabidopsis plants for systematic gain-of-function mutation. We generated >30,000 independent Arabidopsis transgenic lines expressing rice fl-cDNAs (rice FOX Arabidopsis mutant lines). These rice FOX Arabidopsis lines were screened systematically for various criteria such as morphology, photosynthesis, UV resistance, element composition, plant hormone profile, metabolite profile/fingerprinting, bacterial resistance, and heat and salt tolerance. The information obtained from these screenings was compiled into a database named 'RiceFOX'. This database contains around 18,000 records of rice FOX Arabidopsis lines and allows users to search against all the observed results, ranging from morphological to invisible traits. The number of searchable items is approximately 100; moreover, the rice FOX Arabidopsis lines can be searched by rice and Arabidopsis gene/protein identifiers, sequence similarity to the introduced rice fl-cDNA and traits. The RiceFOX database is available at http://ricefox.psc.riken.jp/.

Generation of expressed sequence tags for discovery of genes responsible for floral traits of Chrysanthemum morifolium by next-generation sequencing technology.

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Sasaki, Katsutomo; Mitsuda, Nobutaka; Nashima, Kenji; Kishimoto, Kyutaro; Katayose, Yuichi; Kanamori, Hiroyuki; Ohmiya, Akemi

2017-09-04

Chrysanthemum morifolium is one of the most economically valuable ornamental plants worldwide. Chrysanthemum is an allohexaploid plant with a large genome that is commercially propagated by vegetative reproduction. New cultivars with different floral traits, such as color, morphology, and scent, have been generated mainly by classical cross-breeding and mutation breeding. However, only limited genetic resources and their genome information are available for the generation of new floral traits. To obtain useful information about molecular bases for floral traits of chrysanthemums, we read expressed sequence tags (ESTs) of chrysanthemums by high-throughput sequencing using the 454 pyrosequencing technology. We constructed normalized cDNA libraries, consisting of full-length, 3'-UTR, and 5'-UTR cDNAs derived from various tissues of chrysanthemums. These libraries produced a total number of 3,772,677 high-quality reads, which were assembled into 213,204 contigs. By comparing the data obtained with those of full genome-sequenced species, we confirmed that our chrysanthemum contig set contained the majority of all expressed genes, which was sufficient for further molecular analysis in chrysanthemums. We confirmed that our chrysanthemum EST set (contigs) contained a number of contigs that encoded transcription factors and enzymes involved in pigment and aroma compound metabolism that was comparable to that of other species. This information can serve as an informative resource for identifying genes involved in various biological processes in chrysanthemums. Moreover, the findings of our study will contribute to a better understanding of the floral characteristics of chrysanthemums including the myriad cultivars at the molecular level.

Methods for meta-analysis of multiple traits using GWAS summary statistics.

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Ray, Debashree; Boehnke, Michael

2018-03-01

Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses

Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity.

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Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal S M; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K

2016-02-17

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Beyond the single gene: How epistasis and gene-by-environment effects influence crop domestication.

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Doust, Andrew N; Lukens, Lewis; Olsen, Kenneth M; Mauro-Herrera, Margarita; Meyer, Ann; Rogers, Kimberly

2014-04-29

Domestication is a multifaceted evolutionary process, involving changes in individual genes, genetic interactions, and emergent phenotypes. There has been extensive discussion of the phenotypic characteristics of plant domestication, and recent research has started to identify the specific genes and mutational mechanisms that control domestication traits. However, there is an apparent disconnect between the simple genetic architecture described for many crop domestication traits, which should facilitate rapid phenotypic change under selection, and the slow rate of change reported from the archeobotanical record. A possible explanation involves the middle ground between individual genetic changes and their expression during development, where gene-by-gene (epistatic) and gene-by-environment interactions can modify the expression of phenotypes and opportunities for selection. These aspects of genetic architecture have the potential to significantly slow the speed of phenotypic evolution during crop domestication and improvement. Here we examine whether epistatic and gene-by-environment interactions have shaped how domestication traits have evolved. We review available evidence from the literature, and we analyze two domestication-related traits, shattering and flowering time, in a mapping population derived from a cross between domesticated foxtail millet and its wild progenitor. We find that compared with wild progenitor alleles, those favored during domestication often have large phenotypic effects and are relatively insensitive to genetic background and environmental effects. Consistent selection should thus be able to rapidly change traits during domestication. We conclude that if phenotypic evolution was slow during crop domestication, this is more likely due to cultural or historical factors than epistatic or environmental constraints.

Identification of sheep ovary genes potentially associated with off-season reproduction.

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Chen, Lei; Liu, Ka; Zhao, Zongsheng; Blair, Hugh T; Zhang, Peng; Li, Daquan; Ma, Runlin Z

2012-04-20

Off-season reproduction is a favorable economic trait for sheep industry. Hu sheep, an indigenous Chinese sheep breed, demonstrates a higher productivity of lambs and displays year-around oestrous behavior under proper nutrition and environment. The genetic basis behind these traits, however, is not well understood. In order to identify genes associated with the off-season reproduction, we constructed a suppression subtractive hybridization (SSH) cDNA library using pooled ovary mRNAs of 6 oestrous Hu females as a tester and the pooled ovary mRNAs of 6 non-oestrous Chinese Merino females as a driver. A total of 382 resulting positive clones were obtained after the SSH. We identified 114 differentially up-regulated genes in oestrous Hu sheep by using subsequent screening and DNA sequencing, of which 8 were previously known, 93 were reported for the first time in sheep, and 13 were novel with no significant homology to any sequence in the DNA databases. Functions of the genes identified are related to cell division, signal transduction, structure, metabolism, or cell defense. To validate the results of SSH, 6 genes (Ntrk2, Ppap2b, Htra1, Nid1, Serpine2 and Foxola) were selected for conformational analysis using quantitative real-time PCR (qRT-PCR), and two of them (Htral and Foxo1a) were verified by Northern blot. All of the 6 genes were differentially up-regulated in the ovary of oestrous Hu. It is obvious that off-season reproduction is a complex trait involving multiple genes in multiple organs. This study helps to provide a foundation for the final identification of functional genes involved in the sheep ovary. Copyright © 2012. Published by Elsevier Ltd.

DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

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Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

2015-10-01

The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integration of gene-based markers in a pearl millet genetic map for identification of candidate genes underlying drought tolerance quantitative trait loci

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Sehgal Deepmala

2012-01-01

Full Text Available Abstract Background Identification of genes underlying drought tolerance (DT quantitative trait loci (QTLs will facilitate understanding of molecular mechanisms of drought tolerance, and also will accelerate genetic improvement of pearl millet through marker-assisted selection. We report a map based on genes with assigned functional roles in plant adaptation to drought and other abiotic stresses and demonstrate its use in identifying candidate genes underlying a major DT-QTL. Results Seventy five single nucleotide polymorphism (SNP and conserved intron spanning primer (CISP markers were developed from available expressed sequence tags (ESTs using four genotypes, H 77/833-2, PRLT 2/89-33, ICMR 01029 and ICMR 01004, representing parents of two mapping populations. A total of 228 SNPs were obtained from 30.5 kb sequenced region resulting in a SNP frequency of 1/134 bp. The positions of major pearl millet linkage group (LG 2 DT-QTLs (reported from crosses H 77/833-2 × PRLT 2/89-33 and 841B × 863B were added to the present consensus function map which identified 18 genes, coding for PSI reaction center subunit III, PHYC, actin, alanine glyoxylate aminotransferase, uridylate kinase, acyl-CoA oxidase, dipeptidyl peptidase IV, MADS-box, serine/threonine protein kinase, ubiquitin conjugating enzyme, zinc finger C- × 8-C × 5-C × 3-H type, Hd3, acetyl CoA carboxylase, chlorophyll a/b binding protein, photolyase, protein phosphatase1 regulatory subunit SDS22 and two hypothetical proteins, co-mapping in this DT-QTL interval. Many of these candidate genes were found to have significant association with QTLs of grain yield, flowering time and leaf rolling under drought stress conditions. Conclusions We have exploited available pearl millet EST sequences to generate a mapped resource of seventy five new gene-based markers for pearl millet and demonstrated its use in identifying candidate genes underlying a major DT-QTL in this species. The reported gene

Network-based group variable selection for detecting expression quantitative trait loci (eQTL

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Zhang Xuegong

2011-06-01

Full Text Available Abstract Background Analysis of expression quantitative trait loci (eQTL aims to identify the genetic loci associated with the expression level of genes. Penalized regression with a proper penalty is suitable for the high-dimensional biological data. Its performance should be enhanced when we incorporate biological knowledge of gene expression network and linkage disequilibrium (LD structure between loci in high-noise background. Results We propose a network-based group variable selection (NGVS method for QTL detection. Our method simultaneously maps highly correlated expression traits sharing the same biological function to marker sets formed by LD. By grouping markers, complex joint activity of multiple SNPs can be considered and the dimensionality of eQTL problem is reduced dramatically. In order to demonstrate the power and flexibility of our method, we used it to analyze two simulations and a mouse obesity and diabetes dataset. We considered the gene co-expression network, grouped markers into marker sets and treated the additive and dominant effect of each locus as a group: as a consequence, we were able to replicate results previously obtained on the mouse linkage dataset. Furthermore, we observed several possible sex-dependent loci and interactions of multiple SNPs. Conclusions The proposed NGVS method is appropriate for problems with high-dimensional data and high-noise background. On eQTL problem it outperforms the classical Lasso method, which does not consider biological knowledge. Introduction of proper gene expression and loci correlation information makes detecting causal markers more accurate. With reasonable model settings, NGVS can lead to novel biological findings.

Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

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Santure, Anna W.; Poissant, Jocelyn; Cauwer, De Isabelle; Oers, Van Kees; Robinson, Matthew R.; Quinn, John L.; Groenen, M.A.M.; Visser, M.E.; Sheldon, Ben C.; Slate, Jon

2015-01-01

Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar

Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

NARCIS (Netherlands)

Santure, Anna W; Poissant, Jocelyn; De Cauwer, Isabelle; van Oers, Kees; Robinson, Matthew R; Quinn, John L; Groenen, Martien A M; Visser, Marcel E; Sheldon, Ben C; Slate, Jon

2015-01-01

Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic

Stability of RNA silencing-based traits after virus infection

DEFF Research Database (Denmark)

Jørgensen, Bodil; Albrechtsen, Merete

2007-01-01

with constructs based on virus coat protein (CP) genes or other viral genes has been successfully used to engineer PTGS-mediated virus resistance into a large number of crop plants and some transgenic lines have been commercially exploited. However the discovery that plant viruses encode suppressors of gene...... silencing has raised concerns that virus infection of crop plants might reverse the new silencing-based traits. Most studies of virus suppression of silencing have used model systems based on silencing of reporter genes. A few studies have analysed the effects of virus infections on plants with genetically...... engineered virus resistance based on either a simple sense or an inverted repeat construct. We decided to use genetically engineered virus resistance in potato as a model system for further studies of the effect of virus infection on genetically engineered traits. We present for the first time a comparison...

Intelligence : shared genetic basis between Mendelian disorders and a polygenic trait

NARCIS (Netherlands)

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-01-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a

Genome-Wide Association Study of Major Agronomic Traits Related to Domestication in Peanut

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Xingguo Zhang

2017-09-01

Full Text Available Peanut (Arachis hypogaea consists of two subspecies, hypogaea and fastigiata, and has been cultivated worldwide for hundreds of years. Here, 158 peanut accessions were selected to dissect the molecular footprint of agronomic traits related to domestication using specific-locus amplified fragment sequencing (SLAF-seq method. Then, a total of 17,338 high-quality single nucleotide polymorphisms (SNPs in the whole peanut genome were revealed. Eleven agronomic traits in 158 peanut accessions were subsequently analyzed using genome-wide association studies (GWAS. Candidate genes responsible for corresponding traits were then analyzed in genomic regions surrounding the peak SNPs, and 1,429 genes were found within 200 kb windows centerd on GWAS-identified peak SNPs related to domestication. Highly differentiated genomic regions were observed between hypogaea and fastigiata accessions using FST values and sequence diversity (π ratios. Among the 1,429 genes, 662 were located on chromosome A3, suggesting the presence of major selective sweeps caused by artificial selection during long domestication. These findings provide a promising insight into the complicated genetic architecture of domestication-related traits in peanut, and reveal whole-genome SNP markers of beneficial candidate genes for marker-assisted selection (MAS in future breeding programs.

Molecular Breeding Algae For Improved Traits For The Conversion Of Waste To Fuels And Commodities.

Energy Technology Data Exchange (ETDEWEB)

Bagwell, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2015-10-14

This Exploratory LDRD aimed to develop molecular breeding methodology for biofuel algal strain improvement for applications in waste to energy / commodity conversion technologies. Genome shuffling technologies, specifically protoplast fusion, are readily available for the rapid production of genetic hybrids for trait improvement and have been used successfully in bacteria, yeast, plants and animals. However, genome fusion has not been developed for exploiting the remarkable untapped potential of eukaryotic microalgae for large scale integrated bio-conversion and upgrading of waste components to valued commodities, fuel and energy. The proposed molecular breeding technology is effectively sexual reproduction in algae; though compared to traditional breeding, the molecular route is rapid, high-throughput and permits selection / improvement of complex traits which cannot be accomplished by traditional genetics. Genome fusion technologies are the cutting edge of applied biotechnology. The goals of this Exploratory LDRD were to 1) establish reliable methodology for protoplast production among diverse microalgal strains, and 2) demonstrate genome fusion for hybrid strain production using a single gene encoded trait as a proof of the concept.

Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse.

Science.gov (United States)

Dai, Jiajuan; Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Zhu, Jun; Lu, Lu

2009-11-01

Previous studies have revealed that the subunit alpha 2 (Gabra2) of the gamma-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.

Genetic recombination within the human T-cell receptor α-chain gene complex

International Nuclear Information System (INIS)

Robinson, M.A.; Kindt, T.J.

1987-01-01

Genetic analyses of the human T-cell receptor (TCR) α-chain genes indicate that recombination events may occur frequently within this gene complex. Examination of the inheritance of restriction fragment length polymorphisms (RFLP) detected by using probes for constant or variable region gene segments made it possible to assign TCRα haplotypes to the 16 parents and 43 offspring of eight families studied. A total of six RFLP, three for the constant region and three for variable region segments, were examined in the present studies. Most enzyme and probe combinations tested revealed no polymorphism and those finally selected for the study showed limited polymorphism in that only two or, in one case, three allelic forms of the gene were seen. In spite of limited variability at this level, extensive heterogeneity was observed for the combinations of markers present in haplotypes, suggesting that frequent recombination events have occurred. Most strikingly, multiple combinations of RFLP occurring in close proximity of the TCRα constant region gene were observed in this study. A high recombination frequency for the TCRα gene complex is further supported by the observation that two children, one in each of two families, inherited recombinant TCRα haplotypes

Gene duplication and fragmentation in the zebra finch major histocompatibility complex.

Science.gov (United States)

Balakrishnan, Christopher N; Ekblom, Robert; Völker, Martin; Westerdahl, Helena; Godinez, Ricardo; Kotkiewicz, Holly; Burt, David W; Graves, Tina; Griffin, Darren K; Warren, Wesley C; Edwards, Scott V

2010-04-01

Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC) has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC) sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines. The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH) evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes. The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving chromosomal fission, gene duplication and translocation in the

Gene duplication and fragmentation in the zebra finch major histocompatibility complex

Directory of Open Access Journals (Sweden)

Burt David W

2010-04-01

Full Text Available Abstract Background Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines. Results The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes. Conclusion The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving

Influence of obesity gene in quantitative traits of swine

Directory of Open Access Journals (Sweden)

Graciele Segantini do Nascimento Borges

2002-01-01

-grandparental generation, when the male grandparent is replaced by the great-grandparental generation. The obesity gene did not influence any of the carcass evaluation data from crossbred animals. In pure swine, where the only genotypes were TT and TC, it greatly influenced shoulder weight and meat texture, with the highest average in heterozygotes (shoulder: 4.07 vs. 3.93; texture: 2.62 vs. 1.82, suggesting better carcass quality and worse meat quality than in homozygotes. The obesity gene did not influence any trait in the expected progeny difference (EPD study.

Quantitative Trait Loci Mapping in Brassica rapa Revealed the Structural and Functional Conservation of Genetic Loci Governing Morphological and Yield Component Traits in the A, B, and C Subgenomes of Brassica Species

Science.gov (United States)

Li, Xiaonan; Ramchiary, Nirala; Dhandapani, Vignesh; Choi, Su Ryun; Hur, Yoonkang; Nou, Ill-Sup; Yoon, Moo Kyoung; Lim, Yong Pyo

2013-01-01

Brassica rapa is an important crop species that produces vegetables, oilseed, and fodder. Although many studies reported quantitative trait loci (QTL) mapping, the genes governing most of its economically important traits are still unknown. In this study, we report QTL mapping for morphological and yield component traits in B. rapa and comparative map alignment between B. rapa, B. napus, B. juncea, and Arabidopsis thaliana to identify candidate genes and conserved QTL blocks between them. A total of 95 QTL were identified in different crucifer blocks of the B. rapa genome. Through synteny analysis with A. thaliana, B. rapa candidate genes and intronic and exonic single nucleotide polymorphisms in the parental lines were detected from whole genome resequenced data, a few of which were validated by mapping them to the QTL regions. Semi-quantitative reverse transcriptase PCR analysis showed differences in the expression levels of a few genes in parental lines. Comparative mapping identified five key major evolutionarily conserved crucifer blocks (R, J, F, E, and W) harbouring QTL for morphological and yield components traits between the A, B, and C subgenomes of B. rapa, B. juncea, and B. napus. The information of the identified candidate genes could be used for breeding B. rapa and other related Brassica species. PMID:23223793

Variance Component Quantitative Trait Locus Analysis for Body Weight Traits in Purebred Korean Native Chicken

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Muhammad Cahyadi

2016-01-01

Full Text Available Quantitative trait locus (QTL is a particular region of the genome containing one or more genes associated with economically important quantitative traits. This study was conducted to identify QTL regions for body weight and growth traits in purebred Korean native chicken (KNC. F1 samples (n = 595 were genotyped using 127 microsatellite markers and 8 single nucleotide polymorphisms that covered 2,616.1 centi Morgan (cM of map length for 26 autosomal linkage groups. Body weight traits were measured every 2 weeks from hatch to 20 weeks of age. Weight of half carcass was also collected together with growth rate. A multipoint variance component linkage approach was used to identify QTLs for the body weight traits. Two significant QTLs for growth were identified on chicken chromosome 3 (GGA3 for growth 16 to18 weeks (logarithm of the odds [LOD] = 3.24, Nominal p value = 0.0001 and GGA4 for growth 6 to 8 weeks (LOD = 2.88, Nominal p value = 0.0003. Additionally, one significant QTL and three suggestive QTLs were detected for body weight traits in KNC; significant QTL for body weight at 4 weeks (LOD = 2.52, nominal p value = 0.0007 and suggestive QTL for 8 weeks (LOD = 1.96, Nominal p value = 0.0027 were detected on GGA4; QTLs were also detected for two different body weight traits: body weight at 16 weeks on GGA3 and body weight at 18 weeks on GGA19. Additionally, two suggestive QTLs for carcass weight were detected at 0 and 70 cM on GGA19. In conclusion, the current study identified several significant and suggestive QTLs that affect growth related traits in a unique resource pedigree in purebred KNC. This information will contribute to improving the body weight traits in native chicken breeds, especially for the Asian native chicken breeds.