The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
M C Ledur - One of the best experts on this subject based on the ideXlab platform.
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Large-scale SNP genotyping in crosses between Outbred Lines: how useful is it?
Heredity, 2010Co-Authors: M C Ledur, N Navarro, M Pérez-encisoAbstract:Although genome-wide association (GWA) studies are not worth the effort in crosses between inbred Lines, many crosses are actually made up of divergent yet Outbred populations. Despite its relevance, however, this experimental setting has not been studied at a time when SNP microarrays are available in many species. To assess whether GWA can be useful in this setting, we performed combined coalescence—gene dropping simulations. We studied the influence of marker density, QTL effect and QTL allele frequency on power, false discovery rate (FDR) and accuracy. Our results suggest that GWA in Outbred F_2 crosses is useful, especially in large populations. Under these circumstances, accuracy increased and FDR decreased as compared with classical linkage analysis. However, current SNP densities (in the order of 30–60 K SNPs/genome or equivalent to 10–20 SNPs per cM) may not be much better than linkage analysis and higher SNP densities may be required. SNP ascertainment had an important effect; the best option was to select SNPs as uniformly as possible without setting any restriction on allele frequency. Using only SNPs with fixed alternative alleles in each breed controlled false positive rate but was not useful to detect variability within Lines. Finally, the most significant SNP was not necessarily the closest to the causal SNP, although the closest SNPs were usually above the significance threshold; thus, it is prudent to follow-up significant signals located in regions of interest even if they do not correspond to absolute maxima.
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large scale snp genotyping in crosses between Outbred Lines how useful is it
Heredity, 2010Co-Authors: N Navarro, M C Ledur, Miguel PerezencisoAbstract:Although genome-wide association (GWA) studies are not worth the effort in crosses between inbred Lines, many crosses are actually made up of divergent yet Outbred populations. Despite its relevance, however, this experimental setting has not been studied at a time when SNP microarrays are available in many species. To assess whether GWA can be useful in this setting, we performed combined coalescence--gene dropping simulations. We studied the influence of marker density, QTL effect and QTL allele frequency on power, false discovery rate (FDR) and accuracy. Our results suggest that GWA in Outbred F(2) crosses is useful, especially in large populations. Under these circumstances, accuracy increased and FDR decreased as compared with classical linkage analysis. However, current SNP densities (in the order of 30-60 K SNPs/genome or equivalent to 10-20 SNPs per cM) may not be much better than linkage analysis and higher SNP densities may be required. SNP ascertainment had an important effect; the best option was to select SNPs as uniformly as possible without setting any restriction on allele frequency. Using only SNPs with fixed alternative alleles in each breed controlled false positive rate but was not useful to detect variability within Lines. Finally, the most significant SNP was not necessarily the closest to the causal SNP, although the closest SNPs were usually above the significance threshold; thus, it is prudent to follow-up significant signals located in regions of interest even if they do not correspond to absolute maxima.
Miguel Perezenciso - One of the best experts on this subject based on the ideXlab platform.
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large scale snp genotyping in crosses between Outbred Lines how useful is it
Heredity, 2010Co-Authors: N Navarro, M C Ledur, Miguel PerezencisoAbstract:Although genome-wide association (GWA) studies are not worth the effort in crosses between inbred Lines, many crosses are actually made up of divergent yet Outbred populations. Despite its relevance, however, this experimental setting has not been studied at a time when SNP microarrays are available in many species. To assess whether GWA can be useful in this setting, we performed combined coalescence--gene dropping simulations. We studied the influence of marker density, QTL effect and QTL allele frequency on power, false discovery rate (FDR) and accuracy. Our results suggest that GWA in Outbred F(2) crosses is useful, especially in large populations. Under these circumstances, accuracy increased and FDR decreased as compared with classical linkage analysis. However, current SNP densities (in the order of 30-60 K SNPs/genome or equivalent to 10-20 SNPs per cM) may not be much better than linkage analysis and higher SNP densities may be required. SNP ascertainment had an important effect; the best option was to select SNPs as uniformly as possible without setting any restriction on allele frequency. Using only SNPs with fixed alternative alleles in each breed controlled false positive rate but was not useful to detect variability within Lines. Finally, the most significant SNP was not necessarily the closest to the causal SNP, although the closest SNPs were usually above the significance threshold; thus, it is prudent to follow-up significant signals located in regions of interest even if they do not correspond to absolute maxima.
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exploring alternative models for sex linked quantitative trait loci in Outbred populations application to an iberian x landrace pig intercross
Genetics, 2002Co-Authors: Miguel Perezenciso, Alex Clop, Cristina Óvilo, Josep M. Folch, C Barragan, Maria Angels Oliver, Luis Varona, A Sanchez, José Luis Vázquez NogueraAbstract:We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between Outbred Lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F(2) cross between Iberian x Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component.
Miguel Pérez-enciso - One of the best experts on this subject based on the ideXlab platform.
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Exploring Alternative Models for Sex-Linked Quantitative Trait Loci in Outbred Populations: Application to an Iberian × Landrace Pig Intercross
Genetics, 2002Co-Authors: Miguel Pérez-enciso, Alex Clop, Cristina Óvilo, Josep M. Folch, C Barragan, Maria Angels Oliver, Luis Varona, A Sanchez, José Luis Vázquez NogueraAbstract:Abstract We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between Outbred Lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F2 cross between Iberian × Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component.
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Quantitative Trait Locus Analysis in Crosses Between Outbred Lines With Dominance and Inbreeding
Genetics, 2001Co-Authors: Miguel Pérez-enciso, Rohan L. Fernando, Jean-pierre Bidanel, P. Le RoyAbstract:We provide a theoretical framework for quantitative trait locus (QTL) analysis of a crossed population where parental Lines may be Outbred and dominance as well as inbreeding are allowed for. It can be applied to any pedigree. A biallelic QTL is assumed, and the QTL allele frequencies can be different in each breed. The genetic covariance between any two individuals is expressed as a nonlinear function of the probability of up to 15 possible identity modes and of the additive and dominance effects, together with the allelic frequencies in each of the two parental breeds. The probabilities of each identity mode are obtained at the desired genome positions using a Monte Carlo Markov chain method. Unbiased estimates of the actual genetic parameters are recovered in a simulated F(2) cross and in a six-generation complex pedigree under a variety of genetic models (allele fixed or segregating in the parental populations and additive or dominance action). Results from analyzing an F(2) cross between Meishan and Large White pigs are also presented.
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Quantitative Trait Loci Mapping in F2 Crosses Between Outbred Lines
Genetics, 2000Co-Authors: Miguel Pérez-enciso, Luis VaronaAbstract:Abstract We develop a mixed-model approach for QTL analysis in crosses between Outbred Lines that allows for QTL segregation within Lines as well as for differences in mean QTL effects between Lines. We also propose a method called “segment mapping” that is based in partitioning the genome in a series of segments. The expected change in mean according to percentage of breed origin, together with the genetic variance associated with each segment, is estimated using maximum likelihood. The method also allows the estimation of differences in additive variances between the parental Lines. Completely fixed random and mixed models together with segment mapping are compared via simulation. The segment mapping and mixed-model behaviors are similar to those of classical methods, either the fixed or random models, under simple genetic models (a single QTL with alternative alleles fixed in each line), whereas they provide less biased estimates and have higher power than fixed or random models in more complex situations, i.e., when the QTL are segregating within the parental Lines. The segment mapping approach is particularly useful to determining which chromosome regions are likely to contain QTL when these are linked.
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Quantitative trait loci mapping in F(2) crosses between Outbred Lines.
Genetics, 2000Co-Authors: Miguel Pérez-enciso, Luis VaronaAbstract:We develop a mixed-model approach for QTL analysis in crosses between Outbred Lines that allows for QTL segregation within Lines as well as for differences in mean QTL effects between Lines. We also propose a method called “segment mapping” that is based in partitioning the genome in a series of segments. The expected change in mean according to percentage of breed origin, together with the genetic variance associated with each segment, is estimated using maximum likelihood. The method also allows the estimation of differences in additive variances between the parental Lines. Completely fixed random and mixed models together with segment mapping are compared via simulation. The segment mapping and mixed-model behaviors are similar to those of classical methods, either the fixed or random models, under simple genetic models (a single QTL with alternative alleles fixed in each line), whereas they provide less biased estimates and have higher power than fixed or random models in more complex situations, i.e., when the QTL are segregating within the parental Lines. The segment mapping approach is particularly useful to determining which chromosome regions are likely to contain QTL when these are linked.
Torsten Nygaard Kristensen - One of the best experts on this subject based on the ideXlab platform.
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Inbreeding effects on standard metabolic rate investigated at cold, benign and hot temperatures in Drosophila melanogaster.
Journal of insect physiology, 2014Co-Authors: Palle Jensen, Volker Loeschcke, Johannes Overgaard, Mads Fristrup Schou, Hans Malte, Torsten Nygaard KristensenAbstract:Inbreeding increases homozygosity, which is known to affect the mean and variance of fitness components such as growth, fecundity and mortality rate. Across inbred Lines inbreeding depression is typically observed and the variance between Lines is increased in inbred compared to Outbred Lines. It has been suggested that damage incurred from increased homozygosity entails energetic cost associated with cellular repair. However, little is known about the effects of inbreeding on standard metabolic rate. Using stop-flow respirometry we performed repeated measurements of metabolic rate in replicated Lines of inbred and Outbred Drosophila melanogaster at stressful low, benign and stressful high temperatures. The lowest measurements of metabolic rate in our study are always associated with the low activity period of the diurnal cycle and these measurements therefore serve as good estimates of standard metabolic rate. Due to the potentially added costs of genetic stress in inbred Lines we hypothesized that inbred individuals have increased metabolic rate compared to Outbred controls and that this is more pronounced at stressful temperatures due to synergistic inbreeding by environment interactions. Contrary to our hypothesis we found no significant difference in metabolic rate between inbred and Outbred Lines and no interaction between inbreeding and temperature. Inbreeding however effected the variance; the variance in metabolic rate was higher between the inbred Lines compared to the Outbred control Lines with some inbred Lines having very high or low standard metabolic rate. Thus genetic drift and not inbreeding per se seem to explain variation in metabolic rate in populations of different size.
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NO INBREEDING DEPRESSION FOR LOW TEMPERATURE DEVELOPMENTAL ACCLIMATION ACROSS MULTIPLE DROSOPHILA SPECIES
Evolution; international journal of organic evolution, 2011Co-Authors: Torsten Nygaard Kristensen, Volker Loeschcke, Trine Bilde, Ary A. Hoffmann, Carla M. Sgrò, Kristina Noreikienė, Marti Ondrésik, Jesper BechsgaardAbstract:Populations are from time to time exposed to stressful temperatures. Their thermal resistance levels are determined by inherent and plastic mechanisms, which are both likely to be under selection in natural populations. Previous studies on Drosophila species have shown that inherent resistance is highly species specific, and differs among ecotypes (e.g., tropical and widespread species). Apart from being exposed to thermal stress many small and fragmented populations face genetic challenges due to, for example, inbreeding. Inbreeding has been shown to reduce inherent resistance levels toward stressful temperatures, but whether adaptation to thermal stress through plastic responses also is affected by inbreeding is so far not clear. In this study, we test inherent cold resistance and the ability to respond plastically to temperature changes through developmental cold acclimation in inbred and Outbred Lines of five tropical and five widespread Drosophila species. Our results confirm that tropical species have lower cold resistance compared to widespread species, and show that (1) inbreeding reduces inherent cold resistance in both tropical and widespread species, (2) inbreeding does not affect the ability to respond adaptively to temperature acclimation, and (3) tropical species with low basal resistance show stronger adaptive plastic responses to developmental acclimation compared to widespread species.
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Metabolomic Signatures of Inbreeding at Benign and Stressful Temperatures in Drosophila melanogaster
Genetics, 2008Co-Authors: Kamilla Sofie Pedersen, Torsten Nygaard Kristensen, Volker Loeschcke, Bent O. Petersen, Jens Ø. Duus, Niels Chr. Nielsen, Anders MalmendalAbstract:While the population genetics of inbreeding is fairly well understood, the effects of inbreeding on the physiological and biochemical levels are not. Here we have investigated the effects of inbreeding on the Drosophila melanogaster metabolome. Metabolite fingerprints in males from five Outbred and five inbred Lines were studied by nuclear magnetic resonance spectroscopy after exposure to benign temperature, heat stress, or cold stress. In both the absence and the presence of temperature stress, metabolite levels were significantly different among inbred and Outbred Lines. The major effect of inbreeding was increased levels of maltose and decreased levels of 3-hydroxykynurenine and a galactoside [1-O-(4-O-(2-aminoethyl phosphate)-β-d-galactopyranosyl)-x-glycerol] synthesized exclusively in the paragonial glands of Drosophila species, including D. melanogaster. The metabolomic effect of inbreeding at the benign temperature was related to gene expression data from the same inbred and Outbred Lines. Both gene expression and metabolite data indicate that fundamental metabolic processes are changed or modified by inbreeding. Apart from affecting mean metabolite levels, inbreeding led to an increased between-line variation in metabolite profiles compared to Outbred Lines. In contrast to previous observations revealing interactions between inbreeding and environmental stress on gene expression patterns and life-history traits, the effect of inbreeding on the metabolite profile was similar across the different temperature treatments.
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Inbreeding affects Hsp70 expression in two species of Drosophila even at benign temperatures
Evolutionary Ecology Research, 2002Co-Authors: Torsten Nygaard Kristensen, Jesper Dahlgaard, Volker LoeschckeAbstract:Heat shock proteins (Hsps) are molecular chaperones that help organisms to cope with environmental stress. Here we report the effect of temperature on Hsp70 expression in inbred and Outbred Lines of Drosophila buzzatii and D. melanogaster. For both species, we found significant effects of temperature and inbreeding on Hsp70 expression. In D. buzzatii, inbred larvae expressed more Hsp70 at all temperatures except at very high temperatures close to the physiological limit. In D. melanogaster, the overall pattern was similar to that of D. buzzatii. At benign temperatures, there was a clear trend towards higher Hsp70 expression in inbred than Outbred larvae, whereas at higher temperatures, a trend in the opposite direction was observed. The shift from lower to higher expression in Outbred larvae with increasing temperatures occurs at a lower temperature in D. melanogaster than in D. buzzatii. The reason for this difference may be greater sensitivity to high stressful temperatures in D. melanogaster. These results provide the first direct experimental evidence that inbreeding influences the expression of Hsp70 even at non-stressful temperatures.
Luis Varona - One of the best experts on this subject based on the ideXlab platform.
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exploring alternative models for sex linked quantitative trait loci in Outbred populations application to an iberian x landrace pig intercross
Genetics, 2002Co-Authors: Miguel Perezenciso, Alex Clop, Cristina Óvilo, Josep M. Folch, C Barragan, Maria Angels Oliver, Luis Varona, A Sanchez, José Luis Vázquez NogueraAbstract:We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between Outbred Lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F(2) cross between Iberian x Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component.
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Exploring Alternative Models for Sex-Linked Quantitative Trait Loci in Outbred Populations: Application to an Iberian × Landrace Pig Intercross
Genetics, 2002Co-Authors: Miguel Pérez-enciso, Alex Clop, Cristina Óvilo, Josep M. Folch, C Barragan, Maria Angels Oliver, Luis Varona, A Sanchez, José Luis Vázquez NogueraAbstract:Abstract We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between Outbred Lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F2 cross between Iberian × Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component.
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Quantitative Trait Loci Mapping in F2 Crosses Between Outbred Lines
Genetics, 2000Co-Authors: Miguel Pérez-enciso, Luis VaronaAbstract:Abstract We develop a mixed-model approach for QTL analysis in crosses between Outbred Lines that allows for QTL segregation within Lines as well as for differences in mean QTL effects between Lines. We also propose a method called “segment mapping” that is based in partitioning the genome in a series of segments. The expected change in mean according to percentage of breed origin, together with the genetic variance associated with each segment, is estimated using maximum likelihood. The method also allows the estimation of differences in additive variances between the parental Lines. Completely fixed random and mixed models together with segment mapping are compared via simulation. The segment mapping and mixed-model behaviors are similar to those of classical methods, either the fixed or random models, under simple genetic models (a single QTL with alternative alleles fixed in each line), whereas they provide less biased estimates and have higher power than fixed or random models in more complex situations, i.e., when the QTL are segregating within the parental Lines. The segment mapping approach is particularly useful to determining which chromosome regions are likely to contain QTL when these are linked.
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Quantitative trait loci mapping in F(2) crosses between Outbred Lines.
Genetics, 2000Co-Authors: Miguel Pérez-enciso, Luis VaronaAbstract:We develop a mixed-model approach for QTL analysis in crosses between Outbred Lines that allows for QTL segregation within Lines as well as for differences in mean QTL effects between Lines. We also propose a method called “segment mapping” that is based in partitioning the genome in a series of segments. The expected change in mean according to percentage of breed origin, together with the genetic variance associated with each segment, is estimated using maximum likelihood. The method also allows the estimation of differences in additive variances between the parental Lines. Completely fixed random and mixed models together with segment mapping are compared via simulation. The segment mapping and mixed-model behaviors are similar to those of classical methods, either the fixed or random models, under simple genetic models (a single QTL with alternative alleles fixed in each line), whereas they provide less biased estimates and have higher power than fixed or random models in more complex situations, i.e., when the QTL are segregating within the parental Lines. The segment mapping approach is particularly useful to determining which chromosome regions are likely to contain QTL when these are linked.
