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1.
In a population intended for breeding and selection, questions of interest relative to a specific segregating QTL are the variance it generates in the population, and the number and effects of its alleles. One approach to address these questions is to extract several inbreds from the population and use them to generate multiple mapping families. Given random sampling of parents, sampling strategy may be an important factor determining the power of the analysis and its accuracy in estimating QTL variance and allelic number. We describe appropriate multiple-family QTL mapping methodology and apply it to simulated data sets to determine optimal sampling strategies in terms of family number versus family size. Genomes were simulated with seven chromosomes, on which 107 markers and six QTL were distributed. The total heritability was 0.60. Two to ten alleles were segregating at each QTL. Sampling strategies ranged from sampling two inbreds and generating a single family of 600 progeny to sampling 40 inbreds and generating 40 families of 15 progeny each. Strategies involving only one to five families were subject to variation due to the sampling of inbred parents. For QTL where more than two alleles were segregating, these strategies did not sample QTL alleles representative of the original population. Conversely, strategies involving 30 or more parents were subject to variation due to sampling of QTL genotypes within the small families obtained. Given these constraints, greatest QTL detection power was obtained for strategies involving five to ten mapping families. The most accurate estimation of the variance generated by the QTL, however, was obtained with strategies involving 20 or more families. Finally, strategies with an intermediate number of families best estimated the number of QTL alleles. We conclude that no overall optimal sampling strategy exists but that the strategy adopted must depend on the objective.Communicated by P. Langridge  相似文献   

2.
The aim of this study was to compare the variance component approach for QTL linkage mapping in half-sib designs to the simple regression method. Empirical power was determined by Monte Carlo simulation in granddaughter designs. The factors studied (base values in parentheses) included the number of sires (5) and sons per sire (80), ratio of QTL variance to total genetic variance (λ = 0.1), marker spacing (10 cM), and QTL allele frequency (0.5). A single bi-allelic QTL and six equally spaced markers with six alleles each were simulated. Empirical power using the regression method was 0.80, 0.92 and 0.98 for 5, 10, and 20 sires, respectively, versus 0.88, 0.98 and 0.99 using the variance component method. Power was 0.74, 0.80, 0.93, and 0.95 using regression versus 0.77, 0.88, 0.94, and 0.97 using the variance component method for QTL variance ratios (λ) of 0.05, 0.1, 0.2, and 0.3, respectively. Power was 0.79, 0.85, 0.80 and 0.87 using regression versus 0.80, 0.86, 0.88, and 0.85 using the variance component method for QTL allele frequencies of 0.1, 0.3, 0.5, and 0.8, respectively. The log10 of type I error profiles were quite flat at close marker spacing (1 cM), confirming the inability to fine-map QTL by linkage analysis in half-sib designs. The variance component method showed slightly more potential than the regression method in QTL mapping.  相似文献   

3.
In a simulation study, different designs were compared for efficiency of fine-mapping of QTL. The variance component method for fine-mapping of QTL was used to estimate QTL position and variance components. The design of many families with small size gave a higher mapping resolution than a design with few families of large size. However, the difference is small in half sib designs. The proportion of replicates with the QTL positioned within 3 cM of the true position is 0.71 in the best design, and 0.68 in the worst design applied to 128 animals with a phenotypic record and a QTL explaining 25% of the phenotypic variance. The design of two half sib families each of size 64 was further investigated for a hypothetical population with effective size of 1000 simulated for 6000 generations with a marker density of 0.25 cM and with marker mutation rate 4 × 10-4 per generation. In mapping using bi-allelic markers, 42~55% of replicated simulations could position QTL within 0.75 cM of the true position whereas this was higher for multi allelic markers (48~76%). The accuracy was lowest (48%) when mutation age was 100 generations and increased to 68% and 76% for mutation ages of 200 and 500 generations, respectively, after which it was about 70% for mutation ages of 1000 generations and older. When effective size was linearly decreasing in the last 50 generations, the accuracy was decreased (56 to 70%). We show that half sib designs that have often been used for linkage mapping can have sufficient information for fine-mapping of QTL. It is suggested that the same design with the same animals for linkage mapping should be used for fine-mapping so gene mapping can be cost effective in livestock populations.  相似文献   

4.
Whereas detection and positioning of genes that affect quantitative traits (quantitative trait loci (QTL)) using linkage mapping uses only information from recombinants in the genotyped generations, linkage disequilibrium (LD) mapping uses historical recombinants. Thus, whereas linkage mapping requires large family sizes to detect and accurately position QTL, LD mapping is more dependent on the number of families sampled from the population. In commercial Atlantic salmon breeding programmes, only a small number of individuals per family are routinely phenotyped for traits such as disease resistance and meat colour. In this paper, we assess the power and accuracy of combined linkage disequilibrium linkage analysis (LDLA) to detect QTL in the commercial population using simulation. When 15 half-sib sire families (each sire mated to 30 dams, each dam with 10 progeny) were sampled from the population for genotyping, we were able to detect a QTL explaining 10% of the phenotypic variance in 85% of replicates and position this QTL within 3 cM of the true position in 70% of replicates. When recombination was absent in males, a feature of the salmon genome, power to detect QTL increased; however, the accuracy of positioning the QTL was decreased. By increasing the number of sire families sampled from the population to be genotyped to 30, we were able to increase both the proportion of QTL detected and correctly positioned (even with no recombination in males). QTL with much smaller effect could also be detected. The results suggest that even with the existing recording structure in commercial salmon breeding programmes, there is considerable power to detect and accurately position QTL using LDLA.  相似文献   

5.
QTL detection experiments in livestock species commonly use the half-sib design. Each male is mated to a number of females, each female producing a limited number of progeny. Analysis consists of attempting to detect associations between phenotype and genotype measured on the progeny. When family sizes are limiting experimenters may wish to incorporate as much information as possible into a single analysis. However, combining information across sires is problematic because of incomplete linkage disequilibrium between the markers and the QTL in the population. This study describes formulæ for obtaining MLEs via the expectation maximization (EM) algorithm for use in a multiple-trait, multiple-family analysis. A model specifying a QTL with only two alleles, and a common within sire error variance is assumed. Compared to single-family analyses, power can be improved up to fourfold with multi-family analyses. The accuracy and precision of QTL location estimates are also substantially improved. With small family sizes, the multi-family, multi-trait analyses reduce substantially, but not totally remove, biases in QTL effect estimates. In situations where multiple QTL alleles are segregating the multi-family analysis will average out the effects of the different QTL alleles.  相似文献   

6.
Natural mating and mass spawning in the European sea bass (Dicentrarchus labrax L., Moronidae, Teleostei) complicate genetic studies and the implementation of selective breeding schemes. We utilized a two‐step experimental design for detecting QTL in mass‐spawning species: 2122 offspring from natural mating between 57 parents (22 males, 34 females and one missing) phenotyped for body weight, eight morphometric traits and cortisol levels, had been previously assigned to parents based on genotypes of 31 DNA microsatellite markers. Five large full‐sib families (five sires and two dams) were selected from the offspring (570 animals), which were genotyped with 67 additional markers. A new genetic map was compiled, specific to our population, but based on the previously published map. QTL mapping was performed with two methods: half‐sib regression analysis (paternal and maternal) and variance component analysis accounting for all family relationships. Two significant QTL were found for body weight on linkage group 4 and 6, six significant QTL for morphometric traits on linkage groups 1B, 4, 6, 7, 15 and 23 and three suggestive QTL for stress response on linkage groups 3, 14 and 23. The QTL explained between 8% and 38% of phenotypic variance. The results are the first step towards identifying genes involved in economically important traits like body weight and stress response in European sea bass.  相似文献   

7.
Boulding EG  Culling M  Glebe B  Berg PR  Lien S  Moen T 《Heredity》2008,101(4):381-391
European Atlantic salmon (Salmo salar) differ in skin pigmentation and shape from the North American lineage of Atlantic salmon but the genetic basis of these differences are poorly understood. We created four large (N=300) backcross families by crossing F1 hybrid male siblings to two females from the European and two from the North American aquacultural strains. We recorded 15 morphological landmarks and two skin pigmentation, three growth and three condition traits on parr. The backcross families were genotyped for at least 129 SNPs (single nucleotide polymorphisms) within expressed sequence tags (ESTs) spaced throughout the Atlantic salmon linkage map. The high polymorphism and low rates of crossover in our hybrid sires provided enough statistical power to detect 79 significant associations between SNP markers and quantitative traits after experiment-wide permutation analysis for all families within traits. Linkage group AS22 contained a quantitative trait loci (QTL) for parr mark number; its homolog AS24 contained a large QTL, which explained 26% of the phenotypic variance in parr mark contrast. We found 25 highly significant QTLs for body shape and fin position on seven different linkage groups, and 16 for growth and condition on six different linkage groups. QTL(s) for pectoral fin position, caudal peduncle position, late parr growth and condition index were associated with an SNP on linkage group AS1, which was linked to the sex-determining locus. Our work adds to the evidence that much of the variation in growth rate, shape and skin pigmentation observed among Atlantic salmon parr from different natal streams is genetic.  相似文献   

8.
Investigation on QTL-marker linkage usually requires a great number of observed recombinations, inferred from combined analysis of phenotypes and genotypes. To avoid costly individual genotyping, inferences on QTL position and effects can instead make use of marker allele frequencies. DNA pooling of selected samples makes allele frequency estimation feasible for studies involving large sample sizes. Linkage studies in outbred populations have traditionally exploited half-sib family designs; within the animal production context, half-sibships provide large families that are highly suitable for DNA pooling. Estimators for QTL position and effect have been proposed that make use of information from flanking markers. We present formulas derived by the delta method for the asymptotic variance of these estimators.  相似文献   

9.
In this article, the quantitative genetic aspects of imprinted genes and statistical properties of methods to detect imprinted QTL are studied. Different models to detect imprinted QTL and to distinguish between imprinted and Mendelian QTL were compared in a simulation study. Mendelian and imprinted QTL were simulated in an F2 design and analyzed under Mendelian and imprinting models. Mode of expression was evaluated against the H(0) of a Mendelian QTL as well as the H(0) of an imprinted QTL. It was shown that imprinted QTL might remain undetected when analyzing the genome with Mendelian models only. Compared to testing against a Mendelian QTL, using the H(0) of an imprinted QTL gave a higher proportion of correctly identified imprinted QTL, but also gave a higher proportion of false inference of imprinting for Mendelian QTL. When QTL were segregating in the founder lines, spurious detection of imprinting became more prominent under both tests, especially for designs with a small number of F1 sires.  相似文献   

10.
S. A. Knott  C. S. Haley 《Genetics》1992,132(4):1211-1222
A maximum likelihood method is presented for the detection of quantitative trait loci (QTL) using flanking markers in full-sib families. This method incorporates a random component for common family effects due to additional QTL or the environment. Simulated data have been used to investigate this method. With a fixed total number of full sibs power of detection decreased substantially with decreasing family size. Increasing the number of alleles at the marker loci (i.e., polymorphism information content) and decreasing the interval size about the QTL increased power. Flanking markers were more powerful than single markers. In testing for a linked QTL the test must be made against a model which allows for between family variation (i.e., including an unlinked QTL or a between family variance component) or the test statistic may be grossly inflated. Mean parameter estimates were close to the simulated values in all situations when fitting the full model (including a linked QTL and common family effect). If the common family component was omitted the QTL effect was overestimated in data in which additional genetic variance was simulated and when compared with an unlinked QTL model there was reduced power. The test statistic curves, reflecting the likelihood of the QTL at each position along the chromosome, have discontinuities at the markers caused by adjacent pairs of markers providing different amounts of information. This must be accounted for when using flanking markers to search for a QTL in an outbred population.  相似文献   

11.
Fertility quantitative trait loci (QTL) are of high interest in dairy cattle since insemination failure has dramatically increased in some breeds such as Holstein. High-throughput SNP analysis and SNP microarrays give the opportunity to genotype many animals for hundreds SNPs per chromosome. In this study, due to these techniques a dense SNP marker map was used to fine map a QTL underlying nonreturn rate measured 90 days after artificial insemination previously detected with a low-density microsatellite marker map. A granddaughter design with 17 Holstein half-sib families (926 offspring) was genotyped for a set of 437 SNPs mapping to BTA3. Linkage analysis was performed by both regression and variance components analysis. An additional analysis combining both linkage analysis and linkage-disequilibrium information was applied. This method first estimated identity-by-descent probabilities among base haplotypes. These probabilities were then used to group the base haplotypes in different clusters. A QTL explaining 14% of the genetic variance was found with high significance (P < 0.001) at position 19 cM with the linkage analysis and four sires were estimated to be heterozygous (P < 0.05). Addition of linkage-disequilibrium information refined the QTL position to a set of narrow peaks. The use of the haplotypes of heterozygous sires offered the possibility to give confidence in some peaks while others could be discarded. Two peaks with high likelihood-ratio test values in the region of which heterozygous sires shared a common haplotype appeared particularly interesting. Despite the fact that the analysis did not fine map the QTL in a unique narrow region, the method proved to be able to handle efficiently and automatically a large amount of information and to refine the QTL position to a small set of narrow intervals. In addition, the QTL identified was confirmed to have a large effect (explaining 13.8% of the genetic variance) on dairy cow fertility as estimated by nonreturn rate at 90 days.  相似文献   

12.
Genotype-by-environment interaction is caused by variation in genetic environmental sensitivity (GES), which can be subdivided into macro- and micro-GES. Macro-GES is genetic sensitivity to macro-environments (definable environments often shared by groups of animals), while micro-GES is genetic sensitivity to micro-environments (individual environments). A combined reaction norm and double hierarchical generalised linear model (RN-DHGLM) allows for simultaneous estimation of base genetic, macro- and micro-GES effects. The accuracy of variance components estimated using a RN-DHGLM has been explicitly studied for balanced data and recommendation of a data size with a minimum of 100 sires with at least 100 offspring each have been made. In the current study, the data size (numbers of sires and progeny) and structure requirements of the RN-DHGLM were investigated for two types of unbalanced datasets. Both datasets had a variable number of offspring per sire, but one dataset also had a variable number of offspring within macro-environments. The accuracy and bias of the estimated macro- and micro-GES effects and the estimated breeding values (EBVs) obtained using the RN-DHGLM depended on the data size. Reasonably accurate and unbiased estimates were obtained with data containing 500 sires with 20 offspring or 100 sires with 50 offspring, regardless of the data structure. Variable progeny group sizes, alone or in combination with an unequal number of offspring within macro-environments, had little impact on the dispersion of the EBVs or the bias and accuracy of variance component estimation, but resulted in lower accuracies of the EBVs. Compared to genetic correlations of zero, a genetic correlation of 0.5 between base genetic, macro- and micro-GES components resulted in a slight decrease in the percentage of replicates that converged out of 100 replicates, but had no effect on the dispersion and accuracy of variance component estimation or the dispersion of the EBVs. The results show that it is possible to apply the RN-DHGLM to unbalanced datasets to obtain estimates of variance due to macro- and micro-GES. Furthermore, the levels of accuracy and bias of variance estimates when analysing macro- and micro-GES simultaneously are determined by average family size, with limited impact from variability in family size and/or cohort size. This creates opportunities for the use of field data from populations with unbalanced data structures when estimating macro- and micro-GES.  相似文献   

13.
Large fruit size is a critical trait for any new sweet cherry (Prunus avium L.) cultivar, as it is directly related to grower profitability. Therefore, determining the genetic control of fruit size in relevant breeding germplasm is a high priority. The objectives of this study were (1) to determine the number and positions of quantitative trait loci (QTL) for sweet cherry fruit size utilizing data simultaneously from multiple families and their pedigreed ancestors, and (2) to estimate fruit size QTL genotype probabilities and genomic breeding values for the plant materials. The sweet cherry material used was a five-generation pedigree consisting of 23 founders and parents and 424 progeny individuals from four full-sib families, which were phenotyped for fruit size and genotyped with 78 RosCOS single nucleotide polymorphism and 86 simple sequence repeat markers. These data were analyzed by a Bayesian approach implemented in FlexQTL? software. Six QTL were identified: three on linkage group (G) 2 with one each on groups 1, 3, and 6. Of these QTL, the second G2 QTL and the G6 QTL were previously discovered while other QTL were novel. The predicted QTL genotypes show that some QTL were segregating in all families while other QTL were segregating in a subset of the families. The progeny varied for breeding value, with some progeny having higher breeding values than their parents. The results illustrate the use of multiple pedigree-linked families for integrated QTL mapping in an outbred crop to discover novel QTL and predict QTL genotypes and breeding values.  相似文献   

14.
The genetic architecture underlying variation in embryonic developmental rate (DR) and genetic covariation with age of maturation (MAT) was investigated in rainbow trout Oncorhynchus mykiss. Highly significant additive parental effects and more limited evidence of epistatic effects on progeny hatching time were detected in three diallel sets of families. Genome scans with an average of 142 microsatellite loci from all 29 linkage groups in two families detected significant quantitative trait loci (QTL) for developmental rate on RT-8 and RT-30 with genome-wide and chromosome-wide effects, respectively. The QTL on linkage group RT-8 explained 23·7% of the phenotypic variation and supports results from previous studies. The co-localization of QTL for both DR and MAT to several linkage groups and the observation that alleles associated with faster developmental rate were found significantly more often in early maturing rather than typical and later maturing male ancestors supports the hypothesis of genetic covariation between DR and MAT. The maturation background and schedule of additional sires, however, did not have a consistent association with their progeny hatching times, suggesting that other genetic, environmental and physiological effects contribute to variation in these life-history traits.  相似文献   

15.
S Xu 《Genetics》1998,148(1):517
To avoid a loss in statistical power as a result of homozygous individuals being selected as parents of a mapping population, one can use multiple families of line crosses for quantitative trait genetic linkage analysis. Two strategies of combining data are investigated: the fixed-model and the random-model strategies. The fixed-model approach estimates and tests the average effect of gene substitution for each parent, while the random-model approach treats each effect of gene substitution as a random variable and directly estimates and tests the variance of gene substitution. Extensive Monte Carlo simulations verify that the two strategies perform equally well, although the random model is preferable in combining data from a large number of families. Simulations also show that there may be an optimal sampling strategy (number of families vs. number of individuals per family) in which QTL mapping reaches its maximum power and minimum estimation error. Deviation from the optimal strategy reduces the efficiency of the method.  相似文献   

16.
Analysis of quantitative trait loci (QTL) affecting complex traits is often pursued in single-cross experiments. For most purposes, including breeding, some assessment is desired of the generalizability of the QTL findings and of the overall genetic architecture of the trait. Single-cross experiments provide a poor basis for these purposes, as comparison across experiments is hampered by segregation of different allelic combinations among different parents and by context-dependent effects of QTL. To overcome this problem, we combined the benefits of QTL analysis (to identify genomic regions affecting trait variation) and classic diallel analysis (to obtain insight into the general inheritance of the trait) by analyzing multiple mapping families that are connected via shared parents. We first provide a theoretical derivation of main (general combining ability (GCA)) and interaction (specific combining ability (SCA)) effects on F(2) family means relative to variance components in a randomly mating reference population. Then, using computer simulations to generate F(2) families derived from 10 inbred parents in different partial-diallel designs, we show that QTL can be detected and that the residual among-family variance can be analyzed. Standard diallel analysis methods are applied in order to reveal the presence and mode of action (in terms of GCA and SCA) of undetected polygenes. Given a fixed experiment size (total number of individuals), we demonstrate that QTL detection and estimation of the genetic architecture of polygenic effects are competing goals, which should be explicitly accounted for in the experimental design. Our approach provides a general strategy for exploring the genetic architecture, as well as the QTL underlying variation in quantitative traits.  相似文献   

17.
It is a challenging issue to map Quantitative Trait Loci (QTL) underlying complex discrete traits,which usually show discontinuous distribution and less information,using conventional statisti-cal methods. Bayesian-Markov chain Monte Carlo (Bayesian-MCMC) approach is the key procedure in mapping QTL for complex binary traits,which provides a complete posterior distribution for QTL parameters using all prior information. As a consequence,Bayesian estimates of all interested vari-ables can be obtained straightforwardly basing on their posterior samples simulated by the MCMC algorithm. In our study,utilities of Bayesian-MCMC are demonstrated using simulated several ani-mal outbred full-sib families with different family structures for a complex binary trait underlied by both a QTL and polygene. Under the Identity-by-Descent-Based variance component random model,three samplers basing on MCMC,including Gibbs sampling,Metropolis algorithm and reversible jump MCMC,were implemented to generate the joint posterior distribution of all unknowns so that the QTL parameters were obtained by Bayesian statistical inferring. The results showed that Bayesian-MCMC approach could work well and robust under different family structures and QTL effects. As family size increases and the number of family decreases,the accuracy of the parameter estimates will be im-proved. When the true QTL has a small effect,using outbred population experiment design with large family size is the optimal mapping strategy.  相似文献   

18.
It is a challenging issue to map Quantitative Trait Loci (QTL) underlying complex discrete traits, which usually show discontinuous distribution and less information, using conventional statistical methods. Bayesian-Markov chain Monte Carlo (Bayesian-MCMC) approach is the key procedure in mapping QTL for complex binary traits, which provides a complete posterior distribution for QTL parameters using all prior information. As a consequence, Bayesian estimates of all interested variables can be obtained straightforwardly basing on their posterior samples simulated by the MCMC algorithm. In our study, utilities of Bayesian-MCMC are demonstrated using simulated several animal outbred full-sib families with different family structures for a complex binary trait underlied by both a QTL and polygene. Under the Identity-by-Descent-Based variance component random model, three samplers basing on MCMC, including Gibbs sampling, Metropolis algorithm and reversible jump MCMC, were implemented to generate the joint posterior distribution of all unknowns so that the QTL parameters were obtained by Bayesian statistical inferring. The results showed that Bayesian-MCMC approach could work well and robust under different family structures and QTL effects. As family size increases and the number of family decreases, the accuracy of the parameter estimates will be improved. When the true QTL has a small effect, using outbred population experiment design with large family size is the optimal mapping strategy.  相似文献   

19.
Tiller number (TN) and spike number per plant (SN) are key components of grain yield and/or biomass in wheat. In this study, an introgression line 05210, developed by introgression of chromosomal segments from a synthetic exotic wheat Am3 into an elite cultivar Laizhou953, showed a significantly increased TN and SN, but shorter spike length (SL) and fewer grain number per spike (GNS) than Laizhou953. To investigate the quantitative trait locus (QTL) responsible for these variations, the introgressed segments in 05210 were screened by SSR markers and one follow-up segregation population was developed from the cross 05210/Laizhou953. The population showed 3:1 segregation ratios for SN, SL and GNS, indicating that QTLs for these traits have been dissected into single Mendelian factors. Bulked segregation analysis showed that the markers located on the 4B introgressed segment were polymorphic between the two bulks. Therefore, they were further analyzed in the F2 population to construct a linkage map. Three new QTLs, QSn.sdau-4B, QSl.sdau-4B and QGns.sdau-4B, were detected for SN, SL and GNS, respectively, which explained a large portion of the phenotypic variation (30.1–67.6%) for these traits with overlapping peaks. Correlation analysis and multiple-trait, multiple-interval mapping (MMIM) suggested pleiotropic effects of the QTL on SN, SL and GNS. Therefore, the QTL was designated as QSn.sdau-4B. By a progeny test based on F3 families using SN, the QTL was mapped as a Mendelian factor to the proximal region of 4BL. It is a key QTL responsible for variation in spike number and size, which had not been reported previously. Thus, it is an important QTL for wheat to achieve high and stable biomass and grain yield. Dissection and mapping of this QTL as a Mendelian factor laid a solid foundation for map-based cloning of grain yield-related QTLs in wheat.  相似文献   

20.
Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter designs requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.  相似文献   

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