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Optimal multiple trait selection for multiple linked quantitative trait loci.

A method was developed to optimize selection on multiple traits with multiple quantitative trait loci (QTLs) over multiple generations. The basis of the method was to replace in the objective function the genotypic value of a single trait with an aggregate genotypic value of multiple traits weighted by their corresponding economic weight, and to maximize the weighted sum of the selection response in the planning horizon. The optimization was formulated as a multiple stage optimal control problem and solved by a forward and backward iteration cycle. The practical utility of this method was illustrated in an example of pig breeding population, in which the number born alive (NBA) and days to 100 kg (D100) were used as parameters. The selection response of this method was compared with standard QTL selection and regular best linear unbiased prediction (BLUP) selection. Results showed that optimal selection achieved greater selection response than either standard QTL or regular BLUP selections. The influence of economic weight to optimal selection was significant, and the optimization was better as the economic weight of D100 increased. Optimal selection increased the total selection response by two ways: 1) it sacrificed some QTL responses during early generations and 2) it put more emphasis on D100. Optimal cumulative discounted selection gave more weight to D100 than optimal terminal selection in the longer generations.

Algorithms↗

The effects of spontaneous mutation on quantitative traits. II. Dominance of mutations with effects on life-history traits.

We studied the dominance of the effects of chromosomes carrying unselected mutations on five life-history traits in Drosophila melanogaster. Mutations were accumulated on the second chromosome for 44 generations in the absence of natural selection. Traits studied were female fecundity early and late in adult life, male mating ability, and male and female longevity. Homozygous effects were estimated for 50 mutant lines, and heterozygous effects were estimated by crossing these lines in a partial diallel scheme. Direct estimates of dominance showed that the effects of mutants are at least partially recessive. Heterozygotes had higher trait means than homozygotes in all five cases, and these differences were significant for late fecundity and female longevity. For all traits, genetic variance was larger among homozygous crosses than among heterozygous crosses. These results are consistent with those of many other studies that suggest that both unselected mutations and those found segregating in natural populations are partially recessive.

Animals↗

Quantitative trait loci affecting growth-related traits in wild barley (Hordeum spontaneum) grown under different levels of nutrient supply.

The genetic basis of phenotypic plasticity of relative growth rate (RGR), its components and associated morphological traits was studied in relation to nutrient limitation. In all, 140 F(3) lines from a cross, made between two Hordeum spontaneum (wild barley) accessions sampled in Israel, were subjected to growth analysis under two nutrient levels. Quantitative trait loci (QTLs) were detected for RGR and three of its components, leaf area ratio (LAR), specific leaf area and leaf mass fraction (LMF). Indications for close linkage (potential pleiotropy) were found, for example, for LAR and LMF. An interesting case is on chromosome 6, at which QTLs for RGR and seed mass were detected in the same region. These QTLs had opposite additive effects, supporting earlier results that plants growing from lighter seeds had a higher RGR. Only two QTLs were significant under both nutrient conditions, suggesting large QTL x environment interactions for most traits. For 21 out of 26 QTLs, however, the additive genetic effect was of identical sign in both nutrient environments, but reached the significance threshold in only one of them. Nevertheless, some QTLs detected in one of the two environments had virtually no effect in the other, and QTLs for plasticity were detected for RGR, LAR and LMF, as well as for some morphological traits. QTLs with opposite effects under high and low nutrients were not found. Thus, at the genetic level, there was no evidence for a trade-off between faster growth at high versus low nutrient levels.

Analysis of Variance↗

Mapping quantitative trait loci for complex binary traits in outbred populations.

Complex binary traits have a dichotomous phenotypic expression but do not show a simple Mendelian segregation ratio. These traits are considered to be jointly controlled by the actions of several genes and a random environmental effect. The binary phenotype and the underlying factor are assumed to be linked through a threshold model. The underlying factor, referred to as the liability, is treated as a regular but unobservable quantitative character. Mapping quantitative trait loci (QTL) can be performed directly on the liability. Methods of QTL mapping for the liability of a complex binary trait have been well developed in line-crossing experiments. However, such a method is not available in outbred populations which usually consist of many independent pedigrees (families). In this study, we develop a method to analyse jointly multiple families of an outbred population. The method is developed based on a fixed-model approach, i.e. the QTL effects, rather than the variance, are estimated and tested. After the test, the estimated effects are then converted into a single estimate of the QTL variance by taking into consideration errors in the estimated effects. The QTL effects and variance-covariance matrix of the estimates are obtained by a fast Fisher-scoring method. Monte Carlo simulations show that the method is not only powerful but also generates very accurate estimates of QTL variances.

Algorithms↗

Single- and multiple-trait mapping analysis of linked quantitative trait loci. Some asymptotic analytical approximations.

Estimating the resolution power of mapping analysis of linked quantitative trait loci (QTL) remains a difficult problem, which has been previously addressed mainly by Monte Carlo simulations. The analytical method of evaluation of the expected LOD developed in this article spreads the "deterministic sampling" approach for the case of two linked QTL for single- and two-trait analysis. Several complicated questions are addressed through this evaluation: the dependence of QTL detection power on the QTL effects, residual correlation between the traits, and the effect of epistatic interaction between the QTL for one or both traits on expected LOD (ELOD), etc. Although this method gives only an asymptotic estimation of ELOD, it allows one to get an approximate assessment of a broad spectrum of mapping situations. A good correspondence was found between the ELODs predicted by the model and LOD values averaged over Monte Carlo simulations.

Chromosome Mapping↗

Multiple-trait mapping of quantitative trait loci after selective genotyping using logistic regression.

Experiments to map QTL usually measure several traits, and not uncommonly genotype only those animals that are extreme for some trait(s). Analysis of selectively genotyped, multiple-trait data presents special problems, and most simple methods lead to biased estimates of the QTL effects. The use of logistic regression to estimate QTL effects is described, where the genotype is treated as the dependent variable and the phenotype as the independent variable. In this way selection on phenotype does not bias the results. If normally distributed errors are assumed, the logistic-regression analysis is almost equivalent to a maximum-likelihood analysis, but can be carried out with standard statistical packages. Analysis of a simulated half-sib experiment shows that logistic regression can estimate the effect and position of a QTL without bias and confirms the increased power achieved by multiple-trait analysis.

Genotype↗

Genetic variability at neutral markers, quantitative trait land trait in a subdivided population under selection.

Genetic variability in a subdivided population under stabilizing and diversifying selection was investigated at three levels: neutral markers, QTL coding for a trait, and the trait itself. A quantitative model with additive effects was used to link genotypes to phenotypes. No physical linkage was introduced. Using an analytical approach, we compared the diversity within deme (H(S)) and the differentiation (F(ST)) at the QTL with the genetic variance within deme (V(W)) and the differentiation (Q(ST)) for the trait. The difference between F(ST) and Q(ST) was shown to depend on the relative amounts of covariance between QTL within and between demes. Simulations were used to study the effect of selection intensity, variance of optima among demes, and migration rate for an allogamous and predominantly selfing species. Contrasting dynamics of the genetic variability at markers, QTL, and trait were observed as a function of the level of gene flow and diversifying selection. The highest discrepancy among the three levels occurred under highly diversifying selection and high gene flow. Furthermore, diversifying selection might cause substantial heterogeneity among QTL, only a few of them showing allelic differentiation, while the others behave as neutral markers.

Computer Simulation↗

Mapping of quantitative trait loci affecting quality and production traits in egg layers.

A mapping population segregating for egg quality traits was created by a line cross between two egg layer lines and screened by a genome scan. The F2 generation consisted of 307 hens, which were scored for egg quality and production traits. The mapping population was genotyped for 99 microsatellite loci, spanning nine macrochromosomes and five small linkage groups. The linkage maps were used in mapping QTL affecting 14 traits, by using multiple markers and a least-squares approach. We detected 14 genomewide significant and six suggestive QTL that were located on chromosomes 2, 3, 4, 5, and, 8 and sex chromosome Z. A significant QTL affecting egg white thinning was found on chromosome 2. For eggshell strength, a significant QTL was found on chromosome Z. For production traits, the most interesting area was on chromosome 4, where highly significant QTL effects were detected for BW, egg weight, and feed intake in the same area. The most significant QTL explains 25.8% of the phenotypic variance in F2 of body weight. An area affecting the age at first egg, egg weight, and the number of eggs was located on chromosome Z.

Animals↗

Effectiveness of selective genotyping for detection of quantitative trait loci: an analysis of grain and malt quality traits in three barley populations.

Marker genotype data and grain and malt quality phenotype data from three barley (Hordeum vulgare L.) mapping populations were used to investigate the feasibility of selective genotyping for detection of quantitative trait loci (QTLs). With selective genotyping, only individuals with high and low phenotypic values for the trait of interest are genotyped. Here, genotyping of 10 to 70% of each population (i.e., 5 to 35% in each tail of the phenotypic distribution) was considered. Genomic positions detected by selective genotyping were compared to QTL position estimates from interval mapping analysis using marker genotype data from the entire population. Selective genotyping reliably detected almost all of the mapped QTLs, often with only 10% of the population genotyped. Selective genotyping also detected spurious QTLs in regions of the genome where no significant QTL had been mapped. Even with additional genotyping to verify putative QTLs, the total genotyping effort for detection of QTLs for a single trait by selective genotyping was usually less than 30% of that required for conventional interval mapping. Simultaneous investigation of two or more traits by selective genotyping would require additional genotyping effort, but could still be worthwhile.

Genotype↗

Mapping quantitative trait loci for bean traits and ovule number in Theobroma cacao L.

Quantitative trait loci (QTL) mapping for bean traits and the number of ovules per ovary was carried out in cocoa (Theobroma cacao L.) using three test-cross progenies derived from crosses between a lower Amazon Forastero male parent (Catongo) and three female parents: one upper Amazon Forastero (IMC78) and two Trinitario (DR1 and S52). RFLP (restriction fragment length polymorphism), microsatellite, and AFLP (amplified fragment lengthpolymorphism) markers were used for mapping. Between one and six QTL for bean traits (length, weight, and shape index) and one and four QTL for the number of ovules per ovary were detected using composite interval mapping (CIM). Individual QTL explained between 5 and 24% of the phenotypic variation. QTL clusters were identified on several chromosomes, but particularly on chromosome 4. QTL related to bean traits were detected in the same region in both Trinitario parents and in a close region in the upper Amazon Forastero parent. In reference to a previous diversity study where alleles specific to Criollo and Forastero genotypes were identified, it was possible to speculate on the putative origin (Criollo or Forastero) of favorable QTL alleles segregating in both Trinitario studied.

Cacao↗

Detection of quantitative trait loci for carcass composition traits in pigs.

A quantitative trait locus (QTL) analysis of carcass composition data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. A total of 488 F2 males issued from six F1 boars and 23 F1 sows, the progeny of six LW boars and six MS sows, were slaughtered at approximately 80 kg live weight and were submitted to a standardised cutting of the carcass. Fifteen traits, i.e. dressing percentage, loin, ham, shoulder, belly, backfat, leaf fat, feet and head weights, two backfat thickness and one muscle depth measurements, ham + loin and back + leaf fat percentages and estimated carcass lean content were analysed. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using a line-cross (LC) regression method where founder lines were assumed to be fixed for different QTL alleles and a half/full sib (HFS) maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Additional analyses were performed to search for multiple linked QTL and imprinting effects. Significant gene effects were evidenced for both leanness and fatness traits in the telomeric regions of SSC 1q and SSC 2p, on SSC 4, SSC 7 and SSC X. Additional significant QTL were identified for ham weight on SSC 5, for head weight on SSC 1 and SSC 7, for feet weight on SSC 7 and for dressing percentage on SSC X. LW alleles were associated with a higher lean content and a lower fat content of the carcass, except for the fatness trait on SSC 7. Suggestive evidence of linked QTL on SSC 7 and of imprinting effects on SSC 6, SSC 7, SSC 9 and SSC 17 were also obtained.

Animals↗

Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits.

Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide polymorphism (SNP) maps provides a potentially more powerful option. Using the simulated and Collaborative Study on the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14 (GAW14), we examined how altering the density of SNP marker sets impacted the overall information content, the power to detect trait loci, and the number of false positive results. For the simulated data we used SNP maps with density of 0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from Illumina and Affymetrix to create a map with average density of 0.25 cM and then, using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM, 1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using MERLIN was performed for both dominant and recessive traits derived from marker loci. Our results showed that information content increased with increased map density. For the homogeneous, completely penetrant traits we created, there was only a modest difference in ability to detect trait loci. Additionally, as map density increased there was only a slight increase in the number of false positive results when there was linkage disequilibrium (LD) between markers. The presence of LD between markers may have led to an increased number of false positive regions but no clear relationship between regions of high LD and locations of false positive linkage signals was observed.

Alcoholism↗

A genome scan for quantitative trait loci affecting growth-related traits in an F1 family of Asian seabass (Lates calcarifer).

BACKGROUND: Body weight and length are economically important traits in foodfish species influenced by quantitative trait loci (QTL) and environmental factors. It is usually difficult to dissect the genetic and environmental effects. Asian seabass (Lates calcarifer) is an important marine foodfish species with a compact genome (approximately 700 Mb). The recent construction of a first generation linkage map of Asian seabass with 240 microsatellites provides a good opportunity to determine the number and position of QTL, and the magnitude of QTL effects with a genome scan. RESULTS: We conducted a genome scan for QTL affecting body weight, standard length and condition factors in an F1 family containing 380 full-sib individuals from a breeding stock by using 97 microsatellites evenly covering 24 chromosomes. Interval mapping and multiple QTL model mapping detected five significant and 27 suggestive QTL on ten linkage groups (LGs). Among the five significant QTL detected, three (qBW2-a, qTL2-a and qSL2-a) controlling body weight, total and standard length respectively, were mapped on the same region near Lca287 on LG2, and explained 28.8, 58.9 and 59.7% of the phenotypic variance. The other two QTL affecting body weight, qBW2-b and qBW3, were located on LG2 and 3, and accounted for 6.4 and 8.8% of the phenotypic variance. Suggestive QTL associated with condition factors are located on six different LGs. CONCLUSION: This study presents the first example of QTL detection for growth-related traits in an F1 family of a marine foodfish species. The results presented here will enable further fine-mapping of these QTL for marker-assisted selection of the Asian seabass, eventually identifying individual genes responsible for growth-related traits.

Animals↗

Serum adiponectin concentration: its correlation with diabetes-related traits and quantitative trait loci analysis in mouse SMXA recombinant inbred strains.

Adiponectin is thought to be an important mediator of insulin sensitivity and atherosclerosis. Using mouse 19 SMXA recombinant inbred (RI) strains, a powerful tool for analyzing multifactorial genetic traits, we found relationships between serum adiponectin levels and diabetes-related traits, body mass index, and serum lipid levels, and also determined the loci controlling serum adiponectin levels by quantitative trait loci (QTL) analysis. RI strains exhibited widely ranging serum adiponectin concentration distribution patterns and diabetes-related traits. The serum adiponectin concentration showed the strongest negative correlation with fasting serum insulin concentration, but negative correlations were also observed with serum triglycerides, cholesterol, and liver weight. In contrast, neither the body mass index nor the blood glucose concentration correlated with serum adiponectin levels. These results suggest that hypoadiponectinemia might be used as a predictor of insulin resistance. In addition, two suggestive QTLs for serum adiponectin concentration were detected on Chromosome (Chr) 7, and an A/J allele at these loci was associated with elevated serum adiponectin concentrations. Identification of genes responsible for regulating the serum adiponectin concentration might lead to the development of novel treatments for patients with diabetes concomitant with hypoadiponectinemia.

Adiponectin↗

Identification of quantitative trait loci across recombinant inbred lines and testcross populations for traits of agronomic importance in rice.

This study was conducted to determine whether quantitative trait loci (QTL) controlling traits of agronomic importance detected in recombinant inbred lines (RILs) are also expressed in testcross (TC) hybrids of rice. A genetic map was constructed using an RIL population derived from a cross between B5 and Minghui 63, a parent of the most widely grown hybrid rice cultivar in China. Four TC hybrid populations were produced by crossing the RILs with three maintaining lines for the widely used cytoplasmic male-sterile (CMS) lines and the genic male-sterile line Peiai64s. The mean values of the RILs for the seven traits investigated were significantly correlated to those of the F1 hybrids in the four TC populations. Twenty-seven main-effect QTL were identified in the RILs. Of these, the QTL that had the strongest effect on each of the seven traits in the RILs was detected in two or more of the TC populations, and six other QTL were detected in one TC population. Epistatic analysis revealed that the effect of epistatic QTL was relatively weak and cross combination specific. Searching publicly available QTL data in rice revealed the positional convergence of the QTL with the strongest effect in a wide range of populations and under different environments. Since the main-effect QTL is expressed across different testers, and in different genetic backgrounds and environments, it is a valuable target for gene manipulation and for further application in rice breeding. When a restorer line that expresses main-effect QTL is bred, it could be used in a number of cross combinations.

Chromosome Mapping↗

Quantitative trait loci affecting health traits in Swedish dairy cattle.

The purpose of this study was to map quantitative trait loci (QTL) affecting health traits in Swedish dairy cattle. A genome scan covering 17 chromosomes was performed. Ten grandsire families were used in a granddaughter design. Nine of the families belonged to the Swedish Red and White breed, which is related to other Nordic Ayrshire breeds, and one family was of the Swedish Holstein breed. A total of 417 bulls were genotyped for 116 microsatellite markers distributed over 17 chromosomes. Daughter yield deviations for clinical mastitis, somatic cell count (SCC), and other diseases (OD) were included in the analysis. Least squares interval mapping using putative QTL as cofactors was applied both within and across grandsire families. Significance thresholds were set by permutation tests. In the across-family analysis, we detected 8 suggestive QTL and 3 QTL significant at the genome level. The QTL affecting clinical mastitis were found on 3 chromosomes (9, 11, and 25), 4 QTL for SCC were found (on chromosomes 5, 9, 11, and 23), and we detected 4 QTL for OD (on chromosomes 9, 11, 15, and 25). In addition, we found several QTL that segregated within single families but where the QTL effect was not significant in the across-family analysis. In conclusion, we were able to locate QTL for all 3 analyzed traits, and overlapping QTL for several traits were observed.

Animals↗

Mapping of serum amylase-1 and quantitative trait loci for milk production traits to cattle chromosome 4.

The present study was undertaken to confirm and refine the mapping of a quantitative trait locus in cattle for milk fat percentage that had earlier been reported to be linked to the serum amylase-1 locus, AM1. Five half-sib families from the previous study and 7 new ones were genotyped for nine microsatellite markers spanning chromosome 4. AM1 was mapped between the microsatellite markers BMS648 and BR6303. In a granddaughter design, interval mapping based on multiple-marker regression was utilized for an analysis of five milk production traits: milk yield, fat percentage and yield, and protein percentage and yield. In the families reported on previously, significant effects for fat and protein percentages were detected. In the new families, an effect on milk and fat yields was found. The most likely positions of the quantitative trait locus in both groups of families were in the same area of chromosome 4 in the vicinity of the obese locus. Direct effects of the obese locus were tested for using polymorphism in two closely linked microsatellites located 2.5 and 3.6 top downstream of the coding sequence. No firm evidence was found for an association between the obese locus and the tested traits.

Amylases↗

The genetic basis of adaptive population differentiation: a quantitative trait locus analysis of fitness traits in two wild barley populations from contrasting habitats.

We used a quantitative trait locus (QTL) approach to study the genetic basis of population differentiation in wild barley, Hordeum spontaneum. Several ecotypes are recognized in this model species, and population genetic studies and reciprocal transplant experiments have indicated the role of local adaptation in shaping population differences. We derived a mapping population from a cross between a coastal Mediterranean population and a steppe inland population from Israel and assessed F3 progeny fitness in the natural growing environments of the two parental populations. Dilution of the local gene pool, estimated as the proportion of native alleles at 96 marker loci in the recombinant lines, negatively affected fitness traits at both sites. QTLs for fitness traits tended to differ in the magnitude but not in the direction of their effects across sites, with beneficial alleles generally conferring a greater fitness advantage at their native site. Several QTLs showed fitness effects at one site only, but no opposite selection on individual QTLs was observed across the sites. In a common-garden experiment, we explored the hypothesis that the two populations have adapted to divergent nutrient availabilities. In the different nutrient environments of this experiment, but not under field conditions, fitness of the F3 progeny lines increased with the number of heterozygous marker loci. Comparison of QTL-effects that underlie genotype x nutrient interaction in the common-garden experiment and genotype x site interaction in the field suggested that population differentiation at the field sites may have been driven by divergent nutrient availabilities to a limited extent. Also in this experiment no QTLs were observed with opposite fitness effects in contrasting environments. Our data are consistent with the view that adaptive differentiation can be based on selection on multiple traits changing gradually along ecological gradients. This can occur without QTLs showing opposite fitness effects in the different environments, that is, in the absence of genetic trade-offs in performance between environments.

Adaptation, Biological↗