Genome‐wide association study for body weight in cattle populations from Siberia

Body weight is a complex trait in cattle associated with commonly used commercial breeding measurements related to growth. Although many quantitative trait loci (QTL) for body weight have been identified in cattle so far, searching for genetic determinants in different breeds or environments is promising. Therefore, we carried out a genome‐wide association study (GWAS) in two cattle populations from the Russian Federation (Siberian region) using the GGP HD150K array containing 139 376 single nucleotide polymorphism (SNP) markers. Association tests for 107 550 SNPs left after filtering revealed five statistically significant SNPs on BTA5, considering a false discovery rate of less than 0.05. The chromosomal region containing these five SNPs contains the CCND2 gene, which was previously associated with average daily weight gain and body mass index in US beef cattle populations and in humans respectively. Our study is the first GWAS for body weight in beef cattle populations from the Russian Federation. The results provided here suggest that, despite the existence of breed‐ and species‐specific QTL, the genetic architecture of body weight could be evolutionarily conserved in mammals.     

Quantitative trait loci for magnitude of the plasma cortisol response to confinement in rainbow trout

Better understanding of the mechanisms underlying interindividual variation in stress responses and their links with production traits is a key issue for sustainable animal breeding. In this study, we searched for quantitative trait loci (QTL) controlling the magnitude of the plasma cortisol stress response and compared them to body size traits in five F2 full‐sib families issued from two rainbow trout lines divergently selected for high or low post‐confinement plasma cortisol level. Approximately 1000 F2 individuals were individually tagged and exposed to two successive acute confinement challenges (1 month interval). Post‐stress plasma cortisol concentrations were determined for each fish. A medium density genome scan was carried out (268 markers, overall marker spacing less than 10 cM). QTL detection was performed using qtlmap software, based on an interval mapping method ( http://www.inra.fr/qtlmap ). Overall, QTL of medium individual effects on cortisol responsiveness (<10% of phenotypic variance) were detected on 18 chromosomes, strongly supporting the hypothesis that control of the trait is polygenic. Although a core array of QTL controlled cortisol concentrations at both challenges, several QTL seemed challenge specific, suggesting that responses to the first and to a subsequent exposure to the confinement stressor are distinct traits sharing only part of their genetic control. Chromosomal location of the steroidogenic acute regulatory protein (STAR) makes it a good potential candidate gene for one of the QTL. Finally, comparison of body size traits QTL (weight, length and body conformation) with cortisol‐associated QTL did not support evidence for negative genetic relationships between the two types of traits.     

Rainbow trout resistance to bacterial cold water disease: two new quantitative trait loci identified after a natural disease outbreak on a French farm

In rainbow trout farming, Flavobacterium psychrophilum, the causative agent of bacterial cold water disease, is responsible for important economic losses. Resistance to F. psychrophilum is heritable, and several quantitative trait loci (QTL) with moderate effects have been detected, opening up promising perspectives for the genetic improvement of resistance. In most studies however, resistance to F. psychrophilum was assessed in experimental infectious challenges using injection as the infection route, which is not representative of natural infection. Indeed, injection bypasses external barriers, such as mucus and skin, that likely play a protective role against the infection. In this study, we aimed at describing the genetic architecture of the resistance to F. psychrophilum after a natural disease outbreak. In a 2000‐fish cohort, reared on a French farm, 720 fish were sampled and genotyped using the medium‐throughput Axiom? Trout Genotyping Array. Overall mortality at the end of the outbreak was 25%. Genome‐wide association studies were performed under two different models for time to death measured on 706 fish with validated genotypes for 30 060 SNPs. This study confirms the polygenic inheritance of resistance to F. psychrophilum with a few QTL with moderate effects and a large polygenic background, the heritability of the trait being estimated at 0.34. Two new chromosome‐wide significant QTL and three suggestive QTL were detected, each of them explaining between 1% and 4% of genetic variance.     

Quantitative trait loci for body growth and sex determination in the hermaphrodite teleost fish Sparus aurata L.

Gilthead sea bream (Sparus aurata L.) is an important marine fish in Mediterranean aquaculture. Sex determination by age and/or body weight is a critical life‐history trait, the genetic basis for which is largely unknown in this sequential hermaphrodite species. Herein, we performed a partial genome scan to map quantitative trait loci (QTL) affecting body weight and sex using 74 informative microsatellite markers from 10 paternal half‐sib families to construct nine linkage groups (LG). In total, four growth‐related QTL (two chromosome‐wide and two genome‐wide) and six QTL related to sex determination (three pairs in three different LGs) were detected (two chromosome‐wide and one genome‐wide). The proportion of phenotypic variation explained by the body‐weight QTL ranged from 9.3% to 17.2%, showing their potential for use in marker‐assisted selection. The results obtained offer solid ground to investigate the structure and function of the genomic regions involved in the mechanisms of sex reversal.     

Selection on QTL and complex traits in complex environments

Understanding genetic variation for complex traits in heterogeneous environments is a fundamental problem in biology. In this issue of Molecular Ecology, Fournier‐Level et al. ( 2013 ) analyse quantitative trait loci (QTL) influencing ecologically important phenotypes in mapping populations of Arabidopsis thaliana grown in four habitats across its native European range. They used causal modelling to quantify the selective consequences of life history and morphological traits and QTL on components of fitness. They found phenology QTL colocalizing with known flowering time genes as well as novel loci. Most QTL influenced fitness via life history and size traits, rather than QTL having direct effects on fitness. Comparison of phenotypes among environments found no evidence for genetic trade‐offs for phenology or growth traits, but genetic trade‐offs for fitness resulted because flowering time had opposite fitness effects in different environments. These changes in QTL effects and selective consequences may maintain genetic variation among populations.     

Quantitative trait loci affecting morphology traits in gilthead seabream (Sparus aurata L.)

We report a quantitative trait loci (QTL) mapping study on 18 morphometric characters in gilthead seabream based on a total of 74 informative microsatellite markers genotyped in 409 offspring coming from 10 paternal half‐sib families. Statistical analysis was carried out using a linear regression approach, and various suggestive and significant morphology QTL were detected in three (9, 21 and 25) of nine linkage groups examined. Fitting body weight as a covariate reduced the significance of some QTL but revealed three new QTL in other linkage groups (LG6 and LG10). Current results combined with those obtained from previous studies underline highly significant loci affecting overall growth and morphology in S. aurata.     

More than one way to evolve a weed: parallel evolution of US weedy rice through independent genetic mechanisms

Many different crop species were selected for a common suite of ‘domestication traits’, which facilitates their use for studies of parallel evolution. Within domesticated rice (Oryza sativa), there has also been independent evolution of weedy strains from different cultivated varieties. This makes it possible to examine the genetic basis of parallel weed evolution and the extent to which this process occurs through shared genetic mechanisms. We performed comparative QTL mapping of weediness traits using two recombinant inbred line populations derived from crosses between an indica crop variety and representatives of each of the two independently evolved weed strains found in US rice fields, strawhull (S) and blackhull awned (B). Genotyping‐by‐sequencing provided dense marker coverage for linkage map construction (average marker interval <0.25 cM), with 6016 and 13 730 SNPs mapped in F₅ lines of the S and B populations, respectively. For some weediness traits (awn length, hull pigmentation and pericarp pigmentation), QTL mapping and sequencing of underlying candidate genes confirmed that trait variation was largely attributable to individual loci. However, for more complex quantitative traits (including heading date, panicle length and seed shattering), we found multiple QTL, with little evidence of shared genetic bases between the S and B populations or across previous studies of weedy rice. Candidate gene sequencing revealed causal genetic bases for 8 of 27 total mapped QTL. Together these findings suggest that despite the genetic bottleneck that occurred during rice domestication, there is ample genetic variation in this crop to allow agricultural weed evolution through multiple genetic mechanisms.     

A multiparental cross population for mapping QTL for agronomic traits in durum wheat (Triticum turgidum ssp. durum)

Multiparental cross designs for mapping quantitative trait loci (QTL) provide an efficient alternative to biparental populations because of their broader genetic basis and potentially higher mapping resolution. We describe the development and deployment of a recombinant inbred line (RIL) population in durum wheat (Triticum turgidum ssp. durum) obtained by crossing four elite cultivars. A linkage map spanning 2664 cM and including 7594 single nucleotide polymorphisms (SNPs) was produced by genotyping 338 RILs. QTL analysis was carried out by both interval mapping on founder haplotype probabilities and SNP bi‐allelic tests for heading date and maturity date, plant height and grain yield from four field experiments. Sixteen QTL were identified across environments and detection methods, including two yield QTL on chromosomes 2BL and 7AS, with the former mapped independently from the photoperiod response gene Ppd‐B1, while the latter overlapped with the vernalization locus VRN‐A3. Additionally, 21 QTL with environment‐specific effects were found. Our results indicated a prevalence of environment‐specific QTL with relatively small effect on the control of grain yield. For all traits, functionally different QTL alleles in terms of direction and size of genetic effect were distributed among parents. We showed that QTL results based on founder haplotypes closely matched functional alleles at known heading date loci. Despite the four founders, only 2.1 different functional haplotypes were estimated per QTL, on average. This durum wheat population provides a mapping resource for detailed genetic dissection of agronomic traits in an elite background typical of breeding programmes.     

The genomic bases of morphological divergence and reproductive isolation driven by ecological speciation in Senecio (Asteraceae)

Ecological speciation, driven by adaptation to contrasting environments, provides an attractive opportunity to study the formation of distinct species, and the role of selection and genomic divergence in this process. Here, we focus on a particularly clear‐cut case of ecological speciation to reveal the genomic bases of reproductive isolation and morphological differences between closely related Senecio species, whose recent divergence within the last ~200 000 years was likely driven by the uplift of Mt. Etna (Sicily). These species form a hybrid zone, yet remain morphologically and ecologically distinct, despite active gene exchange. Here, we report a high‐density genetic map of the Senecio genome and map hybrid breakdown to one large and several small quantitative trait loci (QTL). Loci under diversifying selection cluster in three 5 cM regions which are characterized by a significant increase in relative (F_ST), but not absolute (d_XY), interspecific differentiation. They also correspond to some of the regions of greatest marker density, possibly corresponding to ‘cold‐spots’ of recombination, such as centromeres or chromosomal inversions. Morphological QTL for leaf and floral traits overlap these clusters. We also detected three genomic regions with significant transmission ratio distortion (TRD), possibly indicating accumulation of intrinsic genetic incompatibilities between these recently diverged species. One of the TRD regions overlapped with a cluster of high species differentiation, and another overlaps the large QTL for hybrid breakdown, indicating that divergence of these species may have occurred due to a complex interplay of ecological divergence and accumulation of intrinsic genetic incompatibilities.     

Quantitative trait loci segregating in crosses between New Hampshire and White Leghorn chicken lines: IV. Growth performance

Reciprocal crosses between the inbred lines New Hampshire (NHI) and White Leghorn (WL77) comprising 579 F₂ individuals were used to map QTL for body weight and composition. Here, we examine the growth performance until 20 weeks of age. Linkage analysis provided evidence for highly significant QTL on GGA1, 2, 4, 10 and 27 which had specific effects on early or late growth. The highest QTL effects, accounting for 4.6–25.6% of the phenotypic F₂ variance, were found on the distal region of GGA4 between 142 and 170 cM (F ≥ 13.68). The NHI QTL allele increased body mass by 141.86 g at 20 weeks. Using body weight as a covariate in the analysis of body composition traits provided evidence for genes in the GGA4 QTL region affecting fat mass independently of body mass. The QTL effect size differed between sexes and depended on the direction of cross. TBC1D1, CCKAR and PPARGC1A are functional candidate genes in the QTL peak region. Our study confirmed the importance of the distal GGA4 region for chicken growth performance. The strong effect of the GGA4 QTL makes fine mapping and gene discovery feasible.     

Time‐specific and pleiotropic quantitative trait loci coordinately modulate stem growth in Populus

In perennial woody plants, the coordinated increase of stem height and diameter during juvenile growth improves competitiveness (i.e. access to light); however, the factors underlying variation in stem growth remain unknown in trees. Here, we used linkage‐linkage disequilibrium (linkage‐LD) mapping to decipher the genetic architecture underlying three growth traits during juvenile stem growth. We used two Populus populations: a linkage mapping population comprising a full‐sib family of 1,200 progeny and an association mapping panel comprising 435 unrelated individuals from nearly the entire natural range of Populus tomentosa. We mapped 311 quantitative trait loci (QTL) for three growth traits at 12 timepoints to 42 regions in 17 linkage groups. Of these, 28 regions encompassing 233 QTL were annotated as 27 segmental homology regions (SHRs). Using SNPs identified by whole‐genome re‐sequencing of the 435‐member association mapping panel, we identified significant SNPs (P ≤ 9.4 × 10^?7) within 27 SHRs that affect stem growth at nine timepoints with diverse additive and dominance patterns, and these SNPs exhibited complex allelic epistasis over the juvenile growth period. Nineteen genes linked to potential causative alleles that have time‐specific or pleiotropic effects, and mostly overlapped with significant signatures of selection within SHRs between climatic regions represented by the association mapping panel. Five genes with potential time‐specific effects showed species‐specific temporal expression profiles during the juvenile stages of stem growth in five representative Populus species. Our observations revealed the importance of considering temporal genetic basis of complex traits, which will facilitate the molecular design of tree ideotypes.     

Deciphering the genomic architecture of the stickleback brain with a novel multilocus gene‐mapping approach

Quantitative traits important to organismal function and fitness, such as brain size, are presumably controlled by many small‐effect loci. Deciphering the genetic architecture of such traits with traditional quantitative trait locus (QTL) mapping methods is challenging. Here, we investigated the genetic architecture of brain size (and the size of five different brain parts) in nine‐spined sticklebacks (Pungitius pungitius) with the aid of novel multilocus QTL‐mapping approaches based on a de‐biased LASSO method. Apart from having more statistical power to detect QTL and reduced rate of false positives than conventional QTL‐mapping approaches, the developed methods can handle large marker panels and provide estimates of genomic heritability. Single‐locus analyses of an F₂ interpopulation cross with 239 individuals and 15 198, fully informative single nucleotide polymorphisms (SNPs) uncovered 79 QTL associated with variation in stickleback brain size traits. Many of these loci were in strong linkage disequilibrium (LD) with each other, and consequently, a multilocus mapping of individual SNPs, accounting for LD structure in the data, recovered only four significant QTL. However, a multilocus mapping of SNPs grouped by linkage group (LG) identified 14 LGs (1–6 depending on the trait) that influence variation in brain traits. For instance, 17.6% of the variation in relative brain size was explainable by cumulative effects of SNPs distributed over six LGs, whereas 42% of the variation was accounted for by all 21 LGs. Hence, the results suggest that variation in stickleback brain traits is influenced by many small‐effect loci. Apart from suggesting moderately heritable (h² ≈ 0.15–0.42) multifactorial genetic architecture of brain traits, the results highlight the challenges in identifying the loci contributing to variation in quantitative traits. Nevertheless, the results demonstrate that the novel QTL‐mapping approach developed here has distinctive advantages over the traditional QTL‐mapping methods in analyses of dense marker panels.     

Genome‐wide detection of genetic loci and candidate genes for teat number and body conformation traits at birth in Chinese Sushan pigs

Body conformation at birth and teat number are economically important traits in the pig industry, as these traits are usually explored to evaluate the growth and reproductive potential of piglets. To detect genetic loci and candidate genes for these traits, we performed a GWAS on 269 pigs from a recently developed Chinese breed (Sushan) using 38  128 informative SNPs on the Affymetrix Porcine SNP 55K Array. In total, we detected one genome‐wide significant (P = 1.31e‐6) SNP for teat number on chromosome X and 15 chromosome‐wide significant SNPs for teat number, body weight, body length, chest circumference and cannon circumference at birth on chromosomes 1, 3, 4, 6, 7, 9, 10, 13, 14, 15, 17 and 18. The most significant SNP had an additive effect of 0.74 × total teat number, explaining 20% of phenotypic variance. Five significant SNPs resided in the previously reported quantitative trait loci for these traits and seven significant SNPs had a pleiotropic effect on multiple traits. Intriguingly, 12 of the genes nearest to the significant SNPs are functionally related to body conformation and teat number traits, including SPRED2, MKX, TMSB4X and ESR1. GO analysis revealed that candidate genes proximal to the significant SNPs were enriched in the G‐protein coupled receptor and steroid hormone‐mediated signaling pathway. Our findings shed light on the genetic basis of the measured traits and provide molecular markers especially for the genetic improvement of teat number in Sushan and related pigs.     

High‐density linkage map reveals QTL underlying growth traits in AP13×VS16 biparental population of switchgrass

Switchgrass (Panicum virgatum L.), a native warm‐season perennial grass, is being considered as a feedstock for biofuel production in the United States. To expedite its genetic improvement and enhance genetic gain per selection cycle, application of marker‐assisted selection is indispensable. A high‐density linkage map was constructed in a pseudo‐F₁ testcross mapping population of AP13×VS16, consisting of 349 progenies. A total of 8,757 single nucleotide polymorphism (SNP) markers generated through genotype‐by‐sequencing (GBS) were used to construct the linkage map. The total map length spans up to 2,540.2 cM with the marker density of one marker in every 0.25–0.34 cM. Spring green‐up (SG), days to flowering (FL), and the vegetative growth period (VP) data were analyzed and used for quantitative trait loci (QTL) mapping. The population showed significant variations and exhibited transgressive segregation for SG, FL, and VP. QTL analyses were performed using trait mean of each year and location along with BLUP (best linear unbiased prediction) values of the traits. A total of 35, 37, and 34 QTL for SG, FL, and VP, respectively, were identified. Phenotypic variability explained by each QTL ranged from 11.29% to 27.85%. The additive genetic effects of individual QTL ranged from ?1.81 to 2.40, ?6.12 to 7.58, and ?16.01 to 6.38 for SG, FL, and VP, respectively. Comparing major QTL regions in the switchgrass genome, 20 candidate genes were identified which were reported to be involved in growth‐, development‐, and flowering‐related traits in switchgrass.     

Epistasis and the evolutionary dynamics of measured genotypic values during simulated serial bottlenecks

The evolutionary effects of epistasis have been primarily explored analytically and most empirical studies have utilized yeast, viral and bacterial populations. Empirical analyses in multi‐cellular organisms are rare because of experimental constraints. Here, we report the results of a genome‐wide scan for two‐way epistasis in 16 traits related to body size and composition in F₂ mice from the LG/J by SM/J intercross. We analyze two‐locus genotypic values at quantitative trait loci (QTL), which provides an especially detailed view of epistatic architectures, to evaluate their predicted evolutionary consequences via Monte Carlo simulations. Epistatic profiles vary, but all traits show complicated genetic architectures which are largely hidden in single locus QTL scans. On average, detected epistatic effects are comparable in size to marginal effects. Simulations demonstrate an expected preservation, and often inflation, of heritable variance across several generations of small effective population size for many identified epistatic pairs over a range of starting allele frequencies.     

SNP and INDEL detection in a QTL region on chicken chromosome 2 associated with muscle deposition

Genetic improvement is important for the poultry industry, contributing to increased efficiency of meat production and quality. Because breast muscle is the most valuable part of the chicken carcass, knowledge of polymorphisms influencing this trait can help breeding programs. Therefore, the complete genome of 18 chickens from two different experimental lines (broiler and layer) from EMBRAPA was sequenced, and SNPs and INDELs were detected in a QTL region for breast muscle deposition on chicken chromosome 2 between microsatellite markers MCW0185 and MCW0264 (105 849–112 649 kb). Initially, 94 674 unique SNPs and 10 448 unique INDELs were identified in the target region. After quality filtration, 77% of the SNPs (85 765) and 60% of the INDELs (7828) were retained. The studied region contains 66 genes, and functional annotation of the filtered variants identified 517 SNPs and three INDELs in exonic regions. Of these, 357 SNPs were classified as synonymous, 153 as non‐synonymous, three as stopgain, four INDELs as frameshift and three INDELs as non‐frameshift. These exonic mutations were identified in 37 of the 66 genes from the target region, three of which are related to muscle development (DTNA, RB1CC1 and MOS). Fifteen non‐tolerated SNPs were detected in several genes (MEP1B, PRKDC, NSMAF, TRAPPC8, SDR16C5, CHD7, ST18 and RB1CC1). These loss‐of‐function and exonic variants present in genes related to muscle development can be considered candidate variants for further studies in chickens. Further association studies should be performed with these candidate mutations as should validation in commercial populations to allow a better explanation of QTL effects.     

A genome scan for quantitative trait loci influencing carcass,post‐natal growth and reproductive traits in commercial Angus cattle

To gain insight into the number of loci of large effect that underlie variation in cattle, a quantitative trait locus (QTL) scan for 14 economically important traits was performed in two commercial Angus populations using 390 microsatellites, 11 single nucleotide polymorphisms (SNPs) and one duplication loci. The first population comprised 1769 registered Angus bulls born between 1955 and 2003, with Expected Progeny Differences computed by the American Angus Association. The second comprised 38 half‐sib families containing 1622 steers with six post‐natal growth and carcass phenotypes. Linkage analysis was performed by half‐sib least squares regression with gridqtl or Bayesian Markov chain Monte Carlo analysis of complex pedigrees with loki . Of the 673 detected QTL, only 118 have previously been reported, reflecting both the conservative approach to QTL reporting in the literature, and the more liberal approach taken in this study. From 33 to 71% of the genetic variance and 35 to 56% of the phenotypic variance in each trait was explained by the detected QTL. To analyse the effects of 11 SNPs and one duplication locus within candidate genes on each trait, a single marker analysis was performed by fitting an additive allele substitution model in both mapping populations. There were 53 associations detected between the SNP/duplication loci and traits with ?log₁₀P_nominal≥ 4.0, where each association explained 0.92% to 4.4% of the genetic variance and 0.01% to 1.86% of the phenotypic variance. Of these associations, only six SNP/duplication loci were located within 8 cM of a QTL peak for the trait, with two being located at the QTL peak: SST_DG156121:c.362A>G for ribeye muscle area and TG_X05380:c.422C>T for calving ease. Strong associations between several SNP/duplication loci and trait variation were obtained in the absence of any detected linked QTL. However, we reject the causality of several commercialized DNA tests, including an association between TG_X05380:c.422C>T and marbling in Angus cattle.     

Large‐scale GWAS in sorghum reveals common genetic control of grain size among cereals

Grain size is a key yield component of cereal crops and a major quality attribute. It is determined by a genotype’s genetic potential and its capacity to fill the grains. This study aims to dissect the genetic architecture of grain size in sorghum. An integrated genome‐wide association study (GWAS) was conducted using a diversity panel (n = 837) and a BC‐NAM population (n = 1421). To isolate genetic effects associated with genetic potential of grain size, rather than the genotype’s capacity to fill the grains, a treatment of removing half of the panicle was imposed during flowering. Extensive and highly heritable variation in grain size was observed in both populations in 5 field trials, and 81 grain size QTL were identified in subsequent GWAS. These QTL were enriched for orthologues of known grain size genes in rice and maize, and had significant overlap with SNPs associated with grain size in rice and maize, supporting common genetic control of this trait among cereals. Grain size genes with opposite effect on grain number were less likely to overlap with the grain size QTL from this study, indicating the treatment facilitated identification of genetic regions related to the genetic potential of grain size. These results enhance understanding of the genetic architecture of grain size in cereal, and pave the way for exploration of underlying molecular mechanisms and manipulation of this trait in breeding practices.     

Variant discovery in a QTL region on chromosome 3 associated with fatness in chickens

Abdominal fat content is an economically important trait in commercially bred chickens. Although many quantitative trait loci (QTL) related to fat deposition have been detected, the resolution for these regions is low and functional variants are still unknown. The current study was conducted aiming at increasing resolution for a region previously shown to have a QTL associated with fat deposition, to detect novel variants from this region and to annotate those variants to delineate potentially functional ones as candidates for future studies. To achieve this, 18 chickens from a parental generation used in a reciprocal cross between broiler and layer lines were sequenced using the Illumina next‐generation platform with an initial coverage of 18X/chicken. The discovery of genetic variants was performed in a QTL region located on chromosome 3 between microsatellite markers LEI0161 and ADL0371 (33 595 706–42 632 651 bp). A total of 136 054 unique SNPs and 15 496 unique INDELs were detected in this region, and after quality filtering, 123 985 SNPs and 11 298 INDELs were retained. Of these variants, 386 SNPs and 15 INDELs were located in coding regions of genes related to important metabolic pathways. Loss‐of‐function variants were identified in several genes, and six of those, namely LOC771163, EGLN1, GNPAT, FAM120B, THBS2 and GGPS1, were related to fat deposition. Therefore, these loss‐of‐function variants are candidate mutations for conducting further studies on this important trait in chickens.