Significant Quantitative Trait Loci Research Articles

GWAS and Post-GWAS High-Resolution Mapping Analyses Identify Strong Novel Candidate Genes Influencing the Fatty Acid Composition of the Longissimus dorsi Muscle in Pigs.

Fatty acid (FA) composition is one of the most important parameters for the assessment of meat quality in pigs. The FA composition in pork can also affect human health. Our aim was to identify quantitative trait loci (QTLs) and positional candidate genes affecting the FA profile of the longissimus dorsi muscle in a large F2 intercross between Landrace and Korean native pigs comprising 1105 F2 progeny by genome-wide association studies (GWAS) and post-GWAS high-resolution mapping analyses. We performed GWAS using the PorcineSNP60K BeadChip and a linear mixed model. Four genome-wide significant QTL regions in SSC8, SSC12, SSC14, and SSC16 were detected (p < 2.53 × 10−7). Several co-localizations of QTLs in SSC12 for oleic acid, linoleic acid, arachidonic acid, monounsaturated FAs, polyunsaturated FAs, and the polyunsaturated/saturated FA ratio were observed. To refine the QTL region in SSC12, a linkage and linkage disequilibrium analysis was applied and could narrow down the critical region to a 0.749 Mb region. Of the genes in this region, GAS7, MYH2, and MYH3 were identified as strong novel candidate genes based on further conditional association analyses. These findings provide a novel insight into the genetic basis of FA composition in pork and could contribute to the improvement of pork quality.

Genome-Wide Association Mapping of Mixed Linkage (1,3;1,4)-β-Glucan and Starch Contents in Rice Whole Grain.

The glucan content of rice is a key factor defining its nutritional and economic value. Starch and its derivatives have many industrial applications such as in fuel and material production. Non-starch glucans such as (1,3;1,4)-β-D-glucan (mixed-linkage β-glucan, MLG) have many benefits in human health, including lowering cholesterol, boosting the immune system, and modulating the gut microbiome. In this study, the genetic variability of MLG and starch contents were analyzed in rice (Oryza sativa L.) whole grain, by performing a new quantitative analysis of the polysaccharide content of rice grains. The 197 rice accessions investigated had an average MLG content of 252 μg/mg, which was negatively correlated with the grain starch content. A new genome-wide association study revealed seven significant quantitative trait loci (QTLs) associated with the MLG content and two QTLs associated with the starch content in rice whole grain. Novel genes associated with the MLG content were a hexose transporter and anthocyanidin 5,3-O-glucosyltransferase. Also, the novel gene associated with the starch content was a nodulin-like domain. The data pave the way for a better understanding of the genes involved in determining both MLG and starch contents in rice grains and should facilitate future plant breeding programs.

Quantitative trait mapping in Diversity Outbred mice identifies novel genomic regions associated with the hepatic glutathione redox system

The tripeptide glutathione (GSH) is instrumental to antioxidant protection and xenobiotic metabolism, and the ratio of its reduced and oxidized forms (GSH/GSSG) indicates the cellular redox environment and maintains key aspects of cellular signaling. Disruptions in GSH levels and GSH/GSSG have long been tied to various chronic diseases, and many studies have examined whether variant alleles in genes responsible for GSH synthesis and metabolism are associated with increased disease risk. However, past studies have been limited to established, canonical GSH genes, though emerging evidence suggests that novel loci and genes influence the GSH redox system in specific tissues. The present study marks the most comprehensive effort to date to directly identify genetic loci associated with the GSH redox system. We employed the Diversity Outbred (DO) mouse population, a model of human genetics, and measured GSH and the essential redox cofactor NADPH in liver, the organ with the highest levels of GSH in the body. Under normal physiological conditions, we observed substantial variation in hepatic GSH and NADPH levels and their redox balances, and discovered a novel, significant quantitative trait locus (QTL) on murine chromosome 16 underlying GSH/GSSG; bioinformatics analyses revealed Socs1 to be the most likely candidate gene. We also discovered novel QTL associated with hepatic NADP+ levels and NADP+/NADPH, as well as unique candidate genes behind each trait. Overall, these findings transform our understanding of the GSH redox system, revealing genetic loci that govern it and proposing new candidate genes to investigate in future mechanistic endeavors.

Mapping QTLs for Breast Muscle Weight in an F2 Intercross between Native Japanese Nagoya and White Plymouth Rock Chicken Breeds.

Nagoya (NAG), a native Japanese chicken breed, has high quality meat but low meat yield, whereas White Plymouth Rock (WPR), a parental breed of commercial broilers, has rapid growth but high body fat. We previously reported three quantitative trait loci (QTLs) for early postnatal growth in 239 F2 chickens between NAG and WPR breeds. In this study, using the same F2 chickens at 4 weeks of age, we performed genome-wide QTL analysis for breast muscle weight, fat weight and serum and liver levels of biochemical parameters. Two significant QTLs for pectoralis minor and/or major weights were revealed on chromosome 2 between 108 Mb and 127 Mb and chromosome 4 between 10 Mb and 68 Mb. However, no QTL for the other traits was detected. The two QTLs explained 7.0–11.1% of the phenotypic variances, and their alleles derived from WPR increased muscle weights. The chromosome 2 QTL may be a novel locus, whereas the chromosome 4 QTL coincided with a known QTL for meat quality. The findings provide information that is beneficial for genetic improvement of meat yield for the lean NAG breed and, furthermore, provide a better understanding of the genetic basis of chicken muscle development.

Heterophylly Quantitative Trait Loci Respond to Salt Stress in the Desert Tree Populus euphratica.

Heterophylly, or leaf morphological changes along plant shoot axes, is an important indicator of plant eco-adaptation to heterogeneous microenvironments. Despite extensive studies on the genetic control of leaf shape, the genetic architecture of heterophylly remains elusive. To identify genes related to heterophylly and their associations with plant saline tolerance, we conducted a leaf shape mapping experiment using leaves from a natural population of Populus euphratica. We included 106 genotypes grown under salt stress and salt-free (control) conditions using clonal seedling replicates. We developed a shape tracking method to monitor and analyze the leaf shape using principal component (PC) analysis. PC1 explained 42.18% of the shape variation, indicating that shape variation is mainly determined by the leaf length. Using leaf length along shoot axes as a dynamic trait, we implemented a functional mapping-assisted genome-wide association study (GWAS) for heterophylly. We identified 171 and 134 significant quantitative trait loci (QTLs) in control and stressed plants, respectively, which were annotated as candidate genes for stress resistance, auxin, shape, and disease resistance. Functions of the stress resistance genes ABSCISIC ACIS-INSENSITIVE 5-like (ABI5), WRKY72, and MAPK3 were found to be related to many tolerance responses. The detection of AUXIN RESPONSE FACTOR17-LIKE (ARF17) suggests a balance between auxin-regulated leaf growth and stress resistance within the genome, which led to the development of heterophylly via evolution. Differentially expressed genes between control and stressed plants included several factors with similar functions affecting stress-mediated heterophylly, such as the stress-related genes ABC transporter C family member 2 (ABCC2) and ABC transporter F family member (ABCF), and the stomata-regulating and reactive oxygen species (ROS) signaling gene RESPIRATORY BURST OXIDASE HOMOLOG (RBOH). A comparison of the genetic architecture of control and salt-stressed plants revealed a potential link between heterophylly and saline tolerance in P. euphratica, which will provide new avenues for research on saline resistance-related genetic mechanisms.

A variance component estimation approach to infer associations between Mendelian polledness and quantitative production and female fertility traits in German Simmental cattle

BackgroundManaging beneficial Mendelian characteristics in dairy cattle breeding programs implies that the correlated genetic effects are considered to avoid possible adverse effects in selection processes. The Mendelian trait polledness in cattle is traditionally associated with the belief that the polled locus has unfavorable effects on breeding goal traits. This may be due to the inferior breeding values of former polled bulls and cows in cattle breeds, such as German Simmental, or to pleiotropic or linkage effects of the polled locus.MethodsWe focused on a variance component estimation approach that uses a marker-based numerator relationship matrix reflecting gametic relationships at the polled locus to test for direct pleiotropic or linked quantitative trait loci (QTL) effects of the polled locus on relevant traits. We applied the approach to performance, health, and female fertility traits in German Simmental cattle.ResultsOur results showed no evidence for any pleiotropic QTL effects of the polled locus on test-day production traits milk yield and fat percentage, on the mastitis indicator ‘somatic cell score’, and on several female fertility traits, i.e. 56 days non return rate, days open and days to first service. We detected a significant and unfavorable QTL effect accounting for 6.6% of the genetic variance for protein percentage only.ConclusionsPleiotropy does not explain the lower breeding values and phenotypic inferiority of polled German Simmental sires and cows relative to the horned population in the breed. Thus, intensified selection in the polled population will contribute to increased selection response in breeding goal traits and genetic merit and will narrow the deficit in breeding values for production traits.

DArTseq physical mapping of QTLs linked to Karnal bunt (Tilletia indica) resistance in two historical wheat populations

AbstractKarnal bunt, a disease of wheat, durum, rye, and triticale, is subject to strict quarantine restrictions worldwide. The disease is considered a major threat to food security, due to its use as a non‐tariff trade barrier by several wheat‐importing countries. In this paper, we analysed seven years of phenotypic data to search for quantitative trait loci (QTLs) associated with resistance in common wheat, validated the QTLs using an independent population, and assessed the potential of genomic selection as a tool for pre‐emptive breeding. The QTL study used phenotypic data collected from artificially inoculated field experiments involving two historical Karnal bunt resistance populations: WH542 × HD29 and WH542 × W485. QTL analyses detected four significant (p &lt; 0.001) QTLs on chromosomes 1A, 3A, 4B, and 6B, which explained between 13.7% and 15.7% of the phenotypic variation. A panel of 130 cultivars was used to validate QTL effects. These were genotyped with the same DArTseq protocol, and two of the four QTLs were significantly (p &lt; 0.001) associated with Karnal bunt resistance in the validation panel. The potential of genomic selection was investigated by comparing accuracies of a model trained with all available markers and a model based solely on validated QTL information from the biparental populations. Genomic prediction accuracy, based on the two scenarios, averaged 0.43 and 0.33, respectively, suggesting that even in situations where phenotyping is difficult due to quarantine restrictions, the prospects for pre‐emptive breeding against Karnal bunt are encouraging, and resources are now available that will reduce the cost burden.

Assessing the Effect of Phenotyping Scoring Systems and SNP Calling and Filtering Parameters on Detection of QTL Associated with Reaction of Brassica napus to Sclerotinia sclerotiorum

The polyploid nature of canola (Brassica napus) represents a challenge for the accurate identification of single-nucleotide polymorphisms (SNPs) and the detection of quantitative trait loci (QTL). In this study, combinations of eight phenotyping scoring systems and six SNP calling and filtering parameters were evaluated for their efficiency in detection of QTL associated with response to Sclerotinia stem rot, caused by Sclerotinia sclerotiorum, in two doubled haploid canola mapping populations. Most QTL were detected in lesion length, relative areas under the disease progress curve (rAUDPC) for lesion length, and binomial-plant mortality data sets. Binomial data derived from lesion size were less efficient in QTL detection. Inclusion of additional phenotypic sets to the analysis increased the numbers of significant QTL by 2.3-fold; however, the continuous data sets were more efficient. Between two filtering parameters used to analyze genotyping-by-sequencing data, imputation of missing data increased QTL detection in one population with a high level of missing data but not in the other. Inclusion of segregation-distorted SNPs increased QTL detection but did not impact their R2 values significantly. In all, 12 of 16 detected QTL were on chromosomes A02 and C01, and the rest were on A07, A09, and C03. Marker A02-7594120, associated with a QTL on chromosome A02, was detected in both populations. Results of this study suggest that the impact of genotypic variant calling and filtering parameters may be population dependent while deriving additional phenotyping scoring systems such as rAUDPC datasets and mortality binary may improve QTL detection efficiency. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Genome scanning reveals novel candidate genes for vertebral and teat number in the Beijing Black Pig.

Porcine vertebral and teat numbers are variable and important economic traits in pig production. However, the quantitative trait loci (QTL) and candidate genes for both of these traits in the Beijing Black Pig are not yet known. In the present study, number of vertebrae and number of teats were obtained for 891 individuals of the Beijing Black Pig and genotyped using the Illumina Porcine 50K BeadChip. Genome scanning was performed to detect associated variants and candidate genes for both traits using a genome-wide association study by tassel software. For vertebral number, 15 significant SNPs were located on SSC7. According to linkage disequilibrium analysis on SSC7, a haplotype block of 221kb from 97.4 to 97.6Mb was shown to contain a good candidate gene ABCD4. Interestingly, on SSC12, we recorded a novel QTL containing three significant SNPs and 34 annotated genes from 24.0 to 25.7Mb for vertebral number. Of the 34 genes, nine Hox family genes (HOXB 1-7, 9, and 13) were found to be good candidate genes. Using the 34 genes, a gene ontology analysis was performed to detect enrichment of anterior/posterior pattern specification. For teat number, a novel chromosome-wide significant QTL was identified on SSC10. In this QTL region, one significant SNP was identified. The nearest gene, NTRK2, was regarded as a candidate gene. The present results expanded the QTL for vertebral and teat numbers and provided useful molecular markers for breeding in the Beijing Black Pig population.

Large Multi-Ethnic Genome Wide Association Study Reveals Novel Genetic Associations with Childhood Acute Lymphoblastic Leukemia at Chromosomes 8q24 and 17q12

Genome-wide association studies (GWAS) have revealed heritable genetic risk factors for childhood acute lymphoblastic leukemia (ALL), highlighting the role of lymphoid development and cell cycle control genes in disease etiology. Most studies have focused on non-Latino white populations; however, the highest global rates of ALL are found in Latinos in the US and Latin America. To identify novel genetic susceptibility alleles, we carried out a large, multi-ethnic GWAS of ALL in the Californian population.Childhood ALL cases were identified using the California Cancer Registry, and age, gender, and ethnicity-matched controls were identified from the Department of Vital Statistics. Newborn bloodspots from California-born children were obtained from the California Biobank Program. Genome-wide SNP genotyping was carried out for 1,949 Latino, 1,184 non-Latino white, and 130 African-American cases as well as 3,506 controls, using the Affymetrix Axiom World Latin array. Additional controls (n=12,471) from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort (GERA) were genotyped on the same array. For increased statistical power, we carried out a meta-analysis of the three ethnicity-stratified GWAS. Replication of putative novel loci was performed in two independent datasets: the European-ancestry based Children's Oncology Group (COG) (959 cases, plus 2624 controls from the Wellcome Trust Case-Control Consortium), and in Latino subjects from the California Childhood Leukemia Study (CCLS) (530 cases, 511 controls). Local imputation across top association loci was carried out, using 1000 Genomes Project SNP data as a reference, to identify causal variants.Our childhood ALL GWAS meta-analysis of 3,263 cases and 15,977 controls identified two novel genome-wide significant SNP loci (P<5.0 x 10-8) at chromosomes 8q24 (OR=1.27, 95% CI:1.17-1.38) and 17q12 (OR=1.18, 95% CI:1.11-1.25) that replicated in COG and CCLS datasets. The 8q24 locus lies within a 2.5Mb region containing known GWAS hits for multiple phenotypes, including several cancer types and developmental traits. Imputation narrowed the locus to a ~100kb intergenic region, including top hit SNP rs4617118, that demonstrates chromatin looping with the MYC oncogene in lymphoblastoid cell lines. The 17q12 association peak encompasses the lymphoid transcription factor IKZF3, as well as ZPBP2, GSDMB, and ORMDL3. Top SNP rs2290400 disrupts a BLIMP-1 binding motif, and is a highly significant expression quantitative trait locus (eQTL) for both GSDMB and ORMDL3 . Rs2290400 is also a GWAS hit for type 1 diabetes and asthma, with the ALL risk allele conferring protection against these autoimmune conditions. In addition to novel loci, we replicated established GWAS hits in ARID5B, IKZF1, CEBPE, PIP4K2A, and CDKN2A at genome-wide significance, and in GATA3 at P=5.2x10-6. Recently identified loci at LHPP and ELK3 also replicated, at P=5.7x10-6 and P=2.1x10-3 respectively.Capitalizing on the large proportion of Latinos in our study, we utilized the reduced linkage disequilibrium of this genetically admixed population in combination with fine-mapping to identify new putative causal variants at known ALL-associated loci.Our large, multi-ethnic GWAS of childhood ALL has identified two novel genetic associations, at loci that function in hematopoiesis (17q12) and B-cell proliferation (MYC), in addition to pinpointing causal variants at known ALL loci. Further work is required to elucidate the biological mechanisms underlying these associations. Our results suggest that analysis of larger ALL datasets may yield additional genetic risk loci of moderate effect size. DisclosuresMa:Incyte Corp.: Consultancy.

Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges.

Our lab and others have shown that chronic alcohol use leads to gene and miRNA expression changes across the mesocorticolimbic (MCL) system. Circular RNAs (circRNAs) are noncoding RNAs that form closed‐loop structures and are reported to alter gene expression through miRNA sequestration, thus providing a potentially novel neurobiological mechanism for the development of alcohol dependence (AD). Genome‐wide expression of circRNA was assessed in the nucleus accumbens (NAc) from 32 AD‐matched cases/controls. Significant circRNAs (unadj. p ≤ 0.05) were identified via regression and clustered in circRNA networks via weighted gene co‐expression network analysis (WGCNA). CircRNA interactions with previously generated mRNA and miRNA were detected via correlation and bioinformatic analyses. Significant circRNAs (N = 542) clustered in nine significant AD modules (FWER p ≤ 0.05), within which we identified 137 circRNA hubs. We detected 23 significant circRNA–miRNA–mRNA interactions (FDR ≤ 0.10). Among these, circRNA‐406742 and miR‐1200 significantly interact with the highest number of mRNA, including genes associated with neuronal functioning and alcohol addiction (HRAS, PRKCB, HOMER1, and PCLO). Finally, we integrate genotypic information that revealed 96 significant circRNA expression quantitative trait loci (eQTLs) (unadj. p ≤ 0.002) that showed significant enrichment within recent alcohol use disorder (AUD) and smoking genome‐wide association study (GWAS). To our knowledge, this is the first study to examine the role of circRNA in the neuropathology of AD. We show that circRNAs impact mRNA expression by interacting with miRNA in the NAc of AD subjects. More importantly, we provide indirect evidence for the clinical importance of circRNA in the development of AUD by detecting a significant enrichment of our circRNA eQTLs among GWAS of substance abuse.

Genetic mapping of metabolic traits in the blind Mexican cavefish reveals sex-dependent quantitative trait loci associated with cave adaptation

BackgroundDespite a longstanding interest in understanding how animals adapt to environments with limited nutrients, we have incomplete knowledge of the genetic basis of metabolic evolution. The Mexican tetra, Astyanax mexicanus, is a species of fish that consists of two morphotypes; eyeless cavefish that have adapted to a low-nutrient cave environment, and ancestral river-dwelling surface fish with abundant access to nutrients. Cavefish have evolved altered blood sugar regulation, starvation tolerance, increased fat accumulation, and superior body condition. To investigate the genetic basis of cavefish metabolic evolution we carried out a quantitative trait loci (QTL) analysis in surface/cave F2 hybrids. We genetically mapped seven metabolism-associated traits in hybrids that were challenged with a nutrient restricted diet.ResultsWe found that female F2 hybrids are bigger than males and have a longer hindgut, bigger liver, and heavier gonad, even after correcting for fish size. Although there is no difference between male and female blood sugar level, we found that high blood sugar is associated with weight gain in females and lower body weight and fat level in males. We identified a significant QTL associated with 24-h-fasting blood glucose level with the same effect in males and females. Differently, we identified sex-independent and sex-dependent QTL associated with fish length, body condition, liver size, hindgut length, and gonad weight. We found that some of the genes within the metabolism QTL display evidence of non-neutral evolution and are likely to be under selection. Furthermore, we report predicted nonsynonymous changes to the cavefish coding sequence of these genes.ConclusionsOur study reveals previously unappreciated genomic regions associated with blood glucose regulation, body condition, gonad size, and internal organ morphology. In addition, we find an interaction between sex and metabolism-related traits in A. mexicanus. We reveal coding changes in genes that are likely under selection in the low-nutrient cave environment, leading to a better understanding of the genetic basis of metabolic evolution.

Genetic mapping and identification of a QTL determining tolerance to freezing stress in Fragaria vesca L.

Extreme cold and frost cause significant stress to plants which can potentially be lethal. Low temperature freezing stress can cause significant and irreversible damage to plant cells and can induce physiological and metabolic changes that impact on growth and development. Low temperatures cause physiological responses including winter dormancy and autumn cold hardening in strawberry (Fragaria) species, and some diploid F. vesca accessions have been shown to have adapted to low-temperature stresses. To study the genetics of freezing tolerance, a F. vesca mapping population of 143 seedlings segregating for differential responses to freezing stress was raised. The progeny was mapped using ‘Genotyping-by-Sequencing’ and a linkage map of 2,918 markers at 851 loci was resolved. The mapping population was phenotyped for freezing tolerance response under controlled and replicated laboratory conditions and subsequent quantitative trait loci analysis using interval mapping revealed a single significant quantitative trait locus on Fvb2 in the physical interval 10.6 Mb and 15.73 Mb on the F. vesca v4.0 genome sequence. This physical interval contained 896 predicted genes, several of which had putative roles associated with tolerance to abiotic stresses including freezing. Differential expression analysis of the 896 QTL-associated gene predictions in the leaves and crowns from ‘Alta’ and ‘NCGR1363’ parental genotypes revealed genotype-specific changes in transcript accumulation in response to low temperature treatment as well as expression differences between genotypes prior to treatment for many of the genes. The putative roles, and significant interparental differential expression levels of several of the genes reported here identified them as good candidates for the control of the effects of freezing tolerance at the QTL identified in this investigation and the possible role of these candidate genes in response to freezing stress is discussed.

Identification of stable quantitative trait loci and candidate genes for sweetness and acidity in tablegrape using a highly saturated single‐nucleotide polymorphism‐based linkage map

Background and Aims Identifying the genes that participate in the sweetness and acidity of the berry is key, because these traits are quintessential to the flavour and quality of fresh grapes and wine. In this study we focused on the identification of genomic regions that host genes associated with sweetness and acidity in tablegrapes. Methods and Results A highly saturated genetic map was prepared using a Ruby Seedless × Sultanina cross (RxS; n = 138) genotyped using an SNPlex-type platform, and quantitative trait loci (QTLs) were mapped. In the integrated map of this population, 1731 markers were distributed along the 19 linkage groups (LGs) of the species. Three significant QTLs, two in LG5 and one in LG8, were associated with fructose/glucose ratio, TA and tartaric acid concentration; these QTLs explained up to 20% of the phenotypic variance for these traits. Eight candidate genes located within the confidence intervals of the sugar and TA QTLs were chosen and their expression profiles analysed from flowering to berry ripening. A Genome-Wide Association Study (GWAS) analysis revealed the association of single-nucleotide polymorphisms in the same regions as QTLs. Conclusions Quantitative trait loci significant for sugar and acidity were identified on a tablegrape high-quality genetic map; furthermore, an association between acidity or sugar concentration and expression changes for candidate genes was also observed. Significance of the Study These findings could become the basis to develop selection tools for the breeding of these traits in tablegrape.

An independent, replicable, functional and significant risk variant block at intron 3 of CACNA1C for schizophrenia.

Genome-wide association studies have identified a significant risk gene, CACNA1C, for schizophrenia. In this study, we comprehensively investigated a large set of CACNA1C single-nucleotide polymorphisms (SNPs) to identify the replicable risk alleles for schizophrenia and explore their biological functions. One Jewish (1044 cases vs 2052 controls), one European (1350 cases vs 1378 controls) and one exploratory African American samples (98 cases vs 20 controls) were analyzed to identify replicable single-nucleotide polymorphism-schizophrenia associations. The regulatory effects of risk alleles on CACNA1C messenger RNA expression were examined. The most robust risk tagSNP (rs1006737) was meta-analyzed on 17 studies (74,122 cases vs 109,062 controls), and associated with the gray matter volumes of seven subcortical structures in 38,258 Europeans, and the surface areas and thickness of 34 cortical regions in 33,992 Europeans and 2944 non-Europeans. Forty-seven replicable risk single-nucleotide polymorphisms, including a 20-single-nucleotide polymorphism haplotype block, were identified in our samples (1.8 × 10-4 ⩽ p ⩽ 0.049). This variant block was consistently associated with schizophrenia across four independent Psychiatric Genomics Consortium cohorts (79,645 cases vs 109,590 controls; 2.5 × 10-17 ⩽ p ⩽ 0.017). This block showed significant expression quantitative trait loci in three independent European brain cohorts (5.1 × 10-12 ⩽ p ⩽ 8.3 × 10-3) and could be tagged by the most significant risk single-nucleotide polymorphism rs1006737. The minor allele A of rs1006737 significantly increased risk for schizophrenia across the Jewish and European samples (p = 0.029 and 0.004, respectively), and this association was highly significant in the meta-analysis (p = 1.62 × 10-42). This allele also significantly altered the CACNA1C messenger RNA expression in five brain regions (5.1 × 10-12 ⩽ p ⩽ 0.05), decreased the gray matter volume of thalamus (p = 0.010), the surface area of isthmus cingulate cortex (p = 0.013) and the thickness of transverse temporal and superior temporal sulcus cortexes (0.005 ⩽ p ⩽ 0.043). We identified an independent, replicable, functional, and significant risk variant block at CACNA1C for schizophrenia, which could be tagged by the most robust risk marker rs1006737, suggesting an important role of CACNA1C in the pathogenesis of schizophrenia.

Whole-genome resequencing of Osmanthus fragrans provides insights into flower color evolution

Osmanthus fragrans is a well-known ornamental plant that has been domesticated in China for 2500 years. More than 160 cultivars have been found during this long period of domestication, and they have subsequently been divided into four cultivar groups, including the Yingui, Jingui, Dangui, and Sijigui groups. These groups provide a set of materials to study genetic evolution and variability. Here, we constructed a reference genome of O. fragrans ‘Liuyejingui’ in the Jingui group and investigated its floral color traits and domestication history by resequencing a total of 122 samples, including 119 O. fragrans accessions and three other Osmanthus species, at an average sequencing depth of 15×. The population structure analysis showed that these 119 accessions formed an apparent regional cluster. The results of linkage disequilibrium (LD) decay analysis suggested that varieties with orange/red flower color in the Dangui group had undergone more artificial directional selection; these varieties had the highest LD values among the four groups, followed by the Sijigui, Jingui, and Yingui groups. Through a genome-wide association study, we further identified significant quantitative trait loci and genomic regions containing several genes, such as ethylene-responsive transcription factor 2 and Arabidopsis pseudoresponse regulator 2, that are positively associated with petal color. Moreover, we found a frameshift mutation with a 34-bp deletion in the first coding region of the carotenoid cleavage dioxygenase 4 gene. This frameshift mutation existed in at least one site on both alleles in all varieties of the Dangui group. The results from this study shed light on the genetic basis of domestication in woody plants, such as O. fragrans.

Mapping QTL underlying fruit quality traits in an F1 strawberry population

ABSTRACT Understanding how strawberry (Fragaria x ananassa) nutritional and quality traits are genetically regulated and correlated is an essential step towards improving marker-assisted breeding programmes in this crop. A first step to achieve this goal was to construct a single nucleotide polymorphism (SNP)-based genetic map of 140 F1 individuals of a cross between the 2 octoploid parents ‘Redgauntlet’ and ‘Hapil’. The map consisted of 3933 SNPs distributed over 28 linkage groups, representing the 7 homoeologous groups expected in Fragaria (2n = 8x = 56), and covered a total length of 2624.7 cM with an average resolution of 0.7 cM/SNP. Two overlapping subsets of F1 individuals were evaluated in the field and glasshouse at East Malling Research and the University of Reading, respectively. Negative correlation was observed between Pelargonidin and the three traits L*, a*, and b*, whereas positive correlations were observed within L*, a*, and b*, and between Ellagic acid, Pelargonidin, and Cyanidin at both trial locations. Quantitative trait loci (QTL) mapping revealed 29 significant QTL associated with the measured traits and mapped over 16 linkage groups. Two QTL for fruit fresh weight were co-located between day 1 and day 4 of shelf life, accounting for over 62% of the variation. These data will enhance our understanding of the genetic basis and correlation of strawberry quality traits and provide the basis for refining QTL that underpin the genetic regulation of these quality traits.

A Major and Stable Quantitative Trait Locus qSS2 for Seed Size and Shape Traits in a Soybean RIL Population.

Seed size and shape traits are important determinants of seed yield and appearance quality in soybean [Glycine max (L.) Merr.]. Understanding the genetic architecture of these traits is important to enable their genetic improvement through efficient and targeted selection in soybean breeding, and for the identification of underlying causal genes. To map seed size and shape traits in soybean, a recombinant inbred line (RIL) population developed from K099 (small seed size) × Fendou 16 (large seed size), was phenotyped in three growing seasons. A genetic map of the RIL population was developed using 1,485 genotyping by random amplicon sequencing-direct (GRAS-Di) and 177 SSR markers. Quantitative trait locus (QTL) mapping was conducted by inclusive composite interval mapping. As a result, 53 significant QTLs for seed size traits and 27 significant QTLs for seed shape traits were identified. Six of these QTLs (qSW8.1, qSW16.1, qSLW2.1, qSLT2.1, qSWT1.2, and qSWT4.3) were identified with LOD scores of 3.80–14.0 and R2 of 2.36%–39.49% in at least two growing seasons. Among the above significant QTLs, 24 QTLs were grouped into 11 QTL clusters, such as, three major QTLs (qSL2.3, qSLW2.1, and qSLT2.1) were clustered into a major QTL on Chr.02, named as qSS2. The effect of qSS2 was validated in a pair of near isogenic lines, and its candidate genes (Glyma.02G269400, Glyma.02G272100, Glyma.02G274900, Glyma.02G277200, and Glyma.02G277600) were mined. The results of this study will assist in the breeding programs aiming at improvement of seed size and shape traits in soybean.

Angular Leaf Spot Resistance Loci Associated With Different Plant Growth Stages in Common Bean

Angular leaf spot (ALS) is a disease that causes major yield losses in the common bean crop. Studies based on different isolates and populations have already been carried out to elucidate the genetic mechanisms of resistance to ALS. However, understanding of the interaction of this resistance with the reproductive stages of common bean is lacking. The aim of the present study was to identify ALS resistance loci at different plant growth stages (PGS) by association and linkage mapping approaches. An BC2F3 inter-gene pool cross population (AND 277 × IAC-Milênio – AM population) profiled with 1,091 SNPs from genotyping by sequencing (GBS) was used for linkage mapping, and a carioca diversity panel (CDP) genotyped by 5,398 SNPs from BeadChip assay technology was used for association mapping. Both populations were evaluated for ALS resistance at the V2 and V3 PGSs (controlled conditions) and R8 PGS (field conditions). Different QTL (quantitative trait loci) were detected for the three PGSs and both populations, showing a different quantitative profile of the disease at different plant growth stages. For the three PGS, multiple interval mapping (MIM) identified seven significant QTL, and the Genome-wide association study (GWAS) identified fourteen associate SNPs. Several loci validated regions of previous studies, and Phg-1, Phg-2, Phg-4, and Phg-5, among the 5 loci of greatest effects reported in the literature, were detected in the CDP. The AND 277 cultivar contained both the Phg-1 and the Phg-5 QTL, which is reported for the first time in the descendant cultivar CAL143 as ALS10.1UC. The novel QTL named ALS11.1AM was located at the beginning of chromosome Pv11. Gene annotation revealed several putative resistance genes involved in the ALS response at the three PGSs, and with the markers and loci identified, new specific molecular markers can be developed, representing a powerful tool for common bean crop improvement and for gain in ALS resistance.

Systems genetic analysis of nicotine withdrawal deficits in hippocampus-dependent learning.

Cognitive deficits, such as disrupted learning, are a major symptom of nicotine withdrawal. These deficits are heritable, yet their genetic basis is largely unknown. Our lab has developed a mouse model of nicotine withdrawal deficits in learning, using chronic nicotine exposure via osmotic minipumps and fear conditioning. Here, we utilized the BXD genetic reference panel to identify genetic variants underlying nicotine withdrawal deficits in learning. Male and female mice (n = 6-11 per sex per strain, 31 strains) received either chronic saline or nicotine (6.3 mg/kg per day for 12 days), and were then tested for hippocampus-dependent learning deficits using contextual fear conditioning. Quantitative trait locus (QTL) mapping analyses using GeneNetwork identified a significant QTL on Chromosome 4 (82.13 Mb, LRS = 20.03, p < 0.05). Publicly available hippocampal gene expression data were used to identify eight positional candidates (Snacpc3, Mysm1, Rps6, Plaa, Lurap1l, Slc24a2, Hacd4, Ptprd) that overlapped with our behavioral QTL and correlated with our behavioral data. Overall, this study demonstrates that genetic factors impact cognitive deficits during nicotine withdrawal in the BXD recombinant inbred panel and identifies candidate genes for future research.