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•Rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene are both mQTLs and eQTLs.•Unique associations between mQTLs and methylations in CpG sites were in OUD group.•mQTLs and ...eQTLs rs1799971 and rs4654327 were associated with opioid use disorder.
Opioid use disorder (OUD) is a chronic and relapsing brain disease that results in significant mortality worldwide. Genetic factors are estimated to contribute to 40%-60% of the liability, with polymorphisms of opioid receptor genes implicated in this disorder. However, the mechanisms underlying these associations are not yet fully understood. In the present study, we first examined the methylation levels in the promoter region of the OPRM1, OPRD1, and OPRK1 genes in 111 healthy controls (HCs) and 120 patients with OUD, and genotyped three tag SNPs in these genes. Correlations between these SNPs and the methylation levels of the CpG sites and expression levels of the genes were analyzed. After identifying the mQTLs and eQTLs, we determined the associations between the mQTLs/eQTLs and susceptibility to and characteristics of OUD in 930 HCs and 801 patients with OUD. Our results demonstrated that SNPs rs1799971 in the OPRM1 gene and rs4654327 in the OPRD1 gene were both mQTLs and eQTLs. We observed unique correlations between mQTLs and methylation levels of several CpG sites in the OUD group compared to the HC group. Interestingly, both the two mQTLs and eQTLs were associated with the susceptibility to OUD. In conclusion, we suppose that mQTLs and eQTLs in genes may underlie the associations between certain risk genetic polymorphisms and OUD. These mQTLs and eQTLs could potentially serve as promising biomarkers for better management of opioid misuse.
Growth traits can be used as indicators of adaptation to sub-optimal conditions. The current study aimed at identifying quantitative trait loci (QTL) that control performance under variable ...temperature conditions in chickens.
An F2 population was produced by crossing the Taiwan Country chicken L2 line (selected for body weight, comb area, and egg production) with an experimental line of Rhode Island Red layer R- (selected for low residual feed consumption). A total of 844 animals were genotyped with the 60 K Illumina single nucleotide polymorphism (SNP) chip. Whole-genome interval linkage mapping and a genome-wide association study (GWAS) were performed for body weight at 0, 4, 8, 12, and 16 weeks of age, shank length at 8 weeks of age, size of comb area at 16 weeks of age, and antibody response to sheep red blood cells at 11 weeks of age (7 and 14 days after primary immunization). Relevant genes were identified based on functional annotation of candidate genes and potentially relevant SNPs were detected by comparing whole-genome sequences of several birds between the parental lines.
Whole-genome QTL analysis revealed 47 QTL and 714 effects associated with 178 SNPs were identified by GWAS with 5% Bonferroni genome-wide significance. Little overlap was observed between the QTL and GWAS results, with only two chromosomal regions detected by both approaches, i.e. one on GGA24 (GGA for Gallus gallus chromosome) for BW04 and one on GGAZ for six growth-related traits. Based on whole-genome sequence, differences between the parental lines based on several birds were screened in the genome-wide QTL regions and in a region detected by both methods, resulting in the identification of 106 putative candidate genes with a total of 15,443 SNPs, of which 41 were missense and 1698 were not described in the dbSNP archive.
The QTL detected in this study for growth and morphological traits likely influence adaptation of chickens to sub-tropical climate. Using whole-genome sequence data, we identified candidate SNPs for further confirmation of QTL in the F2 design. A strong QTL effect found on GGAZ underlines the importance of sex-linked inheritance for growth traits in chickens.
Soil salinity is one of several major abiotic stresses that constrain maize productivity worldwide. An improved understanding of salt-tolerance mechanisms will thus enhance the breeding of ...salt-tolerant maize and boost productivity. Previous studies have indicated that the maintenance of leaf Na+ concentration is essential for maize salt tolerance, and the difference in leaf Na+ exclusion has previously been associated with variation in salt tolerance between maize varieties.
Here, we report the identification and functional characterization of a maize salt-tolerance quantitative trait locus (QTL), Zea mays Na
+
Content1 (ZmNC1), which encodes an HKT-type transporter (designated as ZmHKT1).
We show that a natural ZmHKT1 loss-of-function allele containing a retrotransposon insertion confers increased accumulation of Na+ in leaves, and salt hypersensitivity. We next show that ZmHKT1 encodes a plasma membrane-localized Na+-selective transporter, and is preferentially expressed in root stele (including the parenchyma cells surrounding the xylem vessels). We also show that loss of ZmHKT1 function increases xylem sap Na+ concentration and causes increased root-to-shoot Na+ delivery, indicating that ZmHKT1 promotes leaf Na+ exclusion and salt tolerance by withdrawing Na+ from the xylem sap.
We conclude that ZmHKT1 is a major salt-tolerance QTL and identifies an important new gene target in breeding for improved maize salt tolerance.
Lower temperature tolerance (LTT) and growth traits are vital to the success of overwintering scallop farming in the North China Sea. Bohai Red, a novel selected scallop strain is the main ...aquaculture species in this region. However, its poor LTT hinders its growth. To improve these traits, the larger Bohai Red scallop was crossed with the smaller bay scallop (A. irradians irradians) which tolerates low temperatures. The full-sib F1 hybrids and the whole-genome resequencing (WGR) method were used to construct a high-density genetic linkage map comprising 5925 single nucleotide polymorphisms (SNPs). The consensus linkage map consisted of 16 linkage groups spanning 1343.46 cM with an average distance of 0.23 cM. Based on this genetic linkage map, 42 potentially significant quantitative trait loci (QTLs) for LTT and growth were detected in eight different linkage groups (LGs) explaining 9.2–18.6% of the phenotypic variation. LG11 may regulate both LTT and growth as 20 QTLs were localized there. Eighteen candidate genes were identified, including 2 (SCARF1, SLC28A3) for LTT and 16 for the growth-related traits. To the best of our knowledge, the present work is one of the first to fine-map the LTT and growth-related QTLs in a genetic linkage map for hybrid Argopecten spp. scallops.
•The first high-density genetic linkage map to be constructed for hybrid Argopecten spp. scallops using the WGR technique.•The lower temperature tolerance (LTT) and growth-related QTLs have been mapped in the genetic linkage map.•The SNP markers associated with relevant traits and candidate genes will facilitate breeding of novel Argopecten scallops.
The predominant genetic defense mechanism against soybean cyst nematode (SCN) in 95% of the North America market is under threat by virulent SCN populations. Usovsky et al. identified GmSNAP02 as an ...SCN susceptibility gene through fine-mapping of unique bi-parental populations. Loss-of-function of GmSNAP02 confers enhanced resistance to more virulent SCN.
The predominant genetic defense mechanism against soybean cyst nematode (SCN) in 95% of the North America market is under threat by virulent SCN populations. Usovsky et al. identified GmSNAP02 as an SCN susceptibility gene through fine-mapping of unique bi-parental populations. Loss-of-function of GmSNAP02 confers enhanced resistance to more virulent SCN.
Defining regulatory mechanisms through which noncoding risk variants influence the cell-mediated pathogenesis of immune-mediated disease (IMD) has emerged as a priority in the post–genome-wide ...association study era.
With a focus on rheumatoid arthritis, we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritize molecular pathways for targeting in this and related immune pathologies.
Whole-genome methylation and transcriptional data from isolated CD4+ T cells and B cells of more than 100 genotyped and phenotyped patients with inflammatory arthritis, all of whom were naive to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with genome-wide association study findings across IMDs and other publicly available resources.
We provide strong evidence that disease-associated DNA variants regulate cis-CpG methylation in CD4+ T and/or B cells at 37% RA loci. Using paired, cell-specific transcriptomic data and causal inference testing, we identify examples where site-specific DNA methylation in turn mediates gene expression, including FCRL3 in both cell types and ORMDL3/GSDMB, IL6ST/ANKRD55, and JAZF1 in CD4+ T cells. A number of genes regulated in this way highlight mechanisms common to RA and other IMDs including multiple sclerosis and asthma, in turn distinguishing them from osteoarthritis, a primarily degenerative disease. Finally, we corroborate the observed effects experimentally.
Our observations highlight important mechanisms of genetic risk in RA and the wider context of immune dysregulation. They confirm the utility of DNA methylation profiling as a tool for causal gene prioritization and, potentially, therapeutic targeting in complex IMD.
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Cottonseed as a by-product of cotton production is an important source of oil and proteins. In this study, the genetic basis of cottonseed fatty acid composition traits was studied through ...quantitative trait locus (QTL) mapping in an interspecific backcross inbred line (BIL) population of 250 lines grown. Based on 7709 single nucleotide polymorphic (SNP) markers, 117 QTLs were identified for the contents of all major fatty acids. Nine stable QTLs were detected in at least three environments, within which six genes were identified as candidate genes. Introduction of Gh_D06G0548, Gh_D06G0571, and Gh_D06G0763 into transformed yeasts led to significant increases in fatty acid contents, especially palmitoleic acid. These findings not only shed more light on the molecular regulations of fatty acid biosynthesis and oil accumulation in cottonseed, but also provide a list of candidate genes for enhancing cottonseed oil content and improving fatty acid composition and its nutritional value.
•117 QTLs were identified for the contents of all major fatty acids in cottonseeds.•Nine major QTLs and eight QTL clusters were found to regulate fatty acid content.•Six candidate genes related to cottonseed fatty acids were identified.•Three genes were found to participate in the dynamic accumulation of fatty acids.•Introduction of three genes into yeasts led to increases in fatty acid contents.
The root system architecture (RSA) of crops can affect their production, particularly in abiotic stress conditions, such as with drought, waterlogging, and salinity. Salinity is a growing problem ...worldwide that negatively impacts on crop productivity, and it is believed that yields could be improved if RSAs that enabled plants to avoid saline conditions were identified. Here, we have demonstrated, through the cloning and characterization of qSOR1 (quantitative trait locus for SOIL SURFACE ROOTING 1), that a shallower root growth angle (RGA) could enhance rice yields in saline paddies. qSOR1 is negatively regulated by auxin, predominantly expressed in root columella cells, and involved in the gravitropic responses of roots. qSOR1 was found to be a homolog of DRO1 (DEEPER ROOTING 1), which is known to control RGA. CRISPR-Cas9 assays revealed that other DRO1 homologs were also involved in RGA. Introgression lines with combinations of gain-of-function and loss-of-function alleles in qSOR1 and DRO1 demonstrated four different RSAs (ultra-shallow, shallow, intermediate, and deep rooting), suggesting that natural alleles of the DRO1 homologs could be utilized to control RSA variations in rice. In saline paddies, near-isogenic lines carrying the qSOR1 loss-of-function allele had soil-surface roots (SOR) that enabled rice to avoid the reducing stresses of saline soils, resulting in increased yields compared to the parental cultivars without SOR. Our findings suggest that DRO1 homologs are valuable targets for RSA breeding and could lead to improved rice production in environments characterized by abiotic stress.
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we ...aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10
), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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