ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs.

The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding the extent to which, and how, host genetics contributes to this variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans2. Here we study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and the abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3 kb deletion in the gene encoding N-acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.

Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers.

BACKGROUND: The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. METHODS: A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. RESULTS: We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. CONCLUSIONS: Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.

Structural and Superconducting Properties of Bi2Rh3(Se1-xSx)2 (x = 0-1.0).

The structural and superconducting properties of the Bi-based superconductor Bi2Rh3(Se1-xSx)2 were investigated over a wide pressure range. Bi2Rh3Se2 is a superconductor with a superconducting transition temperature, Tc, of less than ∼1.0 K, whereas Bi2Rh3S2 is a nonsuperconductor. The former shows a clear charge density wave (CDW) phase transition at 240 K and the latter shows a first-order structural phase transition at 165 K, providing the supercell structure. Both compounds have the same crystal structure at ambient temperature and pressure (monoclinic, space group of C2/m (No. 12)). This implies the possible formation of solid solution-like phases Bi2Rh3(Se1-xSx)2. In this study, we prepared Bi2Rh3(Se1-xSx)2 (x = 0-1.0) and investigated its superconducting properties and phase transitions at different x values. Because the superconducting properties and temperature causing the phase transition (Tpt) are quite different between Bi2Rh3Se2 and Bi2Rh3S2, their variation against x is quite intriguing from the viewpoint of the pursuit of physical properties via the replacement of Se with S. In this study, the features of the superconductivity and crystal structure against x were fully explored to depict the phase diagram. Moreover, we investigated the pressure (p) dependence of superconductivity and phase transition (CDW or the first-order structural transition) to clarify the interplay between the two ordered states.

Pressure Dependence of the Structural and Superconducting Properties of the Bi-Based Superconductor Bi2Pd3Se2.

The structural and superconducting properties of the Bi-based compound Bi2Pd3Se2 were investigated over a wide pressure range. The prepared Bi2Pd3Se2 sample was a superconductor with a superconducting transition temperature, Tc, of approximately 3.0 K, which differed from a previous report (Tc of less than 1.0 K). At ambient pressure, the powder X-ray diffraction (XRD) pattern of the Bi2Pd3Se2 sample was consistent with that previously reported for Bi2Pd3Se2. The Rietveld method was used to refine the crystal structure, which had a space group of C2/m (No. 12), as reported previously. This compound showed no clear anomaly due to the charge-density-wave (CDW) transition, as seen from the temperature dependence of magnetic susceptibility. However, the temperature dependence of electrical resistivity indicated a clear anomaly, presumably because of the CDW transition in the low-pressure range; the CDW transition temperature was approximately 230 K. The XRD patterns of the Bi2Pd3Se2 sample were measured at 0.160-22.7 GPa, and the patterns were well analyzed by both the Le Bail and Rietveld refinement methods, showing no structural phase transitions in the above pressure range. The pressure dependence of Tc of Bi2Pd3Se2 was recorded based on the temperature dependence of the electrical resistance, which showed an almost constant Tc at 0-13.7 GPa, and the Tc-pressure (p) behavior was fully discussed.

Structure of Bi2Rh3Se2 above and below charge density wave transition determined by Bi Lα and Lγ X-ray fluorescence holography.

The local structure of a two-dimensional layered material, Bi2Rh3Se2, in which superconducting (SC) and charge-density wave (CDW) states coexist, was investigated using Bi Lα and Lγ X-ray fluorescence holography (XFH). The crystal of Bi2Rh3Se2 adopts a monoclinic lattice with a space group of C2/m (No. 12) at room temperature; however, the structure below the CDW transition (∼240 K) is still unclear because of the difficulty in analyzing single-crystal X-ray diffraction. Therefore, information on the crystal structure below 240 K is significant to fully investigate the relationship between the SC and CDW states. Precisely, the value of ß has not been definitely determined, i.e., ß âˆ¼ 90° or ∼134° is still unclear. Therefore, the crystal structure above 240 K is still under discussion. In this study, we attempted to determine the crystal structure at 300 and 200 K by comparing the atomic images reconstructed from Bi Lγ holograms with images simulated based on crystal structure models. A Bi Lα hologram was also exploited to determine suitable atomic locations by comparison with the simulated ones. The atomic image simulated with the crystal structure of Bi2Rh3S2 below the structural phase transition temperature reproduced well the experimental atomic image at 200 K. Specifically, the line profiles of the reconstructed images at 300 and 200 K, which exactly reflect the intensity of the atomic spots, clearly indicate the structural variation above and below the CDW transition temperature, i.e., the supercell structure is suggested as the atomic location for Bi2Rh3Se2 below the CDW transition temperature.

Albumin-to-D-dimer ratios: A novel prognostic factor for evaluating first-line chemotherapy efficacy in advanced lung adenocarcinoma patients.

The prognosis of advanced lung adenocarcinoma (LUAD) remains unfavorable, with chemotherapy constituting a primary treatment modality. Discerning the efficacy of chemotherapy for advanced LUAD is imperative. Prior investigations have demonstrated the prognostic value of albumin and D-dimer individually for malignancies; however, the predictive capacity of albumin-to-D-dimer ratios (ADR) for advanced LUAD subjected to first-line platinum-based chemotherapy remains unexplored. A cohort of 313 patients with advanced LUAD was retrospectively examined in this study, spanning from January 2017 to January 2021. ADR threshold values were ascertained via receiver operating characteristic analysis, followed by the evaluation of the association between pretreatment ADR and clinicopathological characteristics, disease control rate (DCR), and overall response rate (ORR) pertinent to first-line chemotherapy. Prognostic factors for progression-free survival (PFS) were determined employing Cox univariate and multivariate analyses. Subsequently, survival data were illustrated utilizing the Kaplan-Meier method and scrutinized through the log-rank test across the entire and subgroup populations. ADR demonstrated a superior area under the curve (AUC) value relative to albumin and D-dimer individually and exhibited enhanced prognostic predictive capability compared to albumin-to-fibrinogen ratios (AFR) for advanced LUAD (AUC: 0.805 vs. 0.640, DeLong test: p<0.001). ADR yielded a cut-off value of 16.608. A greater proportion of non-smokers was observed within the high-ADR group (ADR>16.608) compared to the low-ADR group (ADR≤16.608). Patients in the high-ADR group displayed elevated BMI and Na+ levels and reduced neutrophil count, monocyte count, globulin, and alkaline phosphatase (all p<0.05). Notably, the high-ADR group exhibited heightened DCR (96.7% vs. 89.2%, p=0.008) and ORR rates (70.1% vs. 51.0%, p=0.001) relative to the low-ADR group. Multivariate analysis outcomes indicated that high ADR constituted an independent risk factor for PFS (hazard ratio: 0.24, p<0.001). Furthermore, patients in the high-ADR cohort displayed a significantly prolonged median PFS (254 vs. 142 days, p<0.0001) compared to their low-ADR counterparts. In subpopulations exhibiting favorable implications for PFS, as determined by multivariate analysis, high-ADR patients consistently demonstrated extended PFS durations relative to the low-ADR group (all p<0.0001). Collectively, our findings suggest that ADR constitutes a novel and promising prognostic indicator for advanced LUAD patients, surpassing the accuracy of albumin and D-dimer individually and AFR. ADR thus serves as a potent instrument for assessing treatment effects and PFS in advanced LUAD patients undergoing first-line chemotherapy.

5.32 W ultraviolet laser generation at 266†nm using sum-frequency method with CsB3O5 crystal.

Ultraviolet (UV) beam generation at 266 nm using the sum-frequency (SFG) method with CsB3O5 (CBO) crystals was first suggested in 1997 [Opt. Lett.22, 1840 (1997).10.1364/OL.22.001840]; however, there has been no further research in the past 25 years. Herein, by sum-frequency mixing in CBO crystals, we obtained a high conversion efficiency picosecond (ps) and a high-power nanosecond (ns) 266 nm UV beam output. First, a ps laser device with simultaneously radiated wavelengths of 1064 and 355 nm and repetition frequency of 10 Hz was used as the fundamental laser source, and the conversion efficiency from 1064 + 355 nm to 266 nm reached 20.35%. We then used a 1064 nm ns laser with a high output power and repetition frequency of 10 kHz as the pump source. We accurately modified the optimal phase matching direction of the CBO crystal, and the achieved output power at 266 nm reached 5.32 W.

Pressure Dependence of Superconductivity in a Charge-Density-Wave Superconductor Bi2Rh3Se2.

The structural and superconducting properties of a Bi-based compound, Bi2Rh3Se2, are investigated over a wide pressure range. Bi2Rh3Se2 is a superconductor with a superconducting transition temperature, Tc, of 0.7 K. This compound is in a charge-density-wave (CDW) state below 240 K, which implies the coexistence of superconducting and CDW states at low temperatures. Here, the superconducting properties of Bi2Rh3Se2 are studied from the perspective of the temperature dependence of electrical resistance (R) at high pressures (p's). The pressure dependence of Tc of Bi2Rh3Se2 shows a slow increase in Tc at 0-15.5 GPa, and the Tc slowly decreases with pressure above 15.5 GPa, which is markedly different from that of normal superconductors because the value of Tc should simply decrease owing to the decrease in density of states (DOS) on the Fermi level, N(εF), driven by a simple shrinkage of the lattice under pressure. To ascertain the origin of such a dome-like Tc-p behavior, the crystal structure of Bi2Rh3Se2 was explored over a wide pressure range of 0-20 GPa on the basis of powder X-ray diffraction; no structural phase transitions or simple shrinkage of the lattice was observed. This result implies that the increase in Tc against pressure cannot simply be explained from a structural point of view. In other words, a direct relation between superconductivity and crystal structure was not found. On the other hand, the CDW transition became ambiguous at pressures higher than 3.8 GPa, suggesting that the Tc had been suppressed by the CDW transition in a low pressure range. Thus, the findings suggest that for Bi2Rh3Se2, Tc is enhanced through the suppression of CDW transition, which may be reasonable because the CDW-ordered state restrains the charge fluctuation to weaken the electron-phonon coupling and opens the gap to decrease the density of states on the Fermi level. The obtained dome-like Tc-p behavior indicates the possibility of Bi2Rh3Se2 being an exotic superconductor.

Genomic prediction in pigs using data from a commercial crossbred population: insights from the Duroc x (Landrace x Yorkshire) three-way crossbreeding system.

BACKGROUND: Genomic selection is widely applied for genetic improvement in livestock crossbreeding systems to select excellent nucleus purebred (PB) animals and to improve the performance of commercial crossbred (CB) animals. Most current predictions are based solely on PB performance. Our objective was to explore the potential application of genomic selection of PB animals using genotypes of CB animals with extreme phenotypes in a three-way crossbreeding system as the reference population. Using real genotyped PB as ancestors, we simulated the production of 100,000 pigs for a Duroc x (Landrace x Yorkshire) DLY crossbreeding system. The predictive performance of breeding values of PB animals for CB performance using genotypes and phenotypes of (1) PB animals, (2) DLY animals with extreme phenotypes, and (3) random DLY animals for traits of different heritabilities ([Formula: see text] = 0.1, 0.3, and 0.5) was compared across different reference population sizes (500 to 6500) and prediction models (genomic best linear unbiased prediction (GBLUP) and Bayesian sparse linear mixed model (BSLMM)). RESULTS: Using a reference population consisting of CB animals with extreme phenotypes showed a definite predictive advantage for medium- and low-heritability traits and, in combination with the BSLMM model, significantly improved selection response for CB performance. For high-heritability traits, the predictive performance of a reference population of extreme CB phenotypes was comparable to that of PB phenotypes when the effect of the genetic correlation between PB and CB performance ([Formula: see text]) on the accuracy obtained with a PB reference population was considered, and the former could exceed the latter if the reference size was large enough. For the selection of the first and terminal sires in a three-way crossbreeding system, prediction using extreme CB phenotypes outperformed the use of PB phenotypes, while the optimal design of the reference group for the first dam depended on the percentage of individuals from the corresponding breed that the PB reference data comprised and on the heritability of the target trait. CONCLUSIONS: A commercial crossbred population is promising for the design of the reference population for genomic prediction, and selective genotyping of CB animals with extreme phenotypes has the potential for maximizing genetic improvement for CB performance in the pig industry.

Genetic dissection of 26 meat cut, meat quality and carcass traits in four pig populations.

BACKGROUND: Currently, meat cut traits are integrated in pig breeding objectives to gain extra profit. However, little is known about the heritability of meat cut proportions (MCP) and their correlations with other traits. The aims of this study were to assess the heritability and genetic correlation of MCP with carcass and meat quality traits using single nucleotide polymorphism chips and conduct a genome-wide association study (GWAS) to identify candidate genes for MCP. RESULTS: Seventeen MCP, 12 carcass, and seven meat quality traits were measured in 2012 pigs from four populations (Landrace; Yorkshire; Landrace and Yorkshire hybrid pigs; Duroc, and Landrace and Yorkshire hybrid pigs). Estimates of the heritability for MCP ranged from 0.10 to 0.55, with most estimates being moderate to high and highly consistent across populations. In the combined population, the heritability estimates for the proportions of scapula bone, loin, back fat, leg bones, and boneless picnic shoulder were 0.44 ± 0.04, 0.36 ± 0.04, 0.44 ± 0.04, 0.38 ± 0.04, and 0.39 ± 0.04, respectively. Proportion of middle cuts was genetically significantly positively correlated with intramuscular fat content and backfat depth. Proportion of ribs was genetically positively correlated with carcass oblique length and straight length (0.35 ± 0.08 to 0.45 ± 0.07) and negatively correlated with backfat depth (- 0.26 ± 0.10 to - 0.45 ± 0.10). However, weak or nonsignificant genetic correlations were observed between most MCP, indicating their independence. Twenty-eight quantitative trait loci (QTL) for MCP were detected by GWAS, and 24 new candidate genes related to MCP were identified, which are involved with growth, height, and skeletal development. Most importantly, we found that the development of the bones in different parts of the body may be regulated by different genes, among which HMGA1 may be the strongest candidate gene affecting forelimb bone development. Moreover, as previously shown, VRTN is a causal gene affecting vertebra number, and BMP2 may be the strongest candidate gene affecting hindlimb bone development. CONCLUSIONS: Our results indicate that breeding programs for MCP have the potential to enhance carcass composition by increasing the proportion of expensive cuts and decreasing the proportion of inexpensive cuts. Since MCP are post-slaughter traits, the QTL and candidate genes related to these traits can be used for marker-assisted and genomic selection.

NanoCross: A pipeline that detecting recombinant crossover using ONT sequencing data.

Meiotic recombination is crucial for eukaryotes but varies among taxonomic scales (between individuals, groups, species, etc.) and genome resolutions. Studying how and why recombination rates change can help us understand the molecular basis and mechanisms of genetics and evolution. We introduce a genome-wide identification script called NanoCross, which uses ONT sequences to detect pooled gamete DNA cross recombination events. NanoCross first reduced sequencing errors and then constructed individual haplotypes based on homopolymer-filtered ONT sequences. Then, each molecule read is used to estimate cross recombination. In the case of moderate heterozygous variation density and sequencing depth, simulations revealed that our technique offers a good level of sensitivity and specificity. We constructed a high-resolution recombination map of wild boar genomes using NanoCross and compared it to recombination maps of male breeding pig populations. NanoCross provides us with a method and scripts for constructing a high-resolution individual genome recombination map utilizing long-read sequencing, as well as a novel approach for examining the variation in individual recombination rate. The source code and data mechanism are hosted on GitHub (https://github.com/zuoquanchen/NanoCross).

Human-Mediated Admixture and Selection Shape the Diversity on the Modern Swine (Sus scrofa) Y Chromosomes.

Throughout its distribution across Eurasia, domestic pig (Sus scrofa) populations have acquired differences through natural and artificial selection, and have often interbred. We resequenced 80 Eurasian pigs from nine different Asian and European breeds; we identify 42,288 reliable SNPs on the Y chromosome in a panel of 103 males, among which 96.1% are newly detected. Based on these new data, we elucidate the evolutionary history of pigs through the lens of the Y chromosome. We identify two highly divergent haplogroups: one present only in Asia and one fixed in Europe but present in some Asian populations. Analyzing the European haplotypes present in Asian populations, we find evidence of three independent waves of introgression from Europe to Asia in last 200 years, agreeing well with the literature and historical records. The diverse European lineages were brought in China by humans and left significant imprints not only on the autosomes but also on the Y chromosome of geographically and genetically distinct Chinese pig breeds. We also find a general excess of European ancestry on Y chromosomes relative to autosomes in Chinese pigs, an observation that cannot be explained solely by sex-biased migration and genetic drift. The European Y haplotype is associated with leaner meat production, and we hypothesize that the European Y chromosome increased in frequency in Chinese populations due to artificial selection. We find evidence of Y chromosomal gene flow between Sumatran wild boar and Chinese pigs. Our results demonstrate how human-mediated admixture and selection shaped the distribution of modern swine Y chromosomes.

Origin, evolution, and tissue-specific functions of the porcine repetitive element 1.

BACKGROUND: The porcine repetitive element 1 (PRE1) is the most abundant short interspersed nuclear element (SINE) in the Sus scrofa genome and it has been suggested that some PRE1 can have regulatory functions. The million copies of PRE1 in the porcine genome have accumulated abundant CpG dinucleotides and unique structural variations, such as direct repeats and patterns of sequence degeneration. The aims of this study were to analyse these structural variations to trace the origin and evolutionary pattern of PRE1 and to investigate potential methylation-related functions of PRE1 based on methylation patterns of PRE1 CpG dinucleotides in different tissues. RESULTS: We investigated the evolutionary trajectory of PRE1 and found that PRE1 originated from the ancestral CHRS-S1 family through three main successive partial duplications. We found that the partial duplications and deletions of PRE1 were likely due to RNA splicing events during retrotransposition. Functionally, correlation analysis showed that the methylation levels of 103 and 261 proximal PRE1 were, respectively, negatively and positively correlated with the expression levels of neighboring genes (Spearman correlation, P < 0.01). Further epigenomic analysis revealed that, in the testis, demethylation of proximal PRE1 in the HORMAD1 and HACD3 genes had tissue-specific enhancer and promoter functions, while in the muscle, methylation of proximal PRE1 repeats in the TCEA3 gene had an enhancer function. CONCLUSIONS: The characteristic sequences of PRE1 reflect unique patterns of origin and evolution and provide a structural basis for diverse regulatory functions.

A further look at quantitative trait loci for growth and fatness traits in a White Duroc × Erhualian F3 intercross population.

Genetic analysis of porcine growth and fatness traits is beneficial to the swine industry and provides a reference to understand human obesity. Here, we obtained 29 growth and fatness traits for 473 individuals from a White Duroc × Erhualian F3 intercross population. Basic statistical analyses showed that: (1) Positive correlations between different-stage body weights were detected, the shorter the time interval the stronger the correlation. (2) Strong correlations existed in the paired fatness traits. (3) With the growth of age, the correlation between fatness and body weight was increasing. All pigs were genotyped by Illumina 50 K SNP chips and their whole-genome genotypes were imputed referred to 109 re-sequencing data. We performed common and imputation-based GWASs for these traits. Two genome-wide significant loci on swine chromosome (SSC) 4 and 7 were repeatedly detected. The strongest association (P = 3.24 × 10-19) was detected at 31.96 Mb on SSC7 for leaf fat weight. On this locus, seven major haplotypes were identified, of which two were novel and had an increasing-fatness effect. In the imputation-based GWAS, three new loci were identified. Our findings provide further insights into and enhance our understanding of genetic mechanism of porcine growth and fat deposition.

A whole genome sequence association study of muscle fiber traits in a White Duroc×Erhualian F2 resource population.

OBJECTIVE: Muscle fiber types, numbers and area are crucial aspects associated with meat production and quality. However, there are few studies of pig muscle fibre traits in terms of the detection power, false discovery rate and confidence interval precision of whole-genome quantitative trait loci (QTL). We had previously performed genome scanning for muscle fibre traits using 183 microsatellites and detected 8 significant QTLs in a White Duroc× Erhualian F2 population. The confidence intervals of these QTLs ranged between 11 and 127 centimorgan (cM), which contained hundreds of genes and hampered the identification of QTLs. A whole-genome sequence imputation of the population was used for fine mapping in this study. METHODS: A whole-genome sequences association study was performed in the F2 population. Genotyping was performed for 1,020 individuals (19 F0, 68 F1, and 933 F2). The whole-genome variants were imputed and 21,624,800 single nucleotide polymorphisms (SNPs) were identified and examined for associations to 11 longissimus dorsi muscle fiber traits. RESULTS: A total of 3,201 significant SNPs comprising 7 novel QTLs showing associations with the relative area of fiber type I (I_RA), the fiber number per square centimeter (FN) and the total fiber number (TFN). Moreover, one QTL on pig chromosome 14 was found to affect both FN and TFN. Furthermore, four plausible candidate genes associated with FN (kinase non-catalytic C-lobe domain containing [KNDC1]), TFN (KNDC1), and I_RA (solute carrier family 36 member 4, contactin associated protein like 5, and glutamate metabotropic receptor 8) were identified. CONCLUSION: An efficient and powerful imputation-based association approach was utilized to identify genes potentially associated with muscle fiber traits. These identified genes and SNPs could be explored to improve meat production and quality via marker-assisted selection in pigs.

Muscle glycogen level and occurrence of acid meat in commercial hybrid pigs are regulated by two low-frequency causal variants with large effects and multiple common variants with small effects.

BACKGROUND: Meat production from the commercial crossbred Duroc × (Landrace × Yorkshire) (DLY) pig is predominant in the pork industry, but its meat quality is often impaired by low ultimate pH (pHu). Muscle glycogen level at slaughter is closely associated with pHu and meat technological quality, but its genetic basis remains elusive. The aim of this study was to identify genes and/or causative mutations associated with muscle glycogen level and other meat quality traits by performing a genome-wide association study (GWAS) and additional analyses in a population of 610 DLY pigs. RESULTS: Our initial GWAS identified a genome-wide significant (P = 2.54e-11) quantitative trait locus (QTL) on SSC15 (SSC for Sus scrofa chromosome) for the level of residual glycogen and glucose (RG) in the longissimus muscle at 45 min post-mortem. Then, we demonstrated that a low-frequency (minor allele frequency = 0.014) R200Q missense mutation in the PRKAG3 (RN) gene caused this major QTL effect on RG. Moreover, we showed that the 200Q (RN-) allele was introgressed from the Hampshire breed into more than one of the parental breeds of the DLY pigs. After conditioning on R200Q, re-association analysis revealed three additional QTL for RG on SSC3 and 4, and on an unmapped scaffold (AEMK02000452.1). The SSC3 QTL was most likely caused by a splice mutation (g.8283C>A) in the PHKG1 gene that we had previously identified. Based on functional annotation, the genes TMCO1 on SSC4 and CKB on the scaffold represent promising candidate genes for the other two QTL. There were significant interaction effects of the GWAS tag SNPs at those two loci with PRKAG3 R200Q on RG. In addition, a number of common variants with potentially smaller effects on RG (P < 10-4) were uncovered by a second conditional GWAS after adjusting for the two causal SNPs, R200Q and g.8283C>A. CONCLUSIONS: We found that the RN- allele segregates in the parental lines of our DLY population and strongly influences its meat quality. Our findings also indicate that the genetic basis of RG in DLY can be mainly attributed to two major genes (PRKAG3 and PHKG1), along with many minor genes.

An association study using imputed whole-genome sequence data identifies novel significant loci for growth-related traits in a Duroc × Erhualian F2 population.

The average daily gain (ADG) and body weight (BW) are very important traits for breeding programs and for the meat production industry, which have attracted many researchers to delineate the genetic architecture behind these traits. In the present study, single- and multi-trait genome-wide association studies (GWAS) were performed between imputed whole-genome sequence data and the traits of the ADG and BW at different stages in a large-scale White Duroc × Erhualian F2 population. A bioinformatics annotation analysis was used to assist in the identification of candidate genes that are associated with these traits. Five and seven genome-wide significant quantitative trait loci (QTLs) were identified by single- and multi-trait GWAS, respectively. Furthermore, more than 40 genome-wide suggestive loci were detected. On the basis of the whole-genome sequence association study and the bioinformatics analysis, NDUFAF6, TNS1 and HMGA1 stood out as the strongest candidate genes. The presented single- and multi-trait GWAS analysis using imputed whole-genome sequence data identified several novel QTLs for pig growth-related traits. Integrating the GWAS with bioinformatics analysis can facilitate the more accurate identification of candidate genes. Higher imputation accuracy, time-saving algorithms, improved models and comprehensive databases will accelerate the identification of causal genes or mutations, which will contribute to genomic selection and pig breeding in the future.

Mesorhizobium wenxiniae sp. nov., isolated from chickpea (Cicer arietinum L.) in China.

Three chickpea rhizobial strains (WYCCWR 10195T=S1-3-7, WYCCWR 10198=S1-4-3 and WYCCWR 10200=S1-5-1) isolated from Northwest China formed a group affiliated to Mesorhizobium based on 16S rRNA gene sequence comparison. To clarify their species status, multilocus sequence analysis and average nucleotide identity (ANI) values of whole genome sequences between the novel group and the type strains of the related species were further performed. Similarities of 95.7-96.6 % in the concatenated sequences of atpD-recA-glnII and 91.9-93.1 % of ANI values to the closest-related species Mesorhizobium muleiense, Mesorhizobium mediterraneum and Mesorhizobium temperatum demonstrated the novel group a unique genospecies. The most abundant fatty acid in cells of WYCCWR 10195T were C19 : 0 cyclo ω8c (51.4 %), followed by C18 : 1 ω7c 11-methyl (9.5 %) and C16 : 0 (9.3 %). Its genome size was 6.37 Mbp, comprising 6633 predicted genes with a DNA G+C content of 61.9 mol%. The similarities of 99.0-99.8 % for the nodC gene and 98.3-99.44 % for the nifH gene to those of the chickpea rhizobial species and nodulation with Cicer arietinum L. confirmed the strains of the new genospecies as symbiovar ciceri. The weak utilization of most of the tested sugars/organic acids and non-utilization of l(+)-rhamnose, l-cysteine and l-glycine as sole carbon source, tolerance to 1 % (w/v) NaCl, resistance to 5 µg ml-1 chloromycetin and non-hydrolysis of l-tyrosine distinguished the novel group from the related species and supported this group as a novel species, for which the name Mesorhizobium wenxiniae sp. nov. is proposed, with WYCCWR 10195T (=S1-3-7=HAMBI 3692T=LMG 30254T) as the type strain.

Copy number variation in the MSRB3 gene enlarges porcine ear size through a mechanism involving miR-584-5p.

BACKGROUND: The size and type of ears are important conformation characteristics that distinguish pig breeds. A significant quantitative trait locus (QTL) for ear size has been identified on SSC5 (SSC for Sus scrofa chromosome) but the underlying causative gene and mutation remain unknown. Thus, our aim was to identify the gene responsible for enlarged ears in pig. RESULTS: First, we narrowed down the QTL region on SSC5 to a 137.85-kb interval that harbors only the methionine sulfoxide reductase B3 (MSRB3) gene. Then, we identified a 38.7-kb copy number variation (CNV) that affects the last two exons of MSRB3 and could be the candidate causative mutation for this QTL. This CNV showed complete concordance with genotype at the QTL of the founder animals in a white Duroc × Erhualian F2 intercross and was found only in pigs from six Chinese indigenous breeds with large ears and from the Landrace breed with half-floppy ears. Moreover, it accounted for the significant association with ear size on SSC5 across the five pig populations tested. eQTL mapping revealed that this CNV was significantly associated with the expression of the microRNA (miRNA) miR-584-5p, which interacts with MSRB3, one of its target genes. In vivo and in vitro experiments confirmed that miR-584-5p inhibits the translation of MSRB3 mRNA. Taken together, these results led us to conclude that presence of the 38.7-kb CNV in the genome of some pig breeds affects ear size by altering the expression of miR-584-5p, which consequently hinders the expression of one of its target genes (e.g. MSRB3). CONCLUSIONS: Our findings shed insight into the underlying mechanism of development of external ears in mammals and contribute to a better understanding of how the presence of CNV can regulate gene expression.

Serial translocation by means of circular intermediates underlies colour sidedness in cattle.

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism.