Genome-wide association analysis unveils candidate genes and loci associated with aplasia cutis congenita in pigs.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare genetic disorder characterized by the localized or widespread absence of skin in humans and animals. Individuals with ACC may experience developmental abnormalities in the skeletal and muscular systems, as well as potential complications. Localized and isolated cases of ACC can be treated through surgical and medical interventions, while extensive cases of ACC may result in neonatal mortality. The presence of ACC in pigs has implications for animal welfare. It contributes to an elevated mortality rate among piglets at birth, leading to substantial economic losses in the pig farming industry. In order to elucidate candidate genetic loci associated with ACC, we performed a Genome-Wide Association Study analysis on 216 Duroc pigs. The primary goal of this study was to identify candidate genes that associated with ACC. RESULTS: This study identified nine significant SNPs associated with ACC. Further analysis revealed the presence of two quantitative trait loci, 483 kb (5:18,196,971-18,680,098) on SSC 5 and 159 kb (13:20,713,440-207294431 bp) on SSC13. By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR. CONCLUSIONS: The results of this study further elucidate the potential mechanisms underlying and genetic architecture of ACC and identify reliable candidate genes. These results lay the foundation for treating and understanding ACC in humans.

How broad is the selfing syndrome? Insights from convergent evolution of gene expression across species and tissues in the Capsella genus.

The shift from outcrossing to selfing is one of the main evolutionary transitions in plants. It is accompanied by profound effects on reproductive traits, the so-called selfing syndrome. Because the transition to selfing also implies deep genomic and ecological changes, one also expects to observe a genomic selfing syndrome. We took advantage of the three independent transitions from outcrossing to selfing in the Capsella genus to characterize the overall impact of mating system change on RNA expression, in flowers but also in leaves and roots. We quantified the extent of both selfing and genomic syndromes, and tested whether changes in expression corresponded to adaptation to selfing or to relaxed selection on traits that were constrained in outcrossers. Mating system change affected gene expression in all three tissues but more so in flowers than in roots and leaves. Gene expression in selfing species tended to converge in flowers but diverged in the two other tissues. Hence, convergent adaptation to selfing dominates in flowers, whereas genetic drift plays a more important role in leaves and roots. The effect of mating system transition is not limited to reproductive tissues and corresponds to both adaptation to selfing and relaxed selection on previously constrained traits.

Recombining Your Way Out of Trouble: The Genetic Architecture of Hybrid Fitness under Environmental Stress.

Hybridization between species can either promote or impede adaptation. But we know very little about the genetic basis of hybrid fitness, especially in nondomesticated organisms, and when populations are facing environmental stress. We made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species. We exposed populations to ten toxins and sequenced the most resilient hybrids on low coverage using ddRADseq to investigate four aspects of their genomes: 1) hybridity, 2) interspecific heterozygosity, 3) epistasis (positive or negative associations between nonhomologous chromosomes), and 4) ploidy. We used linear mixed-effect models and simulations to measure to which extent hybrid genome composition was contingent on the environment. Genomes grown in different environments varied in every aspect of hybridness measured, revealing strong genotype-environment interactions. We also found selection against heterozygosity or directional selection for one of the parental alleles, with larger fitness of genomes carrying more homozygous allelic combinations in an otherwise hybrid genomic background. In addition, individual chromosomes and chromosomal interactions showed significant species biases and pervasive aneuploidies. Against our expectations, we observed multiple beneficial, opposite-species chromosome associations, confirmed by epistasis- and selection-free computer simulations, which is surprising given the large divergence of parental genomes (∼15%). Together, these results suggest that successful, stress-resilient hybrid genomes can be assembled from the best features of both parents without paying high costs of negative epistasis. This illustrates the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of genetically diverse hybrid populations.

Hybridization Outcomes Have Strong Genomic and Environmental Contingencies.

AbstractExtreme F2 phenotypes known as transgressive segregants can cause increased or decreased fitness in hybrids beyond the ranges seen in parental populations. Despite the usefulness of transgression for plant and animal breeding and its potential role in hybrid speciation, the genetic mechanisms and predictors of transgressive segregation remain largely untested. We generated seven hybrid crosses between five widely divergent Saccharomyces yeast species and measured the fitness of the parents and their viable F1 and F2 hybrids in seven stressful environments. We found that on average 16.6% of all replicate F2 hybrids had higher fitness than both parents. Against our predictions, transgression frequency was not a function of parental genetic and phenotypic distances across test environments. Within environments, some relationships were significant, but not in the predicted direction; for example, genetic distance was negatively related to transgression in ethanol and hydrogen peroxide. Significant effects of hybrid cross, test environment, and cross × environment interactions suggest that the amount of transgression produced in a hybrid cross is highly context specific and that outcomes of hybridization differ even among crosses made from the same two parents. If the goal is to reliably predict hybrid fitness and forecast the evolutionary potential of admixed populations, we need more efforts to identify patterns beyond the idiosyncrasies caused by specific genomic or environmental contexts.

Evolution of cis- and trans-regulatory divergence in the chicken genome between two contrasting breeds analyzed using three tissue types at one-day-old.

BACKGROUND: Gene expression variation is a key underlying factor influencing phenotypic variation, and can occur via cis- or trans-regulation. To understand the role of cis- and trans-regulatory variation on population divergence in chicken, we developed reciprocal crosses of two chicken breeds, White Leghorn and Cornish Game, which exhibit major differences in body size and reproductive traits, and used them to determine the degree of cis versus trans variation in the brain, liver, and muscle tissue of male and female 1-day-old specimens. RESULTS: We provided an overview of how transcriptomes are regulated in hybrid progenies of two contrasting breeds based on allele specific expression analysis. Compared with cis-regulatory divergence, trans-acting genes were more extensive in the chicken genome. In addition, considerable compensatory cis- and trans-regulatory changes exist in the chicken genome. Most importantly, stronger purifying selection was observed on genes regulated by trans-variations than in genes regulated by the cis elements. CONCLUSIONS: We present a pipeline to explore allele-specific expression in hybrid progenies of inbred lines without a specific reference genome. Our research is the first study to describe the regulatory divergence between two contrasting breeds. The results suggest that artificial selection associated with domestication in chicken could have acted more on trans-regulatory divergence than on cis-regulatory divergence.

PCK1 is negatively regulated by bta-miR-26a, and a single-nucleotide polymorphism in the 3' untranslated region is involved in semen quality and longevity of Holstein bulls.

Phosphoenolpyruvate carboxykinase 1 (PCK1) is a multi-functional enzyme that plays important roles in physiological processes, including reproduction. We previously reported that the PCK1 transcript has five splice variants; PCK1-AS4, which lacks exon 5, is enriched in the testis of Holstein bulls. In the present study, we profiled select PCK1 transcript variants in the testis, epididymus, and semen of high- and low-performance bulls, and examined the possibility that microRNAs may be involved in single nucleotide polymorphism (SNP)-mediated modulation of PCK1 expression. PCK1-AS4 abundance is not significantly different between high- and low-performance bulls. Luciferase reporter assays, however, showed that bovine PCK1 expression is repressed by bta-miR-26a in HepG2 hepatocyte cells. One SNP (c. + 2183 G > T) at the miRNA-binding site of PCK1 does not influence PCK1 expression, but is associated with elevated ejaculation volume, fresh sperm motility, and genomic estimated breeding value of longevity, as well as with reduced values of composite index and calving ease. Collectively, the identified 3'-untranslated-region SNP variant highlights the importance of PCK1 in the fecundity of Holstein bulls, and implicates a role for bta-miR-26a in regulating PCK1 abundance. Further study is needed to assess the effects of other genetic variants in 5'-flanking region and exons of PCK1 on enzyme levels in the testis and sperm. Mol. Reprod. Dev. 83: 217-225, 2016. © 2016 Wiley Periodicals, Inc.

Genome-wide association study revealed genomic regions related to white/red earlobe color trait in the Rhode Island Red chickens.

BACKGROUND: Earlobe color is a naturally and artificially selected trait in chicken. As a head furnishing trait, it has been selected as a breed characteristic. Research has demonstrated that white/red earlobe color was related to at least three loci and sex-linked. However, there has been little work to date to identify the specific genomic regions and genes response to earlobe color in Rhode Island Red chickens. Currently, it is possible to identify the genomic regions responsible for white/red earlobe in Rhode Island Red chicken to eliminate this gap in knowledge by using genome-wide association (GWA) analysis. RESULTS: In the present study, genome-wide association (GWA) analysis was conducted to explore the candidate genomic regions response to chicken earlobe color phenotype. Hens with red dominant and white dominant earlobe was used for case-control analysis by Illumina 600 K SNP arrays. The GWA results showed that 2.38 Mb genomic region (50.13 to 52.51 Mb) with 282 SNPs on chromosome Z were significantly correlated to earlobe color, including sixteen known genes and seven anonymous genes. The sixteen genes were PAM, SLCO4C1, ST8SIA4, FAM174A, CHD1, RGMB, RIOK2, LIX1, LNPEP, SHB, RNF38, TRIM14, NANS, CLTA, GNE, and CPLX1. CONCLUSIONS: The study has revealed the white/red earlobe trait is polygenic and sex-linked in Rhode Island Red chickens. In the genome significant ~2.38 Mb region, twenty-three genes were found and some of them could play critical roles in the formation of white/red earlobe color, especially gene SLCO4C1. Taken together, the candidate genes findings herein can help elucidate the genomic architecture of response to white/red earlobe and provide a new insight on mechanisms underlying earlobe color in Rhode Island Red chickens and other breeds.

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).

Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age­related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

Estimation of water quality variables based on machine learning model and cluster analysis-based empirical model using multi-source remote sensing data in inland reservoirs, South China.

Reservoirs play important roles in the drinking water supply for urban residents, agricultural water provision, and the maintenance of ecosystem health. Satellite optical remote sensing of water quality variables in medium and micro-sized inland waters under oligotrophic and mesotrophic status is challenging in terms of the spatio-temporal resolution, weather conditions and frequent nutrient status changes in reservoirs, etc., especially when quantifying non-optically active components (non-OACs). This study was based on the surface reflectance products of unmanned aerial vehicle (UAV) multispectral images, Sentinel-2B Multispectral instrument (MSI) images and Landsat 7 Enhanced Thematic Mapper Plus (ETM+) by utilizing fuzzy C-means (FCM) clustering algorithm was combined with band combination (BC) model to construct the FCM-BC empirical model, and used mixed density network (MDN), extreme gradient boosting (XGBoost), deep neural network (DNN) and support vector regression (SVR) machine learning (ML) models to invert 12 kinds of optically active components (OACs) and non-OACs. Compared with the unclustered BC (UC) model, the mean coefficient of determination (MR) of the FCM-BC models was improved by at least 46.9%. MDN model showed best accuracy (R2 in the range of 0.60-0.98) and stability (R2 decreased by up to 13.2%). The accuracy of UAV was relatively higher in both empirical methods and machine learning methods. Additionally, the spatio-temporal distribution maps of four water quality variables were mapped based on the MDN model and UAV images, all platforms showed good consistency. An inversion strategy of water quality variables in various monitoring frequencies and weather conditions were proposed finally. The purpose of introducing the UAV platform was to cooperate with the satellite to improve the monitoring response ability of OACs and non-OACs in small and micro-sized oligotrophic and mesotrophic water bodies.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Domestication affects sex-biased gene expression evolution in the duck.

Genes with sex-biased expression are thought to underlie sexually dimorphic phenotypes and are therefore subject to different selection pressures in males and females. Many authors have proposed that sexual conflict leads to the evolution of sex-biased expression, which allows males and females to reach separate phenotypic and fitness optima. The selection pressures associated with domestication may cause changes in population architectures and mating systems, which in turn can alter their direction and strength. We compared sex-biased expression and genetic signatures in wild and domestic ducks (Anas platyrhynchos), and observed changes of sexual selection and identified the genomic divergence affected by selection forces. The extent of sex-biased expression in both sexes is positively correlated with the level of both d N /d S and nucleotide diversity. This observed changing pattern may mainly be owing to relaxed genetic constraints. We also demonstrate a clear link between domestication and sex-biased evolutionary rate in a comparative framework. Decreased polymorphism and evolutionary rate in domesticated populations generally matched life-history phenotypes known to experience artificial selection. Taken together, our work suggests the important implications of domestication in sex-biased evolution and the roles of artificial selection and sexual selection for shaping the diversity and evolutionary rate of the genome.

Identification of Candidate Genes for Economically Important Carcass Cutting in Commercial Pigs through GWAS.

During the process of pork production, the carcasses of pigs are divided and sold, which provides better economic benefits and market competitiveness for pork production than selling the carcass as a whole. Due to the significant cost of post-slaughter phenotypic measurement, the genetic architecture of tenderloin weight (TLNW) and rib weight (RIBW)-important components of pig carcass economic value-remain unknown. In this study, we conducted genome-wide association studies (GWAS) for TLNW and RIBW traits in a population of 431 Duroc × Landrace × Yorkshire (DLY) pigs. In our study, the most significant single nucleotide polymorphism (SNP) associated with TLNW was identified as ASGA0085853 (3.28 Mb) on Sus scrofa chromosome 12 (SSC12), while for RIBW, it was Affx-1115046258 (172.45 Mb) on SSC13. Through haplotype block analysis, we discovered a novel quantitative trait locus (QTL) associated with TLNW, spanning a 5 kb region on SSC12, and a novel RIBW-associated QTL spanning 1.42 Mb on SSC13. Furthermore, we hypothesized that three candidate genes, TIMP2 and EML1, and SMN1, are associated with TLNW and RIBW, respectively. Our research not only addresses the knowledge gap regarding TLNW, but also serves as a valuable reference for studying RIBW. The identified SNP loci strongly associated with TLNW and RIBW may prove useful for marker-assisted selection in pig breeding programs.

Increased Accuracy of Genomic Prediction Using Preselected SNPs from GWAS with Imputed Whole-Genome Sequence Data in Pigs.

Enhancing the accuracy of genomic prediction is a key goal in genomic selection (GS) research. Integrating prior biological information into GS methods using appropriate models can improve prediction accuracy for complex traits. Genome-wide association study (GWAS) is widely utilized to identify potential candidate loci associated with complex traits in livestock and poultry, offering essential genomic insights. In this study, a GWAS was conducted on 685 Duroc × Landrace × Yorkshire (DLY) pigs to extract significant single-nucleotide polymorphisms (SNPs) as genomic features. We compared two GS models, genomic best linear unbiased prediction (GBLUP) and genomic feature BLUP (GFBLUP), by using imputed whole-genome sequencing (WGS) data on 651 Yorkshire pigs. The results revealed that the GBLUP model achieved prediction accuracies of 0.499 for backfat thickness (BFT) and 0.423 for loin muscle area (LMA). By applying the GFBLUP model with GWAS-based SNP preselection, the average prediction accuracies for BFT and LMA traits reached 0.491 and 0.440, respectively. Specifically, the GFBLUP model displayed a 4.8% enhancement in predicting LMA compared to the GBLUP model. These findings suggest that, in certain scenarios, the GFBLUP model may offer superior genomic prediction accuracy when compared to the GBLUP model, underscoring the potential value of incorporating genomic features to refine GS models.

The exon 29 c.3535A>T in the alpha-2-macroglobulin gene causing aberrant splice variants is associated with mastitis in dairy cattle.

Alpha-2-macroglobulin (A2M) binds proteases, thereby acting as defense barriers against pathogens in the plasma and tissues of vertebrates and invertebrates. Quantitative real-time polymerase chain reaction (PCR) and the isobaric tags for relative and absolute quantitation method were used to determine the expression levels of A2M mRNA and proteins in mastitis-infected mammary tissues. A2M mRNA and protein expression were significantly higher in mastitis-infected mammary tissues than those in healthy tissues. We also identified 23 novel A2M splice variants in the bovine mammary tissues using reverse transcription PCR combined with clone sequencing. These splice variants predominantly affected the bait region, the inhibitory region, and the thioester region of the protein, which have the functional key roles in inhibiting the proteases of pathogens. Genomic sequencing analysis revealed a nonsynonymous c.3535A>T single-nucleotide polymorphism (SNP) in exon 29, which is located within a putative exonic splice enhancer and may be the reason why the A2M gene produces the aberrant splice variant A2M-AS4. Our findings suggest that the A2M gene can play its role by alternative splicing mechanism and it may be of significance against mastitis. This study provides clues to better understand the function of the bovine A2M gene and the effects of the exonic SNP on the production of aberrant splice variants.

Genomic Evidence of an Ancient East Asian Divergence Event in Wild Saccharomyces cerevisiae.

Comparative genome analyses have suggested East Asia to be the cradle of the domesticated microbe Brewer's yeast (Saccharomyces cerevisiae), used in the food and biotechnology industry worldwide. Here, we provide seven new, high-quality long-read genomes of nondomesticated yeast strains isolated from primeval forests and other natural environments in China and Taiwan. In a comprehensive analysis of our new genome assemblies, along with other long-read Saccharomycetes genomes available, we show that the newly sequenced East Asian strains are among the closest living relatives of the ancestors of the global diversity of Brewer's yeast, confirming predictions made from short-read genomic data. Three of these strains (termed the East Asian Clade IX Complex here) share a recent ancestry and evolutionary history suggesting an early divergence from other S. cerevisiae strains before the larger radiation of the species, and prior to its domestication. Our genomic analyses reveal that the wild East Asian strains contain elevated levels of structural variations. The new genomic resources provided here contribute to our understanding of the natural diversity of S. cerevisiae, expand the intraspecific genetic variation found in this heavily domesticated microbe, and provide a foundation for understanding its origin and global colonization history.

Publisher Correction: Inheritance patterns of the transcriptome in hybrid chickens and their parents revealed by expression analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Inheritance patterns of the transcriptome in hybrid chickens and their parents revealed by expression analysis.

Although many phenotypic traits of chickens have been well documented, the genetic patterns of gene expression levels in chickens remain to be determined. In the present study, we crossed two chicken breeds, White Leghorn (WL) and Cornish (Cor), which have been selected for egg and meat production, respectively, for a few hundred years. We evaluated transcriptome abundance in the brain, muscle, and liver from the day-old progenies of pure-bred WL and Cor, and the hybrids of these two breeds, by RNA-Seq in order to determine the inheritance patterns of gene expression. Comparison among expression levels in the different groups revealed that most of the genes showed conserved expression patterns in all three examined tissues and that brain had the highest number of conserved genes, which indicates that conserved genes are predominantly important compared to others. On the basis of allelic expression analysis, in addition to the conserved genes, we identified the extensive presence of additive, dominant (Cor dominant and WL dominant), over-dominant, and under-dominant genes in all three tissues in hybrids. Our study is the first to provide an overview of inheritance patterns of the transcriptome in layers and broilers, and we also provide insights into the genetics of chickens at the gene expression level.

Occurrence and distribution of antibiotic resistance genes in the sediments of drinking water sources, urban rivers, and coastal areas in Zhuhai, China.

Antibiotic resistance genes (ARGs) are regarded as emerging contaminants related with human activities. Aquatic environments of an urban city are apt for the persistence and prevalence of ARGs. In this study, we investigated the occurrence and distribution of ARGs and integrase genes in the sediment samples collected from drinking water sources, urban rivers, and coastal areas of Zhuhai, China, in the dry and wet seasons of 2016. The results show that sulfonamide resistance gene of sulII was present at the highest detection frequency (85.71%); and its average concentrations were also the highest in both dry and wet seasons (3.78 × 107 and 9.04 × 107 copies/g sediment, respectively), followed by tetC, tetO, tetA, ermB, dfrA1, and blaPSE-1. Temporally, the concentrations of total ARGs in the wet season were likely higher than those in the dry season; and spatially, the concentrations of total ARGs in the drinking water sources were substantially lower than those in the urban rivers and nearby coastal areas, indicating the different degrees of anthropogenic impact and consequent health risks. Positive correlations were found between intI1 and each quantitative ARG in all wet season samples rather than dry season samples, which suggested higher temperature and more rain in summer might have positive influences on ARG dissemination, especially that mediated by intI1 gene and class I integrons.

Evaluation of genetic resistance to Salmonella Pullorum in three chicken lines.

Resistance to diseases varies considerably among populations of the same species and can be ascribed to both genetic and environmental factors. Salmonella Pullorum (SP) is responsible for significant losses in the poultry industry, especially in developing countries. To better understand SP resistance in chicken populations with different genetic backgrounds, we orally challenged 3 chicken lines with SP-a highly selected commercial breed (Rhode Island Red, RIR), a local Chinese chicken (Beijing You, BY), and a synthetic layer line (dwarf, DW)-at 4 d of age. Two traits related to SP resistance, survival, and bacterial carriage in the spleen were evaluated after infection. Survival rates were recorded up to 40 d of age when all chickens still alive were killed to verify the presence of SP in the spleen to determine carrier state. Mortalities for RIR, BY, and DW chicks were 25.1%, 8.3%, and 22.7%, respectively, and the corresponding carrier-states in the spleens were 17.9%, 0.6%, and 15.8%. Survival and carrier-state heritabilities were estimated using an animal threshold model. Survival heritability was 0.197, 0.091, and 0.167 in RIR, BY, and DW populations, respectively, and the heritabilities of carrier state for DW and RIR were 0.32 and 0.16, respectively. This is the first time that the heritability of the SP carrier state has been evaluated in chickens. Our study provides experimental evidence that chickens with various genetic background exhibited significantly different SP-resistant activities and heritabilities. These results may be useful for selecting lines with better disease resistance.