BMC Genomics最新文献

Background: Trends in the development of genetic markers for the purposes of genomic and marker-assisted selection primarily focus on identifying causative polymorphisms. Using these polymorphisms as markers enables a more accurate association between genotype and phenotype. Bioinformatic analysis allows calculating the impact of missense polymorphisms on the structural and functional characteristics of proteins, which makes it promising for identifying causative polymorphisms. In this study, a bioinformatic approach is applied to evaluate and differentiate polymorphisms based on their causality in genes that affect the production traits of pigs and cows, which are two important livestock species.

Results: The influence of both known causative and candidate missense polymorphisms in the MC4R, NR6A1, PRKAG3, RYR1, and SYNGR2 genes of pigs, as well as the ABCG2, DGAT1, GHR, and MSTN genes of cows, was assessed. The study included an evaluation of the effect of polymorphisms on protein functions, considering the evolutionary and physicochemical characteristics of amino acids at polymorphic sites. Additionally, it examined the impact of polymorphisms on the stability of tertiary protein structures, including changes in folding, binding of protein monomers, and interaction with ligands.

Conclusions: The comprehensive bioinformatic analysis used in this study enables the differentiation of polymorphisms into neutral, where both amino acids in the polymorphic site do not significantly affect the structure and function of the protein, and causative, where one of the amino acids significantly impacts the protein's properties. This approach can be employed in future research to screen extensive sets of polymorphisms in animal genomes, identifying the most promising polymorphisms for further investigation in association studies.

In this study, we applied comparative transcriptomics and proteomics techniques to systematically investigate the dynamic expression patterns of genes and proteins at various stages of early embryonic development of the gastropod Neptunea arthritica cumingii. Twelve cyclin-dependent kinase (CDKs) genes and five downstream proteins associated with these CDKs were identified. Through techniques such as qRT-PCR, our data elucidate for the first time the regulatory functions of CDK family genes and establish CDKs as a pivotal gene cluster in the early embryonic development of N. cumingii. These findings not only enhance the understanding of molecular developmental biology in N. cumingii and marine gastropods in general but also provide significant insights into the mechanisms involved in early embryonic development in N. cumingii. Furthermore, our results provide theoretical guidance for advancing artificial breeding technology for N. cumingii.

Background: Fungal DNA is rarely reported in metagenomic studies of ancient samples. Although fungi are essential for their interactions with all kingdoms of life, limited information is available about ancient fungi. Here, we explore the possibility of the presence of ancient fungal species in the gut of Ötzi, the Iceman, a naturally mummified human found in the Tyrolean Alps (border between Italy and Austria).

Methods: A robust bioinformatic pipeline has been developed to detect and authenticate fungal ancient DNA (aDNA) from muscle, stomach, small intestine, and large intestine samples.

Results: We revealed the presence of ancient DNA associated with Pseudogymnoascus genus, with P. destructans and P. verrucosus as possible species, which were abundant in the stomach and small intestine and absent in the large intestine and muscle samples.

Conclusion: We suggest that Ötzi may have consumed these fungi accidentally, likely in association with other elements of his diet, and they persisted in his gut after his death due to their adaptability to harsh and cold environments. This suggests the potential co-occurrence of ancient humans with opportunistic fungal species and proposes and validates a conservative bioinformatic approach for detecting and authenticating fungal aDNA in historical metagenomic samples.

Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbial pathways using data generated by shotgun metagenomic sequencing (n = 683). Methylation in both cohorts was profiled in blood samples using the Illumina 450K array. Discovery and replication analysis identified two independent CpGs associated with the genus Eggerthella: cg16586104 (P_{meta-analysis} = 3.21 × 10^-11) and cg12234533 (P_{meta-analysis} = 4.29 × 10^-10). We also show that microbiome can mediate the effect of environmental factors on host gene methylation. In this first association study linking epigenome to microbiome, we found and replicated the associations of two CpGs to the abundance of genus Eggerthella and identified microbiome as a mediator of the exposome. These associations are observational and suggest further investigation in larger and longitudinal set-ups.

Background: Insecticide resistance is jeopardising malaria control efforts in Africa. Deciphering the evolutionary dynamics of mosquito populations country-wide is essential for designing effective and sustainable national and subnational tailored strategies to accelerate malaria elimination efforts. Here, we employed genome-wide association studies through pooled template sequencing to compare four eco-geographically different populations of the major vector, Anopheles funestus, across a South North transect in Cameroon, aiming to identify genomic signatures of adaptive responses to insecticides.

Results: Our analysis revealed limited population structure within Northern and Central regions (F_ST<0.02), suggesting extensive gene flow, while populations from the Littoral/Coastal region exhibited more distinct genetic patterns (F_ST>0.049). Greater genetic differentiation was observed at known resistance-associated loci, resistance-to-pyrethroids 1 (rp1) (2R chromosome) and CYP9 (X chromosome), with varying signatures of positive selection across populations. Allelic variation between variants underscores the pervasive impact of selection pressures, with rp1 variants more prevalent in Central and Northern populations (F_ST>0.3), and the CYP9 associated variants more pronounced in the Littoral/Coastal region (F_ST =0.29). Evidence of selective sweeps was supported by negative Tajima's D and reduced genetic diversity in all populations, particularly in Central (Elende) and Northern (Tibati) regions. Genomic variant analysis identified novel missense mutations and signatures of complex genomic alterations such as duplications, deletions, transposable element (TE) insertions, and chromosomal inversions, all associated with selective sweeps. A 4.3 kb TE insertion was fixed in all populations with Njombe Littoral/Coastal population, showing higher frequency of CYP9K1 (G454A), a known resistance allele and TE upstream compared to elsewhere.

Conclusion: Our study uncovered regional variations in insecticide resistance candidate variants, emphasizing the need for a streamlined DNA-based diagnostic assay for genomic surveillance across Africa. These findings will contribute to the development of tailored resistance management strategies crucial for addressing the dynamic challenges of malaria control in Cameroon.

Background: Reproductive efficiency is crucial for the long-term economic sustainability of beef cattle production. Pregnancy loss and stillbirth are complex reproductive traits that do not yet have their genomic background fully understood, especially in zebu breeds (Bos taurus indicus). Hence, this study aimed to perform a genome-wide association study (GWAS) and functional annotation for conception success (CS), pregnancy loss (PL), stillbirth (SB), and pre-weaning calf mortality (PWM) in Nellore cattle. In this study, 3,728 cows with 17,094 reproductive records and 11,785 calves were evaluated. A total of 3,351 genotyped animals and 383,739 SNP markers were considered for GWAS analyses. SNP effects were estimated using the weighted single-step GWAS (WssGWAS), which considered two iterations. The top ten genomic windows with the highest contribution to the additive genetic variance of the traits were selected for gene annotation. Candidate genes were then analyzed for Gene Ontology terms (GO) and metabolic pathways.

Results: The top ten genomic windows that explained the largest proportion of the direct additive genetic variance ([Formula: see text]) for CS, PL, SB, and PWM accounted for 17.03% (overlapping with 79 genes), 16.76% (57 genes), 11.71% (73 genes), and 12.03% (65 genes) of the total [Formula: see text], respectively. For CS, significant GO terms included Somitogenesis (GO:0001756), Somite Development (GO:0061053), and Chromosome Segregation (GO:0007059). Considering PL, the processes annotated were the Regulation of Hormone Secretion (GO:0046883), and Hormone Transport (GO:0009914), along with the Glucagon Signaling Pathway (bta04922). Embryonic Development (GO:0045995), and Cerebellum Development (GO:0021549) were the main biological processes found in the gene enrichment analysis for SB. For PWM, the Regulation of Glucose metabolic processes (GO:0010906), Zinc Ion Homeostasis (GO:0055069), Lactation (GO:0007595), and Regulation of Insulin Secretion (GO:0050796) were the most significant GO terms observed.

Conclusions: These findings provide valuable information on genomic regions, candidate genes, biological processes, and metabolic pathways that may significantly influence the expression of complex reproductive traits in Nellore cattle, offering potential contributions to breeding strategies and future genomic selection strategies.

Background: The salmon louse (Lepeophtheirus salmonis) is a parasite of wild and farmed salmonid fish, causing huge economic damage to the commercial farming of Atlantic salmon (Salmo salar) in the northern hemisphere. The avermectin emamectin benzoate (EMB) is widely used for salmon delousing. While resistance to EMB is widespread in Atlantic populations of L. salmonis, the molecular mechanisms of resistance remain to be elucidated. The aim of the present work was to obtain insights into potential EMB resistance mechanisms by identifying genetic and transcriptomic markers associated with EMB resistance.

Results: Crosses were performed between EMB-susceptible and -resistant L. salmonis, sourced from two parental strains isolated in Scotland, producing fully pedigreed families. The EMB susceptibility of individual parasites was characterised using time-to-response bioassays. Parasites of two families were subjected to double digest restriction site-associated DNA sequencing (ddRAD-seq) for simultaneous discovery of single nucleotide polymorphisms (SNPs) and genotyping. Data analysis revealed that EMB resistance is associated with one quantitative trait locus (QTL) region on L. salmonis chromosome 5. Marker-trait association was confirmed by genotyping assays for 7 SNPs in two additional families. Furthermore, the transcriptome of male parasites of the EMB-susceptible and -resistant L. salmonis parental strains was assessed. Among eighteen sequences showing higher transcript expression in EMB-resistant as compared to drug-susceptible lice, the most strongly up-regulated gene is located in the above QTL region and shows high homology to β spectrin, a cytoskeleton protein that has roles in neuron architecture and function. Further genes differentially regulated in EMB-resistant lice include a glutathione S-transferase (GST), and genes coding for proteins with predicted roles in mitochondrial function, intracellular signalling or transcription.

Conclusions: Major determinants of EMB resistance in L. salmonis are located on Chromosome 5. Resistance can be predicted using a limited number of genetic markers. Genes transcriptionally up-regulated in EMB resistant parasites include a β spectrin, a cytoskeletal protein with still incompletely understood roles in neuron structure and function, as well as glutathione S-transferase, an enzyme with potential roles in the biochemical defence against toxicants.

Background: Aging and tumorigenesis share intricate regulatory processes, that alter the genome, epigenome, transcriptome and immune landscape of tissues. Discovering the link between aging and cancer in terms of multiomics characteristics remains a challenge for biomedical researchers.

Methods: We collected high-throughput datasets for 57 human tumors and 20 normal tissues, including 23,125 samples with age information. On the basis of these sufficient omics data, we introduced six useful modules including genomic (somatic mutation and copy number variation), gene expression, DNA methylation, hallmarks (aging and cancer), immune landscape (immune infiltration, immune pathways, immune signatures, and antitumor immune activities) and survival analysis. Correlation and differential analyses were performed for the multiomic signatures associated with aging at the gene level.

Results: We developed Aging2Cancer ( http://210.37.77.200:8080/Aging2Cancer/index.jsp ), which is a comprehensive database and analysis platform for revealing the associations between aging and cancer. Users can search for and visualize the results of genes of interest to explore the relationships between aging and cancer at the gene level for different omics levels.

Conclusions: We believe that Aging2Cancer is a valuable resource for identifying novel biomarkers and will serve as a bridge for linking aging to cancer.

Background: The ovary is a central organ in the reproductive system that produces oocytes and synthesizes and secretes steroid hormones. Healthy development and regular cyclical change in the ovary is crucial for regulating reproductive processes. However, the key genes and metabolites that regulate ovarian development and pregnancy have not been fully elucidated. This study conducted high-throughput RNA sequencing and untargeted metabolite profiling of the ovarian tissues from Chenghua pigs at four stages, including postnatal day 3 (D3), puberty at the age of about 125 days (Pub), sexual maturity at the age of about 365 days (Y1), and 105 days after pregnancy at the age of about 360 days (Pre).

Results: A total of 9,264 and 1,593 differentially expressed genes (DEGs) were identified during ovarian development and pregnancy. Several key genes involved in ovarian development, including SQLE, HMGCS1, MSMO1, SCARB1, CYP11A1, HSD3B1, HSD17B1, and SERPINE1 were identified. Similarly, LUM, FN1, PLAUR, SELP, SDC1, and VCAN were considered to be associated with pregnancy maintenance. Overexpression of HSD17B1 in granulosa cells significantly upregulated estrogen synthesis-related genes (HSD3B1, CYP11A1, and STAR); meanwhile, overexpression of PLAUR promotes granulosa cell proliferation. Furthermore, 66, 24, 77, and 7 differentially expressed miRNAs (DEMis) were found, leading to the selection of key miRNAs such as ssc-miR-206, ssc-miR-107, ssc-miR-429, ssc-miR-210, and ssc-miR-133a-3p by differential miRNA-targeted mRNA interaction network; meanwhile, ssc-miR-133a-3p was validated to have a targeting relationship with KCNA1 by dual-luciferase reporter systems assay. At the metabolic levels, androstenedione, 17a-hydroxyprogesterone, dehydroepiandrosterone, and progesterone were identified, with their synthesis regulated by these DEGs in the ovarian steroidogenesis pathway. Furthermore, treatment of cells with androstenedione upregulated the expression of HSD3B1, CYP11A1, and STAR.

Conclusions: This study revealed the dynamic changes in the transcriptome and metabolome of pig ovaries across developmental stages and gestation, indicating that it may provide new theoretical insights for improving sow fertility.