Correction to: Diet induced the change of mtDNA copy number and metabolism in Angus cattle.
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ABSTRACT:
SUBMITTER: Bai Y
PROVIDER: S-EPMC7446046 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Correction to: Diet induced the change of mtDNA copy number and metabolism in Angus cattle.
Bai Ying Y Carrillo José A JA Li Yaokun Y He Yanghua Y Song Jiuzhou J
Journal of animal science and biotechnology 20200825
[This corrects the article DOI: 10.1186/s40104-020-00482-x.]. ...[more]
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Project description:Background:Grass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects mitochondrial function and dynamic behavior in response to changes in energy demand and supply. In this study, we examined the mtDNA copy number, mitochondria-related genes expression, and metabolic biomarkers in grass-fed and grain-fed Angus cattle. Results:We found that the grass-fed group had a higher mtDNA copy number than the grain-fed group. Among different tissues, the mtDNA copy number was the highest in the liver than muscle, rumen, and spleen. Based on the transcriptome of the four tissues, a lower expression of mtDNA-encoded genes in the grass-fed group compared to the grain-fed group was discovered. For the mitochondria-related nuclear genes, however, most of them were significantly down-regulated in the muscle of the grass-fed group and up-regulated in the other three tissues. In which, COX6A2, POLG2, PPIF, DCN, and NDUFA12, involving in ATP synthesis, mitochondrial replication, transcription, and maintenance, might contribute to the alterations of mtDNA copy number and gene expression. Meanwhile, 40 and 23 metabolic biomarkers were identified in the blood and muscle of the grain-fed group compared to a grass-fed group, respectively. Integrated analysis of the altered metabolites and gene expression revealed the high expression level of MDH1 in the grain-fed group might contribute to the mitochondrial NADH oxidation and spermidine metabolism for adapting the deletion mtDNA copy number. Conclusions:Overall, the study may provide further deep insight into the adaptive and regulatory modulations of the mitochondrial function in response to different feeding systems in Angus cattle.
| S-EPMC7372754 | biostudies-literature
Project description:Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits with either method in regions of high copy number compared to no correction.
| S-EPMC6067744 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pone.0152705.].
| S-EPMC4878746 | biostudies-literature
Project description:BackgroundCopy number variation (CNV) represents another important source of genetic variation complementary to single nucleotide polymorphism (SNP). High-density SNP array data have been routinely used to detect human CNVs, many of which have significant functional effects on gene expression and human diseases. In the dairy industry, a large quantity of SNP genotyping results are becoming available and can be used for CNV discovery to understand and accelerate genetic improvement for complex traits.ResultsWe performed a systematic analysis of CNV using the Bovine HapMap SNP genotyping data, including 539 animals of 21 modern cattle breeds and 6 outgroups. After correcting genomic waves and considering the pedigree information, we identified 682 candidate CNV regions, which represent 139.8 megabases (~4.60%) of the genome. Selected CNVs were further experimentally validated and we found that copy number "gain" CNVs were predominantly clustered in tandem rather than existing as interspersed duplications. Many CNV regions (~56%) overlap with cattle genes (1,263), which are significantly enriched for immunity, lactation, reproduction and rumination. The overlap of this new dataset and other published CNV studies was less than 40%; however, our discovery of large, high frequency (> 5% of animals surveyed) CNV regions showed 90% agreement with other studies. These results highlight the differences and commonalities between technical platforms.ConclusionsWe present a comprehensive genomic analysis of cattle CNVs derived from SNP data which will be a valuable genomic variation resource. Combined with SNP detection assays, gene-containing CNV regions may help identify genes undergoing artificial selection in domesticated animals.
| S-EPMC3053260 | biostudies-literature
Project description:BackgroundThe small intestine, while serving as the main absorption organ, also possesses a unique bacterial environment and holds the critical function of conversion of primary bile acids. Bile acids are, in turn, able to regulate bacterial composition and promote the growth of bacteria that convert primary bile acids to secondary bile acids. However, in beef cattle, few studies have explored the influence of diets on jejunal bacterial communities and examined its relationships with bile acids. Here, we examined the impact of grain- and grass-based diets on jejunal and fecal bacterial communities' composition and investigated possible association of bacterial features with bile acids.ResultsWe demonstrated that the influences of diets on intestinal bacteria can be observed in young beef cattle after weaning. A significantly higher level of microbial diversity was documented in feces of grass-fed cattle comparing to grain-fed cattle. Top 20 important genera identified with random forest analysis on fecal bacterial community can be good candidates for microbial biomarkers. Moreover, the jejunal bacteria of adult Angus beef cattle exhibited significant differences in microbial composition and metabolic potential under different diets. Global balances and bacteria signatures predictive of bile acids were identified, indicative of the potential association of bacterial features with bile acids.ConclusionsThe findings from this study provided novel insights into the relationships between jejunal bacteria and bile acids under different diets in Angus beef cattle. Our results should help us gain a better understanding of potential health benefits of grass-fed beef.
| S-EPMC7807434 | biostudies-literature
Project description:Mitochondrial DNA (mtDNA) is a maternally inherited, high-copy-number genome required for oxidative phosphorylation1. Heteroplasmy refers to the presence of a mixture of mtDNA alleles in an individual and has been associated with disease and ageing. Mechanisms underlying common variation in human heteroplasmy, and the influence of the nuclear genome on this variation, remain insufficiently explored. Here we quantify mtDNA copy number (mtCN) and heteroplasmy using blood-derived whole-genome sequences from 274,832 individuals and perform genome-wide association studies to identify associated nuclear loci. Following blood cell composition correction, we find that mtCN declines linearly with age and is associated with variants at 92 nuclear loci. We observe that nearly everyone harbours heteroplasmic mtDNA variants obeying two principles: (1) heteroplasmic single nucleotide variants tend to arise somatically and accumulate sharply after the age of 70 years, whereas (2) heteroplasmic indels are maternally inherited as mixtures with relative levels associated with 42 nuclear loci involved in mtDNA replication, maintenance and novel pathways. These loci may act by conferring a replicative advantage to certain mtDNA alleles. As an illustrative example, we identify a length variant carried by more than 50% of humans at position chrM:302 within a G-quadruplex previously proposed to mediate mtDNA transcription/replication switching2,3. We find that this variant exerts cis-acting genetic control over mtDNA abundance and is itself associated in-trans with nuclear loci encoding machinery for this regulatory switch. Our study suggests that common variation in the nuclear genome can shape variation in mtCN and heteroplasmy dynamics across the human population.
| S-EPMC10447254 | biostudies-literature
Project description:The mitochondrial (mt) genome is present in many copies in human cells, and intra-individual variation in mtDNA sequences is known as heteroplasmy. Recent studies found that heteroplasmies are highly tissue-specific, site-specific, and allele-specific, however the functional implications have not been explored. This study investigates variation in mtDNA copy numbers (mtCN) in 12 different tissues obtained at autopsy from 152 individuals (ranging in age from 3 days to 96 years). Three different methods to estimate mtCN were compared: shotgun sequencing (in 4 tissues), capture-enriched sequencing (in 12 tissues) and droplet digital PCR (ddPCR, in 2 tissues). The highest precision in mtCN estimation was achieved using shotgun sequencing data. However, capture-enrichment data provide reliable estimates of relative (albeit not absolute) mtCNs. Comparisons of mtCN from different tissues of the same individual revealed that mtCNs in different tissues are, with few exceptions, uncorrelated. Hence, each tissue of an individual seems to regulate mtCN in a tissue-related rather than an individual-dependent manner. Skeletal muscle (SM) samples showed an age-related decrease in mtCN that was especially pronounced in males, while there was an age-related increase in mtCN for liver (LIV) samples. MtCN in SM samples was significantly negatively correlated with both the total number of heteroplasmic sites and with minor allele frequency (MAF) at two heteroplasmic sites, 408 and 16327. Heteroplasmies at both sites are highly specific for SM, accumulate with aging and are part of functional elements that regulate mtDNA replication. These data support the hypothesis that selection acting on these heteroplasmic sites is reducing mtCN in SM of older individuals.
| S-EPMC4792396 | biostudies-literature
Project description:Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or approximately 1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.
| S-EPMC2860171 | biostudies-literature
Project description:Heteroplasmic mtDNA mutations typically act in a recessive way and cause mitochondrial disease only if present above a certain threshold level. We have experimentally investigated to what extent the absolute levels of wild-type (WT) mtDNA influence disease manifestations by manipulating TFAM levels in mice with a heteroplasmic mtDNA mutation in the tRNAAla gene. Increase of total mtDNA levels ameliorated pathology in multiple tissues, although the levels of heteroplasmy remained the same. A reduction in mtDNA levels worsened the phenotype in postmitotic tissues, such as heart, whereas there was an unexpected beneficial effect in rapidly proliferating tissues, such as colon, because of enhanced clonal expansion and selective elimination of mutated mtDNA. The absolute levels of WT mtDNA are thus an important determinant of the pathological manifestations, suggesting that pharmacological or gene therapy approaches to selectively increase mtDNA copy number provide a potential treatment strategy for human mtDNA mutation disease.
| S-EPMC6447380 | biostudies-literature
Project description:ObjectiveMitochondria are factories for energy production and genetic alterations in mtDNA will directly impact OXPHOS function. The copy number of mtDNA (i.e., the number of mtDNA per spermatozoon) is one of the major mitochondrial genetic features. Besides mtDNA copy number, the change of either mtDNA or nDNA integrity is another important factor causing asthenospermia, or poor sperm motility in infertile men. In this study, we investigated the mtDNA copy number and the integrities of mtDNA and nDNA respectively in semen samples from different donors at 5,300 m altitudes.MethodsTotal DNA was extracted from semen samples from donors in two different altitudes. Quantitative PCR was performed to evaluate the mtDNA copy number. PCR amplification was used to examine the integrity of sperm mtDNA. Flow cytometry was carried out to investigate sperm nDNA integrity. All data were analyzed to show the statistical significance.ResultsSperm mtDNA copy number for those living at high altitude (5,300 m) for one month was significantly higher (P < 0.05) than for those at the lower altitude (1,400 m) or in donors who had been living at the 5,300 m altitude for 1 year. In addition, sperm mtDNA copy numbers were remarkably decreased (P < 0.05) in those who had lived at the greater altitude for 1 year compared to those who had lived there for one month. The ratio of nDNA integrity among the 10,000 sperms at high altitude for one month was significantly lower (P < 0.05) than that at the lower altitude (1,400 m) or at 5,300 m for 1 year, and the ratio of nDNA integrity sperms at high altitude for 1 year was increased, and higher than that for at the lower altitude (P < 0.05).ConclusionHigh altitude can alter the mtDNA copy number and nDNA integrity in the sperms.
| S-EPMC3220446 | biostudies-literature