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Early-onset acute myocardial infarction (AMI) may have a higher genetic predisposition than late-onset AMI. The present study aimed to identify and characterize germline variants that affect early-onset AMI using whole-genome sequencing (WGS). We performed a genome-wide association study based on the WGS of 1239 Koreans, including 596 early-onset AMI patients and 643 healthy individuals. Patients with AMI who underwent percutaneous coronary intervention (PCI) caused by atherothrombotic occlusive lesions were included in the study. A total of 29 novel loci were found to be associated with early-onset AMI. These loci are involved in thrombosis, fibrinolysis, inflammation, and lipid metabolism. One of the associated single nucleotide variants (SNVs), rs1614576, located upstream of PRKCB, is known to be associated with thrombus formation. Additionally, the results revealed a novel locus, rs78631167, located upstream of PLAUR which plays a critical role in regulating plasminogen activation and is related to fibrinolysis. The association between early-onset AMI and rs9357455, which is located upstream of PHACTR1 and regulates inflammation in AMI, was found. Moreover, we identified a lipid metabolism related genetic risk locus, rs5072, in the APOA1-AS gene. This study provides new evidence supporting the genetic association between early-onset AMI and thrombosis and fibrinolysis, as well as inflammation and lipid metabolism, by analyzing the whole-genome of 596 patients with early-onset AMI who have been treated with PCI. Our findings highlight potential genetic markers for the prediction and management of AMI, as well as for understanding the etiology of AMI. [ABSTRACT FROM AUTHOR]

Viruses are the most common and abundant organisms in the marine environment. To better understand how cetaceans have adapted to this virus-rich environment, we compared cetacean virus-responsive genes to those from terrestrial mammals. We identified virus-responsive gene sequences in seven species of cetaceans, which we compared with orthologous sequences in seven terrestrial mammals. As a result of evolution analysis using the branch model and the branch-site model, 21 genes were selected using at least one model. IFN-ε, an antiviral cytokine expressed at mucous membranes, and its receptor IFNAR1 contain cetacean-specific amino acid substitutions that might change the interaction between the two proteins and lead to regulation of the immune system against viruses. Cetacean-specific amino acid substitutions in IL-6, IL-27, and the signal transducer and activator of transcription (STAT)1 are also predicted to alter the mucosal immune response of cetaceans. Since mucosal membranes are the first line of defense against the external environment and are involved in immune tolerance, our analysis of cetacean virus-responsive genes suggests that genes with cetacean-specific mutations in mucosal immunity-related genes play an important role in the protection and/or regulation of immune responses against viruses. [ABSTRACT FROM AUTHOR]

Big cats (Genus: Panthera) are among the most threatened mammal groups of the world, owing to hunting, habitat loss, and illegal transnational trade. Conservation genetic studies and effective curbs on poaching are important for the conservation of these charismatic apex predators. A limited number of microsatellite markers exists for Panthera species and researchers often cross-amplify domestic cat microsatellites to study these species. We conducted data mining of seven Panthera genome sequences to discover microsatellites for conservation genetic studies of four threatened big cat species. A total of 32 polymorphic microsatellite loci were identified in silico and tested with 152 big cats, and were found polymorphic in most of the tested species. We propose a set of 12 novel microsatellite markers for use in conservation genetics and wildlife forensic investigations of big cat species. Cumulatively, these markers have a high discriminatory power of one in a million for unrelated individuals and one in a thousand for siblings. Similar PCR conditions of these markers increase the prospects of achieving efficient multiplex PCR assays. This study is a pioneering attempt to synthesise genome wide microsatellite markers for big cats. [ABSTRACT FROM AUTHOR]

Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging. [ABSTRACT FROM AUTHOR]

We provide a Kazakh whole genome sequence (MJS) and analyses with the largest comparative Kazakh genomic data available to date. We found 102,240 novel SNVs and a high level of heterozygosity. ADMIXTURE analysis confirmed a significant proportion of variations in this individual coming from all continents except Africa and Oceania. A principal component analysis showed neighboring Kalmyk, Uzbek, and Kyrgyz populations to have the strongest resemblance to the MJS genome which reflects fairly recent Kazakh history. MJS's mitochondrial haplogroup, J1c2, probably represents an early European and Near Eastern influence to Central Asia. This was also supported by the heterozygous SNPs associated with European phenotypic features and strikingly similar Kazakh ancestral composition inferred by ADMIXTURE. Admixture (f3) analysis showed that MJS's genomic signature is best described as a cross between the Neolithic East Asian (Devil's Gate1) and the Bronze Age European (Halberstadt_LBA1) components rather than a contemporary admixture. [ABSTRACT FROM AUTHOR]

Background: The total length of the cattle genome is approximately ~ 3 billion base pairs. About half of the bovine genome (46.5%) is composed of transposable elements (TEs). The TEs could be a major source of genomic structural variations (SVs) between cattle breeds. These SVs have led to genomic fluidity and rearrangements between interspecies.Objective: TE-mediated insertion and deletion events could have a strong influence on the bovine genome. This study aimed to investigate TE-mediated deletion events that are common to 12 Hanwoo genome resequencing data.Results: We compared 12 Hanwoo genome resequencing data with the cattle reference genome (Bos taurus_UMD_3.1.1) and six other open source data (2 Jersey, 2 Holstein, 2 Angus). By using BreakDancer program, the common SVs to the 12 Hanwoo genomes were detected. A total of 299 Hanwoo-specific SV candidates were detected. Among them, 56 Hanwoo-specific TE-mediated deletion candidate loci were validated by PCR and Sanger sequencing. Finally, we identified one locus, DEL_96, which is an authentic Hanwoo-specific deletion. The DEL_96 event occurred by nonallelic homologous end-joining between LINE (BovB) and unique sequence with 1 bp microhomology. The 370 bp deletion event appeared to be only in the Hanwoo individuals after the divergence of Hanwoo and Holstein lineages.Conclusion: Our study showed that one of the SVs, TE-mediated deletion, could be utilized as a molecular maker to distinguish between Hanwoo and Holstein. [ABSTRACT FROM AUTHOR]

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases. [ABSTRACT FROM AUTHOR]

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28–37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50–33 thousand years ago (kya), followed by East Asian (~ 40–15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component. [ABSTRACT FROM AUTHOR]

The translocations of mitochondrial DNA into chromosomal DNA (nuclear mitochondrial DNA, Numt) are ubiquitous in eukaryotes including yeasts, plants, and animals. The features of Numt and the recent sequencing technology can facilitate an expanded application of Numt into a valuable phylogenetic marker for unresolved taxa. To date, the phylogeny of extant cetaceans has been studied by a variety of morphological and molecular data and still has long attracted attention. Here, the Numts of cattle, two baleen whale and four toothed whales were detected by BLAST-search of the mitochondrial sequences of each species against its corresponding nuclear genome and we investigated the characteristics of cetacean Numt and revisited the phylogeny and evolution of cetartiodactyl using Numts. The content and distribution of Numt length showed similar patterns among six cetacean genomes. Under-representation of D-loop region-derived Numts and different abundance of Numt across D-loop sub-domains were observed in cetacean Numts except sperm whale. Examination of Numt location in cetacean nuclear genomes showed that some of orthologous Numts were integrated into exons, introns, and pseudogenes, suggesting that cetacean Numts may contribute to cetacean biology and evolution. Our phylogenetic study with cetacean Numt based on the maximum likelihood method corresponded to the study from other phylogenetic markers. [ABSTRACT FROM AUTHOR]

DNA methylation is an essential biochemical modification that regulates gene expression. Exercise induces changes in gene expression that adapt as metabolic changes in the blood. We provide a database for the epigenetic changes after horse exercise (). Horse Exercise Epigenetic Database (HExDB) explicates the change in genome-wide DNA methylation patterns after exercise. Exercise changes the genome-wide epigenetic patterns, and understanding the regions that change is important for confirming exercise physiological mechanisms. For this purpose, our database provides information on differentially methylated regions after exercise that pass a set threshold. A total of 784 genes based on NCBI RefSeq were identified as differentially methylated in equines after exercise. Our database provides clues for the study of exercise-related epigenetic pathways in the thoroughbred horse. [ABSTRACT FROM AUTHOR]

The ripe fruit of Momordica cochinchinensis Spreng, known as gac, is featured by very high carotenoid content. Although this plant might be a good resource for carotenoid metabolic engineering, so far, the genes involved in the carotenoid metabolic pathways in gac were unidentified due to lack of genomic information in the public database. In order to expedite the process of gene discovery, we have undertaken Illumina deep sequencing of mRNA prepared from aril of gac fruit. From 51,446,670 high-quality reads, we obtained 81,404 assembled unigenes with average length of 388 base pairs. At the protein level, gac aril transcripts showed about 81.5 % similarity with cucumber proteomes. In addition 17,104 unigenes have been assigned to specific metabolic pathways in Kyoto Encyclopedia of Genes and Genomes, and all of known enzymes involved in terpenoid backbones biosynthetic and carotenoid biosynthetic pathways were also identified in our library. To analyze the relationship between putative carotenoid biosynthesis genes and alteration of carotenoid content during fruit ripening, digital gene expression analysis was performed on three different ripening stages of aril. This study has revealed putative phytoene synthase, 15-cis-phytone desaturase, zeta-carotene desaturase, carotenoid isomerase and lycopene epsilon cyclase might be key factors for controlling carotenoid contents during aril ripening. Taken together, this study has also made availability of a large gene database. This unique information for gac gene discovery would be helpful to facilitate functional studies for improving carotenoid quantities. [ABSTRACT FROM AUTHOR]

The unicellular cyanobacterium Synechocystis sp. PCC 6803 glides toward a light source through the interplay of positive phototaxis genes and proteins. In genetic analysis, the complete disruption of the hybrid sensory kinase sll0043 produced negative phototaxis. Furthermore, Sll0043 was found to be a hub protein by in silico prediction of protein-protein interaction, in which Sll0043 was predominantly linked to seven two-component proteins with high confidence. To understand the regulation and networking of positive phototaxis proteins, the proteomic profile of the sll0043 mutant was compared to that of wild-type. In the sll0043 mutant, 18 spots corresponding to 15 unique proteins were altered by 1.3 to 59 fold; the spots were identified by 2-DE/MALDI-MS analysis. Down-regulated proteins in the sll0043 null-mutant included chaperonins, superoxide dismutase, and phycocyanin β-subunit. In contrast, nine proteins involved in photosynthesis, translation, regulatory function, and other functions were up-regulated. In particular, a twitching motility protein (PilT1) was induced over 2-fold in sll0043 mutant. Moreover, semi-quantitative and quantitative RT-PCR analysis revealed that pilin ( pilA1), pili motor ( pilT1), and pili switch gene ( pilT2) were significantly increased in sll0043 mutant. These results suggest that the hybrid kinase Sll0043 regulates positive phototaxis by suppressing the expression of pili biosynthesis and regulatory genes and through the interplay with positive phototaxis/motility two-component proteins. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/ncomms13637 [ABSTRACT FROM AUTHOR]

Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair. An evolutionary analysis revealed signatures of positive selection for FGF3 and FGF11, genes related to ear and tooth development and hypoxia, respectively. We found a D203G substitution in cetacean FGF9, which was predicted to affect FGF9 homodimerization, suggesting that this gene plays a role in the acquisition of rigid flippers for efficient manoeuvring. Cetaceans utilize low bone density as a buoyancy control mechanism, but the underlying genes are not known. We found that the expression of FGF23, a gene associated with reduced bone density, is greatly increased in the cetacean liver under hypoxic conditions, thus implicating FGF23 in low bone density in cetaceans. Altogether, our results provide novel insights into the roles of FGFs in cetacean adaptation to the aquatic environment. [ABSTRACT FROM AUTHOR]