Temporal trends in risk of bisphenol A, benzophenone-3 and triclosan exposure among U.S. children and adolescents aged 6-19 years: Findings from the National Health and Nutrition Examination Survey 2005-2016.

BACKGROUND: Phenolic compounds with potential adverse health effects are gradually being replaced. Little is known about the potential health risks of BPA, BP3, and TCS exposure in children and adolescents aged 6-19 years in the United States. OBJECTIVES: To determine trends and rates of change in hazard indices (HI) for three phenolics in U.S. children and adolescents for BPA, BP3, TCS, and to assess changes in gender, race/ethnicity, age, and potential health risks. METHODS: Metabolic biomonitoring data from field-collected urine samples from the National Health and Nutrition Examination Survey (NHANES) were utilized. Daily intake of three phenols (bisphenol A, benzophenone-3, and triclosan) between 2005 and 2016 in children and adolescents were obtained. Cumulative risk indicators, including hazard quotient (HQ), hazard index (HI), and maximum cumulative ratio (MCR), were used for the health risk assessment of the three phenols. RESULTS: During this period, the change in LSGM HI was -2.9% per cycle [95% Cl: (-3.7%, -2.2%)], and the percentage of participants with HI > 0.1 decreased from 15.6% to 10.5%. Children (6-11 years) had higher mean HI values than adolescents (12-19 years), while female had higher LSGM HI values than male. MCR values were generally low and negatively correlated with HI. However, the average value of MCR increased from 1.722 to 2.107 during this period. CONCLUSION: Exposure to phenolics among U.S. children and adolescents has changed in recent decades. However, gaps in data limit the interpretation of trends but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Moreover, there are growing concerns about the potential health risks associated with exposure to multiple phenols in children and adolescents.

Association of dietary inflammatory index and metabolic syndrome in the elderly over 55 years in Northern China.

We assessed the association between the dietary inflammatory index (DII) and the development of metabolic syndrome in the elderly over 55 years in Northern China. The data of 1936 Chinese adults aged 55 years and over from a community-based neurological disease cohort study from 2018 to 2019 were analysed. Multiple logistic regression and restricted cubic splines regression were used for analysis, and social demographics, lifestyle and health-related factors were adjusted. In the fully adjusted model, the risk of metabolic syndrome increased by 1·28-fold in people with a pro-inflammatory diet. When we divide the metabolic syndrome by its components, high pro-inflammatory diet and hyperglycaemia, TAG, hypertension and abdominal obesity, we failed to observe a significant association between a high pro-inflammatory diet and HDL-cholesterol. However, these associations are moving in the expected direction. At the same time, the results of BMI subgroup analysis showed that with the increase of DII, obese people are at increased risk of metabolic syndrome, hyperglycaemia, high TAG, hypertension and abdominal obesity. Also in overweight people, the increase in DII is accompanied by an increased risk of hyperglycaemia and abdominal obesity. Higher inflammatory diet is related to metabolic syndrome, hypertension, hyperglycaemia, abdominal obesity and hypertriglyceridaemia. Further research is needed to confirm the role of inflammation and diet in the development of metabolic syndrome; however, it is desirable to reduce the dietary components associated with inflammation.

Association of dietary patterns with blood uric acid concentration and hyperuricemia in northern Chinese adults.

BACKGROUND: Studies have shown that a direct association exists between the diet and blood uric acid concentrations. However, works on the association of dietary patterns with blood uric acid concentrations and hyperuricemia remain limited.  OBJECTIVE: This study aims to evaluate the association of dietary patterns with blood uric acid concentrations and hyperuricemia. METHODS: The relationship between dietary patterns and hyperuricemia was explored through a nutritional epidemiological survey in China (n = 4855). Three statistical methods, including principal component analysis, reduced rank regression (RRR), and partial least squares regression, were used to extract dietary patterns. General linear regression and logistic regression analyses were utilized to explore the relationship of dietary patterns with blood uric acid concentrations and hyperuricemia. RESULTS: After adjusting for potential confounding factors, the score for the plant-based dietary pattern was found to be negatively correlated with blood uric acid levels (ß = - 3.225) and that for the animal dietary pattern was discovered to be directly correlated with blood uric acid levels (ß = 3.645). The participants in the highest quartile of plant-based dietary pattern scores were at a low risk of hyperuricemia (OR = 0.699; 95% CI: 0.561-0.870, P < 0.05), whereas those in the highest quartile of animal dietary pattern scores were at a high risk of hyperuricemia (OR = 1.401; 95% CI: 1.129-1.739, P < 0.05). The participants in the third quartile of scores for the RRR dietary pattern, which was characterized by the relatively high intake of poultry, sugary beverages, and animal organs and the low intake of desserts and snacks, had a significantly higher risk of hyperuricemia than those in the first quartile of scores for the RRR dietary pattern (OR = 1.421; 95% CI: 1.146-1.763, P < 0.05). CONCLUSIONS: Our research indicated that plant-based dietary pattern analyzed by PCA was negatively associated with blood uric acid concentrations, while animal-based dietary pattern was directly associated with blood uric acid concentrations. The RRR dietary pattern may have the potential to induce elevations in blood uric acid concentrations.

Associations between sedentary behaviour patterns and depression among people aged 60 and older in Hebei Province of China.

BACKGROUND: Sedentary behaviours (SBs) are now considered a risk factor for depression. Older adults are sedentary most of the time and are at a high risk of depression. However, not all types of SBs have adverse effects on mental health. Passive SBs (such as watching TV) increase the risk of depression, whereas mentally active SBs (such as using the internet and reading) decrease the risk of depression. The aim of this study was to explore the associations between type of SBs (i.e., passive and mentally active SBs) and depression among people aged 60 years and older in the Hebei Province of China. METHODS: This cross-sectional study used data from the baseline survey of the Community-based Cohort Study on Nervous System Diseases. A total of 2679 older adults aged ≥60 years from the Hebei Province of China were included in this study. The type and time spent on SBs were self-reported. Watching TV was defined as a passive SB, whereas internet use, reading, and social SBs (including communicating with others and playing chess) were defined as mentally active SBs. Depression was evaluated using the Geriatric Depression Scale. The maximal possible score was 30 points, and ≥ 11 points indicated depression. Logistic regression analysis was used to assess the relationship between SBs and depression. Covariates included sex, age, education, employment, smoking, alcohol consumption, sleep duration, domestic work, physical exercise, body mass index (BMI), and chronic diseases. RESULTS: At baseline, the participants who spent two or more hours and 0 h on passive SBs (i.e., TV viewing) had a greater risk of depression (=0 h: adjusted OR = 2.09, 95% CI = 1.18-3.76; 2-3 h: OR = 2.21, 95% CI = 1.16-4.16; > 3 h: OR = 3.59, 95% CI = 1.93-6.68) than the participants who spent 1-2 h on passive SBs. The participants who spent > 1 h on mentally active SBs had a lower risk of depression (adjusted OR = 0.26, 95% CI = 0.06-0.71) than the participants who did not engage in mentally active SBs. Not all mentally active SBs were linked to depression. The participants who engaged in social SBs had a lower risk of depression (adjusted OR: 0.24, 95% CI: 0.06-0.66) than the participants who did not engage in social SBs. CONCLUSIONS: Spending 2 h or more per day on passive SBs (watching TV) was associated with a high risk of depression among people aged 60 years and older in the Hebei Province of China. Mentally active SBs (predominantly social SBs) could reduce the risk of depression. Some participants with depression probably did not watch TV. These findings suggested that spending more time on social SBs (such as communicating with others and playing chess) rather than watching TV may have important public health implications for preventing and managing depression among older Chinese adults. Moreover, society should attend to the mental health of elderly adults who do not watch TV as they may be more prone to suffer from depressive symptoms.

Genomic analyses of diverse wild and cultivated accessions provide insights into the evolutionary history of jujube.

The Chinese jujube (Ziziphus jujuba Mill.), a member of the Rhamnaceae family, is an important perennial fruit tree crop of substantial economic, ecological and nutritional value, and is also used as a traditional herbal medicine. Here, we report the resequencing of 493 jujube accessions, including 202 wild and 291 cultivated accessions at >16× depth. Our population genomic analyses revealed that the Shanxi-Shaanxi area of China was jujube's primary domestication centre and that jujube was then disseminated into East China before finally extending into South China. Divergence events analysis indicated that Ziziphus acidojujuba and Ziziphus jujuba diverged around 2.7 Mya, suggesting the interesting possibility that a long pre-domestication period may have occurred prior to human intervention. Using the large genetic polymorphism data set, we identified a 15-bp tandem insertion in the promoter of the jujube ortholog of the POLLEN DEFECTIVE IN GUIDANCE 1 (POD1) gene, which was strongly associated with seed-setting rate. Integrating genome-wide association study (GWAS), transcriptome data, expression analysis and transgenic validation in tomato, we identified a DA3/UBIQUITIN-SPECIFIC PROTEASE 14 (UBP14) ortholog, which negatively regulate fruit weight in jujube. We also identified candidate genes, which have likely influenced the selection of fruit sweetness and crispness texture traits among fresh and dry jujubes. Our study not only illuminates the genetic basis of jujube evolution and domestication and provides a deep and rich genomic resource to facilitate both crop improvement and hypothesis-driven basic research, but also identifies multiple agriculturally important genes for this unique perennial tree fruit species.

Procyanidins inhibit fine particulate matter-induced vascular smooth muscle cells apoptosis via the activation of the Nrf2 signaling pathway.

The functional role of procyanidins (PC) in PM2.5-induced cardiovascular diseases (CVD) is largely unexplored. This study aimed to explore the protective effect of PC against PM2.5-induced vascular smooth muscle cells (VSMCs) apoptosis and underlying mechanisms. Sprague Dawley rats were pretreated with three doses of PC (50, 100, and 200 mg/kg) and exposed to 10 mg/kg PM2.5 by intratracheal instillation three times a week. VSMCs were exposed to 5, 10, and 20 µM PC before the addition of 100 µg/mL PM2.5. In vivo, the PM2.5 exposure induced apoptosis in the thoracic aorta of rats. The PM2.5 exposure significantly elevated the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and decreased the superoxide dismutase activity. Also, PC supplementation increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), and its downstream antioxidant genes, i.e., NAD(P)H dehydrogenase (quinine) 1 and heme oxygenase 1, attenuated oxidative stress and vascular apoptosis. In vitro, PM2.5 induced cytotoxicity in VSMCs in a dose-dependent manner. Besides, PC abolished the PM2.5-induced cytotoxicity by activating the Nrf2 signal pathway, alleviating oxidative stress, and decreasing apoptosis. In conclusion, this work is the first study to demonstrate that PC can suppress the PM2.5-induced VSMCs apoptosis via the activation of the Nrf2 signal pathway.

Editing the cystine knot motif of MSTN enhances muscle development of Liang Guang Small Spotted pigs.

Myostatin (MSTN) is a member of the transforming growth factor-ß (TGF-ß) family, and functions as an inhibitor of muscle growth. Disrupting the inhibitory effect of MSTN on growth can provide an effective way to increase the muscle yield of livestock and poultry. The cysteine knot motif of TGF-ß can stabilize the structure of MSTN protein and plays an important regulatory role in the biological function of MSTN. Accordingly, in this study, we used the CRISRP/Cas9 to edit the exon 3 of MSTN in the kidney cells of Liang Guang Small Spotted pig (LPKCs), in order to disrupt the cysteine knot motif of MSTN and remove the inhibitory effect of MSTN on its target genes.MSTN-edited LPKCs were obtained through fluorescence-activated cell sorting (FACS) and used as donor cells for somatic cell nuclear transfer (SCNT) to generate cloned embryos, which were then transferred to surrogate sows to finally obtain eight MSTN-edited Liang Guang Small Spotted piglets. Among them, two survived to 10 days old. Genotyping revealed that these two piglets were gene edited heterozygotes with base deletion and substitution occurred within the coding sequence of C106 and C108 at the cystine knot motif of MSTN. These changes resulted in frameshift mutations, and conversion of C106 and C108 to other amino acids. More developments of muscles were observed at the shoulders and hips of the heterozygotes of MSTN-edited Liang Guang Small Spotted pigs. H&E analysis showed that the cross-sectional area (CSA) of myofiber inMSTN-edited pigs was significantly decreased, and the number of myofiber were significantly increased. Western blot analysis showed that the disruption of C106 and C108 did not affect the expression of MSTN protein, but significantly up-regulated the expression of its target genes such as Myf5, MyoD, Myogenin and other myogenic regulatory factors. In summary, the gene-edited pig model obtained in this study did not cause complete loss of MSTN expression, and could retain other biological functions of MSTN, thereby promoting muscle growth while minimizing the potential adverse effects on complete loss of MSTN in the Liang Guang Small Spotted pigs.

Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies.

Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (Sus scrofa), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.

Precise editing of myostatin signal peptide by CRISPR/Cas9 increases the muscle mass of Liang Guang Small Spotted pigs.

Myostatin (MSTN), a member of the transforming growth factor-ß superfamily, is a negative regulator of muscle growth and development. Disruption of the MSTN gene in various mammalian species markedly promotes muscle growth. Previous studies have mainly focused on the disruption of the MSTN peptide coding region in pigs but not on the modification of the signal peptide region. In this study, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system was used to successfully introduce two mutations (PVD20H and GP19del) in the MSTN signal peptide region of the indigenous Chinese pig breed, Liang Guang Small Spotted pig. Both mutations in signal peptide increased the muscle mass without inhibiting the production of mature MSTN peptide in the cells. Histological analysis revealed that the enhanced muscle mass in MSTN+/PVD20H pig was mainly due to an increase in the number of muscle fibers. The expression of MSTN in the longissimus dorsi muscle of MSTN+/PVD20H and MSTNKO/PVD20H pigs was significantly downregulated, whereas that of myogenic regulatory factors, including MyoD, Myogenin, and Myf-5, was significantly upregulated when compared to those in the longissimus dorsi muscle of wild-type pigs. Meanwhile, the mutations also activated the PI3K/Akt pathway. The results of this study indicated that precise editing of the MSTN signal peptide can enhance porcine muscle development without markedly affecting the expression of mature MSTN peptide, which could exert other beneficial biological functions in the edited pigs.

Disruption of the ZBED6 binding site in intron 3 of IGF2 by CRISPR/Cas9 leads to enhanced muscle development in Liang Guang Small Spotted pigs.

Insulin-like growth factor 2 (IGF2) plays an important role in the development of the foetus and in post-natal growth and development. A SNP within intron 3 of porcine IGF2 disrupts a binding site for the repressor, zinc finger BED-type containing 6 (ZBED6), leading to up-regulation of IGF2 in skeletal muscle and major effects on muscle growth, heart size, and fat deposition. This favourable mutation is common in Western commercial pig populations, but is not present in most indigenous Chinese pig breeds. Here, we described the efficient disruption of the ZBED6 binding site motif in intron 3 of IGF2 by CRISPR/Cas9 in porcine embryonic fibroblasts (PEFs) from the indigenous Chinese pig breed, Liang Guang Small Spotted pig. Disruption of the binding motif led to a drastic up-regulation of IGF2 expression in PEFs and enhanced myogenic potential and cell proliferation of PEFs. IGF2-edited pigs were then generated using somatic cell nuclear transfer. Enhanced muscle development was evident in one pig with biallelic deletion of the ZBED6 binding site motif, implying that the release of ZBED6 repression has a major effect on porcine muscle development. Our study confirmed the important effect of a mutation in the ZBED6 binding site motif on IGF2 expression and myogenesis, thus providing the basis for breeding a new line of Liang Guang Small Spotted pigs with improved lean meat percentage, a trait of great commercial value to pig producers.

pBACode: a random-barcode-based high-throughput approach for BAC paired-end sequencing and physical clone mapping.

Applications that use Bacterial Artificial Chromosome (BAC) libraries often require paired-end sequences and knowledge of the physical location of each clone in plates. To facilitate obtaining this information in high-throughput, we generated pBACode vectors: a pool of BAC cloning vectors, each with a pair of random barcodes flanking its cloning site. In a pBACode BAC library, the BAC ends and their linked barcodes can be sequenced in bulk. Barcode pairs are determined by sequencing the empty pBACode vectors, which allows BAC ends to be paired according to their barcodes. For physical clone mapping, the barcodes are used as unique markers for their linked genomic sequence. After multi-dimensional pooling of BAC clones, the barcodes are sequenced and deconvoluted to locate each clone. We generated a pBACode library of 94,464 clones for the flounder Paralichthys olivaceus and obtained paired-end sequence from 95.4% of the clones. Incorporating BAC paired-ends into the genome preassembly improved its continuity by over 10-fold. Furthermore, we were able to use the barcodes to map the physical locations of each clone in just 50 pools, with up to 11 808 clones per pool. Our physical clone mapping located 90.2% of BAC clones, enabling targeted characterization of chromosomal rearrangements.

The Jujube Genome Provides Insights into Genome Evolution and the Domestication of Sweetness/Acidity Taste in Fruit Trees.

Jujube (Ziziphus jujuba Mill.) belongs to the Rhamnaceae family and is a popular fruit tree species with immense economic and nutritional value. Here, we report a draft genome of the dry jujube cultivar 'Junzao' and the genome resequencing of 31 geographically diverse accessions of cultivated and wild jujubes (Ziziphus jujuba var. spinosa). Comparative analysis revealed that the genome of 'Dongzao', a fresh jujube, was ~86.5 Mb larger than that of the 'Junzao', partially due to the recent insertions of transposable elements in the 'Dongzao' genome. We constructed eight proto-chromosomes of the common ancestor of Rhamnaceae and Rosaceae, two sister families in the order Rosales, and elucidated the evolutionary processes that have shaped the genome structures of modern jujubes. Population structure analysis revealed the complex genetic background of jujubes resulting from extensive hybridizations between jujube and its wild relatives. Notably, several key genes that control fruit organic acid metabolism and sugar content were identified in the selective sweep regions. We also identified S-locus genes controlling gametophytic self-incompatibility and investigated haplotype patterns of the S locus in the jujube genomes, which would provide a guideline for parent selection for jujube crossbreeding. This study provides valuable genomic resources for jujube improvement, and offers insights into jujube genome evolution and its population structure and domestication.

Genetic Alterations in Esophageal Tissues From Squamous Dysplasia to Carcinoma.

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer. Little is known about the genetic changes that occur in esophageal cells during the development of ESCC. We performed next-generation sequence analyses of esophageal nontumor, intraepithelial neoplasia (IEN), and ESCC tissues from the same patients to track genetic changes during tumor development. METHODS: We performed whole-genome, whole-exome, or targeted sequence analyses of 227 esophageal tissue samples from 70 patients with ESCC undergoing resection at Shantou University Medical College in China from 2012 through 2015 (no patients had received chemotherapy or radiation therapy); we analyzed normal tissues, tissues with simple hyperplasia, dysplastic tissues (IEN), and ESCC tissues collected from different regions of the esophagus at the same time. We also obtained 1191 nontumor esophageal biopsy specimens from the Chaoshan region (a high-risk region for ESCC) of China (a high-risk region for ESCC) and performed immunohistochemical and histologic analyses to detect inflammation. RESULTS: IEN and ESCC tissues had similar mutations and copy number alterations, at similar frequencies; these differed from mutations detected in tissues with simple hyperplasia. IEN tissues had mutations associated with apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like-mediated mutagenesis (a DNA damage mutational signature). Genetic analyses indicated that most ESCCs were formed from early stage IEN clones. Trunk mutations (mutations shared by >10% of paired IEN and ESCC tissues) were in genes that regulate DNA repair and cell apoptosis, proliferation and adhesion. Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1), 3q (contains SOX2), 2q (contains NFE2L2), and 9p (contains CDKN2A) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples. In the esophageal biopsy samples from high-risk individuals (residing in the Chaoshan region), 68.9% had an evidence of chronic inflammation; the level of inflammation was correlated with atypical cell structures and markers of DNA damage. CONCLUSIONS: We analyzed mutations and gene copy number changes in nontumor, IEN, and ESCC samples, collected from 70 patients. IEN and ESCCs each had similar mutations and markers of genomic instability, including apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like. Genomic changes observed in precancerous lesions might be used to identify patients at risk for ESCC.

Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp.

Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies.

Population Genomics Reveals Low Genetic Diversity and Adaptation to Hypoxia in Snub-Nosed Monkeys.

Snub-nosed monkeys (genus Rhinopithecus) are a group of endangered colobines endemic to South Asia. Here, we re-sequenced the whole genomes of 38 snub-nosed monkeys representing four species within this genus. By conducting population genomic analyses, we observed a similar load of deleterious variation in snub-nosed monkeys living in both smaller and larger populations and found that genomic diversity was lower than that reported in other primates. Reconstruction of Rhinopithecus evolutionary history suggested that episodes of climatic variation over the past 2 million years, associated with glacial advances and retreats and population isolation, have shaped snub-nosed monkey demography and evolution. We further identified several hypoxia-related genes under selection in R. bieti (black snub-nosed monkey), a species that exploits habitats higher than any other nonhuman primate. These results provide the first detailed and comprehensive genomic insights into genetic diversity, demography, genetic burden, and adaptation in this radiation of endangered primates.

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.

Mapping copy number variation by population-scale genome sequencing.

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

Genome sequence and analysis of the tuber crop potato.

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.

SOAPindel: efficient identification of indels from short paired reads.

We present a new approach to indel calling that explicitly exploits that indel differences between a reference and a sequenced sample make the mapping of reads less efficient. We assign all unmapped reads with a mapped partner to their expected genomic positions and then perform extensive de novo assembly on the regions with many unmapped reads to resolve homozygous, heterozygous, and complex indels by exhaustive traversal of the de Bruijn graph. The method is implemented in the software SOAPindel and provides a list of candidate indels with quality scores. We compare SOAPindel to Dindel, Pindel, and GATK on simulated data and find similar or better performance for short indels (<10 bp) and higher sensitivity and specificity for long indels. A validation experiment suggests that SOAPindel has a false-positive rate of ∼10% for long indels (>5 bp), while still providing many more candidate indels than other approaches.

The sequence and de novo assembly of the giant panda genome.

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.