Significance The Antarctic environment is famously inhospitable to most terrestrial biodiversity, traditionally viewed as a driver of species extinction. Combining population- and species-level molecular data, we show that beetles on islands along the Antarctic Polar Front diversified in response to major climatic events over the last 50 Ma in surprising synchrony with the region’s marine organisms. Unique algae- and moss-feeding habits enabled beetles to capitalize on cooling conditions, which resulted in a decline in flowering plants—the typical hosts for beetles elsewhere. Antarctica’s cooling paleoclimate thus fostered the diversification of both terrestrial and marine life. Climatically driven evolutionary processes since the Miocene may underpin much of the region’s diversity, are still ongoing, and should be further investigated among Antarctic biota.

Abstract Full-length cDNA (FLcDNA) libraries consisting of 172,000 clones were constructed from a two-row malting barley cultivar (Hordeum vulgare ‘Haruna Nijo’) under normal and stressed conditions. After sequencing the clones from both ends and clustering the sequences, a total of 24,783 complete sequences were produced. By removing duplicates between these and publicly available sequences, 22,651 representative sequences were obtained: 17,773 were novel barley FLcDNAs, and 1,699 were barley specific. Highly conserved genes were found in the barley FLcDNA sequences for 721 of 881 rice (Oryza sativa) trait genes with 50% or greater identity. These FLcDNA resources from our Haruna Nijo cDNA libraries and the full-length sequences of representative clones will improve our understanding of the biological functions of genes in barley, which is the cereal crop with the fourth highest production in the world, and will provide a powerful tool for annotating the barley genome sequences that will become available in the near future.

AbstractThe eukaryotic nucleolus is multifunctional and involved in the metabolism and assembly of many different RNAs and ribonucleoprotein particles as well as in cellular functions, such as cell division and transcriptional silencing in plants. We previously showed that Arabidopsis thaliana exon junction complex proteins associate with the nucleolus, suggesting a role for the nucleolus in mRNA production. Here, we report that the plant nucleolus contains mRNAs, including fully spliced, aberrantly spliced, and single exon gene transcripts. Aberrant mRNAs are much more abundant in nucleolar fractions, while fully spliced products are more abundant in nucleoplasmic fractions. The majority of the aberrant transcripts contain premature termination codons and have characteristics of nonsense-mediated decay (NMD) substrates. A direct link between NMD and the nucleolus is shown by increased levels of the same aberrant transcripts in both the nucleolus and in Up-frameshift (upf) mutants impaired in NMD. In addition, the NMD factors UPF3 and UPF2 localize to the nucleolus, suggesting that the Arabidopsis nucleolus is therefore involved in identifying aberrant mRNAs and NMD.

Background. Our aim was to investigate the association between the genetics of the angiopoietin protein-like 8 (ANGPTL8) rs2278426 (C/T) polymorphism with prediabetes (pre-DM) and type 2 diabetes (T2DM) in a Han Chinese population in Hebei Province, China. Methods. We enrolled 1,460 participants into this case-control study: healthy controls, n = 524; pre-DM, n = 460; and T2DM: n = 460. Ligase assays on blood samples from all participants were used to identify polymorphisms. Differences in genotype and allele distributions were compared by the chi-square test and one-way analysis of variance, and a post hoc pairwise analysis was performed using the Bonferroni test. The logistic regression technique was adjusted for age, sex, and body mass index. Results. The frequency of the TT (10.9%) genotype was significantly higher in pre-DM patients than in controls (odds ratio [OR] = 1.696, 95% confidence interval [CI] = 1.026–2.802, $P=0.039$ ). In the T2DM group, the CT (48%) and TT (15%) genotypes were significantly higher compared with those in the control group (CT : OR = 1.384, 95% CI = 1.013–1.890, $P=0.041$ ; TT : OR = 2.530, 95% CI = 1.476–4.334, $P=0.001$ ). The frequency of the T allele was significantly higher in the pre-DM (32.8%) and T2DM (39%) groups compared with the control group (26.9%) and was significantly associated with an increased risk of pre-DM (OR = 1.253, 95% CI = 1.017–1.544, $P=0.034$ ) and T2DM (OR = 1.518, 95% CI = 1.214–1.897, $P=0.001$ ). Furthermore, insulin levels in the pre-DM and T2DM groups were significantly decreased in those with the TT genotype compared with the CC and CT genotypes. Conclusion. ANGPTL8 rs2278426 may be involved in the mechanism of insulin secretion and could lead to an increased risk of pre-DM and T2DM.

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all $P>0.05$ ). Association between the genotype effects of dominant, recessive models was also not found (all $P>0.05$ ). No significant difference in plasma leptin levels was detected between RA patients and controls ( $P>0.05$ ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

The scientific consensus is now on developing a biocontrol agent that can cause cellular metabolic reprogramming against agricultural pathogens. Biosynthesis of silver nanoparticles was performed by using phytopathogenic fungi (Alternaria sp.) isolated from banana cultivated soil. Alternaria sp. can grow very fast and produce high enough bioactive compounds. This study aims to biosynthesize silver nanoparticles (AgNPs) using fungal Alternaria sp.’s metabolites as a safe antifungal agent against plant pathogenic fungi (Fusarium spp. and Alternaria sp.). To visualize the formation of AgNPs, analytical instruments were used, such as ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, scanning transmission electron microscopy (STEM), energy dispersive X-ray (EDX), and elemental mapping. The UV-visible spectra showed a peak at 435 nm. Analysis of scanning transmission electron microscopy (STEM) micrographs evidenced that the size of synthesized silver nanoparticles ranged between 3 and 10 nm. The resulting AgNPs showed distinct antifungal activity against selected plant pathogenic fungi. Synthesized AgNPs have demonstrated remarkable potential for the use of antifungal compounds to combat plant diseases.

Dextranase is a useful enzyme that catalyzes the degradation of dextran to low-molecular-weight fractions, which have many critical commercial and clinical applications. Endophytic fungi represent a source of both high heat-stable and pH-stable enzymes. In this study, from Delonix regia bark by plate assay, out of 12 isolated fungal strains, hyaline zones were detected in only one strain. By using the standard ITS rDNA sequencing analysis, the isolated strain was identified as Talaromyces sp. In the case of carbon source, in a medium containing 1% dextran T2000 as the sole carbon source, the maximum dextranase activity reached approximately 120 U/ml after incubation of 2 days where the optimum pH was 7.4. Peptone addition to the production medium as a sole nitrogen source was accompanied by a significant increase in the dextranase production. Similarly, some metal ions, such as Fe2+ and Zn2+, increased significantly enzyme production. However, there was no significant difference resulting from the addition of Cu2+. The crude dextranase was purified by ammonium sulfate fractionation, followed by Sephadex G100 chromatography with 28-fold purification. The produced dextranase was 45 kDa with an optimum activity at 37°C and a pH of 7. Moreover, the presence of MgSO4, FeSO4, and NH4SO4 increased the purified dextranase activity; however, SDS and EDTA decreased it. Interestingly, the produced dextranase expressed remarkable pH stability, temperature stability, and biofilm inhibition activity, reducing old-established biofilm by 86% and biofilm formation by 6%.

Poultries including chickens, ducks, geese, and pigeons are widely used in the biological and medical research in many aspects. The genetic quality of experimental poultries directly affects the results of the research. In this study, following electrophoresis analysis and short tandem repeat (STR) scanning, we screened out the microsatellite loci for determining the genetic characteristics of Chinese experimental chickens, ducks, geese, and pigeons. The panels of loci selected in our research provide a good choice for genetic monitoring of the population genetic diversity of Chinese native experimental chickens, ducks, geese, and ducks.

Background. Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. Methods. Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for β-catenin gene were performed. Results. There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma ( $P=0.109$ ). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and β-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs ( $P=0.040$ ). β-catenin gene mutation was not detected in any patients. Conclusions. MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.

Abstract Background: Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, we measured relatedness of Plasmodium falciparum infections in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods: All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS).Results: As expected, genetic diversity was high (mean heterozygosity [He]=0.73), and the majority (76.5%) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 meters) vs. lower elevation (mean 1015 meters) was modest (1.4 malaria cases per person-year versus 1.9 per person-year, respectively), we found a significant difference in multiplicity of infection (2.2 versus 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3% vs 0.9%, p = 0.0005) at higher elevation compared to lower elevation. Conclusions: Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, our study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

Abstract BackgroundGenomic information for Allium cepa L. is limited as it is heterozygous and its genome is very large. To elucidate potential SNP markers obtained by NGS, we used a complete set of A. fistulosum L.-A. cepa monosomic addition lines (MALs) and doubled haploids (DHs). These were the parental lines of an A. cepa mapping population for transcriptome-based SNP genotyping.ResultsWe mapped the transcriptome sequence reads from a series of A. fistulosum-A. cepa MALs onto the unigene sequence of the doubled haploid shallot A. cepa Aggregatum group (DHA) and compared the MAL genotype call for parental bunching onion and shallot transcriptome mapping data. We identified SNP sites with at least four reads on 25,462 unigenes. They were anchored on eight A. cepa chromosomes. A single SNP site was identified on 3,278 unigenes and multiple SNPs were identified on 22,184 unigenes. The chromosome marker information was made public via the web database Allium TDB (http://alliumtdb.kazusa.or.jp/). To map these markers, we gathered RNA sequence data from 96 lines of a DHA × doubled haploid bulb onion A. cepa common onion group (DHC) mapping population. After selecting co-dominant SNP sites, 16,872 SNPs were identified in 5,339 unigenes. Of these, at least two SNPs with identical genotypes were found in 1,435 unigenes. We developed a linkage map using genotype information from these unigenes. All unigene markers mapped onto the eight chromosomes and graphical genotyping was conducted based on the unigene order information. Another 2,963 unigenes were allocated onto the eight chromosomes. To confirm the accuracy of this transcriptome-based genetic linkage map, conventional PCR-based markers were used for linkage analysis. All SNP - and PCR-based markers were mapped onto the expected linkage groups and no inconsistency was found among these chromosomal locations.ConclusionsEffective transcriptome analysis with unique Allium resources successfully associated numerous chromosome markers with unigene information and an ultrahigh-density A. cepa linkage map. The information on these unigene markers is valuable in genome sequencing and useful trait detection in Allium.

Abstract BACKGROUND Keratoconus (KC) is characterized by bilateral progressive corneal thinning and ectasia. The prevalence of KC is approximately 8.8 to 54.4 per 100,000 individuals across the globe. Genetic factors have been shown to contribute to the pathogenesis of KC. This study will identify new mutations in the susceptibility gene of keratoconus (KC) in the Chinese Han population. METHODS A total of fifty-two patients with primary KC were recruited. Blood samples were collected, and genomic DNA was isolated from peripheral blood leukocytes. The entire coding region, intron–exon junctions, and promoter regions of sixteen known KC susceptibility genes were screened with next-generation sequencing technology, and all identified variants were further confirmed using the Sanger sequencing technology. The Sorting Intolerant from Tolerant (SIFT), Mutation Taster and PolyPhen 2 programs were used to predict the effect of amino acid substitution on protein. RESULTS After removing twelve known SNPs (single nucleotide polymorphisms) and three variants predicted to be harmless, nine novel mutations were identified in eight of the fifty-two patients, including c.455C > T:p.P152L in FNDC3B, c.3636_3637del:p.R1212fs in COL4A4, c.5015G > T:p.R1672L, c.3798dupA:p.P1267fs and c.28G > A:p.A10T in MPDZ, c.1940C > T:p.P647L in DOCK9, c.127_128insGGC:p.Q43delinsRQ in POLG, c.3019G > A:p.V1007I in IPO5, and c.624 + 7->A in TGFBI. All nine mutations in the patients with KC were heterozygote. CONCLUSION This study enlarged the gene profile of KC and should be further confirmed by well-powered, genome-wide association studies (GWAS) of Han Chinese patients.

Abstract BackgroundDelimiting cryptic species in elasmobranchs is a major challenge in modern taxonomy due the lack of available phenotypic features. Employing stand-alone genetics in splitting a cryptic species may prove problematic for further studies and for implementing conservation management. In this study, we examined mitochondrial DNA and genome-wide nuclear single nucleotide polymorphisms (SNPs) in the brown-banded bambooshark, Chiloscyllium punctatum to evaluate potential cryptic species and the species-population boundary in the group.ResultsOur results found four operational taxonomic units (OTUs) within C. punctatum from the Indo-Australian region. Each OTU can be interpreted differently depending on available supporting information. Similarly, we confirmed that comprehensive sampling over the species' geographic distribution was essential to determine the boundary between population and cryptic species.ConclusionWe provide suggestions about what should be considered prior to split cryptic species and the designation of new species.

Abstract Background: Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses severe threat to public health. Chicken meat and egg are the main source of SE. DNA methylation, an important epigenetic modification, involves in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole genome bisulfite sequencing in the current study. Results: There were 185,362,463 clean reads and 126,098,724 unique reads in the control group, and 180,530,750 clean Reads, 126,782,896 unique reads in the inoculated group. We found that the methylation density in gene body was higher than that in the upstream and downstream regions of gene. There were 8,946 differentially methylated genes (3,639 hypo-methylated genes, 5,307 hyper-methylated genes) obtained between inoculated and control groups. Methylated genes were mainly enriched in immune-related Gene Ontology (GO) terms and metabolic process terms. Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, FoxO signaling pathway, Wnt signaling pathway and several metabolism-related pathways were significantly enriched. The density of differentially methylated cytosines in miRNAs was the highest. HOX genes were widely methylated and mainly distributed in Chr2 and 7. Conclusions: We firstly analyzed the genome-wide DNA methylation in the response to SE inoculation in chicken. SE inoculation promoted the DNA methylation in chicken cecum and caused methylation alteration in immune- and metabolic- related genes. Wnt signal pathway, miRNAs and HOX gene family may play a crucial role in the methylation regulation of SE infection in chicken. The findings herein will deepen the understanding of epigenetic regulation in the response to SE inoculation in chicken.

Abstract BackgroundAn inevitable hepatic injury at the early phase after liver transplantation vitally affects the late phase hepatocellular carcinoma (HCC) recurrence. However, their linkage and underlying risk factors of HCC recurrence are unclear. This study aimed to clarify the clinical impact and functional roles of glutathione S-transferase A2 (GSTA2) in affecting HCC recurrence after liver transplantation.MethodsExpression significance and prognostic value of hepatic and circulating GSTA2 in HCC recipients were examined. The polymorphism of GSTA2 transcript was analysed by Sanger sequencing. The functions and molecular mechanisms of GSTA2 in the proliferation and metastasis of HCC were characterized by molecular, cellular and animal experiments. ResultsThe GSTA2 expression was significantly correlated with the early phase hepatic and systemic injury and reactive oxygen species (ROS) level after liver transplantation. Importantly, the level of the early phase circulating GSTA2 protein was a significant predictor of HCC recurrence and survival of HCC recipients. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. The GSTA2 expression was positively correlated with the aggressiveness of HCCs. Overexpression of GSTA2, by endogenous or exogenous approaches, could enhance the proliferation and invasion of HCCs through activating epithelial-mesenchymal-transition promoting proteins. Targeted inhibition of GSTA2 remarkably suppressed the proliferation and metastasis of HCCs. Increased level of GSTA2 could compensate the H2O2-induced ROS stress and therefore protect the HCC cells from damage. Alteration of GSTA2 expression in HCC cells could influence the activation of ROS-associated JNK and AKT signaling pathways and the expression of ROS-associated genes in responding to the H2O2 condition. ConclusionsOur research discovered GSTA2 to be the significant risk factor of HCC recurrence via providing a favorable ROS environment for HCC to survival and progress. This study presents a novel functional biomarker for combating HCC recurrence after liver transplantation.

In this study, mycelial filtrate of Aspergillus terreus BA6 was used to reduce AgNO3 to form silver nanoparticles (AgNPs). The effect of seven independent variables on the diameter of AgNPs was studied by applying design of experiments (DOE). At optimal conditions, the diameter of AgNPs was reduced by approximately 26.7% compared to the basal culture condition and AgNO3 concentration was found to be the most significant factor affecting the diameter of AgNPs. A. terreus nano-Ag was characterized using UV-visible spectroscopy, transmission electron microscopy, energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zeta potential. The maximum UV absorption was obtained at 420 nm and the microscopic results showed particles with narrow size distribution ranging from 7 to 23 nm. XRD pattern of AgNPs revealed four diffraction peaks of metallic silver and the EDX spectrum showed a strong signal attributed to Ag nano-crystals. AgNPs mycofabricated by A. terreus showed potent minimum inhibitory concentration (MIC) and broad minimum bactericidal/fungicidal concentration (MBC/MFC) against 12 reference microorganisms. The MIC and MBC/MFC values of AgNPs were 0.312 to 1.25 μg/ml and 0.625 to 10 μg/ml, respectively. Nevertheless, AgNPs did not demonstrate any antagonistic activity against Coxsackie B virus. The in vitro cytotoxicity of the mycosynthesized AgNPs showed significant antitumor activity against adenocarcinoma epithelial cells from human breast cancer (Mcf-7) cell line with an inhibitory concentration (IC50) of 87.5 μg/ml.

Peroxisome biogenesis disorders within the Zellweger spectrum (PBD-ZSDs) are most frequently associated with the c.2528G>A (p.G843D) mutation in the PEX1 gene (PEX1-G843D), which results in impaired import of peroxisomal matrix proteins and, consequently, defective peroxisomal functions. A recent study suggested that treatment with autophagy inhibitors, in particular hydroxychloroquine, would be a potential therapeutic option for PBD-ZSD patients carrying the PEX1-G843D mutation. Here, we studied whether autophagy inhibition by chloroquine, hydroxychloroquine and 3-methyladenine indeed can improve peroxisomal functions in four different cell types with the PEX1-G843D mutation, including primary patient cells. Furthermore, we studied whether autophagy inhibition may be the mechanism underlying the previously reported improvement of peroxisomal functions by L-arginine in PEX1-G843D cells. In contrast to L-arginine, we observed no improvement but a worsening of peroxisomal metabolic functions and peroxisomal matrix protein import by the autophagy inhibitors, while genetic knock-down of ATG5 and NBR1 in primary patient cells resulted in only a minimal improvement. Our results do not support the use of autophagy inhibitors as potential treatment for PBD-ZSD patients, whereas L-arginine remains a therapeutically promising compound.

It is widely accepted that the structure of RNA plays important roles in a number of biological processes, such as polyadenylation, splicing, and catalytic functions. Dynamic changes in RNA structure are able to regulate the gene expression programme and can be used as a highly specific and subtle mechanism for governing cellular processes. However, the nature of most RNA secondary structures in Plasmodium falciparum has not been determined. To investigate the genome-wide RNA secondary structural features at single-nucleotide resolution in P. falciparum, we applied a novel high-throughput method utilizing the chemical modification of RNA structures to characterize these structures. Structural data from parasites are in close agreement with the known 18S ribosomal RNA secondary structures of P. falciparum and can help to predict the in vivo RNA secondary structure of a total of 3,396 transcripts in the ring-stage and trophozoite-stage developmental cycles. By parallel analysis of RNA structures in vivo and in vitro during the Plasmodium parasite ring-stage and trophozoite-stage intraerythrocytic developmental cycles, we identified some key regulatory features. Recent studies have established that the RNA structure is a ubiquitous and fundamental regulator of gene expression. Our study indicate that there is a critical connection between RNA secondary structure and mRNA abundance during the complex biological programme of P. falciparum. This work presents a useful framework and important results, which may facilitate further research investigating the interactions between RNA secondary structure and the complex biological programme in P. falciparum. The RNA secondary structure characterized in this study has potential applications and important implications regarding the identification of RNA structural elements, which are important for parasite infection and elucidating host-parasite interactions and parasites in the environment.

In the current study, we aimed to determine the association of single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated (ATM) gene with cardiac structure and human longevity. Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan Province, China, the current study enrolled 547 centenarians, 250 young participants aged 20–45 years, and 250 middle-aged and elderly participants aged 46–90 years. The frequency of TT genotype was significantly higher and that of CC genotype was significantly lower in middle-aged and elderly participants than in young (P = 0.012) and centenarian (P = 0.041) participants. There were no significant differences in the genotype and allele frequencies of SNP rs189037 between young and centenarian participants. Compared with CT genotype, TT genotype was positively and significantly associated with interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in centenarian (IVST: P = 0.049; LVPWT: P = 0.047) and middle-aged and elderly (IVST: P = 0.008; LVPWT: P = 0.004) participants. Compared with CC genotype, TT genotype was positively and significantly associated with LVPWT in centenarian (P = 0.030) and middle-aged and elderly (P = 0.013) participants. Compared with CC genotype, CT genotype was negatively and significantly associated with left ventricular end-diastolic diameter (LVEDD) in centenarian (P = 0.011) and middle-aged and elderly (P = 0.040) participants. The current study demonstrated that mutant rs189037 in the ATM gene was more commonly identified in middle-aged and elderly participants than in young and centenarian participants, was significantly associated with increased left ventricular wall thickness and volume, and could induce left ventricular eccentric hypertrophy and shorten human lifespan. Therefore, rs189037 without mutation might be an indicator of youth health and successful aging, whereas mutant rs189037 might hinder human longevity.

Pheochromocytoma/paraganglioma (PPGL) has a high genetic heterogeneity with 40% germline variants in known pathogenic genes. Data in Chinese on this aspect are scanty. To detect the genetic and clinical profile of Chinese PPGL patients, we examined the variants of 12 known germline pathogenic genes (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) by next-generation sequencing and Sanger sequencing in 314 Chinese PPGL subjects. Twenty nine percent of Chinese PPGL patients had germline variants and SDHB was the most frequently mutated (14.6%). The most frequent SDHB variants were in exon 2, exon 7, and IVS 7. Pathogenic variants were more likely to occur in metastatic PPGL patients, paragangliomas, and patients under 30, with the ratio being 50.7% (35/69), 35.9% (56/156), and 49.5% (52/105), respectively. Our cohort included 314 patients from a single setting. The genetic and clinical features of Chinese PPGL patients were unique in some aspects compared to their non-Chinese counterparts. Identification of genotype-phenotype relation can serve as an effective tool for genetic prioritization and clinical decision-making.