Evaluation of Four Candidate VNTR Loci for Genotyping 225 Chinese Clinical Mycobacterium Tuberculosis Complex Strains

Objective To evaluate four candidate variable number tandem repeat （VNTR） loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains （CCDC5079 and CCDC5180） were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index （HGI） for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.

Metagenome of microorganisms associated with the toxic Cyanobacteria Microcystis aeruginosa analyzed using the 454 sequencing platform

In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States(1992–2015)

Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

A Novel Small Deletion in the A TP2A2 Gene in a Patient with Sporadic Darier's Disease and Concomitant Depression: A Case Report

Introduction:Darier's disease is a rare autosomal dominant skin disorder caused by mutations in ATP2A2.Recently,the high prevalence of neuropsychiatric symptoms is frequently reported in Darier's disease patients.We present a case of patient with concurrence of Darier's disease and depression and detected the mutations in Case presentation:A 29-year-old man presented with a 15-year history of brown,harsh keratotic papules on his scalp,face,neck,trunk,axilla,ingunia and upper limbs.Meanwhile,he had persistent depression.He was diagnosed as Darier's disease according to clinical manifestations and result of histological examination.We sequenced all coding regions of ATP2A2.The mutation c.2993_2994del(p.Val998Alafs*33)in exon 20 of ATP2A2 was detected.Discussion:Darier's disease has been associated with several extracutaneous manifestations,in particular neuropsychiatric morbidity.Likely gene disrupting mutations in ATP2A2 was reported to have a close relationship to Darier's disease cases with reported co-occurring neuropsychiatric features.Consistent with the previous reports,an likely gene disrupting mutations was detected in our patient with concurrence of DD end depression.Conclusion:The psychiatric disorders in patients with Darier's disease should be well appreciated.The underlying mechanism in correlation between the mutation in ATP2A2 and neuropsychiatric phenotypes in Darier's disease remain unclarified and warrants further investigation.

DBLiPro:A Database for Lipids and Proteins in Human Lipid Metabolism

To help researchers in the field of biology,medicine,chemistry,and materials science to use lipidomic data conveniently,there is an urgent need to develop a platform that provides a systematic knowledgebase of human lipid metabolism and lipidome-centric omics analysis tools.DBLiPro is a user-friendly webserver allowing for access to human metabolism-related lipids and proteins knowledge database and an interactive bioinformatics integrative analysis workflow for lipidomics,transcriptomics,and proteomics data.In DBLiPro,there are 3109 lipid-associated proteins(LAPs)and 2098 lipid metabolites in the knowledge base section,which were obtained from Uniprot,Kyoto Encyclopedia of Genes and Genomes(KEGG)and were further annotated by information from other public resources in the knowledge base section,such as RaftProt and PubChem.DBLiPro offers a step-by-step interactive analysis workflow for lipidomics,transcriptomics,proteomics,and their integrating multi-omics analysis focusing on the human lipid metabolism.In summary,DBLiPro is capable of helping users discover key molecules(lipids and proteins)in human lipid metabolism and investigate lipid–protein functions underlying mechanisms based on their own omics data.The DBLiPro is freely available at http://lipid.cloud na.cn/home.

Unraveling the Acidithiobacillus caldus complete genome and its central metabolisms for carbon assimilation

Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome （2,932,225 bp） and four plasmids （pLAtcl, pLAtc2, pLAtc3, pLAtcm） and it is rich in repetitive sequences （accounting for 11% of the total genome）, which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtcl have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO2 via the classical Calvin-Bassham--Benson （CBB） cycle, and can operate complete Embden-Meyerhof pathway （EMP）, pentose phosphate pathway （PPP）, and gluconeogenesis. It has an incomplete tricarboxylic acid cycle （TCA）. Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.

Fine genetic mapping of the chromosome 11q23.3 region in a Han Chinese population:insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances

The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional interpretation.The present study identified new meaningful genetic associations that were not simply determined by statistical significance.In addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids.Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses.rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility.Similarly,multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol.Our findings provided novel insights into this genomic locus in the Chinese population.

ASSOCIATION ANALYSIS OF POLYMORPHISMS IN SIX GENES WITHIN THE GH/IGF-1 AXIS IN PATIENTS WITH IDIOPATHIC SHORT STATURE IN THE CHINESE HAN POPULATION

Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.

Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice

Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are stll a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants.Here,we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family.Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration,motility,and deformed acrosomes.Further mechanistic analyses reveal that MFsD6L,as an acrosome membrane protein,plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1.Moreover,poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice.Collectively,our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping.The deficiency of MFsD6L affects male fertility and causes oligoasthenoter-atozoospermia in humans and mice.

Insights into the Bamboo Genome:Syntenic Relationships to Rice and Sorghum

Bamboo occupies an important phylogenetic node in the grass family and plays a significant role in the forest industry.We produced 1.2 Mb of tetraploid moso bamboo （Phyllostachys pubescens E.Mazel ex H.de Leh.） sequences from 13 bacterial artificial chromosome （BAC） clones,and these are the largest genomic sequences available so far from the subfamily Bambusoideae.The content of repetitive elements （36.2%） in bamboo is similar to that in rice.Both rice and sorghum exhibit high genomic synteny with bamboo,which suggests that rice and sorghum may be useful as models for decoding Bambusoideae genomes.

NGSmirPlant： comprehensive characterization of the small RNA transcriptomes of plants

MicroRNAs （miRNAs） are short, endogenously expressed RNAs （-21-22 nt） processed from stem-loop regions of longer RNA precursors by a Dicer-like enzyme （Jones- Rhoades et al., 2006）. In plants, microRNAs play an essential role in regulating many fundamental molecular in- teractions, including plant growth, development and re- sponse to environmental stress （Rogers and Chen, 2013）. In comparison with the roles of microRNAs in animals, bio- genesis and function of microRNAs in plants appears to be drastically different （Llave et al., 2002; Zhang et al., 2007）.