The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Rapid and sensitive pathogen detection cuts off routes of transmission and improves patient outcomes by enabling early treatment and appropriate antibiotic usage. 1 Several rapid methods having different adaptation, cost, sensitivity, and specificity, have been developed for pathogen detection. 2 Rapid pathogen detection, based on detection of nucleic acids via polymerase chain reaction (PCR), is often costly, requires specific equipment, and must be conducted in the laboratory environment. 3 Sequencing technology is still being perfected and cannot be directly used for clinical diagnosis. 4 This highlights the urgent need for a low-cost, simple, and highly

The leaf epidermis of 16 species and one putative species of Fritillaria was examined using light microscopy (LM) and scanning electron microscopy (SEM). The results showed that the stomatal and other epidermal features were constant within species. Epidermal cells of Fritillaria under LM were usually polygonal and anticlinal cell walls were straight or curved. In a few species they were irregular, with sinuous anticlinal cell walls. The cuticular membrane of Fritillaria was usually striated, and the wax ornamentations were flaked, granular or concomitant. Based on leaf epidermal characteristics, the subdivision of Fritillaria is discussed, and the statistical t-test method was used to ascertain the significance level of the differences in the stomata of each species. All orientations of the stomatal poles in Fritillaria were the same, and this phenomenon was named 'stomatal orientation'. The stomatal characteristics support the origin of section Fritillaria in China from two floristic elements.

To identify genes that may be relevant to the molecular action of antidepressants, we investigated transcriptional changes induced by the selective serotonin reuptake inhibitor paroxetine in a serotonergic cell line. We examined gene expression changes after acute treatment with paroxetine and sought to validate microarray results by quantitative PCR (qPCR). Concordant transcriptional changes were confirmed for 14 genes by qPCR and five of these, including the adrenomedullin gene (Adm), either approached or reached statistical significance. Reporter gene assays showed that a SNP (rs11042725) in the upstream flanking region of ADM significantly altered expression. Association analysis demonstrated rs11042725 to be significantly associated with response to paroxetine (odds ratio ¼ 0.075, Po0.001) but not with response to either fluoxetine or citalopram. Our results suggest that ADM is involved with the therapeutic efficacy of paroxetine, which may have pharmacogenetic utility.

Tetrahydrobiopterin (BH 4 ) is an essential cofactor for synthesis of many neurotransmitters including serotonin. In serotonergic neurons, BH 4 is tightly regulated by GTP-cyclohydrolase I feedback regulator (GFRP). Given the pivotal role of the serotonergic system in mood disorders and selective serotonin reuptake inhibitors (SSRIs) antidepressant function, we tested the hypothesis that GFRP gene (GCHFR) variants would modify response to antidepressants in subjects with major depression. Two single nucleotide polymorphisms (rs7164342 and rs7163862) in the GCHFR promoter were identified and occurred as two haplotypes (GA or TT). A multiple regression analysis revealed that homozygous individuals for the TT haplotype were less likely to respond to the SSRI fluoxetine than to the tricyclic antidepressant nortriptyline (P ¼ 0.037). Moreover, the TT haplotype showed a reduced transcription rate in luciferase reporter gene assays, which may impact on BH 4 -mediated neurotransmitter production, thus suggesting a biological process through which GCHFR promoter variants might influence antidepressant response.

The karyotypes of 16 populations belonging to eight species of Polygonatum from China were analysed. The chromosome numbers and karyotypes of P. omeiense, P. adnatum and P. hirtellum and the diploidy of P. tessellatum are reported for the first time. The basic chromosome numbers were x = 11, 13, 14 and 15. Based on Stebbins' karyotypic classification, the four karyotypes were recognized as 2B, 3B, 2C and 3C. Considering the arm ratio and individual chromosome size, it was concluded that the possible evolutionary trend of the karyotypes in Polygonatum was from 2B to 3C. The results show that: (1) satellite heterozygosity occurs in many species of this genus;(2) mixoploidy and B chromosomes occur in some species; and (c) karyotypes are different in different species and even in different populations of the same species.

One of the key barriers for early identification and intervention of severe influenza cases is a lack of reliable immunologic indicators. In this study, we utilized differentially expressed genes screening incorporating weighted gene co‐expression network analysis in one eligible influenza GEO data set ( GSE111368 ) to identify hub genes associated with clinical severity. A total of 10 genes ( PBI , MMP8 , TCN1 , RETN , OLFM4 , ELANE , LTF , LCN2 , DEFA4 and HP ) were identified. Gene set enrichment analysis (GSEA) for single hub gene revealed that these genes had a close association with antimicrobial response and neutrophils activity. To further evaluate these genes' ability for diagnosis/prognosis of disease developments, we adopted double validation with (a) another new independent data set ( GSE101702 ); and (b) plasma samples collected from hospitalized influenza patients. We found that 10 hub genes presented highly correlation with disease severity. In particular, BPI and MMP8 encoding proteins in plasma achieved higher expression in severe and dead cases, which indicated an adverse disease development and suggested a frustrating prognosis. These findings provide new insight into severe influenza pathogenesis and identify two significant candidate genes that were superior to the conventional clinical indicators. These candidate genes or encoding proteins could be biomarker for clinical diagnosis and therapeutic targets for severe influenza infection.

Influenza A virus still represents a noticeable epidemic risk to international public health at present, despite the extensive use of vaccines and anti-viral drugs. In the fight against pathogens, the immune defence lines consisting of diverse lymphocytes are indispensable for humans. However, the role of virus infection of lymphocytes and subsequent abnormal immune cell death remains to be explored. Different T cell subpopulations have distinct characterizations and functions, and we reveal the high heterogeneity of susceptibility to viral infection and biological responses such as apoptosis in various CD4 + T and CD8 + T cell subsets through single-cell transcriptome analyses. Effector memory CD8 + T cells (CD8 + T EM ) that mediate protective memory are identified as the most susceptible subset to pandemic influenza A virus infection among primary human T cells. Non-productive infection is established in CD8 + T EM and naïve CD8 + T cells, which indicate the mechanism of intracellular antiviral activities for inhibition of virus replication such as abnormal viral splicing efficiency, incomplete life cycles and up-regulation of interferon-stimulated genes in human T cells. These findings provide insights into understanding lymphopenia and the infectious mechanisms of pandemic influenza A virus and broad immune host–pathogen interactional atlas in primary human T cells.