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Graphical Abstract Highlights d Genome sequencing from low-pass noninvasive prenatal testing samples d GWAS of 141,431 low-pass genomes reveals 16 unknown genetic associations d Patterns of clinically relevant viral infection in maternal plasma d Insights into the genetic structure and history of the Chinese population SUMMARYWe analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the present day distribution of alleles is a function of both ancient migration and very recent population movements. We reveal novel phenotype-genotype associations, including several replicated associations with height and BMI, an association between maternal age and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique pattern of circulating viral DNA in plasma with high prevalence of hepatitis B and other clinically relevant maternal infections. A GWAS for viral infections identifies an exceptionally strong association between integrated herpesvirus 6 and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI protein function. These findings demonstrate the great value and potential of accumulating NIPT data for worldwide medical and genetic analyses. BLAST Sayers et al., 2009 https://blast.ncbi.nlm.nih.gov/Blast.cgi

BackgroundMyopia is the leading cause of preventable blindness in children and young adults. Multiple epidemiological studies have confirmed a high prevalence of myopia in Asian countries. However, fewer longitudinal studies have been performed to evaluate the secular changes in the prevalence of myopia, especially high myopia in China. In the present study, we investigated trends in the prevalence of myopia among high school students in Fenghua city, eastern China, from 2001 to 2015.MethodsThis was a population-based, retrospective study. Data were collected among 43,858 third-year high school students. Noncycloplegic autorefraction was used to determine refractive error, which was defined as low myopia, moderate myopia, high myopia and very high myopia according to the spherical equivalent from the worse eye of each participant. The prevalence of myopia was calculated and the annual percentage change (APC) was used to quantify the time trends. All analyses were conducted using the SPSS, Stata and Graphpad Prism software.ResultsFrom 2001 to 2015, the prevalence of overall myopia increased from 79.5% to 87.7% (APC =0.59%), with a significant increase of moderate myopia (38.8% to 45.7%, APC = 0.78%), high myopia (7.9% to 16.6%, APC = 5.48%) and very high myopia (0.08% to 0.92%, APC = 14.59%), while the prevalence of low myopia decreased from 32.7% to 24.4% (APC = − 1.73%). High myopia and very high myopia contributed the major part of the increasing trend of myopia prevalence (contribution rate 27.00% and 69.07%, respectively).ConclusionsDuring the 15-year period, there was a remarkable increase in the prevalence of high and very high myopia among high school students, which might become a serious public health problem in China for the next few decades.Electronic supplementary materialThe online version of this article (10.1186/s12886-018-0829-8) contains supplementary material, which is available to authorized users.

BackgroundCombination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics.ResultsBy combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance.ConclusionsOur findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1196-0) contains supplementary material, which is available to authorized users.

The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalyzed DNA elongation. Here we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.