Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains

BackgroundCirculating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors.ResultsWe perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures.ConclusionsWe generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0645-x) contains supplementary material, which is available to authorized users.     

HaploShare: identification of extended haplotypes shared by cases and evaluation against controls

Recent founder mutations may play important roles in complex diseases and Mendelian disorders. Detecting shared haplotypes that are identical by descent (IBD) could facilitate discovery of these mutations. Several programs address this, but are usually limited to detecting pair-wise shared haplotypes and not providing a comparison of cases and controls. We present a novel algorithm and software package, HaploShare, which detects extended haplotypes that are shared by multiple individuals, and allows comparisons between cases and controls. Testing on simulated and real cases demonstrated significant improvements in detection power and reduction of false positive rate by HaploShare relative to other programs.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0662-9) contains supplementary material, which is available to authorized users.     

Climate warming increases biological control agent impact on a non‐target species

Climate change may shift interactions of invasive plants, herbivorous insects and native plants, potentially affecting biological control efficacy and non‐target effects on native species. Here, we show how climate warming affects impacts of a multivoltine introduced biocontrol beetle on the non‐target native plant Alternanthera sessilis in China. In field surveys across a latitudinal gradient covering their full distributions, we found beetle damage on A. sessilis increased with rising temperature and plant life history changed from perennial to annual. Experiments showed that elevated temperature changed plant life history and increased insect overwintering, damage and impacts on seedling recruitment. These results suggest that warming can shift phenologies, increase non‐target effect magnitude and increase non‐target effect occurrence by beetle range expansion to additional areas where A. sessilis occurs. This study highlights the importance of understanding how climate change affects species interactions for future biological control of invasive species and conservation of native species.     

Gender specific effect of LIPC C‐514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children

Hepatic lipase (LIPC) is a key rate‐limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C‐514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case‐controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C‐514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta‐analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL‐C) in obese boys, and triglyceride (TG), TC and LDL‐C in non‐obese girls (all P < 0.05). In the meta‐analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL‐C in the overall and boys, and LDL‐C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta‐analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.     

基于Maxent的大洋臀纹粉蚧和南洋臀纹粉蚧在中国的适生区分析

大洋臀纹粉蚧Planococcus minor Maskell和南洋臀纹粉蚧P.lilacinus Cockerell是我国有重要检疫意义的有害生物。这两种粉蚧从东盟进口水果口岸检疫中频繁截获,且已在广东、海南、云南等地发现大洋臀纹粉蚧入侵,这对我国热带、亚热带的水果和观赏植物等已构成严重威胁。本研究以大洋臀纹粉蚧和南洋臀纹粉蚧在国内外的分布数据为基础,利用Maxent生态位模型和Arc GIS对两种粉蚧在中国的潜在适生区进行预测。预测结果表明,大洋臀纹粉蚧和南洋臀纹粉蚧的适生区主要分布在长江流域以南地区,其适生区面积分别占全国面积的22.14%、18.17%,其中高度适生区域集中分布在广西、广东、云南、福建、四川、台湾、海南等地区,与我国热带水果的主要种植区域具有高度的一致性。大洋臀纹粉蚧已成功入侵,一旦南洋臀纹粉蚧传入便可迅速扩散蔓延,并对我国热带水果生产造成严重危害。因此,各口岸应加强对东盟进口水果的检验检疫,预防其新的进入和扩散。