An atlas of CNV maps in cattle, goat and sheep

Copy number variation(CNV)is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans,animals and plants.However,the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain unknown.Here,we generated CNV region(CNVR)datasets which were diverged or shared among cattle,goat,and sheep,including 886 individuals from 171 diverse populations.Using 9 environmental factors for genome-wide association study(GWAS),we identified a series of candidate CNVRs,including genes relating to immunity,tick resistance,multi-drug resistance,and muscle development.The number of CNVRs shared between species is significantly higher than expected(P<0.00001),and these CNVRs may be more persist than the single nucleotide polymorphisms(SNPs)shared between species.We also identified genomic regions under long-term balancing selection and uncovered the potential diversity of the selected CNVRs close to the important functional genes.This study provides the evidence that balancing selection might be more common in mammals than previously considered,and might play an important role in the daily activities of these ruminant species.

GGVD:A goat genome variation database for tracking the dynamic evolutionary process of selective signatures and ancient introgressions

Understanding the evolutionary history and adaptive process depends on the knowledge that we can acquire from both ancient and modern genomic data.With the availability of a deluge of whole-genome sequencing data from ancient and modern goat samples,a user-friendly database making efficient reuse of these important resources is needed.Here,we use the genomes of 208 modern domestic goats,24 bezoars,46 wild ibexes,and 82 ancient goats to present a comprehensive goat genome variation database(GGVD).GGVD hosts a total of~41.44 million SNPs,~5.14 million indels,6,193 selected loci,and 112 introgression regions.Users can freely visualize the frequency of genomic variations in geographical maps,selective sweeps in interactive tables,Manhattan plots,or line charts,as well as the heatmap patterns of the SNP genotype.Ancient data can be shown in haplotypes to track the state of genetic variants of selection and introgression events in the early,middle,and late stages.For facilitating access to sequence features,the UCSC Genome Browser,BLAT,BLAST,Lift Over,and pcadapt are also integrated into GGVD.GGVD will be a convenient tool for population genetic studies and molecular marker designing in goat breeding programs,and it is publicly available at http://animal.nwsuaf.edu.cn/Goat Var.

Robust and Tumor-Environment-Activated DNA Cross-Linker Driving Nanoparticle Accumulation for Enhanced Therapeutics

Agglomeration of therapeutic nanoparticles in response to tumor microenvironments is a promising approach to enhance drug accumulation and improve therapeutic efficacy.Cytosine-rich DNA sequences show potential as ideal cross-linkers to drive nanoparticle agglomeration because they can sensitively respond to weak acidity and form interchain folding.However,the in vivo application of DNA is generally limited by its poor biostability;as a consequence,modifications with unprotected DNA cross-linkers can enhance the accumulation of nanoparticles twofold at the tumor site.Facing this challenge,we have designed and developed a protection and tumor-environment activation strategy to enable the in vivo application of a DNA cross-linker.Specifically,reactive oxygen species(ROS)-responsive polyethylene glycol(PEG)was modified on the nanoparticle surface together with the DNA crosslinker,which protects DNA from degradation during the blood circulation;meanwhile,when arriving at the tumor site,the nanoparticles shed the PEG shell as a response to ROS to uncover and activate the DNA cross-linkers.Using this strategy,a sevenfold enhancement in tumor accumulation was achieved owing to both superior pH sensitivity and improved stability of DNA cross-linkers.Finally,significantly improved therapeutic efficacy in in vivo anticancer treatment was realized by using this agglomeration strategy driven by protected and stimuli-activated DNA cross-linkers.