Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional ∼66.5 Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression level are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based GWAS identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size QTL located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.

Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs. Graphical Abstract

Aeromonas veronii strain B565 was isolated from aquaculture pond sediment in China. We present here the complete genome sequence of B565 and compare it with 2 published genome sequences of pathogenic strains in the Aeromonas genus. The result represents an independent stepwise acquisition of virulence factors of pathogenic strains in this genus.Aeromonas veronii is a Gram-negative, rod-shaped bacterium, commonly isolated from clinical, environmental, and food samples (1). It can cause wound infections, diarrhea, or septicaemia in immunocompromised patients (4,6,10). A. veronii is also the causative agent of bacterial hemorrhagic septicemia in fish and is becoming a major economic problem in the fish-farming industry (2). A. veronii strain B565, isolated from aquaculture pond sediment in Tianjin, China, was found to have the ability to produce chitinase to control fungal or Myxozoa-related diseases in a separate study.Whole-genome sequencing of A. veronii B565 was performed with a combined strategy involving Roche/454 (8) and Solexa paired-end sequencing technology (3). Genomic libraries containing 5.8-kb inserts were constructed, and 225,134 paired-end reads were generated using the GS FLX system, giving 18.8-fold coverage of the genome. A total of 94.65% of the reads were assembled into 3 large scaffolds, including 62 nonredundant contigs, using a 454 Newbler assembler (454 Life Science, Branford, CT). A total of 4,340,032 reads (2-kb insert) were generated to reach a depth of 95-fold coverage with an Illumina Solexa GA IIx and mapped to the scaffolds using a Burrows-Wheeler alignment (BWA) tool (7). The interscaffold and intrascaffold gaps were filled by local assembly of Roche and Solexa reads around or sequencing PCR products using an ABI 3730 capillary sequencer. The analysis of the genome was performed as described previously (5, 13).The complete genome sequence of B565 contains a circular 4,551,783-bp chromosome, with a GC content of 58.72%. There are 4,057 protein-coding genes, 10 rRNA operons, and 102 tRNA genes in its genome. B565 encodes some putative virulence factors, such as hemolysins, RTX protein, adhesion factor, flagella, and mannose-sensitive hemagglutinin (MSHA) (12), all of which were shared with at least one of the sequenced genomes for Aeromonas hydrophila ATCC 7966 (11) and A. salmonicida A449 (9). There are 5 genes encoding chitinase in B565, and all could be found in ATCC 7966 and A449, indicating an important role for these conserved chitinases in Aeromonas.There are fewer virulence genes in B565 than in ATCC 7966 and A449, suggesting a less virulent or nonvirulent character. There are 346 genes shared by ATCC 7966 and A449 but absent in B565. Some of these genes encode putative virulence factors such as hemolysins and the type III secretion protein. There are 329 and 666 unique genes in ATCC 7966 and A449, respectively, some of which are virulence genes and often form large clusters, such as the rtx cluster in ATCC 7966 and the flagellar gene cluster in A449, or are related to mobile ...

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Specific DNA mutations underlying several genetic defects associated with embryo loss or reduced calf survivability have been identified in dairy cattle, and a convenient and cost-effective platform is required for their routine screening. We developed Kompetitive allele-specific PCR (KASP) assays for discrimination of the wild-type alleles from the associated defective alleles at each of 8 common genetic defects in Holstein cattle, involving 5 SNP [HH1, HH3, HH4, bovine leukocyte adhesion deficiency (BLAD), and complex vertebral malformation (CVM)] and 3 insertion or deletion mutations [HH5, haplotype for cholesterol deficiency (HCD), and brachyspina (BS)]. A total of 390 cows from a Chinese Holstein herd were genotyped and the carriers identified at 7 of these 8 loci (except HH4), with the highest carrier frequencies found for CVM (10.5%) and HH1 (10.0%), followed by HH3 (2.6%), BS (2.1%), HCD (1.3%), HH5 (0.8%), and BLAD (0.5%). Surprisingly, 102 cows (26.2%) carried at least 1 of the 7 defective alleles. Our results demonstrate that these KASP assays are simple, rapid, and reliable for the detection of multiple genetic defects. The high carrier frequency of these genetic defects indicates an urgent need for routine molecular testing to eliminate the deleterious alleles from Chinese Holstein cattle.

Background: Ketosis is a common metabolic disease during the transition period in dairy cattle, resulting in longterm economic loss to the dairy industry worldwide. While genetic selection of resistance to ketosis has been adopted by many countries, the genetic and biological basis underlying ketosis is poorly understood. Results: We collected a total of 24 blood samples from 12 Holstein cows, including 4 healthy and 8 ketosisdiagnosed ones, before (2 weeks) and after (5 days) calving, respectively. We then generated RNA-Sequencing (RNA-Seq) data and seven blood biochemical indicators (bio-indicators) from leukocytes and plasma in each of these samples, respectively. By employing a weighted gene co-expression network analysis (WGCNA), we detected that 4 out of 16 gene-modules, which were significantly engaged in lipid metabolism and immune responses, were transcriptionally (FDR < 0.05) correlated with postpartum ketosis and several bio-indicators (e.g., high-density lipoprotein and low-density lipoprotein). By conducting genome-wide association signal (GWAS) enrichment analysis among six common health traits (ketosis, mastitis, displaced abomasum, metritis, hypocalcemia and livability), we found that 4 out of 16 modules were genetically (FDR < 0.05) associated with ketosis, among which three were correlated with postpartum ketosis based on WGCNA. We further identified five candidate genes for ketosis, including GRINA, MAF1, MAFA, C14H8orf82 and RECQL4. Our phenome-wide association analysis (Phe-WAS) demonstrated that human orthologues of these candidate genes were also significantly associated with many metabolic, endocrine, and immune traits in humans. For instance, MAFA, which is involved in insulin secretion, glucose response, and transcriptional regulation, showed a significantly higher association with metabolic and endocrine traits compared to other types of traits in humans.