Incomplete-penetrant hypertrophic cardiomyopathy MYH7 G256E mutation causes hypercontractility and elevated mitochondrial respiration.

Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the ß-myosin heavy chain (MYH7) can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant MYH7 G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions. We developed a collaborative pipeline to characterize myosin function across protein, myofibril, cell, and tissue levels to determine the multiscale effects on structure-function of the contractile apparatus and its implications for gene regulation and metabolic state. The G256E mutation disrupts the transducer region of the S1 head and reduces the fraction of myosin in the folded-back state by 33%, resulting in more myosin heads available for contraction. Myofibrils from gene-edited MYH7WT/G256E human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibited greater and faster tension development. This hypercontractile phenotype persisted in single-cell hiPSC-CMs and engineered heart tissues. We demonstrated consistent hypercontractile myosin function as a primary consequence of the MYH7 G256E mutation across scales, highlighting the pathogenicity of this gene variant. Single-cell transcriptomic and metabolic profiling demonstrated upregulated mitochondrial genes and increased mitochondrial respiration, indicating early bioenergetic alterations. This work highlights the benefit of our multiscale platform to systematically evaluate the pathogenicity of gene variants at the protein and contractile organelle level and their early consequences on cellular and tissue function. We believe this platform can help elucidate the genotype-phenotype relationships underlying other genetic cardiovascular diseases.

Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation.

The salt-inducible kinases (SIK) 1-3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing has limited the study of the optimal SIK isoform selectivity profile for suppressing inflammation in vivo. To overcome this challenge, we devised a structure-based design strategy for developing potent SIK inhibitors that are highly selective against other kinases by engaging two differentiating features of the SIK catalytic site. This effort resulted in SIK1/2-selective probes that inhibit key intracellular proximal signaling events including reducing phosphorylation of the SIK substrate cAMP response element binding protein (CREB) regulated transcription coactivator 3 (CRTC3) as detected with an internally generated phospho-Ser329-CRTC3-specific antibody. These inhibitors also suppress production of pro-inflammatory cytokines while inducing anti-inflammatory interleukin-10 in activated human and murine myeloid cells and in mice following a lipopolysaccharide challenge. Oral dosing of these compounds ameliorates disease in a murine colitis model. These findings define an approach to generate highly selective SIK1/2 inhibitors and establish that targeting these isoforms may be a useful strategy to suppress pathological inflammation.

A new chromosome-scale duck genome shows a major histocompatibility complex with several expanded multigene families.

BACKGROUND: The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck's adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC). RESULTS: We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIß, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model. CONCLUSIONS: These observations supported the hypothesis that duck's adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.

nf-core/isoseq: simple gene and isoform annotation with PacBio Iso-Seq long-read sequencing.

MOTIVATION: Iso-Seq RNA long-read sequencing enables the identification of full-length transcripts and isoforms, removing the need for complex analysis such as transcriptome assembly. However, the raw sequencing data need to be processed in a series of steps before annotation is complete. Here, we present nf-core/isoseq, a pipeline for automatic read processing and genome annotation. Following nf-core guidelines, the pipeline has few dependencies and can be run on any of platforms. AVAILABILITY AND IMPLEMENTATION: The pipeline is freely available online on the nf-core website (https://nf-co.re/isoseq) and on GitHub (https://github.com/nf-core/isoseq) under MIT License (DOI: 10.5281/zenodo.7116979).

Selection on the promoter regions plays an important role in complex traits during duck domestication.

BACKGROUND: Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood. RESULTS: We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment. CONCLUSIONS: This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.

Identification of alternative splicing events related to fatty liver formation in duck using full-length transcripts.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of most common diseases in the world. Recently, alternative splicing (AS) has been reported to play a key role in NAFLD processes in mammals. Ducks can quickly form fatty liver similar to human NAFLD after overfeeding and restore to normal liver in a short time, suggesting that ducks are an excellent model to unravel molecular mechanisms of lipid metabolism for NAFLD. However, how alternative splicing events (ASEs) affect the fatty liver process in ducks is still unclear. RESULTS: Here we identify 126,277 unique transcripts in liver tissue from an overfed duck (77,237 total transcripts) and its sibling control (69,618 total transcripts). We combined these full-length transcripts with Illumina RNA-seq data from five pairs of overfed ducks and control individuals. Full-length transcript sequencing provided us with structural information of transcripts and Illumina RNA-seq data reveals the expressional profile of each transcript. We found, among these unique transcripts, 30,618 were lncRNAs and 1,744 transcripts including 155 lncRNAs and 1,589 coding transcripts showed significantly differential expression in liver tissues between overfed ducks and control individuals. We also detected 27,317 ASEs and 142 of them showed significant relative abundance changes in ducks under different feeding conditions. Full-length transcript profiles together with Illumina RNA-seq data demonstrated that 10 genes involving in lipid metabolism had ASEs with significantly differential abundance in normally fed (control) and overfed ducks. Among these genes, protein products of five genes (CYP4F22, BTN, GSTA2, ADH5, and DHRS2 genes) were changed by ASEs. CONCLUSIONS: This study presents an example of how to identify ASEs related to important biological processes, such as fatty liver formation, using full-length transcripts alongside Illumina RNA-seq data. Based on these data, we screened out ASEs of lipid-metabolism related genes which might respond to overfeeding. Our future ability to explore the function of genes showing AS differences between overfed ducks and their sibling controls, using genetic manipulations and co-evolutionary studies, will certainly extend our knowledge of genes related to the non-pathogenic fatty liver process.

Psychopathology in adults with copy number variants.

BACKGROUND: Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood. METHODS: We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18-76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology. RESULTS: The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32-16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3-36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases. CONCLUSIONS: Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.

Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth.

The clinical benefits of pan-mTOR active-site inhibitors are limited by toxicity and relief of feedback inhibition of receptor expression. To address these limitations, we designed a series of compounds that selectively inhibit mTORC1 and not mTORC2. These 'bi-steric inhibitors' comprise a rapamycin-like core moiety covalently linked to an mTOR active-site inhibitor. Structural modification of these components modulated their affinities for their binding sites on mTOR and the selectivity of the bi-steric compound. mTORC1-selective compounds potently inhibited 4EBP1 phosphorylation and caused regressions of breast cancer xenografts. Inhibition of 4EBP1 phosphorylation was sufficient to block cancer cell growth and was necessary for maximal antitumor activity. At mTORC1-selective doses, these compounds do not alter glucose tolerance, nor do they relieve AKT-dependent feedback inhibition of HER3. Thus, in preclinical models, selective inhibitors of mTORC1 potently inhibit tumor growth while causing less toxicity and receptor reactivation as compared to pan-mTOR inhibitors.

RNAseq reveals modulation of genes involved in fatty acid biosynthesis in chicken liver according to genetic background, sex, and diet.

Increases in chicken production are mainly due to specialised breeds. However, local breeds are of increasing importance, known for ability to adapt to the environment and unique products. Conventional poultry products contain lower levels of n-3 fatty acids (FAs) compared to those obtained from local breeds, therefore the aim of this study was to evaluate the modulation of expression of genes involved in long-chain polyunsaturated FA (PUFA) biosynthesis pathways according to genetic background, diet conditions, and sex. Animals from two local breeds and a commercial line were fed different diets: control and experimental diet (10% linseed supplementation). For each breed and diet group, both sexes were reared. The RNA was extracted from 36 liver samples and sequenced by RNAseq method. Bioinformatic analysis was carried out to find differentially expressed genes from comparisons between experimental groups. Results showed low impact of diet on differentially expressed genes related to FA biosynthesis, but linseed diet increased percentage of n-3 FAs of liver. Sex and genetic background determined the differential expression of genes related to long-chain PUFA biosynthesis. Specifically, females of local breeds shared 23 up-regulated genes when compared to their respective commercial line groups. Some of the shared genes had a role in de novo triglyceride biosynthesis (MTTPL and GPAM), and in de novo FA biosynthesis (ACACA and SCD) was detected. In conclusion, local breeds are able to better adapt to a diet rich in PUFA, by triggering certain transcriptomic shifts in the liver that allow birds to process the high PUFA content provided by diet.

The roles of school racial climate and science, technology, engineering, and mathematics classroom climate in adolescents' gender and racial peer inclusion and attribution decisions.

Adolescents use social identities and reasoning to make peer inclusion and attribution decisions. School climate plays a role in these decisions. Thus, this study analyzed how school racial climate and STEM (science, technology, engineering, and math) classroom climate were associated with the choices of adolescents (N = 294; Mage = 15.72 years; 52.3 % female; 36.7 % White/European American, 32.9 % Black/African American, 11.2 % Latino/Hispanic [the most common racial/ethnic groups in the schools where data collection took place]) in two tasks: peer inclusion and attribution of ability. On the peer inclusion task, participants were more likely to choose a non-White peer for a STEM activity if they had lower perceptions of stereotyping at school, and they were more likely to choose a female peer if they were female. Participants were more likely to use reasoning based on personal characteristics when choosing a peer, but female participants who chose a female peer were more likely to use reasoning based on gender. On the attribution task, participants were more likely to choose a non-White peer if they perceived greater STEM connectedness, and they were more likely to choose a White or male peer if they had more positive relationships with their STEM teachers. Therefore, students' perceptions of school racial climate relate to adolescents' peer inclusion decisions, and their perceptions of STEM classroom climate relate to adolescents' ability attributions. Schools may need to focus on creating welcoming school and classroom environments as a way to promote equity in STEM.

Integrated Environmental and Genomic Analysis Reveals the Drivers of Local Adaptation in African Indigenous Chickens.

Breeding for climate resilience is currently an important goal for sustainable livestock production. Local adaptations exhibited by indigenous livestock allow investigating the genetic control of this resilience. Ecological niche modeling (ENM) provides a powerful avenue to identify the main environmental drivers of selection. Here, we applied an integrative approach combining ENM with genome-wide selection signature analyses (XPEHH and Fst) and genotype-environment association (redundancy analysis), with the aim of identifying the genomic signatures of adaptation in African village chickens. By dissecting 34 agro-climatic variables from the ecosystems of 25 Ethiopian village chicken populations, ENM identified six key drivers of environmental challenges: One temperature variable-strongly correlated with elevation, three precipitation variables as proxies for water availability, and two soil/land cover variables as proxies of food availability for foraging chickens. Genome analyses based on whole-genome sequencing (n = 245), identified a few strongly supported genomic regions under selection for environmental challenges related to altitude, temperature, water scarcity, and food availability. These regions harbor several gene clusters including regulatory genes, suggesting a predominantly oligogenic control of environmental adaptation. Few candidate genes detected in relation to heat-stress, indicates likely epigenetic regulation of thermo-tolerance for a domestic species originating from a tropical Asian wild ancestor. These results provide possible explanations for the rapid past adaptation of chickens to diverse African agro-ecologies, while also representing new landmarks for sustainable breeding improvement for climate resilience. We show that the pre-identification of key environmental drivers, followed by genomic investigation, provides a powerful new approach for elucidating adaptation in domestic animals.

Genetic variation in chicken interferon signalling pathway genes in research lines showing differential viral resistance.

Avian viruses of economic interest are a significant burden on the poultry industry, affecting production traits and resulting in mortality. Furthermore, the zoonosis of avian viruses risks pandemics developing in humans. Vaccination is the most common method of controlling viruses; however current vaccines often lack cross-protection against multiple strains of each virus. The mutagenicity of these viruses has also led to virulent strains emerging that can overcome the protection offered by vaccines. Breeding chickens with a more robust innate immune response may help in tackling current and emerging viruses. Understanding the genetic evolution of different lines will thus provide a useful tool in helping the host in the fight against pathogens. This study focuses on the interferon genes and their receptors in different chicken lines that are known to be more resistant or susceptible to particular avian viruses. Comparing genotypic differences in these core immune genes between the chicken lines may explain the phenotypic differences observed and aid the identification of causative variations. The relative resistance/susceptibility of each line to viruses of interest (Marek's disease virus, infectious bursal disease, infectious bronchitis virus and avian influenza virus) has previously been determined. Here we identify single nucleotide polymorphisms in interferons and downstream genes. Functional prediction tools were used to identify variants that may be affecting protein structure, mRNA secondary structure or transcription factor and micro-RNA binding sites. These variants were then considered in the context of the research lines and their distribution between phenotypes. We highlight 60 variants of interest in the interferon pathway genes that may account for susceptibility/resistance to viral pathogens.

Reviving rare chicken breeds using genetically engineered sterility in surrogate host birds.

In macrolecithal species, cryopreservation of the oocyte and zygote is not possible due to the large size and quantity of lipid deposited within the egg. For birds, this signifies that cryopreserving and regenerating a species from frozen cellular material are currently technically unfeasible. Diploid primordial germ cells (PGCs) are a potential means to freeze down the entire genome and reconstitute an avian species from frozen material. Here, we examine the use of genetically engineered (GE) sterile female layer chicken as surrogate hosts for the transplantation of cryopreserved avian PGCs from rare heritage breeds of chicken. We first amplified PGC numbers in culture before cryopreservation and subsequent transplantation into host GE embryos. We found that all hatched offspring from the chimera GE hens were derived from the donor rare heritage breed broiler PGCs, and using cryopreserved semen, we were able to produce pure offspring. Measurement of the mutation rate of PGCs in culture revealed that 2.7 × 10-10 de novo single-nucleotide variants (SNVs) were generated per cell division, which is comparable with other stem cell lineages. We also found that endogenous avian leukosis virus (ALV) retroviral insertions were not mobilized during in vitro propagation. Taken together, these results show that mutation rates are no higher than normal stem cells, essential if we are to conserve avian breeds. Thus, GE sterile avian surrogate hosts provide a viable platform to conserve and regenerate avian species using cryopreserved PGCs.

Following the Trace of HVS II Mitochondrial Region Within the Nine Iranian Ethnic Groups Based on Genetic Population Analysis.

The Iranian gene pool is seen as an important human genetic resource for investigating the region connecting Mesopotamia and the Iranian plateau. The main objective of this study was to explore gene flow in nine Iranian ethnic/subpopulation groups (402 samples) by examining mtDNA HVS2 sequence variations. This then allowed us to detect mtDNA HVS2 sequence mutations in two independent thalassemia and cystic fibrosis patient sample groups. The patient groups did not explicitly belong to any of the aforementioned nine subpopulations. Across all subpopulations, the haplogroups B4a1c3a, H2a2a1, N10b, H2a2a2, and J1 were seen to be predominant. High haplogroup diversities along with admixture of the exotic groups were observed in this study. The Arab subpopulation was shown to be independent from the others. It was revealed that there is a far distant relationship between Arab and Azeri groups. The thalassemia patient group, represented an almost random sample of most Iranian ethnic groups, and revealed few significant differences (P < 0.05) in their HVS2 sequence. It turned out that the IVS II-I (G → A) mutation in the thalassemia ß-globin gene was highly significant. Since the thalassemia patients in the present study represent many unique haplotypes, we can begin to comprehend the importance of mtDNA with this disease and the necessity for more studies in this context.

Mississippi INBRE Outreach Scholars program: adapting a summer scholars program to the virtual world amidst the COVID-19 pandemic.

The Mississippi IDeA Networks of Biomedical Research Excellence (INBRE) supported by the National Institute of General Medical Sciences (Grant P20GM103476) launched the new Mississippi INBRE Outreach Scholars (MIOS) summer research program in 2019. The program was designed to offer students community outreach and research experiences related to the study of behavioral and health disparities life sciences. The program was adapted in early 2020 to offer the program in a fully online format in the summer of 2020. This article details the program adaptations and discusses program evaluation data related to scholars' perceptions of program benefits and expectations and their confidence in research-related skills. The program evaluation was a mixed-method approach that included a qualitative postprogram survey and a pre-post quantitative survey. Scholars identified technical and communication skill building and resilience as areas of personal growth. Overall, the program met scholars' expectations for the program and significantly improved their confidence on 8 of the 19 (with confidence interval estimated differences from 0.3 to 2.56, where a difference of 1 is an improvement across 1 anchor on a Likert-type scale) various research-related tasks/skills after completion of the program. The analyses presented demonstrated that a combined qualitative and quantitative analysis approach is useful for examining the extent to which programs such as Mississippi INBRE are meeting goals of providing a rich research experience in health disparities for a diverse student body. Future longitudinal data may be examined to explore the long-term impact of MIOS on career preparation and choices and graduate education.NEW & NOTEWORTHY The Mississippi INBRE Outreach Scholars program is a summer research program for Mississippi college students that was successfully adapted to a fully online environment amidst the coronavirus-19 pandemic.

A Dog with an Office: The Process of Embedding a Wellness Dog Intervention in a University Setting.

Universities are places to promote the wellbeing of people who learn, work, and live within them. This article reports on an innovative, holistic, and embedded wellness dog program that was developed by the Faculty of Nursing to support the wellbeing of students, faculty, and staff. The innovation included a collaborative partnership between two faculties (the faculties of Veterinary Medicine and Nursing), and the targeted purchase, training, and socialization of a wellness dog. Pet wellness programs have the potential to be an important mental health intervention on university campuses. While the program was postponed due to COVID-19, the purpose of this article is to share processes used to create the wellness dog program, with suggestions regarding implementation and evaluation.

Exploring Mental Health and Well-Being Among University Faculty Members: A Qualitative Study.

The current exploratory qualitative study describes how environmental factors, social interactions, personal experiences, and stigma affect mental health and help-seeking. In-depth, semi-structured interviews were conducted with nine university faculty members who self-identified as having mental illness-related concerns. Using Bronfenbrenner's ecological systems framework and thematic analysis, four domains were determined: (1) macrosystem (i.e., influences of academic culture); (2) mesosystem (i.e., influences of faculty leadership and interpersonal dynamics); (3) microsystem (i.e., influences of individual mental health experiences); and (4) exosystem (i.e., influences of stigma across structural, interpersonal, and intrapersonal levels). These domains included barriers to and facilitators of mental health and help-seeking. Findings suggest that competitiveness and individualism may perpetuate stereotypes that mental illnesses are inherent weaknesses, and that seeking help is a barrier to academic success. Recommendations for future research are provided. [Journal of Psychosocial Nursing and Mental Health Services, 60(11), 17-25.].

Transcriptomic analysis of caecal tissue in inbred chicken lines that exhibit heritable differences in resistance to Campylobacter jejuni.

BACKGROUND: Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans and the handling or consumption of contaminated poultry meat is a key source of infection. Selective breeding of poultry that exhibit elevated resistance to Campylobacter is an attractive control strategy. Here we studied the global transcriptional response of inbred chicken lines that differ in resistance to C. jejuni colonisation at a key site of bacterial persistence. RESULTS: Three-week-old chickens of line 61 and N were inoculated orally with C. jejuni strain M1 and caecal contents and tonsils were sampled at 1 and 5 days post-infection. Caecal colonisation was significantly lower in line 61 compared to line N at 1 day post-infection, but not 5 days post-infection. RNA-Seq analysis of caecal tonsils of both lines revealed a limited response to C. jejuni infection compared to age-matched uninfected controls. In line N at days 1 and 5 post-infection, just 8 and 3 differentially expressed genes (DEGs) were detected (fold-change > 2 and false-discovery rate of < 0.05) relative to uninfected controls, respectively. In the relatively resistant line 61, a broader response to C. jejuni was observed, with 69 DEGs relating to immune regulation, cell signalling and metabolism at 1 day post-infection. However, by day 5 post-infection, no DEGs were detected. By far, the greatest number of DEGs were between uninfected birds of the two lines implying that differential resistance to C. jejuni is intrinsic. Of these genes, several Major Histocompatibility Complex class I-related genes (MHCIA1, MHCBL2 and MHCIY) and antimicrobial peptides (MUC2, AvBD10 and GZMA) were expressed to a greater extent in line N. Two genes within quantitative trait loci associated with C. jejuni colonisation were also more highly expressed in line N (ASIC4 and BZFP2). Quantitative reverse-transcriptase PCR analysis of a subset of transcripts confirmed the RNA-Seq results. CONCLUSIONS: Our data indicate a limited transcriptional response in the caecal tonsils of inbred chickens to intestinal colonisation by Campylobacter but identify a large number of differentially transcribed genes between lines 61 and N that may underlie variation in heritable resistance to C. jejuni.

The wild species genome ancestry of domestic chickens.

BACKGROUND: Hybridisation and introgression play key roles in the evolutionary history of animal species. They are commonly observed within several orders in wild birds. The domestic chicken Gallus gallus domesticus is the most common livestock species. More than 65 billion chickens are raised annually to produce meat and 80 million metric tons of egg for global human consumption by the commercial sector. Unravelling the origin of its genetic diversity has major application for sustainable breeding improvement programmes. RESULTS: In this study, we report genome-wide analyses for signatures of introgression between indigenous domestic village chicken and the four wild Gallus species. We first assess the genome-wide phylogeny and divergence time across the genus Gallus. Genome-wide sequence divergence analysis supports a sister relationship between the Grey junglefowl G. sonneratii and Ceylon junglefowl G. lafayettii. Both species form a clade that is sister to the Red junglefowl G. gallus, with the Green junglefowl G. varius the most ancient lineage within the genus. We reveal extensive bidirectional introgression between the Grey junglefowl and the domestic chicken and to a much lesser extent with the Ceylon junglefowl. We identify a single case of Green junglefowl introgression. These introgressed regions include genes with biological functions related to development and immune system. CONCLUSIONS: Our study shows that while the Red junglefowl is the main ancestral species, introgressive hybridisation episodes have impacted the genome and contributed to the diversity of the domestic chicken, although likely at different levels across its geographic range.

The quail genome: insights into social behaviour, seasonal biology and infectious disease response.

BACKGROUND: The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. RESULTS: We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organisation, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated after H5N1 infection, and this may be key to the susceptibility of quail to H5N1. CONCLUSIONS: We have produced a high-quality genome of the quail which will facilitate further studies into diverse research questions using the quail as a model avian species.