Project description:Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduces the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals were still colonized (non-responders). To understand the underlying mechanism, we conducted 3 larger scale vaccination and challenge studies using 135 broiler birds and found a similar responder/non responder effect. The submitted data were used for a genome-wide association study of the chicken responses to glycoconjugate vaccination against Campylobacter jejuni.
Project description:Beak deformities (BD) of different forms have been documented in many wild birds. The phenomenon is termed as “the largest epizootic of gross abnormalities ever recorded among wild bird populations.” Frequencies of 1% to 3% of BD (crossed beaks) were found in several indigenous chickens including Silkies, Qingyuan Partridge, Huxu, and the Beijing-You (BJY) chickens (studied here). Birds with deformed beaks have poor production performance and induce higher mortality. Therefore, BD represents an economic as well as a welfare problem. Our lab have focused and performed studies on this complex trait/disease for 7 years. Therefore, we performed a single SNP, a pathways-based genome-wide association study (GWAS), and a genome-wide CNV detection with the genotype data of 48 BD (case) and 48 normal (control) birds from Affymetrix 600K HD genotyping arrays, using ROADTRIPS, SNP ratio test (SRT) and PennCNV, respectively. To the best of our knowledge, this is the first GWAS and CNV study to investigate the mutations and genomic structural variations in the deformed and normal beaks of chickens. The findings herein are worth of further functional characterization for better understanding the genetic mechanisms of BD in chickens and wild birds as well.
Project description:Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ). The differentiation of avian sex chromosomes from ancestral autosomes entailed the loss of most genes from the W chromosome during evolution. However, to what extent mechanisms evolved that counterbalance the consequences of this extensive gene dosage reduction in female birds has remained unclear. Here we report functional in vivo and evolutionary analyses of a Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression that was previously proposed to play a key role in sex chromosome dosage compensation1. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality of homozygous knockout males, likely due to the highly specific upregulation of dosage-sensitive Z-linked target genes of miR-2954. Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution. Altogether, our work unveils a scenario where evolutionary pressures on females following W gene loss led to the evolution of transcriptional upregulation of dosage-sensitive genes on the Z not only in female but also in male birds. The resulting overabundance of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. Our findings demonstrate that birds have evolved a unique sex chromosome dosage compensation system in which a microRNA has become essential for male survival.
Project description:Sex-chromosome dosage represents a challenge for heterogametic species to maintain correct proportion of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance of X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZW/ZZ system) have been found to lack efficient compensation at RNA level, challenging the necessity of resolving major gene-dosage discrepancies in avian cells. Through allele-resolved multiome analyses, we comprehensively examined dosage compensation in female (ZW), male (ZZ), and rare intersex (ZZW) chicken. Remarkably, this revealed that females exhibit upregulation of their single Z through increased transcriptional burst frequency similar to mammalian X-upregulation, and that Z-protein levels are further balanced via enhanced translation efficiency in females. Global analyses of transcriptional kinetics elements in birds demonstrate remarkable conservation of the genomic encoding of burst kinetics between mammals and birds. Our study uncovers new mechanisms for achieving sex-chromosome dosage compensation and highlights the importance of gene-dosage balance across diverse species.
Project description:Sex-chromosome dosage represents a challenge for heterogametic species to maintain correct proportion of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance of X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZZ/ZW system) have been found to lack full compensation at RNA level, challenging the necessity of resolving major gene-dosage discrepancies in avian cells. Through allele-resolved multiome analyses, we comprehensively examined dosage compensation in female (ZW), male (ZZ), and rare intersex (ZZW) chicken. Remarkably, this revealed that females exhibit upregulation of their single Z through increased transcriptional burst frequency, similar to mammalian X-upregulation, and that Z-protein levels are balanced via enhanced translation efficiency in females. Global analyses of transcriptional kinetics elements in birds demonstrates a remarkable conservation of the genomic encoding of burst kinetics between mammals and birds. Our study uncovers new mechanisms for achieving sex-chromosome dosage compensation and highlights the importance of gene-dosage balance across diverse species.