Chromosomal mapping and candidate gene discovery of chicken developmental mutants and genome-wide variation analysis of MHC congenics.

The chicken has been widely used in experimental research given its importance to agriculture and its utility as a model for vertebrate biology and biomedical pursuits for over 100 years. Herein we used advanced technologies to investigate the genomic characteristics of specialized chicken congenic genetic resources developed on a highly inbred background. An Illumina 3K chicken single nucleotide polymorphism (SNP) array was utilized to study variation within and among major histocompatibility complex (MHC)-congenic lines as well as investigate line-specific genomic diversity, inbreeding coefficients, and MHC B haplotype-specific GGA 16 SNP profiles. We also investigated developmental mutant-congenic lines to map a number of single-gene mutations using both the Illumina 3K array and a recently developed Illumina 60K chicken SNP array. In addition to identifying the chromosomes and specific subregions, the mapping results affirmed prior analyses indicating recessive or dominant and autosomal or sex chromosome modes of inheritance. Priority candidate genes are described for each mutation based on association with similar phenotypes in other vertebrates. These single-gene mutations provide a means of studying amniote development and in particular serve as invaluable biomedical models for similar malformations found in human.

Case study of sequence capture enrichment technology: identification of variation underpinning developmental syndromes in an amniote model.

Chicken developmental mutants are valuable for discovering sequences and pathways controlling amniote development. Herein we applied the advanced technologies of targeted sequence genomic capture enrichment and next-generation sequencing to discover the causative element for three inherited mutations affecting craniofacial, limb and/or organ development. Since the mutations (coloboma, diplopodia-1 and wingless-2) were bred into a congenic line series and previously mapped to different chromosomes, each targeted mutant causative region could be compared to that of the other two congenic partners, thereby providing internal controls on a single array. Of the ~73 million 50-bp sequence reads, ~76% were specific to the enriched targeted regions with an average target coverage of 132-fold. Analysis of the three targeted regions (2.06 Mb combined) identified line-specific single nucleotide polymorphism (SNPs) and micro (1-3 nt) indels. Sequence content for regions indicated as gaps in the reference genome was generated, thus contributing to its refinement. Additionally, Mauve alignments were constructed and indicated putative chromosomal rearrangements. This is the first report of targeted capture array technology in an avian species, the chicken, an important vertebrate model; the work highlights the utility of employing advanced technologies in an organism with only a "draft stage" reference genome sequence.

Telomere biology of the chicken: a model for aging research.

Division-dependent telomere shortening correlating with age triggers senescence on a cellular level and telomere dysfunction can facilitate oncogenesis. Therefore, the study of telomere biology is critical to the understanding of aging and cancer. The domestic chicken, a classic model for the study of developmental biology, possesses a telomere genome with highly conserved aspects and distinctive features which make it uniquely suited for the study of telomere maintenance mechanisms, their function and dysfunction. The purpose of this review is to highlight the chicken as a model for aging research, specifically as a model for telomere and telomerase research, and to increase its utility as such by describing developments in the study of chicken telomeres and telomerase in the context of related research in human and mouse.