A. Project Funded by National Science Foundation
Allelic Expression Dynamics During Development And Its Roles In Genotype-Phenotype Relationships
Muscle growth and development provide an excellent opportunity to study the dynamic regulation of gene expression and its interplay with metabolism. From proliferation to differentiation and maturation, muscle precursor cells progress through multiple critical metabolic states. By studying dynamic effects during these critical developmental stages, this project will identify alleles that play a key role in reprograming or acquiring specialized cellular metabolic state. We will then examine the precise roles of a subset of these alleles using primary muscle cell cultures from multiple species and a muscle cell line to validate interspecies generalizability of results. The project takes the advantage of recent progresses in genomics and uses cutting-edge techniques in bio-imaging, metabolomics, and single-cell spatial transcriptomics to advance our understanding of developmental mechanisms. We will use the chicken (Gallus gallus) as an outstanding system for developmental biology. Due to in ovo (egg) embryonic development, extensive genetic diversity among domestic breeds, and availability of high-quality genomic resources, the chicken is an excellent system for developmental biology and investigating the genetic basis of complex traits.
B. Project Funded by USDA-NIFA
Genetic Basis of Muscle Diseases in Modern Broiler Chickens
Another focus area of our research group is identifying genes causing muscle diseases in modern broiler chickens. One of these disorders is Wooden Breast (WB), characterized by extreme hardness of the breast muscle, which causes a substantial economic issue for poultry producers on a global scale. Since affected meat is not fit to be used for human consummation, addressing WB will benefit the economy and positively impact the environment through saving natural resources and energy that go into the production. We are looking for ways to prevent this muscle condition by identification of morphological changes and molecular mechanisms associated with the onset and development of WB. Our research on WB has been supported by Agriculture and Food Research Initiative competitive grants (Award no. 2016-67015-25027 and 2021-67015-34543) from the U.S. Department of Agriculture.
Progression of phlebitis in the p. major muscle of broilers (Papah et al., 2017). Our study revealed that the earliest microscopic lesions observed in the p. major muscles were associated with vascular perturbations.
Our genome-wide association study identified numerous QTL for WB and WS in an 8.3-Mb region on chicken chromosome 5 where there is highly conserved synteny between the chicken chromosome 5 and human chromosome 11 (despite over 300 million years since the great radiation of birds). This wooden breast QTL-rich region of chicken chromosome 5 (GGA5) has highly conserved synteny with human chromosome 11 (HSA11), especially compared to homologous regions in the mouse genome on chromosomes 2 (MMU2) and 7 (MMU7). In humans, this area is associated with a high number of growth and metabolic disorders, which are highlighted here based on existing knowledge of wooden breast and white striping, including a hypothesis suggesting dysregulation of lipid and glucose metabolism as an important underlying factor in development of the myopathies. The scatter plot on GGA5 represents GWAS results from the present study with significant SNPs in red. Red bands on GGA5 indicate previously identified selective sweeps in commercial purebred broiler lines that are susceptible to wooden breast with overlapping selective sweep regions in dark red. The centromere (pink) and G-banding (grey and white) are shown on HSA11 to improve visualization. Defic: deficiency, ID: insulin-dependent, NID: non-insulin-dependent, PN: permanent neonatal, TN: transient neonatal. (Lake et al., 2021)