Selected Grantee Publications
- Clear All
- 5 results found
- ncats
- nhgri
- Pediatrics
Identifying Potential Dietary Treatments for Inherited Metabolic Disorders Using Drosophila Nutrigenomics
Martelli et al., Cell Reports. 2024.
https://www.sciencedirect.com/science/article/pii/S221112472400189X?via%3Dihub=
Inherited metabolic disorders are known to cause severe neurological impairment and child mortality and can sometimes respond to dietary treatment; however, a suitable paradigm for testing diets is lacking for developing effective dietary treatment. In this study, researchers found that 26 of 35 Drosophila amino acid disorder models screened for disease–diet interactions displayed diet-altered development and/or survival. Among these models, researchers showed that dietary cysteine depletion normalizes metabolic profile and rescues development, neurophysiology, behavior, and life span in a model for isolated sulfite oxidase deficiency. These findings demonstrate the value of using Drosophila in studying diet-sensitive metabolic disorders and developing potential dietary therapies. Supported by ORIP (R24OD031447) and NHGRI.
Effects of Acute Femoral Head Ischemia on the Growth Plate and Metaphysis in a Piglet Model of Legg-Calvé-Perthes Disease
Armstrong et al., Osteoarthritis and Cartilage. 2023.
https://pubmed.ncbi.nlm.nih.gov/36696941/
Legg-Calvé-Perthes disease (LCPD) can lead to permanent deformity of the femoral head and premature osteoarthritis, but the underlying cause remains unknown. More work is needed to determine optimal treatment methods for LCPD. Using a piglet model for LCPD, researchers assessed the effects of acute femoral head ischemia on the proximal femoral growth plate and metaphysis. They reported that alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. These findings suggest that growth disruption may occur sooner after the onset of ischemia than researchers had hypothesized previously. Supported by ORIP (T32OD010993, K01OD021293), NIAMS, and NCATS.
A Novel DPH5-Related Diphthamide-Deficiency Syndrome Causing Embryonic Lethality or Profound Neurodevelopmental Disorder
Shankar et al., Genetics in Medicine. 2022.
https://www.doi.org/10.1016/j.gim.2022.03.014
Neurodevelopmental disorders (NDDs) affect more than 3% of the pediatric population and often have associated neurologic or multisystem involvement. The underlying genetic etiology of NDDs remains unknown in many individuals. Investigators characterized the molecular basis of NDDs in children of both sexes with nonverbal NDDs from three unrelated families with distinct overlapping craniofacial features. The investigators also used a mouse model of both sexes to determine the pathogenicity of variants of uncertain significance, as well as genes of uncertain significance, to advance translational genomics and provide precision health care. They identified several variants in DPH5 as a potential cause of profound NDD. Their findings provide strong clinical, biochemical, and functional evidence for DPH5 variants as a novel cause of embryonic lethality or profound NDD with multisystem involvement. Based on these findings, the authors propose that “DPH5-related diphthamide deficiency syndrome” is a novel autosomal-recessive Mendelian disorder. Supported by ORIP (K01OD026608, U42OD012210) and NHGRI.
The Early Life Microbiota Mediates Maternal Effects on Offspring Growth in a Nonhuman Primate
Petrullo et al., iScience. 2022.
https://www.doi.org/10.1016/j.isci.2022.103948
Mammalian mothers influence offspring development by providing nutrients and other bioactive compounds through the placenta or milk. A relatively unexplored mechanism for maternal effects is vertical transmission of bacteria through milk to the infant gut. Infants that receive more glycan-utilizing bacteria from milk might better exploit oligosaccharides, which could improve nutrition and accelerate growth. Researchers found that first-time vervet mothers harbored a milk bacterial community that was less diverse due to the dominance of Bacteroides fragilis, a glycan-utilizing bacteria. These low-parity females had infants that grew faster, suggesting that vertical transmission of bacteria via milk can mediate maternal effects on growth. These results indicate non-nutritive milk constituents play important roles in development. Commercial milk formula might need to be improved or supplemented to better support infant health. Supported by ORIP (P40OD010965) and NCATS.
Heritability of Social Behavioral Phenotypes and Preliminary Associations with Autism Spectrum Disorder Risk Genes in Rhesus Macaques: A Whole Exome Sequencing Study
Gunter et al., Autism Research. 2022.
https://onlinelibrary.wiley.com/doi/full/10.1002/aur.2675
Investigators quantified individual variation in social interactions among juvenile rhesus macaques of both sexes using both a standard macaque ethogram (a catalogue of animal behavior over time) and a macaque-relevant modification of the human Social Responsiveness Scale to study genetic influences on key aspects of social behavior and interactions. The analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with quantitative genetic effects similar to autism spectrum disorder (ASD) in human children. The significant genetic and sequencing data may be used to examine potential genetic associations with human ASD. Supported by ORIP (P51OD011132), NHGRI and NIMH.