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Semenkovich publishes research on how parent-of-origin effects shape metabolic traits

Clay F. Semenkovich, MD

In March, Clay F. Semenkovich, MD and colleagues had their work titled “Parent-of-origin effects propagate through networks to shape metabolic traits,” published in “eLife.” 

Parent-of-origin effects (POE) are a class of genetic effects transmitted from parents to their offspring and are “unexpectedly common in complex traits, including metabolic and neurological traits.” Environmental factors can modify POE, but “the architecture of these gene-by-environmental effects on phenotypes remains to be unraveled.” 

When analyzing pre-existing data, Dr. Semenkovich and collaborators speculated that additional mechanisms are needed to explain the POE phenomena. To identify the gene networks that cause POE propagation, they leveraged orthogonal evidence by using multiple populations and incorporated genetic, genomic and physiological data.  

They found “a network comprised of 3 imprinted and 6 non-imprinted genes that show POE,” which “forms a nutritional responsive pathway and the genes comprising it jointly serve cellular functions associated with growth.” Single-cell RNAseq also revealed that “Nnat expression increases and F2r expression decreases in preadipocytes along an adipogenic trajectory.” They concluded that these results exhibited consistency with their observations in bulk white adipose tissue. 

Parent-of-origin effects propagate through networks to shape metabolic traits