1Departments of Anthropology and Biology, Pennsylvania State University, 2Department of Human Genetics, McGill University, 3Centre de Recherche CHU Sainte-Justine, Université de Montréal, 4Department of Medicine, University of Chicago
March 28, 2019 2:30, CC Room 26 C
Body size is a fundamental aspect of biology and health. A considerable portion of the inter- and intra-population variation in human body size and stature is attributable to genetic factors. However, despite recent gains in understanding the genetic underpinnings of this important component of health, the proximate mechanisms that lead to variation in body size are largely unknown. We explored gene expression responses to growth factors in cell lines from individuals from two different populations: Batwa rainforest hunter-gatherers from Southwest Uganda with the "pygmy" phenotype (mean adult stature: males = 152.9 cm; females = 145.7) and their taller subsistence agriculturalist neighbors, the Bakiga (males = 165.4 cm; females = 155.1). Based on our previous work, the inter-population height difference is at least partly genetically mediated. In the present study, we exposed immortalized lymphoblastoid cells (LCLs) to growth hormone (GH) and insulin-like growth factor-1 (IGF1) and then used RNA-seq to characterize the transcriptome-wide gene expression response at 0, 2, and 6 hours post initial exposure. We also developed and implemented the use of a synthetic antisense oligonucleotide to silence the GH gene and halt endogenous GH production, allowing careful assessment of induced response to exogenous growth factor concentrations. We observe response expression differences in the GH/IGF1 pathway between the populations, with the Batwa having, for example, reduced expression of SOCS2, a gene that interacts with growth hormone receptor (GHR) and insulin-like growth factor-1 receptor (IGF1R).
Funding was provided by NIH R01-GM115656, F32 GM125228, and F32 GM123634.