Corticotropin releasing hormone (CRH) is a robust human biomarker in maternal serum that predicts risk for preterm birth, but understanding its regulation has proven challenging because it is only made in the placenta, the source of the maternal serum CRH, in anthropoid primates. This study utilized comparative genomic analysis to demonstrate a retroviral long terminal repeat initiated human placental CRH expression, and that mice expressing CRH in the placental manifest an alteration in birth timing.
Wu, G; Ruben, MD; Schmidt, RE; Francey, LJ; Smith, DF; Anafi, RC; Hughey, JJ; Tasseff, R; Sherrill, JD; Oblong, JE; Mills, KJ; Hogenesch, JB. Population-level rhythms in human skin with implications for circadian medicine. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115(48):12313-12318.
Population-level rhythms: This study investigated the role of the circadian clock in the transcriptional regulation of epidermis in which a limited set of human subjects were sampled throughout the 24-h cycle and a larger population were sampled once. It found a robust circadian oscillator in human epidermis at the population level using pairwise correlations of clock and clock-associated genes. Overall, this work reveals rhythms in human epidermis that persist at the population scale and describe a path to develop robust single-sample circadian biomarkers.
Whole genome SNP genotyping data from 694 Idiopathic Pulmonary Arterial Hypertension (PAH) patients of European descent enrolled in the PAH Biobank housed here at Cincinnati Children's Hospital Medical Center were used in a genome wide association (GWAS) study that included two discovery cohorts of PAH patients from three European and one US (PAH Biobank) cohort. This international collaboration included the largest number of PAH patients ever analyzed. Analysis of each discovery cohort independently identified two regions of association: in an enhancer near the SOX17 locus and in the HLA locus at HLA-DPA1/DPB1. This is the first report that common genetic variation can drive significant clinical differences in presentation and outcomes for PAH.
Luo, S; Valencia, CA; Zhang, J; Lee, NC; Slone, J; Gui, B; Wang, X; Li, Z; Dell, S; Brown, J; Chen, SM; Chien, YH; Hwu, WL; Fan, PC; Wong, LJ; Atwal, PS; Huang, T. Biparental inheritance of mitochondrial DNA in humans. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115(51):13039-13044.
This study challenged and refuted the notion that the mitochondrial genome is only transmitted through the maternal genome. The experiments convincingly demonstrated families with biparental inheritance of the mitochondrial genome in some individuals. This finding has widespread relevance to interpretation of population evolution and disease pathogenesis.
Many proteins undergo attachment to cell membranes through GPI linkage, a glycosylation event. Lukacs et al. generated mice with genetic variants that blocked created mouse models with genetic GPI anchors from forming appropriately, and investigated the developmental consequences. They found that loss of GPI anchors early in embryonic development causes the cells that produce the face to die, resulting in cleft palate, and other abnormalities.
