Christina A. Scherer

Association of the FTO gene with BMI.

Variants in the FTO gene have been strongly associated with obesity in a very large sample (38,759) of diabetic and control subjects. To replicate these findings, the previously reported SNP in the FTO gene (rs9939609, T/A) was genotyped in 5,607 subjects from five different Utah studies. The studies included a random sample of the Utah population, families selected for aggregation of extreme thinness, families selected for severe obesity, a series of unrelated severe obesity subjects, and families participating in a 25‐year longitudinal study of cardiovascular disease and aging. Results show a strong significant increase in the rs9939609 A allele frequency with increasing BMI (P < 0.0001). In the longitudinal study, FTO genotypes were significantly associated with BMI at a baseline exam, a 2½‐year follow‐up exam and a 25‐year follow‐up exam using an additive genetic model. The mean genotype difference in BMI ranged from 1.3 to 2.1 kg/m2 across exams. The genotype difference in BMI means was established in youth, and at‐risk subjects under age 20 at baseline had a significantly larger 25‐year BMI increase (10.0 for A/A; 9.7 for A/T, and 8.5 kg/m2 for T/T, P = 0.05). We conclude that the BMI increases associated with FTO genotypes begin in youth and are maintained throughout adulthood.

Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.

Extracellular 2′-5′ Oligoadenylate Synthetase Stimulates RNase L-Independent Antiviral Activity: a Novel Mechanism of Virus-Induced Innate Immunity

ABSTRACT The 2′-5′ oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins. However, several studies demonstrate a correlation between the concentration of freely circulating OAS protein in sera from hepatitis C patients and their clinical prognosis. Here we demonstrate that extracellular OAS1 enters into cells and possesses a strong antiviral activity, both in vitro and in vivo, which is independent of RNase L. The OAS protein directly inhibits viral proliferation and does not require the activation of known antiviral signaling pathways. We propose that OAS produced by cells infected with viruses is released to the extracellular space, where it acts as a paracrine antiviral agent. Thus, the OAS protein represents the first direct antiviral compound released by virus-infected cells.