Decreasing sequencing costs have driven a rapid expansion of novel genotyping methods. One of these methods is the exploitation of restriction enzyme cut sites to generate genome-wide but reduced representation sequencing libraries (RRLs), alternatively termed genotyping by sequencing or restriction-site associated DNA sequencing. Without a reference genome, the resulting short sequence reads must be assembled de novo.
View Article and Find Full Text PDFAlthough human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice.
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