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PLOS Papers on LDL Uptake, Chagas Disease Diversity, Mitochondrial Mutations in AMD

In PLOS Genetics, investigators from the University of Michigan present findings from a CRISPR gene editing-based screen for genetic factors influencing low-density lipoprotein (LDL) cholesterol uptake. Starting with a genome-wide CRISPR screen for contributors to LDL uptake in a liver-derived human hepatocellular carcinoma cell line grown under low or high lipoprotein conditions, the team focused in on a set of nearly 200 potential positive- or negative-regulators of LDL uptake for additional testing in a targeted, secondary gene editing strain. "While many molecules involved in LDL uptake have been characterized, we hypothesized that other currently unrecognized genetic interactions are also involved in this process," the authors write, noting that the screening strategies "confirm the role of genes previously known to participate in LDL uptake and also provide novel insight into the overall regulation of this process."

A team from the University of Georgia takes a look at genomic features in strains of Trypanosoma cruzi parasites behind Chagas disease for a paper in PLOS Pathogens. Using a long-read sequencing, Hi-C and Chicago proximity ligation methods, and other approaches, the researchers put together 45.5- to 47.2-million-base genome assemblies for the so-called Brazil A4 clone and the Y clone C6 strains believed to represent ancestral T. cruzi lineages, comparing the sequences to one another and to available T. cruzi genomes. Their analyses highlight the extent of genomic flexibility found in T. cruzi — from major gene family diversity to the amplification, recombination, and other events behind such diversification. "The process of diversification is so efficient that two isolates share not a single identical gene among the thousands of antigenic variants in their genomes," the authors write, "thus making the likelihood of generating protective vaccines low."

University of California, Irvine, researchers reporting in PLOS One explore the role of heteroplasmic mitochondrial DNA mutations in age-related macular degeneration (AMD). Based on deep mitochondrial genome sequencing on neural retinal, retinal pigment epithelial-choroid [RPE+choroid], and blood samples from three deceased individuals with AMD, the team characterized homoplasmic and heteroplasmic SNPs in the tissues, tracking down hot spots for SNP heteroplasmy in mitochondrial DNA in different tissue types that were subsequently tested in hundreds more individuals. "Using NGS methodology, larger numbers of heteroplasmy SNPs were identified in blood compared to retina and [RPE+choroid], suggesting significant protection in these tissues," the authors report, adding that the "majority of heteroplasmy SNPs were transition mutations … which suggests that accumulation of heteroplasmy may be occurring through replication errors rather than oxidative damage."