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PLOS Papers on East Coast Fever Tolerance in Cattle, Macaque Colorectal Cancer Model, ActSeq

In PLOS Genetics, researchers from the UK and Kenya describe a genetic locus in Bos indicus cattle that appears to be linked to survival following infection with Theileria parva, a tick-transmitted parasite that causes a potentially deadly disease known as East Coast fever. The team used linkage analyses, whole-genome sequencing, and array-based genotyping on 121 cattle from two generations of the same pedigree, as well as dozens more unrelated cattle, to narrow in on a survival-associated region on chromosome 15 region. Bringing in additional white blood cell transcriptome profiles for 29 animals, the authors traced this association to a protective variant in the FAF1 gene, which was linked to East Coast fever survival in cattle within and outside of the pedigree. "This genetic variant can therefore support marker-assisted selection, allowing farmers to breed tolerant cattle and offers a route to introduce this beneficial DNA to non-native breeds, enabling reduced disease incidence and increased productivity, which would be of benefit to millions of rural smallholder farmers across Africa," they write.

For another paper in PLOS Genetics, a team from the University of Texas MD Anderson Cancer Center and elsewhere presents findings from a genomic study of rhesus macaque monkeys that spontaneously developed a mismatch repair-deficient (MMRd) form of colorectal cancer (CRC). With PCR-based microsatellite instability (MSI), RNA sequencing, reduced-representation bisulfite sequencing, and/or targeted methylation testing on up to 41 CRC samples, the researchers found features resembling those reported in human CRC, including Lynch Syndrome-related MLH1 alterations, frequently high levels of MSI, and related gene expression shifts. "Our study aimed to provide a detailed molecular characterization of rhesus CRC for cross-comparison with human MMRd CRC," the authors write, noting that "findings from this study support the use of rhesus macaques as an alternative animal model to mice to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches relevant to sporadic [MSI-high] and [Lynch Syndrome] CRC in humans."

University of Notre Dame, South Bend Medical Foundation, and Indiana University researchers describe a targeted sequencing panel aimed at uncovering clinically relevant cancer mutations, particularly SNPs and short insertions or deletions. The approach, called ActSeq, relies on custom hybridization capture probes spanning the coding regions of 141 genes, together with paired-end short read sequencing and bioinformatics. After validating the method with DNA containing more than 100 known variants, the team applied ActSeq to several cancer cell lines and dozens of clinical samples. "Our results illustrate the feasibility for a panel development in a community pathology lab, suitable for clinical application, improving diagnosis, prognosis, and personalized therapeutic decisions," they write in PLOS One.

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