In PLOS Genetics, researchers from France describe a missense mutation in the KIF1C gene that appears to cause progressive ataxia in Charolais cattle in its homozygous form. The team used a bovine array to genotype 46 Charolais cattle that appeared to have the neurodegenerative condition. By incorporating homozygosity mapping, haplotype analyses, and whole-genome sequencing on three animals with or without the condition, the investigators narrowed in on a suspicious substitution in KIF1C — a gene previously implicated in spastic paraplegia type 58 and spastic ataxia 2 in humans. They went on to start characterizing the alteration with immunohistochemistry and other approaches, uncovering a potential role for the protein in myelin function.
A VU University Medical Center-led team proposes ties between advanced colorectal cancer and expression levels for half a dozen microRNAs for a paper appearing in PLOS One. Using high-throughput sequencing, the researchers profiled small RNAs in fresh frozen tumor samples from 88 individuals with metastatic colorectal cancer, followed by real-time quantitative PCR on samples from another 81 metastatic colorectal cancer patients. In the process, they pinpointed six miRNAs — miR-17-5p, miR-20a-5p, miR-92a-3p, miR-92b-3p, and miR-98-5p — with expression levels that appeared to coincide with response to fluoropyrimidine treatment. Together with a handful of other clinicopathological factors, the miRNA signature showed promise for predicting treatment response compared to stable disease, though the authors their validation analyses did not verify its ability to distinguish individuals with progressive disease.
Researchers from South Africa and elsewhere present an analysis of tuberculosis-causing Mycobacterium tuberculosis genotypes, and their distribution across the African continent, for another PLOS One paper. Starting with available spoligotype and genotype data for almost 15,000 M. tuberculosis isolates represented in published studies and databases such as SITVIT2, the team used profiles for more than 13,600 isolates to explore phylogenetic relationships and population structure for M. tuberculosis in Africa. With this approach, the authors identified 10 main lineages and additional sub-lineages, which differed in representation depending on the location considered, along with 1,120 isolates that were not assigned to a major lineage. More broadly, the strain clusters presented provided insights into tuberculosis spread, the authors explain, noting that "M. tuberculosis … may have been introduced from either Europe or Asia and has spread through pastoralism, mining, and war."