In PLOS Genetics, researchers from the University of Veterinary Medicine Hannover, the University of Bern, and the University of Helsinki describe a missense variant in the TSEN54 gene in dogs from the standard Schnauzer breed that appears to coincide with hereditary leukodystrophy — a progressive cerebral white matter condition. Along with linkage analyses and homozygosity mapping on dogs from two families of affected pooches, the team did whole-genome sequencing on one Schnauzer with leukodystrophy. A further comparison with genome sequences from more than 200 unaffected pups pointed to a missense change in TSEN54, a gene coding for an endonuclease enzyme subunit involved in transfer RNA splicing. In a broader analysis of nearly 1,000 unaffected dogs and a dozen more Schnauzers with leukodystrophy, the authors found that the TSEN54 variant continued to line up with the presence of disease.
A team from Japan searches for genetic variants involved in a chemotherapy side effect known as drug-induced interstitial lung disease (DIILD) for a paper appearing in PLOS One. Based on whole-genome sequences for 26 individuals with DIILD, along with data for unaffected participants in the Japanese Genome Variation Database, the researchers narrowed in on a few dozens suspicious SNPs. After validating 42 apparent SNP associations with data for another 18 individuals with DIILD, they focused in on two DIILD-associated loci found in a combined analysis of the discovery and validation cohorts, as well as a handful of SNPs with potential ties to a specific type of DIILD found in those treated with tyrosine kinase inhibitors targeting EGFR. "Our results may provide insight into the underlying mechanisms of DIILD," the authors write, "and aid in the development of a diagnostic system for predicting the risk of this life-threatening adverse event."
Researchers at Harvard Medical School, the University of Colorado, and elsewhere compare two RNA sequencing-based strategies for mapping expression quantitative trait loci (eQTLs) that involve rare variants for another PLOS One paper. The team considered one method that uses negative binomial regression or Poisson regression to assess rare variants that have been collapsed in a region of interest and another method, known as the "Sequence Kernel Association Test" (SKAT) Burden test, that relies on normalized read counts. It also combined these analyses into a test known as SKAT-O. Based on their simulations and analyses on data from the 1000 Genomes Project, the authors suggest that the SKAT methods may apply to broader sample size sets and rare eQTL searches. "[W]e recommend using SKAT with normalized read counts over the other approaches considered here," they conclude.