Skip to main content
Premium Trial:

Request an Annual Quote

PNAS Papers on Myelopathy GWAS in Japan, Hypertrophic Cardiomyopathy, MRSA Methylation

Investigators in Japan share findings from a genome-wide association study focused on a progressive central nervous system inflammatory condition called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) that has been linked to proviral levels of the human T cell leukemia virus type 1 (HTLV-1) retrovirus. Using array-based genotyping profiles and targeted human leukocyte antigen (HLA) sequence data for more than 750 Japanese individuals with HAM/TSP and nearly 900 unaffected controls from the same population, the team narrowed in on specific HLA alleles with ties to HAM/TSP. "[W]e found that HLA-DRB1 alleles carrying leucine at the antigen presenting groove domain (DRB-GB-7-Leu) increased the susceptibility to HAM/TSP," the authors report, noting that this association appeared to hold regardless of proviral load. "These findings identify DRB1-GB-7-Leu as a genetic risk marker of HAM/TSP development."

A team from Harvard Medical School, Brigham and Women's Hospital, and elsewhere presents genomic data on pairs of identical twins with distinct hypertrophic cardiomyopathy (HCM) features, reasoning that background variants may impact the expression of pathogenic variants in HCM-related sarcomere genes. The researchers did whole-genome sequencing on individuals from 11 HCM-discordant identical twin pairs followed over time, searching for additional variants associated with atrial and ventricular features measured by echocardiogram. The available genome sequence data for half a dozen of the discordant twin pairs "did not reveal notable somatic genetic variants that might explain their clinical differences," the authors report. "Our study underscores the important contribution of epigenetics and environment in disease progression in genetically diagnosed HCM patients."

Researchers at the University of California, Los Angeles, describe DNA methylation differences detected in individuals with persistent methicillin-resistant Staphylococcus aureus (MRSA) infections that do not resolve after treatment. Based on reduced-representation bisulfite sequencing data on circulating immune cells in peripheral blood samples from 70 antibiotic-persistent cases and 72 MRSA cases resolved by treatment, the team came up with a DNA methylation-based classifier for distinguishing individuals with persistent MRSA from those with MRSA infections that were treated successfully, including 160 sites with lower-than-usual methylation and 116 loci with enhanced methylation in those with persistent MRSA. GenomeWeb has more on the study, here.