Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
In a study appearing online in the Proceedings of the National Academy of Sciences, a Turkish-led team describes a mutation in the mitochondrial serine protease-coding gene HTRA2 that can cause an inherited form of essential tremor, a movement disorder that may progress to Parkinson's disease. Starting from a six-generation family from Turkey that was frequently afflicted with essential tremor and/or Parkinson's disease, the researchers performed exome sequencing on three affected individuals to find the HTRA2 glitch. In those with two mutant alleles, tremors tended to appear earlier in life, progressing to Parkinson's disease when individuals reached middle age.
Researchers from Stanford University used a combination of microfluidics-based amplification and targeted sequencing to do single-cell profiling on almost 1,500 individual acute lymphoblastic leukemia (ALL) cells from six individuals with childhood ALL. After identifying genomic regions prone to heterogeneity through bulk sequencing on childhood ALL samples, the team did targeted sequencing on specific sequences, deletions, and single nucleotide variants in 1,479 individual tumor cells. The study's authors then used mutation patterns detected in single cells from each individual's tumor to identify co-dominant clones in each tumor. "Taken together," they write, "these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution."
Finally, there's a look at systemic lupus erythematosus from a team based in China that did genomic and methylomic sequencing on blood plasma samples from two dozen individuals with the condition and 11 without. Among the differences the researchers detected in the blood of those SLE was an over-representation of very short DNA fragments, notable declines in DNA methylation density, shifts in representation by DNA from different parts of the genome — features that seemed to stem, in part, from enhanced immunoglobulin binding of DNA in the blood of those with the disease. The study's authors argue that such findings "may provide new molecular markers for SLE," while raising potential red flags for those interpreting non-invasive prenatal tests or circulating cancer DNA test results in those with SLE.