Zoonotic transmission of methicillin-resistant Staphylococcus aureus (MRSA) between animals and humans has been further expanded by recent descriptions of mecC, a divergent homologue of the antibiotic resistance gene mecA. Researchers performed whole-genome sequencing with Illumina technology to investigate two human cases of mecC MRSA linked to a livestock reservoir. Sequence and phylogenetic analysis confirmed farm-specific transmission from livestock to the patients.
Harrison EM, Paterson GK, Holden MT, Larsen J, Stegger M, et al.
Whole-genome sequencing identifies zoonotic transmission of MRSA isolates with the novel mecA homologue mecC EMBO Molecular Medicine
Researchers performed targeted and whole-genome sequencing on HiSeq platforms to identify somatic genomic alterations and quantify circulating tumor DNA in breast cancer patients. Circulating tumor DNA demonstrated higher sensitivity than circulating tumor cells, reflected progressive disease, and often provided the earliest measurement of treatment response. Analysis indicated that circulating tumor DNA is a sensitive and specific biomarker of metastatic breast cancer.
Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, et al.
Analysis of circulating tumor DNA to monitor metastatic breast cancer New England Journal of Medicine
Pathogen specimens often contain host DNA contamination, which can reduce sequencing efficiency. Using MiSeq and HiSeq 2000 systems, researchers developed an enzymatic treatment method to deplete host contamination from malaria samples prior to sequencing. This approach takes advantage of differences in methylation patterns between host and pathogen genomes, providing a selective method for removing human DNA from malaria samples.
Oyola SO, Gu Y, Manske M, Otto TD, O’Brien J, et al.
Efficient depletion of host DNA contamination in malaria clinical sequencing Journal of Clinical Microbiology
Neuroblastoma is a malignancy of the nervous system that often presents with widespread metastatic disease in early childhood. To determine the spectrum of somatic mutation in high-risk neuroblastoma, researchers used a combination of whole-exome, genome, and transcriptome sequencing on Illumina technologies to study affected individuals. Results identified genes with significant somatic mutation frequencies, providing insight for future therapeutic development.
Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, et al.
The genetic landscape of high-risk neuroblastoma Nature Genetics
Clonal evolution is a key feature of cancer progression and relapse. Researchers performed whole-exome sequencing with the HiSeq 2000 system to study intratumoral heterogeneity in chronic lymphocytic leukemia (CLL) samples. Analysis of clonal evolution in CLL cases identified a subclonal driver mutation as an independent risk factor for disease progression and provided patterns of clonal evolution in CLL.
Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, et al.
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia Cell
To characterize the role of rare complete human knockouts in autism spectrum disorders (ASD), researchers sequenced the exomes of affected individuals using Illumina technology. They identified genes with loss-of-function variants, and detected increases in complete knockouts of autosomal genes and rare hemizygous knockouts on the X chromosome. Results support hypotheses that these events are inherited risk factors for ASD.
Lim ET, Raychaudhuri S, Sanders SJ, Stevens C, Sabo A, et al.
Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders Neuron
To investigate the molecular mechanism that reprograms progenitor cells into leukemia stem cells, researchers sequenced the transcriptomes of chronic myeloid leukemia (CML) progenitors using the HiSeq 2000 system. Whole-transcriptome sequencing identified gene expression changes during CML progression, including enhanced ADAR1 expression. Further experiments implicated the adenosine deaminases in the ADAR1 family in promoting the self-renewal capacity and reprogramming of CML progenitors.
Jiang Q, Crews LA, Barrett CL, Chun HJ, Court AC, et al.
ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia PNAS
The Carbosap strain of Bacillus anthracis is used for vaccination against anthrax in animals, but shows attenuation of virulence in some species. To explain this attenuation, researchers sequenced the Carbosap genome with the MiSeq system and compared it to fully virulent B. anthracis. Analysis indicates candidate genes linked to virulence and presents opportunities for further investigation into B. anthracis pathogenesis.
Harrington R, Ondov BD, Radune D, Friss MB, Klubnik J, et al.
Genome sequence of the attenuated Carbosap vaccine strain of Bacillus anthracis Genome Announcements