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Genomics in the Journals: Jun 5, 2014

NEW YORK (GenomeWeb News) – In Nature Genetics, an international team led by investigators in the US, the UK, and France described rare, germline variants in the breast and ovarian cancer risk gene BRCA2 and the cell cycle control gene CHEK2 that can drive up the risk of certain lung cancers.

Using imputation information from the 1000 Genomes Project — along with genotyping data for almost 11,350 individuals with lung cancer and 15,861 without from genome-wide association studies done in European populations — the researchers found low-frequency BRCA2 and CHEK2 variants that were more common in those with the squamous cell form of non-small cell lung cancer.

Validation testing in tens of thousands more newly genotyped cases and controls confirmed that association, suggesting that the BRCA2 mutation may put smokers at especially higher risk of developing lung cancer.

The team also saw ties between risk of the common non-small cell lung cancer subtype adenocarcinoma and a variant in the TP63 gene, which has been implicated in lung cancer risk in individuals of Asian ancestry.


A Nature Communications study looked at the genetics of adaptation to stressful conditions by the blind mole rat, Spalax galili, which lives underground in low-light, low-oxygen, and high-carbon dioxide environments. Like the naked mole rat, Heterocephalus glaber, the animal is also cancer resistant, generating further interest in its genetic makeup.

Researchers from Israel, China, and elsewhere used Illumina's HiSeq 2000 to sequence genomic DNA from a female blind mole rat's brain sample. Along with their genome sequencing, assembly, and annotation analyses, they also used RNA sequencing to take a look at transcripts found in the placentas of blind mole rats from the S. galili and S. carmeli species and in tissues from animals exposed to low oxygen conditions.

In the process, the team identified 22,168 predicted protein-coding genes in almost 12,800 gene families in the blind rat genome. The animal appears to belong to a lineage that diverged from the ancestors of mice, rats, and the Chinese hamster some 47 million years ago. It is even more distantly related to the naked mole rat, from which it diverged an estimated 71 million years ago.

Within the blind mole rat genome, the researchers saw a large collection of short interspersed repeat elements and evidence of rampant DNA and RNA editing, but a dearth of chromosomal rearrangements — features that they said may boost the animal's adaptability while reducing its cancer risk.

"The remarkable traits of the [blind mole rat], together with its genomic and transcriptomic information, enhance our understanding of adaptation to extreme environments," the study's authors wrote, "and will enable the utilization of [blind mole rat] models for biomedical research in the fight against cancer, stroke, and cardiovascular disease."


In a New England Journal of Medicine study, researchers from Saudi Arabia provided genetic evidence for transmission of the Middle Eastern respiratory virus coronavirus (MERS-CoV) from camels to humans.

Starting with MERS-CoV-positive nasal swab samples from a 44-year-old man treated at the King Abdulaziz University Hospital last November and nine camels in a herd that the patient owned, the team collected additional samples and cultured viral isolates in the lab.

The investigators' full genome analysis of viral RNA in the cell culture supernatant revealed that the patient was infected with a version of MERS-CoV that was 100 percent identical to the corresponding camel isolate. In a phylogenetic framework, they found that the patient and camel samples were similar to other MERS-CoV isolates and to betacoronavirus isolates characterized in the past.

The study authors concluded that the infected patient in this case, who ultimately succumbed to the infection, was likely infected by MERS-CoV as a consequence of close contact with an infected camel from his herd.