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Genomics in the Journals: Oct 31, 2013

NEW YORK (GenomeWeb News) – In Nature Genetics, researchers from University College London, the Wellcome Trust Sanger Institute, and elsewhere described mutations in a pair of histone-coding genes that appear to characterize two rare forms of benign bone tumors called chondroblastoma and giant cell tumors.

The team started by doing genome sequencing on matched tumor and normal samples from half a dozen individuals with chondroblastoma. Sorting through those sequences, the group unearthed alterations in the histone H3.3-coding genes H3F3A, found on chromosome 1, and in the chromosome 17 gene H3F3B.

Each of the six chondroblastoma tumors assessed initially contained glitches in at least one of the two genes. And through targeted sequencing of H3F3A and H3F3B in hundreds more individuals with chondroblastoma or other types of bone tumors, investigators found that mutations in the genes characterized 95 percent of the chondroblastomas tested, as well as 92 percent of the giant cell tumors of bone.

In particular, they reported, each of the benign tumor types contained genetic changes affecting a different amino acid in the resulting histone H3.3 protein. Mutations in the histone H3.3-coding genes were also found in a small subset of clear-cell chondrosarcoma, osteosarcoma, and conventional chondrosarcoma samples.

"Our findings will be highly beneficial to clinicians as we now have a diagnostic marker to differentiate chondroblastoma and giant cell tumor of bones from other bone tumors," University College London researcher Adrienne Flanagan, the study's corresponding author, said in a statement.

Variants in and around at least four genes appear to influence how well individuals in the Han Chinese population can naturally clear hepatitis B virus infections, according to another Nature Genetics study.

An international team led by investigators in China used a three-stage genome-wide association study to get a look at genetic factors found in Han Chinese individuals with chronic HBV infections and in individuals from the same population who have cleared the virus, which can eventually lead to liver cancer.

By comparing genotyping profiles from 951 individuals with chronic HBV infections and 937 individuals who had experienced acute HBV infections that cleared naturally, researchers initially homed in on 14 suspicious SNPs. From there, they did multiple rounds of follow-up testing involving validation cohorts comprised of either HBV cases and controls with naturally cleared infections or HBV cases and unaffected controls from the broader population.

Along variants near human leukocyte antigen, or HLA, genes already implicated in chronic HBV infection risk, the group saw statistically significant associations for chromosome 6 and chromosome 22 SNPs in the vicinity of the HLA-C gene and UBE2L3, another gene involved in immune response.

Members of the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study projects presented a study in the journal eLife that focuses on the interplay between sequence diversity in HIV-1, genetic variants found in infected human hosts, and control of viral load during infection.

The group did array-based SNP genotyping on blood samples from 1,071 HIV-1-infected individuals of western European descent who had not yet been treated with anti-retroviral drugs. Matched HIV-1 samples from each of the participants were sequenced to assess viral diversity and its relationship to host genetic patterns and to viral load in patients' blood plasma.

The approach revealed significant associations between variants in host HLA genes and four-dozen amino acid variations in HIV-1, researchers reported. More generally, they noted, results of the analysis suggest searches for human genetic features affecting viral infection can benefit from information on variation in the virus itself, which can be gleaned without additional information on individuals' clinical features.

"The proposed genome-to-genome approach highlights sites of genomic conflict, and is a strategy generally applicable to studies of host-pathogen interaction," co-corresponding authors Jacques Fellay, with the Swiss Federal Institute of Technology and the Swiss Institute of Bioinformatics, and the University of Lausanne's Amalio Telenti, and their colleagues wrote.

Texas-based researchers took a look at the microbial communities contributing to human decomposition after death — work they described in PLOS One. Using 16S ribosomal RNA gene sequencing, the team tallied up the bacteria present in microbial communities in samples from two cadavers at the beginning and end of the so-called "bloat" stage of decomposition.

Results of the analysis revealed apparent shifts in microbial contributors as the decomposition process progressed. At each of the body sites tested, investigators saw anaerobic bacteria replacing aerobic bugs over the span of a couple months, between the start and conclusion of the bloat stage. They were also able to begin identifying specific species that tended to dominate various body sites during the stages of decomposition considered.

If similar patterns hold in future studies, authors of the analysis argued, it may ultimately be possible to use bacterial profiling as a source of information about an individual's time of death during forensics investigations.

"This study is the first to catalogue bacteria present internally at the onset and end of the bloat stage of human decomposition," co-author Aaron Lynne, a biology researcher with Sam Houston State University, said in a statement. "Ultimately, we hope to come up with a cumulative systems approach to look at decomposition in a way that might complement existing forensic models at determining the post-mortem interval (time since death)."