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Genomics In The Journals: May 24, 2012

NEW YORK (GenomeWeb News) – Efforts to discern the domestication history and origins of dogs are complicated by past interbreeding between the animals, according to a Proceedings of the National Academy of Sciences study.

An international team led by investigators from the UK, US, and Sweden brought together archeological information with autosomal SNP data for 19 wolves and nearly 1,400 dogs from dozens of breeds, comparing genetic signatures in these animals with those reported in the past. While their phylogenetic tree did identify a handful of existing dog breeds with far different genetic signatures than those found in most breeds, the investigators noted that these patterns are largely owing to the geographic isolation of these breeds rather than especially close relationships to ancient dogs.

"Ironically, the ubiquity of dogs combined with their deep history has obscured their origins and made it difficult for us to know how dogs became man's best friend," Durham University evolutionary biologist Greger Larson, the study's first author, said in statement. "All dogs have undergone significant amounts of cross-breeding to the point that we have not yet been able to trace all the way back to their very first ancestors."

Also in PNAS, a look at the relationships between genetic variants and metabolite profiles in maize leaves.

Using a genome-wide association approach, a German and Saudi Arabian research team looked for variants influencing leaf metabolite concentrations in field-grown plants from 289 inbred maize lines. Based on genotyping data at more than 56,000 SNPs, combined with information on the levels of 118 compounds in plant leaves, the team tracked variants associated with levels of 26 metabolites, along with 15 SNP-metabolite associations on nine maize chromosomes that each explain an estimated 15 percent of the observed genetic variance. The analysis turned up fewer associations with different predicted genetic variance than past metabolic quantitative trait locus studies, the study's authors noted, perhaps due to population structure, differences in the significance threshold used, and so on.

Even so, they argued that looking specifically for metabolite associations in maize and other plants may serve as a straightforward way to investigate more complicated but related traits.

"[O]ur results suggest that studying less complex connecting links between genotype and phenotype, such as metabolites, may be a reasonable alternative for [genome-wide association] mapping of highly complex traits in plants," University of Hohenheim researcher Albrecht Melchinger, the study's corresponding author, and colleagues wrote.

A study in mBio relied on comparative genomics to retrace the processes that led to resistance to the antibiotic vancomycin in North American Staphylococcus aureus strains that were already methicillin resistant.

Researchers from the US and UK sequenced as many vancomycin-resistant S. aureus strains as they could get their hands on, comparing a dozen of these high quality VRSA draft genome sequences with one another and with existing S. aureus sequence data, including information on other S. aureus strains from the same clonal cluster, known as CC5. From their analyses, the investigators estimated that the VRSA strains shared a common ancestor some 50 years ago, prior to the advent of vancomycin resistance, which was first recognized about a decade ago. Since then, the analysis suggests, VRSA strains have acquired resistance independently — adaptations that appear have been augmented by genetic features in CC5 strains that make them prone to pilfering resistance genes from other bacteria and effectively using these pirated sequences.

A team from the Translational Genomics Research Institute and Scottsdale Healthcare used genome sequencing to look for mutations behind a rare nasal cancer called olfactory neuroblastoma — work that they report in PLoS ONE.

The researchers did whole-genome sequencing on tumor and matched normal blood samples from a 29-year old man with a metastatic form of the disease before doing comparisons between the metastatic tumor and a primary tumor sample. For instance, they reported that both tumors contained alterations affecting the TP53, TAOK2, and MAP4K2 genes, whereas the metastatic tumor harbored additional changes to MYC, KDR, SIN3B, and NLRC4 genes that weren't present in the primary sample.

"This work provides novel insights into the underpinnings of a rare but terrible form of cancer," senior author John Carpten, TGen deputy director and director of the center's integrated cancer genomics division, said in a statement. "Hopefully we can translate these findings into tools for improved clinical management of rare tumors such as this."

In Science, researchers from the Brigham and Women's Hospital, the Dana Farber Cancer Institute, and the Broad Institute consider the sorts of genes that fall in sites of hemizygous deletions that recur across several cancer types.

The group did a screen in immortalized human mammary epithelial cells with almost 75,000 short hairpin RNAs directed at 19,011 genes to help classify the genes as either "GO" genes that promote proliferation or "STOP" genes that inhibit it. Results of the initial screen and follow-up validation experiments — coupled with information on the sites of recurrent focal deletion in thousands of tumors — point to a slew of apparent STOP genes but a dearth of GO genes in these previously described hemizygous deleted regions. The findings prompted researchers to suggest a model whereby so-called "Cancer Gene Islands" contribute to tumorigenesis through an accumulation of haploinsufficiency involving genes that normally curb proliferation.

"Given the prevalence of multiple, large recurring hemizygous deletions encompassing skewed distributions of growth control genes in tumors, we propose that the elimination of cancer gene islands that optimize fitness through cumulative haploinsufficiencies may play an important role in driving tumorigenesis," they wrote.

Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.

The Scan

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.

Using Bees to Gain Insights into Urban Microbiomes

As bees buzz around, they pick up debris that provides insight into the metagenome of their surroundings, researchers report in Environmental Microbiome.

Age, Genetic Risk Tied to Blood Lipid Changes in New Study

A study appearing in JAMA Network Open suggests strategies to address high lipid levels should focus on individuals with high genetic risk and at specific ages.

Study Examines Insights Gained by Adjunct Trio RNA Sequencing in Complex Pediatric Disease Cases

Researchers in AJHG explore the diagnostic utility of adding parent-child RNA-seq to genome sequencing in dozens of families with complex, undiagnosed genetic disease.