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Genomics In The Journals: Nov 10, 2011

NEW YORK (GenomeWeb News) – In Nature Genetics, researchers from the UK and the Netherlands used Sleeping Beauty transposons to search for genes involved in intestinal tumor formation in mice. The insertional mutagenesis strategy is similar to that described last year by researchers who used PiggyBac transposons to screen for genes involved in hematopoietic cancers. For the new study, investigators looked for shared Sleeping Beauty transposon insertion sites in nearly 450 intestinal tumors from mice that were genetically modified to have mutations in a gene called Apc, which often undergoes loss-of-function changes in early colorectal cancer development. In the process, the team found hundreds of genes suspected of acting as intestinal cancer drivers, including components of Wnt signaling pathways and other genes implicated in past studies of human colorectal cancer.

"[W]e performed large-scale insertional mutagenesis in mice with somatic or germline mutations of Apc using the Sleeping Beauty transposon system to create a comprehensive catalog of the candidate drivers of intestinal tumorigenesis," senior author David Adams, an experimental cancer genetics researcher at the Wellcome Trust Sanger Institute, and co-authors wrote. "We identify several hundred genes that potentially drive tumorigenesis, thereby allowing the exploration of new interactions between genes and conserved pathways."

Members of the International Initiative for Pigeonpea Genomics used a combination of Illumina and Sanger sequencing to come up with a draft genome for pigeonpea, a protein-rich legume grown in parts of Asia, sub-Saharan Africa, South and Central America, and the Caribbean. As they report in Nature Biotechnology, the researchers' analyses of the nearly 606 million base draft genome sequence — which represents around 73 percent of the plant's estimated 833 million base genome — uncovered 48,680 predicted protein-coding genes. Along with clues to pigeonpea evolution and domestication, those involved in the effort say the genome sequence may serve as a resource for future pigeonpea improvement.

"Having the pigeonpea genome sequence as a reference will significantly speed up and reduce the cost of screening the 'good genes' within the stored pigeonpea seed collections in gene banks like that of [India's International Crops Research Institute for the Semi-Arid Tropics (ICRISAT)]," corresponding author Rajeev Varshney, who is affiliated with ICRISAT and with the Consultative Group on International Agricultural Research Generation Challenge Programme in Mexico, said in a statement.

A Proceedings of the National Academy of Sciences study outlines an algorithm for discerning copy number patterns from whole-genome sequence data based on sequence read depth. Using the Bayesian information criterion-based method, dubbed BIC-seq, researchers showed that it was possible to find copy number variants as small as 40 base pairs long in a glioblastoma genome that had been sequenced to about 10 times coverage. In contrast, they reported, the smallest CNV that they could detect in the same genome using array comparative genomic hybridization was larger than 15,000 bases.

"We propose this statistical approach as a principled yet practical and efficient method to estimate CNVs in whole-genome sequencing data," corresponding author Peter Park, a bioinformatics researcher affiliated with Harvard Medical School, Brigham and Women's Hospital, and the Children's Hospital Informatics Program, and co-authors wrote.

In the journal Cancer Discovery, researchers from the Dana-Farber Cancer Institute and Broad Institute present findings from a tumor sequencing study that focused on finding clinically actionable genetic changes — mutations, insertions, deletions, and copy number changes that could be used to help direct an individual's treatment. Using their targeted, massively parallel sequencing method, which they presented at the American Society of Clinical Oncology annual meeting this year, the team found that it was possible to find at least one of these genetic changes in every formalin-fixed paraffin-embedded tumor samples that they tested.

"Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested," Dana-Farber Cancer Institute researcher Levi Garraway, the study's senior author, and colleagues wrote.

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

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