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Agilent CGH microarrays help provide process insights of the human genome

Agilent Technologies Europe : 22 May, 2008  (Company News)
A group of researchers has provided new insight into processes shaping the human genome by employing a variety of technologies for validation and characterization, including Agilent CGH microarrays, they identified 1,695 sites of structural change, half of which were seen in more than one individual.
They used a clone-based method to build a comprehensive, fine-scale map of structural variation in eight human genomes from diverse geographic ancestry. The work also detected 525 segments of novel sequence not found in the reference human genome sequence.

Custom Agilent CGH microarrays were used to validate structurally variant sequences and to further characterize the novel insertion sequences found by cloning. 'We designed array probes based on the novel sequences to measure whether these sequences are copy-number variable among different humans,' said Laurakay Bruhn, PhD, a member of the four-person Agilent team that participated in the study. 'We found that nearly half of these sequences show copy-number differences between eight individuals, showing they are a rich source of structural variation in the human genome.'

Agilent's ability to quickly design and fabricate custom microarrays with high sensitivity and specificity for measuring copy-number differences in genomic DNA proved to be an asset for validation and further study of new sequences. Agilent maintains a database of 20 million copy-number variation probes that facilitate experimental design.

The results are published in the May 2008 issue of Nature (vol. 453) in the paper ‘Mapping and sequencing of structural variation from eight human genomes’. Contributors included researchers from the Howard Hughes Medical Institute and the University of Washington School of Medicine; Agilent Technologies; Agencourt Biosciences; Washington University Genome Sequencing Center; Human Genome Research Institute, National Institutes of Health; Laboratory of Genetics, University of Wisconsin; Illumina; and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard.

'The clone resource and the subsequent sequencing and characterization of these genomes will provide a gold standard for future characterization of structural variation,' said Evan Eichler, PhD, corresponding author.

The authors wrote that the understanding of genomic variation on an intermediate scale - 'particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs' - provides new insights into the different mutational processes that have shaped the human genome.
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