Where the genome breaks

25 Jun 2012

Human genetic variation is not only caused by mutations that alter the sequence. Structural variation, in which regions of the genome are for example duplicated or deleted, is also an important source of genetic diversity between individuals. One, by now well-known form of structural variation is the so-called copy-number variation (CNV). Here, the variation does not relate to the sequence of a particular gene, but lies in the number of copies present. One of the reasons for CNV to gain a lot of attention lately is that de novo CNVs have been linked to a number of disorders and diseases.

To learn more about the fundamental mechanisms that underlie genome plasticity and genomic rearrangement processes, it is essential to determine the exact breakpoints within the genomic regions that are duplicated. Such repetitive regions, segmental duplications, are characterized by high sequence identity, which makes it very difficult to precisely localize the breakpoints. Furthermore, gaps in the human genome reference often occur precisely at the expected breakpoints.

By combining somatic cell hybrids, array comparative genomic hybridization and next-generation sequencing, Andy Itsara (University of Washington) and colleagues (including NBIC faculty member Edwin Cuppen of the Hubrecht Institute) managed to determine CNV breakpoints with molecular resolution in three individuals diagnosed with the 17q21.31 microdeletion syndrome.

Itsara A, Vissers LELM, Meltz Steinberg K, Meyer KJ, Zody MC, Koolen DA, de Ligt J, Cuppen E, Baker C, Lee C, Graves TA, Wilson RK, Jenkins RB, Veltman JA and Eichler EE
Resolving the Breakpoints of the 17q21.31 Microdeletion Syndrome with Next-Generation Sequencing
Am. J. Hum. Gen 2012, Vol 90(4):599-613

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