Tumor cells frequently exhibit large-scale changes in their genome, including genome rearrangements (e.g. chromosome inversions and translocations), duplications, and deletions. Such genomic changes are directly implicated in the pathogenesis of cancer and can alter gene structure and regulation. While many individual rearrangements and duplications in tumors have been identified, little is kno...

Large genomic rearrangements are recognized as playing a pathogenic role in an increasing number of human genetic diseases. It is important to develop efficient methods for the routine detection and confirmation of these germline defects. Multiplex ligation-dependent probe amplification (MLPA) is considered an early step for molecular diagnosis of several genetic disorders. However, artifacts m...

Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called ‘‘quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM),’’ which combines qPCR and HRM to obtain a rap...

Chromosome rearrangements are a significant cause of intellectual disability and birth defects. Subtelomeric rearrangements, including deletions, duplications and translocations of chromosome ends, were first discovered over 40 years ago and are now recognized as being responsible for several genetic syndromes. Unlike the deletions and duplications that cause some genomic disorders, subtelomeri...

Agenesis of the corpus callosum (ACC) is a common brain malformation of variable clinical expression that is seen in many syndromes of various etiologies. Although ACC is predominantly genetic, few genes have as yet been identified. We have constructed and analyzed a comprehensive map of ACC loci across the human genome using data generated from 374 patients with ACC and structural chromosome r...

Genomic instability is a well-known hallmark of cancer. Recent genome sequencing studies have led to the identification of novel phenomena called chromothripsis and chromoanasynthesis in which complex genomic rearrangements are thought to be derived from a single catastrophic event rather than by several incremental steps. A new term chromoanagenesis or chromosomal rebirth was coined recently t...