ABSTRACT
Chromosomal rearrangements that cause deletions, duplications, inversions or marker chromosome formation often result in human disease due to alteration in the dosage of a gene or genes that leads to the phenotypic effects observed. The human diseases that result from these rearrangements are referred to as genomic disorders. The type of genomic disorder is comprised of single gene disorders that are associated with both point mutations and recurrent chromosomal rearrangements that alter expression of the functional copy of a single gene. Contiguous gene syndromes is characterized by large chromosomal rearrangements with complex phenotypes associated with the dosage effects of multiple, unrelated genes and is referred to as a contiguous gene syndrome. Two pathways for DNA repair are recognized that predisopose to chromosomal rearrangements termed homologous recombination and nonhomologous DNA end-joining. Homologous recombination involving misaligned duplicons in a tandem or direct orientation on sister chromatids or homologous chromosomes causes formation of reciprocal deletions and duplications.
