Gene Dosage Analysis by Multiplex Amplifiable Probe Hybridization

DNA-based measurement of copy number can be useful in a number of applications in human genetics, through its detection of rearrangements of chromosomal structure too small to be detected by standard cytogenetic analyses. In some cases, deletions or duplications may involve several linked genes (such as subtelomeric deletions and unbalanced translocations in idiopathic mental retardation [1 –3 ]), and in others individual genes may have undergone duplications or deletions of the entire gene—for example, of PMP22 in HSMN and HNPP (4 )—or of exons within a gene—for example, in DMD (5 ) or BRCA1 (6 ,7 ). The complete analysis of subtelomeric deletions and the analysis of exonic copy number of genes such as BRCA1 (23 exons) requires the parallel measurement of copy number at more than 20 loci. Multiplex amplifiable probe hybridization (MAPH) provides a high-resolution assay for relative copy number at numerous loci (currently up to 60) in a single test (8 ).