TY - JOUR
T1 - High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage
AU - Wang, Nicholas J.
AU - Liu, Dahai
AU - Parokonny, Alexander S.
AU - Schanen, N. Carolyn
N1 - Funding Information:
We are very grateful to the patient families and the IsoDicentric 15 Exchange, Advocacy, and Support (IDEAS) group for participating in our study and to Naghmeh Dorrani for coordinating patient enrollment. We thank Barb Malone, Dianne York, and Suzanne Mann for technical assistance. We are grateful to David Ledbetter, Judy Fantes, Roger Schultz, Mariano Rocchi, and Anne-Marie Poustka for generously providing genomic clones. We would like to thank Christina Zheng for her assistance with figure preparation. This study was supported by grants from the National Institutes of Health Collaborative Programs for Excellence in Autism (NIH-U19-HD-35470), Nemours, and the F & F Foundation.
PY - 2004/8
Y1 - 2004/8
N2 - Maternally derived duplication of the imprinted region of chromosome 15q11-q14 leads to a complex neurobehavioral phenotype that often includes autism, cognitive deficits, and seizures. Multiple repeat elements within the region mediate a variety of rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi and Angelman syndromes. To elucidate the molecular structure of these duplication chromosomes, we designed a high-resolution array comparative genomic hybridization (array CGH) platform. The array contains 79 clones that form a gapped contig across the critical region on chromosome 15q11-q14 and 21 control clones from other autosomes and the sex chromosomes. We used this array to examine a set of 48 samples from patients with segmental aneuploidy of chromosome 15q. Using the array, we were able to determine accurately the dosage, which ranged from 1 to 6 copies, and also to detect atypical and asymmetric rearrangements. In addition, the increased resolution of the array allowed us to position two previously reported breakpoints within the contig. These results indicate that array CGH is a powerful technique to study rearrangements of proximal chromosome 15q.
AB - Maternally derived duplication of the imprinted region of chromosome 15q11-q14 leads to a complex neurobehavioral phenotype that often includes autism, cognitive deficits, and seizures. Multiple repeat elements within the region mediate a variety of rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi and Angelman syndromes. To elucidate the molecular structure of these duplication chromosomes, we designed a high-resolution array comparative genomic hybridization (array CGH) platform. The array contains 79 clones that form a gapped contig across the critical region on chromosome 15q11-q14 and 21 control clones from other autosomes and the sex chromosomes. We used this array to examine a set of 48 samples from patients with segmental aneuploidy of chromosome 15q. Using the array, we were able to determine accurately the dosage, which ranged from 1 to 6 copies, and also to detect atypical and asymmetric rearrangements. In addition, the increased resolution of the array allowed us to position two previously reported breakpoints within the contig. These results indicate that array CGH is a powerful technique to study rearrangements of proximal chromosome 15q.
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U2 - 10.1086/422854
DO - 10.1086/422854
M3 - Article
C2 - 15197683
AN - SCOPUS:3242710286
SN - 0002-9297
VL - 75
SP - 267
EP - 281
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -