Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 3, 712-722, 3 March 2008
doi:10.1016/j.ajhg.2008.01.011
Article
Characterization of Apparently Balanced Chromosomal Rearrangements from the Developmental Genome Anatomy Project
Anne W. Higgins1, Fowzan S. Alkuraya2, Amy F. Bosco3, Kerry K. Brown4, Gail A.P. Bruns5, Diana J. Donovan1, Robert Eisenman5, Yanli Fan2, Chantal G. Farra1, Heather L. Ferguson3, James F. Gusella4, 6, David J. Harris7, Steven R. Herrick1, Chantal Kelly3, Hyung-Goo Kim6, Shotaro Kishikawa6, Bruce R. Korf8, Shashikant Kulkarni9, Eric Lally1, Natalia T. Leach3, Emma Lemyre10, Janine Lewis6, Azra H. Ligon1, Weining Lu11, Richard L. Maas2, Marcy E. MacDonald6, 12, Steven D.P. Moore3, Roxanna E. Peters1, Bradley J. Quade1, Fabiola Quintero-Rivera6, Irfan Saadi2, Yiping Shen6, Jay Shendure4, Robin E. Williamson4, 13 and Cynthia C. Morton1, 3, 13, 
, 
1 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
2 Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
3 Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
4 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
5 Genetics Division, Department of Pediatrics, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
6 Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
7 Division of Genetics, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
8 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
9 Division of Laboratory and Genomic Medicine, Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
10 Medical Genetics Division, Hôpital Ste. Justine, University of Montreal, Montreal H3T 1C5, Canada
11 Renal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA
12 Department of Neurology, Harvard Medical School, Boston, MA 02114, USA
Corresponding author13 All editorial responsibility for this article was handled by an associate editor of the Journal.
Abstract
Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes. Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation.
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