title: Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anne W
authors.initials: AW
authors.lastname: Higgins
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
authors.forename: Amy F
authors.initials: AF
authors.lastname: Bosco
authors.forename: Kerry K
authors.initials: KK
authors.lastname: Brown
authors.forename: Gail A P
authors.initials: GA
authors.lastname: Bruns
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Donovan
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authors.lastname: Eisenman
authors.forename: Yanli
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authors.lastname: Fan
authors.forename: Chantal G
authors.initials: CG
authors.lastname: Farra
authors.forename: Heather L
authors.initials: HL
authors.lastname: Ferguson
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: David J
authors.initials: DJ
authors.lastname: Harris
authors.forename: Steven R
authors.initials: SR
authors.lastname: Herrick
authors.forename: Chantal
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authors.lastname: Kelly
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Shotaro
authors.initials: S
authors.lastname: Kishikawa
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Korf
authors.forename: Shashikant
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Eric
authors.initials: E
authors.lastname: Lally
authors.forename: Natalia T
authors.initials: NT
authors.lastname: Leach
authors.forename: Emma
authors.initials: E
authors.lastname: Lemyre
authors.forename: Janine
authors.initials: J
authors.lastname: Lewis
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.forename: Weining
authors.initials: W
authors.lastname: Lu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Maas
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Steven D P
authors.initials: SD
authors.lastname: Moore
authors.forename: Roxanna E
authors.initials: RE
authors.lastname: Peters
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Quade
authors.forename: Fabiola
authors.initials: F
authors.lastname: Quintero-Rivera
authors.forename: Irfan
authors.initials: I
authors.lastname: Saadi
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.forename: Robin E
authors.initials: RE
authors.lastname: Williamson
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D019457:Chromosome Breakage; D002874:Chromosome Mapping; D000013:Congenital Abnormalities / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006803:Human Development; D016045:Human Genome Project; D006801:Humans