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