Identification of cryptic imbalance in phenotypically normal and abnormal translocation carriers
Open Access
- 30 August 2006
- journal article
- research article
- Published by Springer Nature in European Journal of Human Genetics
- Vol. 14 (12) , 1255-1262
- https://doi.org/10.1038/sj.ejhg.5201710
Abstract
Approximately one in 500 individuals carries a reciprocal translocation. Of the 121 monosomy 1p36 subjects ascertained by our laboratory, three independent cases involved unbalanced translocations of 1p and 9q, all of which were designated t(1;9)(p36.3;q34). These derivative chromosomes were inherited from balanced translocation carrier parents. To understand better the causes and consequences of chromosome breakage and rearrangement in the human genome, we characterized each derivative chromosome at the DNA sequence level and identified the junctions between 1p36 and 9q34. The breakpoint regions were unique in all individuals. Insertions and duplications were identified in two balanced translocation carrier parents and their unbalanced offspring. Sequence analyses revealed that the translocation breakpoints disrupted genes. This study demonstrates that apparently balanced reciprocal translocations in phenotypically normal carriers may have cryptic imbalance at the breakpoints. Because disrupted genes were identified in the phenotypically normal translocation carriers, caution should be exercised when interpreting data on phenotypically abnormal carriers with apparently balanced rearrangements that disrupt putative candidate genes.Keywords
This publication has 24 references indexed in Scilit:
- Identification of sequence motifs at the breakpoint junctions in three t(1;9)(p36.3;q34) and delineation of mechanisms involved in generating balanced translocationsHuman Genetics, 2006
- Molecular characterization of a novel translocation t(5;14)(q21;q32) in a patient with congenital abnormalitiesJournal of Human Genetics, 2006
- Molecular genetic analysis of a de novo balanced translocation t(6;17)(p21.31;q11.2) associated with hypospadias and anorectal malformationHuman Genetics, 2006
- Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15)(q27;q11.2) associated with Prader-Willi syndromeBMC Medical Genetics, 2005
- Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well-characterized 1p36 deletionsHuman Molecular Genetics, 2003
- Physical Map of 1p36, Placement of Breakpoints in Monosomy 1p36, and Clinical Characterization of the SyndromeAmerican Journal of Human Genetics, 2003
- A candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocationHuman Genetics, 2002
- FISHing for mechanisms of cytogenetically defined terminal deletions using chromosome-specific subtelomeric probesEuropean Journal of Human Genetics, 2000
- Nonhomologous Robertsonian translocations form predominantly during female meiosisNature Genetics, 1997
- Molecular Analysis of a Constitutional X-Autosome Translocation in a Female with Muscular DystrophyScience, 1987