title: Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals.
abstract: To test the hypothesis that translocation breakpoints in normal individuals are simple and do not disrupt genes, we characterised the breakpoints in 13 phenotypically normal individuals incidentally ascertained with an apparently balanced reciprocal translocation. Cases were karyotyped, and the breakpoints were refined by fluorescence in situ hybridisation until breakpoint-spanning clones were identified. 1 Mb array-CGH was performed as a whole genome analysis tool to detect any imbalances in chromatin not directly involved in the breakpoints. Breakpoint-associated imbalances were not found in any of the patients analysed in this study. However, breakpoints which disrupted known genes were identified in two patients, with RYR2 disrupted in one patient and COL13A1 in the other. In a further eight patients, Ensembl mapping data suggested that a gene might be disrupted by a breakpoint. In one further patient, the translocation was shown to be nonreciprocal. This study shows that apparently balanced reciprocal translocations in phenotypically normal patients do not have imbalances at the breakpoints, in contrast to phenotypically abnormal patients where the translocation breakpoints are often associated with cryptic imbalances. However, phenotypically normal individuals, and phenotypically abnormal individuals may have genes disrupted and therefore inactivated by one of the breakpoints. The significance of these disruptions remains to be determined.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire, UK. Julia.baptista@salisbury.nhs.uk
authors.forename: Julia
authors.initials: J
authors.lastname: Baptista
authors.forename: Elena
authors.initials: E
authors.lastname: Prigmore
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gribble
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jacobs
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
mesh_terms: D002460:Cell Line; D019457:Chromosome Breakage / Q000235:genetics*; D003094:Collagen / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012016:Reference Values; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D018168:Receptors, Retinoic Acid; D019837:Ryanodine Receptor Calcium Release Channel; C082925:retinoic acid receptor beta; D003094:Collagen