Abstract
G band cytogenetic analysis often leads to the discovery of unbalanced karyotypes that require further characterisation by molecular cytogenetic studies. In particular, G band analysis usually does not show the chromosomal origin of small marker chromosomes or of a small amount of extra material detected on otherwise normal chromosomes. Comparative genomic hybridisation (CGH) is one of several molecular approaches that can be applied to ascertain the origin of extra chromosomal material. CGH is also capable of detecting loss of material and thus is also applicable to confirming or further characterising subtle deletions. We have used comparative genomic hybridisation to analyse 19 constitutional chromosome abnormalities detected by G band analysis, including seven deletions, five supernumerary marker chromosomes, two interstitial duplications, and five chromosomes presenting with abnormal terminal banding patterns. CGH was successful in elucidating the origin of extra chromosomal material in 10 out of 11 non-mosaic cases, and permitted further characterisation of all of the deletions that could be detected by GTG banding. CGH appears to be a useful adjunct tool for either confirming deletions or defining their breakpoints and for determining the origin of extra chromosomal material, even in cases where abnormalities are judged to be subtle. We discuss internal quality control measures, such as the mismatching of test and reference DNA in order to assess the quality of the competitive hybridisation effect on the X chromosome. Keywords: comparative genomic hybridisation; constitutional chromosome studies
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- Barber J. C., Joyce C. A., Collinson M. N., Nicholson J. C., Willatt L. R., Dyson H. M., Bateman M. S., Green A. J., Yates J. R., Dennis N. R. Duplication of 8p23.1: a cytogenetic anomaly with no established clinical significance. J Med Genet. 1998 Jun;35(6):491–496. doi: 10.1136/jmg.35.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bateman J. B., Maumenee I. H., Sparkes R. S. Peters' anomaly associated with partial deletion of the long arm of chromosome 11. Am J Ophthalmol. 1984 Jan;97(1):11–15. doi: 10.1016/0002-9394(84)90440-9. [DOI] [PubMed] [Google Scholar]
- Browne C. E., Dennis N. R., Maher E., Long F. L., Nicholson J. C., Sillibourne J., Barber J. C. Inherited interstitial duplications of proximal 15q: genotype-phenotype correlations. Am J Hum Genet. 1997 Dec;61(6):1342–1352. doi: 10.1086/301624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bryndorf T., Kirchhoff M., Rose H., Maahr J., Gerdes T., Karhu R., Kallioniemi A., Christensen B., Lundsteen C., Philip J. Comparative genomic hybridization in clinical cytogenetics. Am J Hum Genet. 1995 Nov;57(5):1211–1220. [PMC free article] [PubMed] [Google Scholar]
- Erdel M., Duba H. C., Verdorfer I., Lingenhel A., Geiger R., Gutenberger K. H., Ludescher E., Utermann B., Utermann G. Comparative genomic hybridization reveals a partial de novo trisomy 6q23-qter in an infant with congenital malformations: delineation of the phenotype. Hum Genet. 1997 May;99(5):596–601. doi: 10.1007/s004390050412. [DOI] [PubMed] [Google Scholar]
- Flint J., Wilkie A. O., Buckle V. J., Winter R. M., Holland A. J., McDermid H. E. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995 Feb;9(2):132–140. doi: 10.1038/ng0295-132. [DOI] [PubMed] [Google Scholar]
- Forozan F., Karhu R., Kononen J., Kallioniemi A., Kallioniemi O. P. Genome screening by comparative genomic hybridization. Trends Genet. 1997 Oct;13(10):405–409. doi: 10.1016/s0168-9525(97)01244-4. [DOI] [PubMed] [Google Scholar]
- Ghaffari S. R., Boyd E., Tolmie J. L., Crow Y. J., Trainer A. H., Connor J. M. A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation. J Med Genet. 1998 Mar;35(3):225–233. doi: 10.1136/jmg.35.3.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight S. J., Horsley S. W., Regan R., Lawrie N. M., Maher E. J., Cardy D. L., Flint J., Kearney L. Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur J Hum Genet. 1997 Jan-Feb;5(1):1–8. [PubMed] [Google Scholar]
- Levy B., Gershin I. F., Desnick R. J., Babu A., Gelb B. D., Hirschhorn K., Cotter P. D. Characterization of a de novo unbalanced chromosome rearrangement by comparative genomic hybridization and fluorescence in situ hybridization. Cytogenet Cell Genet. 1997;76(1-2):68–71. doi: 10.1159/000134518. [DOI] [PubMed] [Google Scholar]
- Lichter P., Tang C. J., Call K., Hermanson G., Evans G. A., Housman D., Ward D. C. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science. 1990 Jan 5;247(4938):64–69. doi: 10.1126/science.2294592. [DOI] [PubMed] [Google Scholar]
- Speicher M. R., Gwyn Ballard S., Ward D. C. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet. 1996 Apr;12(4):368–375. doi: 10.1038/ng0496-368. [DOI] [PubMed] [Google Scholar]