Molecular investigations of structural and numerical chromosome abnormalities in man
Molecular investigations of structural and numerical chromosome abnormalities in man
This thesis concerns two areas of investigation. (1) The chromosomal origins and in some cases the molecular composition of 76 autosomal supernumerary marker chromosomes (SMC) were identified using fluorescence in situ hybridisation (FISH) and polymerase chain reaction (PCR) techniques. Forty seven were de novo, 9 maternally and 7 paternally transmitted and in 13 cases the parental origin is not known. Thirty four cases were non-mosaic and 42 mosaics, with 26 cases ascertained prenatally and 50 postnatally. Thirty two of the SMCs were shown to be derived from chromosome 15. Sixteen de novo SMC(15)s were maternal in origin, contained proximal 15q euchromatin and were invariably ascertained in patients with moderate to severe mental retardation. By contrast, the majority of SMC(15) without 15q euchromatin were found in normal individuals. Three out of 6 patients with SMC(22) were shown to contain proximal 22q euchromatin but no straightforward correlation between the extent of additional material in the SMC(22) and phenotypic effects were observed. Of the 38 SMCs derived from other autosomes, euchromatin was detected in 9 out of 18 tested with paints and/or PCR; abnormal phenotypes were most commonly observed in patients with small ring shaped SMCs containing euchromatic sequences. Uniparental disomy for chromosomes 6 and 15 respectively were detected amongst the 47 cases examined.
(2) Twenty six patients, with either isolated aniridia, with one or more of the WAGR (Wilms' tumour, aniridia, genital anomalies and mental retardation) syndrome or other anomalies were analysed by FISH with selected 11p13 markers including cosmids, FO2121, PAX6 (aniridia), D11S324 and WT1 (Wilms' tumour predisposition). Overall 8/26 (�30%) had abnormalities resolvable with FISH. Three patients with isolated aniridia were abnormal; the first with an apparently balanced reciprocal 7;11 translocation and an 11p13 breakpoint which by FISH was shown to be �30kb distal to the aniridia (PAX6) gene.
University of Southampton
Crolla, John Anthony Cesidio
1997
Crolla, John Anthony Cesidio
Crolla, John Anthony Cesidio
(1997)
Molecular investigations of structural and numerical chromosome abnormalities in man.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis concerns two areas of investigation. (1) The chromosomal origins and in some cases the molecular composition of 76 autosomal supernumerary marker chromosomes (SMC) were identified using fluorescence in situ hybridisation (FISH) and polymerase chain reaction (PCR) techniques. Forty seven were de novo, 9 maternally and 7 paternally transmitted and in 13 cases the parental origin is not known. Thirty four cases were non-mosaic and 42 mosaics, with 26 cases ascertained prenatally and 50 postnatally. Thirty two of the SMCs were shown to be derived from chromosome 15. Sixteen de novo SMC(15)s were maternal in origin, contained proximal 15q euchromatin and were invariably ascertained in patients with moderate to severe mental retardation. By contrast, the majority of SMC(15) without 15q euchromatin were found in normal individuals. Three out of 6 patients with SMC(22) were shown to contain proximal 22q euchromatin but no straightforward correlation between the extent of additional material in the SMC(22) and phenotypic effects were observed. Of the 38 SMCs derived from other autosomes, euchromatin was detected in 9 out of 18 tested with paints and/or PCR; abnormal phenotypes were most commonly observed in patients with small ring shaped SMCs containing euchromatic sequences. Uniparental disomy for chromosomes 6 and 15 respectively were detected amongst the 47 cases examined.
(2) Twenty six patients, with either isolated aniridia, with one or more of the WAGR (Wilms' tumour, aniridia, genital anomalies and mental retardation) syndrome or other anomalies were analysed by FISH with selected 11p13 markers including cosmids, FO2121, PAX6 (aniridia), D11S324 and WT1 (Wilms' tumour predisposition). Overall 8/26 (�30%) had abnormalities resolvable with FISH. Three patients with isolated aniridia were abnormal; the first with an apparently balanced reciprocal 7;11 translocation and an 11p13 breakpoint which by FISH was shown to be �30kb distal to the aniridia (PAX6) gene.
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Published date: 1997
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Local EPrints ID: 462980
URI: http://eprints.soton.ac.uk/id/eprint/462980
PURE UUID: aaee8fae-9f8e-49cb-ad7b-fa5682c3321e
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Date deposited: 04 Jul 2022 20:34
Last modified: 04 Jul 2022 20:34
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Author:
John Anthony Cesidio Crolla
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