Jean-louis Blouin - Academia.edu (original) (raw)
Papers by Jean-louis Blouin
European Journal of Human Genetics, 1993
Human Genetics, Dec 1, 1992
To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down s... more To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down syndrome (D21S55-MX1), we used pulsed field gel electrophoresis (PFGE) to isolate a 600-kbNruI DNA fragment from the WA17 hybrid cell line, which has retained chromosome 21 as the only human material. This fragment, which contains the oncogene ETS2, was used to construct a partial genomic library. Among the 14 unique sequences that were isolated, 3 were polymorphic markers and contained sequences that are conserved in mammals. Five of these markers mapped on the ETS2-containing NruI fragment and allowed us to define an 800-kb high-resolution PFGE map.
European Journal of Human Genetics, 1993
Genetics and Alzheimer’s Disease, 1988
The possibility of a genetic link between Alzheimer’s disease (AD) and Down’s syndrome (DS) is su... more The possibility of a genetic link between Alzheimer’s disease (AD) and Down’s syndrome (DS) is supported by the similarity of the neuropathological and neurochemical changes found in the brain of AD patients and middle-aged DS patients. To test this hypothesis we performed gene dosage experiments with DNA sequences that we found duplicated in DS patients with partial trisomy. Various parameters which could modify the results of gene dosage have been tested. Among these parameters, RNase treatment was shown to introduce significant variations: in fibroblasts from one AD patient that we have studied extensively, dosage of the (β-amyloid gene and the protooncogene ETS2 gave the same values for RNase-untreated DNA and increased copy number for RNase-treated DNA from fibroblasts. DS models for AD suggest that overexpression of one or a few chromosome 21 genes leads to AD pathology. Thus it is potentially interesting to study chromosome 21 gene expression in AD. RNA quantification experiments were run on fibroblast cultures from five AD patients, three age-matched controls and two DS patients: mRNA for CuZn superoxide dismutase was significantly increased in four AD patients and two DS patients as compared to actin RNA. A t-test common to the five blots showed a significant increase (p < 0.001). For ETS2 sequences qualitative results were obtained: the level of ETS2 RNA was higher in AD patients and DS patients than in controls. For AD patients these results could be explained by variations of the regulation of gene expression, either at the transcriptional level or through the control of the stability of RNA. However, the observed increase is similar in DS and AD patients. Furthermore, in one AD patient gene dosage and RNA level quantification were performed on the same fibroblasts; increased values were found for both ETS2 DNA sequences and ETS2 RNA sequences. Therefore these results are also compatible with duplication of some chromosome 21 sequences in some AD patients.
Research and Perspectives in Alzheimer’s Disease, 1988
The presence of "plaques" and "tangles" in the brain is considered as the hallmark of Alzheimer's... more The presence of "plaques" and "tangles" in the brain is considered as the hallmark of Alzheimer's disease. The major constituent of the plaques is a protein ("A-beta") which is split off from a much larger parent protein called Amyloid Precursor Protein (APP), and that of tangles is the protein tau, which normally functions to stabilize microtubules within neuronal axons. There are several possibilities that elaborate the change in amyloid formation and its consequences on the neuronal death to bring AD; the first is the amyloid cascade hypothesis that describes how early-onset AD is induced by mutations in APP, the presenilins and apoE4. The second possibility is the calcium hypothesis of Alzheimer's disease, which argues the calcium-induced memory loss in Alzheimer's disease. Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that the chromosome 21 gene product was a principal neuropathogenic culprit in the AD as well as DS. The main objective of this review was elucidate the possible hypothesis of Alzheimer's disease and to pinpoint the chromosome 21 gene product as principal neuropathogenic culprit in the pathogenesis of AD and DS. Different articles on pathogenesis of AD and its link to DS were revised. As conclusion, different hypothesis on AD pathogenesis discussed on this review illustrated well about the pathogenesis of AD, its link to DS and potential target for certain therapeutic agents to act on the treatment of AD and DS.
Progress in clinical and biological research, 1993
American journal of human genetics, 1990
As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots us... more As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots using specific and reference probes, we designed a "slot blot" method for the evaluation of the copy number of unique chromosome 21 sequences. Varying amounts of denatured DNA from a normal control, a trisomy 21 patient, and the subject to be analyzed were loaded on the same membrane. Successive hybridizations with reference probes and chromosome 21 probes were then carried out. Intensities of the signals on autoradiograms were quantified by densitometric scanning. Graphic and statistical analysis of the linear regressions between reference and chromosome 21 probe signals were performed, and the conclusion that the DNA from the studied subject had two or three copies for a given chromosome 21 sequence was assessed by statistical comparison of the slopes. As a test for the validation of this method, 10 coded blood DNAs from five normal controls and from five trisomy 21 patients we...
New Vistas in Drug Research, 1990
Down syndrome is defined by the association of a number of features usually observed in patients ... more Down syndrome is defined by the association of a number of features usually observed in patients with trisomy of chromosome 21. Different forms of aneuploidy are encountered: free trisomy 21 (the most frequent), partial trisomy 21, unbalanced translocation, mosaicism, and microduplications of a short chromosomic fragment. Comparison of genotype and phenotype permitted us to define a critical region for the pathogenesis of Down syndrome, on the proximal part ar 21 q 22.3. Down syndrome is also associated with early manifestation of aging and Alzheimer like neuropathology; this pathology results from the presence of an extra copy of one or few genes on chromosome 21. We hypothesize that Alzheimer’s disease might, at least in certain patients, be secondary to a chromosome 21 defect susceptible to induce the overexpression of this or these genes. Experimental approaches for testing this hypothesis have been recently developed, both in familial and sporadic Alzheimer’s disease.
Human Genetics, 1992
To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down s... more To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down syndrome (D21S55-MX1), we used pulsed field gel electrophoresis (PFGE) to isolate a 600-kbNruI DNA fragment from the WA17 hybrid cell line, which has retained chromosome 21 as the only human material. This fragment, which contains the oncogene ETS2, was used to construct a partial genomic library. Among the 14 unique sequences that were isolated, 3 were polymorphic markers and contained sequences that are conserved in mammals. Five of these markers mapped on the ETS2-containing NruI fragment and allowed us to define an 800-kb high-resolution PFGE map.
Genomics, 1992
Using a slot-blot method for the dosage of single-copy sequences, the copy numbers of 30 chromoso... more Using a slot-blot method for the dosage of single-copy sequences, the copy numbers of 30 chromosome 21 markers were assessed in the blood DNA of 11 patients with partial trisomy or monosomy 21 and in the DNA of a patient-derived human-hamster hybrid cell line carrying a microduplication of chromosome 21. The physical order of these markers on chromosome 21 was thereby determined.
Biomedicine & Pharmacotherapy, 1994
American Journal of Medical Genetics, 2005
We have analysed the DNA of 2 patients with many manifestations of Down syndrome and partial dupl... more We have analysed the DNA of 2 patients with many manifestations of Down syndrome and partial duplication of distinct regions of chromosome 21, respectively, q11.205 + q22.300 and q22.300qter (Rahmani et al.: Proceedings of the National Academy of Sciences of the United States of America 865958-5962, 1989). Assessment of the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) has shown that D21S55 was duplicated in both cases. The size of the common duplicated region can be estimated between 400 and 3,000 Kb, after the results of pulsed-field gel analysis and from the knowledge of regional mapping of the probes D21S17, D21S55, and ETS2. This region, located on the proximal part of 21q22.3, is postulated to contain genes the overexpression of which plays a major role in the pathogenesis of Down syndrome.
Proceedings of the National Academy of Sciences, 1989
The duplication of a specific region of chromosome 21 could be responsible for the main features ... more The duplication of a specific region of chromosome 21 could be responsible for the main features of Down syndrome. To define and localize this region, we analyzed at the molecular level the DNA of two patients with partial duplication of chromosome 21. These patients belong to two groups of Down syndrome patients characterized by different partial trisomies 21: (i) duplication of the long arm, proximal to 21q22.2, and (ii) duplication of the end of the chromosome, distal to 21q22.2 We assessed the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) and found that D21S55 was duplicated in both cases. By means of pulsed-field gel analysis and with the knowledge of regional mapping of the probes D21S17, D21S55 and ETS2, we estimated the size of the common duplicated region to be between 400 and 3000 kilobases. This region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis ...
The American Journal of Human Genetics
In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, we genotyped 17 fam... more In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, we genotyped 17 families with mosaic trisomy 21 probands, using 28 PCR-detectable DNA polymorphic markers that map in the pericentromeric region and long arm of chromosome 21. The percentage of cells with trisomy 21 in the probands' blood lymphocytes was 6%-94%. There were two classes of autoradiographic results: In class I, a "third allele" of lower intensity was detected in the proband's DNA for at least two chromosome 21 markers. The interpretation of this result was that the proband had inherited three chromosomes 21 after meiotic nondisjunction (NDJ) (trisomy 21 zygote) and subsequently lost one because of mitotic (somatic) error, the lost chromosome 21 being that with the lowest-intensity polymorphic allele. The parental origin and the meiotic stage of NDJ could also be determined. In class II, a "third allele" was never detected. In these cases, the mosaicism probably occurred either by a postzygotic, mitotic error in a normal zygote that followed a normal meiosis (class IIA mechanism); by premeiotic, mitotic NDJ yielding an aneusomic zygote after meiosis, and subsequent mitotic loss (class IIB mechanism); or by a meiosis II error with lack of crossover in the preceding meiosis I, followed by mitotic loss after fertilization (class IIC mechanism). Among class II mechanisms, the most likely is mechanism IIA, while IIC is the least likely. There were 10 cases of class I and 7 cases of class II results. Within class I, there were nine cases with maternal meiotic errors (six meiosis I and three meiosis II errors, on the basis of pericentromeric markers) and one with paternal meiosis I error. The postzygotic loss of chromosome 21 was determined in eight maternal class I cases, and it was maternally derived in five cases and paternally derived in three; this suggests that the postzygotic loss of chromosome 21 is probably random. The mean maternal age in meiotic class I errors was 31.4 years and in mitotic class II errors was 27.4 years, as expected.
Cytogenetics and cell genetics
The American Journal of Human Genetics
As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots us... more As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots using specific and reference probes, we designed a "slot blot" method for the evaluation of the copy number of unique chromosome 21 sequences. Varying amounts of denatured DNA from a normal control, a trisomy 21 patient, and the subject to be analyzed were loaded on the same membrane. Successive hybridizations with reference probes and chromosome 21 probes were then carried out. Intensities of the signals on autoradiograms were quantified by densitometric scanning. Graphic and statistical analysis of the linear regressions between reference and chromosome 21 probe signals were performed, and the conclusion that the DNA from the studied subject had two or three copies for a given chromosome 21 sequence was assessed by statistical comparison of the slopes. As a test for the validation of this method, 10 coded blood DNAs from five normal controls and from five trisomy 21 patients we...
Revue médicale suisse, Jan 25, 2005
Recent advances in molecular genetics have resulted in the identification of pathogenic mutations... more Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.
Swiss surgery = Schweizer Chirurgie = Chirurgie suisse = Chirurgia svizzera, 2001
The aim of this study was to assess the feasibility and success of multidisciplinary approach for... more The aim of this study was to assess the feasibility and success of multidisciplinary approach for the management of hereditary colorectal cancer. From November 1998 to November 2000, 32 individuals with putative familial/hereditary predisposition to colorectal cancer were investigated for adenomatous polyposis (attenuated or classical familial adenomatous polyposis coli, FAP) or for hereditary nonpolyposis colorectal cancer (HNPCC). Amsterdam criteria (I and II) and Bethesda guidelines were used to select putative HNPCC kindreds. Clinical data including endoscopy, pathological and operative reports as well as family history were collected. Pre- and post-test genetic counseling was offered to at-risk individuals. Genetic testing included microsatellite instability (MSI) and search for germline mutations in the APC, hMSH2 and hMLH1 genes. Immunohistochemistry (IHC) of hMSH2 and hMLH1 protein expression in tumour samples was also performed. 11 APC mutations were characterized, whereas ...
Progress in clinical and biological research, 1993
European journal of human genetics : EJHG, 1993
To determine which regions of chromosome 21 are involved in the pathogenesis of specific features... more To determine which regions of chromosome 21 are involved in the pathogenesis of specific features of Down syndrome, we analysed, phenotypically and molecularly, 10 patients with partial trisomy 21. Six minimal regions for 24 features were defined by genotype-phenotype correlations. Nineteen of these features could be assigned to just 2 regions: short stature, joint hyperlaxity, hypotonia, major contribution to mental retardation and 9 anomalies of the face, hand and foot to the region D21S55, or Down syndrome chromosome region (DCR), located on q22.2 or very proximal q22.3, and spanning 0.4-3 Mb; 6 facial and dermatoglyphic anomalies to the region D21S55-MX1, including the DCR and spanning a maximum of 6 Mb on q22.2 and part of q22.3. Thus, the complex phenotype that constitutes Down syndrome may in large part simply result from the overdosage of only one or a few genes within the DCR and/or region D21S55-MX1.
European Journal of Human Genetics, 1993
Human Genetics, Dec 1, 1992
To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down s... more To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down syndrome (D21S55-MX1), we used pulsed field gel electrophoresis (PFGE) to isolate a 600-kbNruI DNA fragment from the WA17 hybrid cell line, which has retained chromosome 21 as the only human material. This fragment, which contains the oncogene ETS2, was used to construct a partial genomic library. Among the 14 unique sequences that were isolated, 3 were polymorphic markers and contained sequences that are conserved in mammals. Five of these markers mapped on the ETS2-containing NruI fragment and allowed us to define an 800-kb high-resolution PFGE map.
European Journal of Human Genetics, 1993
Genetics and Alzheimer’s Disease, 1988
The possibility of a genetic link between Alzheimer’s disease (AD) and Down’s syndrome (DS) is su... more The possibility of a genetic link between Alzheimer’s disease (AD) and Down’s syndrome (DS) is supported by the similarity of the neuropathological and neurochemical changes found in the brain of AD patients and middle-aged DS patients. To test this hypothesis we performed gene dosage experiments with DNA sequences that we found duplicated in DS patients with partial trisomy. Various parameters which could modify the results of gene dosage have been tested. Among these parameters, RNase treatment was shown to introduce significant variations: in fibroblasts from one AD patient that we have studied extensively, dosage of the (β-amyloid gene and the protooncogene ETS2 gave the same values for RNase-untreated DNA and increased copy number for RNase-treated DNA from fibroblasts. DS models for AD suggest that overexpression of one or a few chromosome 21 genes leads to AD pathology. Thus it is potentially interesting to study chromosome 21 gene expression in AD. RNA quantification experiments were run on fibroblast cultures from five AD patients, three age-matched controls and two DS patients: mRNA for CuZn superoxide dismutase was significantly increased in four AD patients and two DS patients as compared to actin RNA. A t-test common to the five blots showed a significant increase (p < 0.001). For ETS2 sequences qualitative results were obtained: the level of ETS2 RNA was higher in AD patients and DS patients than in controls. For AD patients these results could be explained by variations of the regulation of gene expression, either at the transcriptional level or through the control of the stability of RNA. However, the observed increase is similar in DS and AD patients. Furthermore, in one AD patient gene dosage and RNA level quantification were performed on the same fibroblasts; increased values were found for both ETS2 DNA sequences and ETS2 RNA sequences. Therefore these results are also compatible with duplication of some chromosome 21 sequences in some AD patients.
Research and Perspectives in Alzheimer’s Disease, 1988
The presence of "plaques" and "tangles" in the brain is considered as the hallmark of Alzheimer's... more The presence of "plaques" and "tangles" in the brain is considered as the hallmark of Alzheimer's disease. The major constituent of the plaques is a protein ("A-beta") which is split off from a much larger parent protein called Amyloid Precursor Protein (APP), and that of tangles is the protein tau, which normally functions to stabilize microtubules within neuronal axons. There are several possibilities that elaborate the change in amyloid formation and its consequences on the neuronal death to bring AD; the first is the amyloid cascade hypothesis that describes how early-onset AD is induced by mutations in APP, the presenilins and apoE4. The second possibility is the calcium hypothesis of Alzheimer's disease, which argues the calcium-induced memory loss in Alzheimer's disease. Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that the chromosome 21 gene product was a principal neuropathogenic culprit in the AD as well as DS. The main objective of this review was elucidate the possible hypothesis of Alzheimer's disease and to pinpoint the chromosome 21 gene product as principal neuropathogenic culprit in the pathogenesis of AD and DS. Different articles on pathogenesis of AD and its link to DS were revised. As conclusion, different hypothesis on AD pathogenesis discussed on this review illustrated well about the pathogenesis of AD, its link to DS and potential target for certain therapeutic agents to act on the treatment of AD and DS.
Progress in clinical and biological research, 1993
American journal of human genetics, 1990
As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots us... more As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots using specific and reference probes, we designed a "slot blot" method for the evaluation of the copy number of unique chromosome 21 sequences. Varying amounts of denatured DNA from a normal control, a trisomy 21 patient, and the subject to be analyzed were loaded on the same membrane. Successive hybridizations with reference probes and chromosome 21 probes were then carried out. Intensities of the signals on autoradiograms were quantified by densitometric scanning. Graphic and statistical analysis of the linear regressions between reference and chromosome 21 probe signals were performed, and the conclusion that the DNA from the studied subject had two or three copies for a given chromosome 21 sequence was assessed by statistical comparison of the slopes. As a test for the validation of this method, 10 coded blood DNAs from five normal controls and from five trisomy 21 patients we...
New Vistas in Drug Research, 1990
Down syndrome is defined by the association of a number of features usually observed in patients ... more Down syndrome is defined by the association of a number of features usually observed in patients with trisomy of chromosome 21. Different forms of aneuploidy are encountered: free trisomy 21 (the most frequent), partial trisomy 21, unbalanced translocation, mosaicism, and microduplications of a short chromosomic fragment. Comparison of genotype and phenotype permitted us to define a critical region for the pathogenesis of Down syndrome, on the proximal part ar 21 q 22.3. Down syndrome is also associated with early manifestation of aging and Alzheimer like neuropathology; this pathology results from the presence of an extra copy of one or few genes on chromosome 21. We hypothesize that Alzheimer’s disease might, at least in certain patients, be secondary to a chromosome 21 defect susceptible to induce the overexpression of this or these genes. Experimental approaches for testing this hypothesis have been recently developed, both in familial and sporadic Alzheimer’s disease.
Human Genetics, 1992
To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down s... more To generate new chromosome 21 markers in a region that is critical for the pathogenesis of Down syndrome (D21S55-MX1), we used pulsed field gel electrophoresis (PFGE) to isolate a 600-kbNruI DNA fragment from the WA17 hybrid cell line, which has retained chromosome 21 as the only human material. This fragment, which contains the oncogene ETS2, was used to construct a partial genomic library. Among the 14 unique sequences that were isolated, 3 were polymorphic markers and contained sequences that are conserved in mammals. Five of these markers mapped on the ETS2-containing NruI fragment and allowed us to define an 800-kb high-resolution PFGE map.
Genomics, 1992
Using a slot-blot method for the dosage of single-copy sequences, the copy numbers of 30 chromoso... more Using a slot-blot method for the dosage of single-copy sequences, the copy numbers of 30 chromosome 21 markers were assessed in the blood DNA of 11 patients with partial trisomy or monosomy 21 and in the DNA of a patient-derived human-hamster hybrid cell line carrying a microduplication of chromosome 21. The physical order of these markers on chromosome 21 was thereby determined.
Biomedicine & Pharmacotherapy, 1994
American Journal of Medical Genetics, 2005
We have analysed the DNA of 2 patients with many manifestations of Down syndrome and partial dupl... more We have analysed the DNA of 2 patients with many manifestations of Down syndrome and partial duplication of distinct regions of chromosome 21, respectively, q11.205 + q22.300 and q22.300qter (Rahmani et al.: Proceedings of the National Academy of Sciences of the United States of America 865958-5962, 1989). Assessment of the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) has shown that D21S55 was duplicated in both cases. The size of the common duplicated region can be estimated between 400 and 3,000 Kb, after the results of pulsed-field gel analysis and from the knowledge of regional mapping of the probes D21S17, D21S55, and ETS2. This region, located on the proximal part of 21q22.3, is postulated to contain genes the overexpression of which plays a major role in the pathogenesis of Down syndrome.
Proceedings of the National Academy of Sciences, 1989
The duplication of a specific region of chromosome 21 could be responsible for the main features ... more The duplication of a specific region of chromosome 21 could be responsible for the main features of Down syndrome. To define and localize this region, we analyzed at the molecular level the DNA of two patients with partial duplication of chromosome 21. These patients belong to two groups of Down syndrome patients characterized by different partial trisomies 21: (i) duplication of the long arm, proximal to 21q22.2, and (ii) duplication of the end of the chromosome, distal to 21q22.2 We assessed the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) and found that D21S55 was duplicated in both cases. By means of pulsed-field gel analysis and with the knowledge of regional mapping of the probes D21S17, D21S55 and ETS2, we estimated the size of the common duplicated region to be between 400 and 3000 kilobases. This region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis ...
The American Journal of Human Genetics
In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, we genotyped 17 fam... more In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, we genotyped 17 families with mosaic trisomy 21 probands, using 28 PCR-detectable DNA polymorphic markers that map in the pericentromeric region and long arm of chromosome 21. The percentage of cells with trisomy 21 in the probands' blood lymphocytes was 6%-94%. There were two classes of autoradiographic results: In class I, a "third allele" of lower intensity was detected in the proband's DNA for at least two chromosome 21 markers. The interpretation of this result was that the proband had inherited three chromosomes 21 after meiotic nondisjunction (NDJ) (trisomy 21 zygote) and subsequently lost one because of mitotic (somatic) error, the lost chromosome 21 being that with the lowest-intensity polymorphic allele. The parental origin and the meiotic stage of NDJ could also be determined. In class II, a "third allele" was never detected. In these cases, the mosaicism probably occurred either by a postzygotic, mitotic error in a normal zygote that followed a normal meiosis (class IIA mechanism); by premeiotic, mitotic NDJ yielding an aneusomic zygote after meiosis, and subsequent mitotic loss (class IIB mechanism); or by a meiosis II error with lack of crossover in the preceding meiosis I, followed by mitotic loss after fertilization (class IIC mechanism). Among class II mechanisms, the most likely is mechanism IIA, while IIC is the least likely. There were 10 cases of class I and 7 cases of class II results. Within class I, there were nine cases with maternal meiotic errors (six meiosis I and three meiosis II errors, on the basis of pericentromeric markers) and one with paternal meiosis I error. The postzygotic loss of chromosome 21 was determined in eight maternal class I cases, and it was maternally derived in five cases and paternally derived in three; this suggests that the postzygotic loss of chromosome 21 is probably random. The mean maternal age in meiotic class I errors was 31.4 years and in mitotic class II errors was 27.4 years, as expected.
Cytogenetics and cell genetics
The American Journal of Human Genetics
As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots us... more As an alternative to the methods of gene dosage based on either RFLP studies or Southern blots using specific and reference probes, we designed a "slot blot" method for the evaluation of the copy number of unique chromosome 21 sequences. Varying amounts of denatured DNA from a normal control, a trisomy 21 patient, and the subject to be analyzed were loaded on the same membrane. Successive hybridizations with reference probes and chromosome 21 probes were then carried out. Intensities of the signals on autoradiograms were quantified by densitometric scanning. Graphic and statistical analysis of the linear regressions between reference and chromosome 21 probe signals were performed, and the conclusion that the DNA from the studied subject had two or three copies for a given chromosome 21 sequence was assessed by statistical comparison of the slopes. As a test for the validation of this method, 10 coded blood DNAs from five normal controls and from five trisomy 21 patients we...
Revue médicale suisse, Jan 25, 2005
Recent advances in molecular genetics have resulted in the identification of pathogenic mutations... more Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.
Swiss surgery = Schweizer Chirurgie = Chirurgie suisse = Chirurgia svizzera, 2001
The aim of this study was to assess the feasibility and success of multidisciplinary approach for... more The aim of this study was to assess the feasibility and success of multidisciplinary approach for the management of hereditary colorectal cancer. From November 1998 to November 2000, 32 individuals with putative familial/hereditary predisposition to colorectal cancer were investigated for adenomatous polyposis (attenuated or classical familial adenomatous polyposis coli, FAP) or for hereditary nonpolyposis colorectal cancer (HNPCC). Amsterdam criteria (I and II) and Bethesda guidelines were used to select putative HNPCC kindreds. Clinical data including endoscopy, pathological and operative reports as well as family history were collected. Pre- and post-test genetic counseling was offered to at-risk individuals. Genetic testing included microsatellite instability (MSI) and search for germline mutations in the APC, hMSH2 and hMLH1 genes. Immunohistochemistry (IHC) of hMSH2 and hMLH1 protein expression in tumour samples was also performed. 11 APC mutations were characterized, whereas ...
Progress in clinical and biological research, 1993
European journal of human genetics : EJHG, 1993
To determine which regions of chromosome 21 are involved in the pathogenesis of specific features... more To determine which regions of chromosome 21 are involved in the pathogenesis of specific features of Down syndrome, we analysed, phenotypically and molecularly, 10 patients with partial trisomy 21. Six minimal regions for 24 features were defined by genotype-phenotype correlations. Nineteen of these features could be assigned to just 2 regions: short stature, joint hyperlaxity, hypotonia, major contribution to mental retardation and 9 anomalies of the face, hand and foot to the region D21S55, or Down syndrome chromosome region (DCR), located on q22.2 or very proximal q22.3, and spanning 0.4-3 Mb; 6 facial and dermatoglyphic anomalies to the region D21S55-MX1, including the DCR and spanning a maximum of 6 Mb on q22.2 and part of q22.3. Thus, the complex phenotype that constitutes Down syndrome may in large part simply result from the overdosage of only one or a few genes within the DCR and/or region D21S55-MX1.