Michael Morris - Academia.edu (original) (raw)
Papers by Michael Morris
European Journal of Human Genetics, 2013
Revue médicale de la Suisse romande, 1996
American journal of human genetics, 1995
We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and c... more We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and characterize a new dinucleotide repeat polymorphism (D21S1575) close to 21qter. This marker is < 120 kb from the telomeric (TTAGGG)n sequences and is the most distal highly polymorphic marker on chromosome 21q. This marker has a heterozygosity of 71% because of a variable (TA)n repeat embedded within a long interspersed element (LINE) element. Genotyping of the CEPH families and linkage analysis provided a more accurate determination of the full length of the chromosome 21 genetic map. A highly significant difference was detected between male and female recombination rates in the telomeric region: in the most telomeric 2.3 Mb of chromosome 21q, recombination was only observed in male meioses.
Pediatric Rheumatology, 2011
Neuro-Ophthalmology, 1993
... 245 Page 4. MA Morris 3 %mutant rntDNA Fig. 3. Heteroplasmy and the threshold effect. ... in ... more ... 245 Page 4. MA Morris 3 %mutant rntDNA Fig. 3. Heteroplasmy and the threshold effect. ... in a patient with (for example) a Kearns-Sayre syndrome, a false-negative 'normal' result almost invariably ensues - a muscle biopsy will be required to detect the mutation. ...
Neurology, 2004
The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of ... more The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of affected monozygotic twins. An earlier onset was associated with a more disabling course of disease. Whereas monozygosity was genetically proven, the search for pathogenic mutations in the GTP-cyclohydrolase-1 gene was negative. The contribution of environmental factors appeared minimal. Intrafamilial variability of DRD phenotype may be related to yet unknown non-Mendelian epigenetic or proteomic factors.
Nature Neuroscience, 2005
Although schizophrenia is strongly hereditary, there are limited data regarding biological risk f... more Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-Omethyltransferase low-activity allele (COMT L) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.
Nature Genetics, 2005
The developmental regulation of vertebrate Hox gene transcription relies on the interplay between... more The developmental regulation of vertebrate Hox gene transcription relies on the interplay between local and longrange controls. To study this complex genomic organization, we designed a strategy combining meiotic and targeted recombinations to induce large chromosomal rearrangements in vivo without manipulating embryonic stem cells. With this simple approach (called STRING), we engineered a large 7-cM inversion, which split the Hoxd cluster into two independent pieces. Expression analyses showed a partition of global enhancers, allowing for their precise topographic allocation on either side of the cluster. Such a functional organization probably contributed to keeping these genes clustered in the course of vertebrate evolution. This approach can be used to study the relationship between genome architecture and gene expression, such as the effects of genome rearrangements in human diseases or during evolution.
The Lancet, 1995
's health a challenge to us all. London: HM Stationery Office, 1992. 4 Garraway WM, MacLeod DAD, ... more 's health a challenge to us all. London: HM Stationery Office, 1992. 4 Garraway WM, MacLeod DAD, Sharp JCM. Rugby injuries: the need for case registers. BMJ 1991; 303: 1082-03.
The Journal of Pediatrics, 2002
Journal of Allergy and Clinical Immunology, 2013
Immunogenetics, 1988
In development, T cells first express their c~/3 antigen receptors in the thymus, where they may ... more In development, T cells first express their c~/3 antigen receptors in the thymus, where they may undergo selection processes leading to major histocompatibility complex (MHC) restriction and tolerance. A high proportion of thymocytes are thought to fail this selection in some way and to be destined for intrathymic death. These cells are categorized as the" cortical type" since they constitute most of the cortical cells; they express both CD4 and CD8 antigens but only very low levels of MHC class I antigens. One suggested cause of thymocyte death is a failure to produce a functional c~/3 T cell receptor (Tcr) due to errors in the rearrangements of germline DNA, resulting in V regions being absent or incorrectly spliced to the other segments of the transcribed gene. We have sequenced from the C region through to the V region of 14 rat Tcr /3 Chain clones isolated from thymocyte cDNA libraries. Of the 14, 13 have complete and correct rearrangements, whereas one was expressed from an unrearranged gene. Most of these clones are likely to be derived from the cortical population, for Northern blot analysis showed that these cells and total thymocytes expressed similar amounts of/3 chain mRNA. Furthermore, the RNA from cortical-type cells contained a very similar ratio of full-length to truncated/3 chain mRNA as did activated thymocytes and mature T lymphocytes. The data imply that defective/3 chain gene rearrangement is not a major cause of failure in the selection of thymocytes. The sequences of the rat Tcr c~ and /3 chain constant regions are also reported.
Human Mutation, 1997
MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of majo... more MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of major histocompatibility complex class II (MHC-II) gene expression. It is genetically heterogeneous and can result from defects in at least four different trans-acting regulatory genes required for transcription of MHC-II genes. One of these genes has recently been shown to encode a novel DNA binding protein called RFX5, which is one subunit of a heteromeric protein complex (RFX) that binds to the promoters of MHC-II genes. We have characterised the mutations in all four patients known to harbour a defect in the RFX5 gene and have mapped this new human disease gene to chromosome 1 band q21, a region frequently exhibiting chromosomal aberrations in a variety of preneoplastic and neoplastic diseases.
Human Mutation, 2011
Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis:... more Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis: the established traditional nomenclature system and the more recent Human Genome Variation Society (HGVS) nomenclature system. We have evaluated the use of both systems in the laboratory reports of 217 participants in the cystic fibrosis external quality assessment scheme of 2009. The mutation c.1521_1523delCTT (p.Phe508del, F508del) was described by traditional and HGVS nomenclature by 32 of 216 (15%) laboratories that correctly identified the mutation, whereas 171 (79%) laboratories used traditional nomenclature only and 13 (6%) laboratories used HGVS nomenclature only. Overall, 29 of 631 (5%) reports used nomenclature that was evaluated as being seriously incorrect and/or misleading and 136 (22%) reports contained attempts at HGVS coding, of which 104 (76%) contained no coding errors; just 33 (24%) mentioned the correct cDNA name and cited the nucleotide reference sequence. We recognized an urgent need for more consistent and correct usage of nomenclature. We recommended that cystic fibrosis transmembrane conductance regulator testing reports should include a description of the identified sequence variants in both HGVS and traditional nomenclature and provided basic recommendations and other guidance.
European Journal of Human Genetics, 2013
Revue médicale de la Suisse romande, 1996
American journal of human genetics, 1995
We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and c... more We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and characterize a new dinucleotide repeat polymorphism (D21S1575) close to 21qter. This marker is < 120 kb from the telomeric (TTAGGG)n sequences and is the most distal highly polymorphic marker on chromosome 21q. This marker has a heterozygosity of 71% because of a variable (TA)n repeat embedded within a long interspersed element (LINE) element. Genotyping of the CEPH families and linkage analysis provided a more accurate determination of the full length of the chromosome 21 genetic map. A highly significant difference was detected between male and female recombination rates in the telomeric region: in the most telomeric 2.3 Mb of chromosome 21q, recombination was only observed in male meioses.
Pediatric Rheumatology, 2011
Neuro-Ophthalmology, 1993
... 245 Page 4. MA Morris 3 %mutant rntDNA Fig. 3. Heteroplasmy and the threshold effect. ... in ... more ... 245 Page 4. MA Morris 3 %mutant rntDNA Fig. 3. Heteroplasmy and the threshold effect. ... in a patient with (for example) a Kearns-Sayre syndrome, a false-negative 'normal' result almost invariably ensues - a muscle biopsy will be required to detect the mutation. ...
Neurology, 2004
The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of ... more The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of affected monozygotic twins. An earlier onset was associated with a more disabling course of disease. Whereas monozygosity was genetically proven, the search for pathogenic mutations in the GTP-cyclohydrolase-1 gene was negative. The contribution of environmental factors appeared minimal. Intrafamilial variability of DRD phenotype may be related to yet unknown non-Mendelian epigenetic or proteomic factors.
Nature Neuroscience, 2005
Although schizophrenia is strongly hereditary, there are limited data regarding biological risk f... more Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-Omethyltransferase low-activity allele (COMT L) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.
Nature Genetics, 2005
The developmental regulation of vertebrate Hox gene transcription relies on the interplay between... more The developmental regulation of vertebrate Hox gene transcription relies on the interplay between local and longrange controls. To study this complex genomic organization, we designed a strategy combining meiotic and targeted recombinations to induce large chromosomal rearrangements in vivo without manipulating embryonic stem cells. With this simple approach (called STRING), we engineered a large 7-cM inversion, which split the Hoxd cluster into two independent pieces. Expression analyses showed a partition of global enhancers, allowing for their precise topographic allocation on either side of the cluster. Such a functional organization probably contributed to keeping these genes clustered in the course of vertebrate evolution. This approach can be used to study the relationship between genome architecture and gene expression, such as the effects of genome rearrangements in human diseases or during evolution.
The Lancet, 1995
's health a challenge to us all. London: HM Stationery Office, 1992. 4 Garraway WM, MacLeod DAD, ... more 's health a challenge to us all. London: HM Stationery Office, 1992. 4 Garraway WM, MacLeod DAD, Sharp JCM. Rugby injuries: the need for case registers. BMJ 1991; 303: 1082-03.
The Journal of Pediatrics, 2002
Journal of Allergy and Clinical Immunology, 2013
Immunogenetics, 1988
In development, T cells first express their c~/3 antigen receptors in the thymus, where they may ... more In development, T cells first express their c~/3 antigen receptors in the thymus, where they may undergo selection processes leading to major histocompatibility complex (MHC) restriction and tolerance. A high proportion of thymocytes are thought to fail this selection in some way and to be destined for intrathymic death. These cells are categorized as the" cortical type" since they constitute most of the cortical cells; they express both CD4 and CD8 antigens but only very low levels of MHC class I antigens. One suggested cause of thymocyte death is a failure to produce a functional c~/3 T cell receptor (Tcr) due to errors in the rearrangements of germline DNA, resulting in V regions being absent or incorrectly spliced to the other segments of the transcribed gene. We have sequenced from the C region through to the V region of 14 rat Tcr /3 Chain clones isolated from thymocyte cDNA libraries. Of the 14, 13 have complete and correct rearrangements, whereas one was expressed from an unrearranged gene. Most of these clones are likely to be derived from the cortical population, for Northern blot analysis showed that these cells and total thymocytes expressed similar amounts of/3 chain mRNA. Furthermore, the RNA from cortical-type cells contained a very similar ratio of full-length to truncated/3 chain mRNA as did activated thymocytes and mature T lymphocytes. The data imply that defective/3 chain gene rearrangement is not a major cause of failure in the selection of thymocytes. The sequences of the rat Tcr c~ and /3 chain constant regions are also reported.
Human Mutation, 1997
MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of majo... more MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of major histocompatibility complex class II (MHC-II) gene expression. It is genetically heterogeneous and can result from defects in at least four different trans-acting regulatory genes required for transcription of MHC-II genes. One of these genes has recently been shown to encode a novel DNA binding protein called RFX5, which is one subunit of a heteromeric protein complex (RFX) that binds to the promoters of MHC-II genes. We have characterised the mutations in all four patients known to harbour a defect in the RFX5 gene and have mapped this new human disease gene to chromosome 1 band q21, a region frequently exhibiting chromosomal aberrations in a variety of preneoplastic and neoplastic diseases.
Human Mutation, 2011
Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis:... more Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis: the established traditional nomenclature system and the more recent Human Genome Variation Society (HGVS) nomenclature system. We have evaluated the use of both systems in the laboratory reports of 217 participants in the cystic fibrosis external quality assessment scheme of 2009. The mutation c.1521_1523delCTT (p.Phe508del, F508del) was described by traditional and HGVS nomenclature by 32 of 216 (15%) laboratories that correctly identified the mutation, whereas 171 (79%) laboratories used traditional nomenclature only and 13 (6%) laboratories used HGVS nomenclature only. Overall, 29 of 631 (5%) reports used nomenclature that was evaluated as being seriously incorrect and/or misleading and 136 (22%) reports contained attempts at HGVS coding, of which 104 (76%) contained no coding errors; just 33 (24%) mentioned the correct cDNA name and cited the nucleotide reference sequence. We recognized an urgent need for more consistent and correct usage of nomenclature. We recommended that cystic fibrosis transmembrane conductance regulator testing reports should include a description of the identified sequence variants in both HGVS and traditional nomenclature and provided basic recommendations and other guidance.