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RFLP linkage study in schizophrenia on chromosome 2
89
I.A.2
I. Genetics
A LINKAGE STUDY OF SCHIZOPHRENIA WITH DNA MARKERS FROM THE LONG ARM OF CHROMOSOME 11
LA. MOLECULAR GENETIC LINKAGE AND ASSOCIATION STUDIES
M. Gill’, P. McGuffin3, E. Parfitt3*4 R. Mant3*4, P. Asherson’, H. Vallada’, D. Collier’, J. Powell’, C. Taylor’, M. Sargeant3, A. Clements’, S. Nanko’, S. Whatley’, R. Murray’ and M. 0wen3*4-
1.A.I RFLP LINKAGE STUD%’ IN SCHIZOPHRENIA ON CHROMOSOME ,
2
H.N. Aschauer’, K. Meszaros’, G. Aschauer-Treiber’, K.E. Isenberg2, U. Willinger’, K. Fuchs’, W. Sieghart’, H. Beran’, M. Lang’, R. Strobl’, R.D. Todd’, T. Reich’ and C.R. C10ninger2
’ University of Vienna, Department of Psychiatry, Wiihringer Giirtel 18-20. A-1090 Vienna, Austria, and ‘Washington University, Department of Psychiatry, St. Louis, MO U.S.A.
A RFLP linkage study was performed in a collaboration between the Departments of Psychiatry at Washington University, St. Louis and the University of Vienna. Families were ascertained and sampled in the U.S.A. and Austria using the same methods (affected sib-pairs); interviews were performed and blind consensus diagnoses (DSM IIIR) were done. Genotyping for various RFLPs was performed at both sites for the respective families. Linkage analyses were performed together (LINKAGE program). Previous publications were used for assumptions with respect to RFLP markers, including the presumed order of loci on chromosome 2. Different models of affection status were calculated: a narrow model with only schizophrenics as affected cases, an intermediate model including schizophrenia and ‘spectrum diagnoses’, a broad model including all diagnoses on axis I in the affected cases. Penetrances were fixed at 1.0 and 0.001 for the two homozygotes and were varied for the heterozygotes with regard to the different affection status models. In addition we calculated a model coding all unaffected cases as ‘unknown’. Two-point MLINK runs showed LOD-scores above +2. LINKMAP analyses were performed and resulted also in LODscores above +2. Together with a report of a translocation between chromosome 2 and chromosome I8 in a family of a schizophrenic patient and his psychiatrically affected child, our linkage result should encourage further studies in this region. Supported by FWF, Vienna, Pr.Nr. 225M and 7639.
‘Genetics Section, Department of Psychiatry, Institute of Psychiatry, DeCrespigny Park, London SE5 8AE U.K., ‘Department of Neurosciences. Institute of Psychiatry, 3Department of Psychological Medicine, 4Department of Medical Genetics, University of Wales College of Medicine, Card& (I. K. and 5Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan
We report the results of a collaborative linkage study using 9 polymorphic markers (8 loci) from chromosome I Iq and 23 families affected with schizophrenia and other related disorders. 186 members of the families were genotyped; these included 69 diagnoses of schizophrenia, IO of schizoaffective disorder, 6 atypical psychoses, IO major depressions and 5 bipolar affective disorders. In order to avoid the possibility of false negative results we have analysed our data using a range of single gene models from near dominant to recessive. Our results suggest that most of the region can be excluded from containing a gene of major effect it the aetiology of this disease, including the candidate genes DRD2, N-CAM and PBGD. Analysis of data from the marker at DllS35 assuming an intermediate genetic model, which best fits the observed distribution of schizophrenia in the general population and in the relatives of schizophrenics, gives a Z,,, of 3.08 at 0= 0.10. When this is conservatively corrected for the number of genetic and diagnostic models tested, the Z,,, = 1.8 and thus should be interpreted as only suggestive evidence for linkage. In support of the finding is that the Z,,,,, occurs at the approximate position of the translocation breakpoint reported by St Clair et al. (1990; Lancet 336: 13-19).
I.A.3 LINKAGE ANALYSIS OF SCHIZOPHRENIA ON CHROMOSOME 22 David A. Collier’, Michael Gill’, Shen Nanko’, Owen3 and Homer0 Vallada’a*
Mike
‘The Institute of Psychiatry, Denmark Hill, London SE5 8AE U.K., ‘Teikyo School of Medicine, Tokyo, Japan and ‘University of Wales College of Medicine, Cardtfl, U.K.
Despite strong evidence for a major genetic contribution to the etiology of schizophrenia, genetic markers have not been reproducibly linked to this disease in either family genetic
I.A.2
I. Genetics
A LINKAGE STUDY OF SCHIZOPHRENIA WITH DNA MARKERS FROM THE LONG ARM OF CHROMOSOME 11
LA. MOLECULAR GENETIC LINKAGE AND ASSOCIATION STUDIES
M. Gill’, P. McGuffin3, E. Parfitt3*4 R. Mant3*4, P. Asherson’, H. Vallada’, D. Collier’, J. Powell’, C. Taylor’, M. Sargeant3, A. Clements’, S. Nanko’, S. Whatley’, R. Murray’ and M. 0wen3*4-
1.A.I RFLP LINKAGE STUD%’ IN SCHIZOPHRENIA ON CHROMOSOME ,
2
H.N. Aschauer’, K. Meszaros’, G. Aschauer-Treiber’, K.E. Isenberg2, U. Willinger’, K. Fuchs’, W. Sieghart’, H. Beran’, M. Lang’, R. Strobl’, R.D. Todd’, T. Reich’ and C.R. C10ninger2
’ University of Vienna, Department of Psychiatry, Wiihringer Giirtel 18-20. A-1090 Vienna, Austria, and ‘Washington University, Department of Psychiatry, St. Louis, MO U.S.A.
A RFLP linkage study was performed in a collaboration between the Departments of Psychiatry at Washington University, St. Louis and the University of Vienna. Families were ascertained and sampled in the U.S.A. and Austria using the same methods (affected sib-pairs); interviews were performed and blind consensus diagnoses (DSM IIIR) were done. Genotyping for various RFLPs was performed at both sites for the respective families. Linkage analyses were performed together (LINKAGE program). Previous publications were used for assumptions with respect to RFLP markers, including the presumed order of loci on chromosome 2. Different models of affection status were calculated: a narrow model with only schizophrenics as affected cases, an intermediate model including schizophrenia and ‘spectrum diagnoses’, a broad model including all diagnoses on axis I in the affected cases. Penetrances were fixed at 1.0 and 0.001 for the two homozygotes and were varied for the heterozygotes with regard to the different affection status models. In addition we calculated a model coding all unaffected cases as ‘unknown’. Two-point MLINK runs showed LOD-scores above +2. LINKMAP analyses were performed and resulted also in LODscores above +2. Together with a report of a translocation between chromosome 2 and chromosome I8 in a family of a schizophrenic patient and his psychiatrically affected child, our linkage result should encourage further studies in this region. Supported by FWF, Vienna, Pr.Nr. 225M and 7639.
‘Genetics Section, Department of Psychiatry, Institute of Psychiatry, DeCrespigny Park, London SE5 8AE U.K., ‘Department of Neurosciences. Institute of Psychiatry, 3Department of Psychological Medicine, 4Department of Medical Genetics, University of Wales College of Medicine, Card& (I. K. and 5Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan
We report the results of a collaborative linkage study using 9 polymorphic markers (8 loci) from chromosome I Iq and 23 families affected with schizophrenia and other related disorders. 186 members of the families were genotyped; these included 69 diagnoses of schizophrenia, IO of schizoaffective disorder, 6 atypical psychoses, IO major depressions and 5 bipolar affective disorders. In order to avoid the possibility of false negative results we have analysed our data using a range of single gene models from near dominant to recessive. Our results suggest that most of the region can be excluded from containing a gene of major effect it the aetiology of this disease, including the candidate genes DRD2, N-CAM and PBGD. Analysis of data from the marker at DllS35 assuming an intermediate genetic model, which best fits the observed distribution of schizophrenia in the general population and in the relatives of schizophrenics, gives a Z,,, of 3.08 at 0= 0.10. When this is conservatively corrected for the number of genetic and diagnostic models tested, the Z,,, = 1.8 and thus should be interpreted as only suggestive evidence for linkage. In support of the finding is that the Z,,,,, occurs at the approximate position of the translocation breakpoint reported by St Clair et al. (1990; Lancet 336: 13-19).
I.A.3 LINKAGE ANALYSIS OF SCHIZOPHRENIA ON CHROMOSOME 22 David A. Collier’, Michael Gill’, Shen Nanko’, Owen3 and Homer0 Vallada’a*
Mike
‘The Institute of Psychiatry, Denmark Hill, London SE5 8AE U.K., ‘Teikyo School of Medicine, Tokyo, Japan and ‘University of Wales College of Medicine, Cardtfl, U.K.
Despite strong evidence for a major genetic contribution to the etiology of schizophrenia, genetic markers have not been reproducibly linked to this disease in either family genetic