Sex-Linked Traits X chromosome Y chromosome Boy or Girl? The Y Chromosome “Decides”
Chromosome 22 workshop report
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Chromosome 22 Workshop Report Chair: Sibylle G. Schwab;* Co-Chair: Dieter B. Wildenauer Department of Psychiatry, University of Bonn, Germany Participants: D.A. Collier (Institute of Psychiatry, London, U.K.) A. Ekelund (National Public Health Institute, Helsinki, Finland) P. Gejman (University of Chicago, Chicago, Illinois) J. Hallmayer (University of Western Australia, Perth, Australia) J.R. Kelsoe (University of California, San Diego, California) A. von Gontard (University of Cologne, Cologne, Germany) D.B. Wildenauer (University of Bonn, Bonn, Germany) The chromosome 22 workshop took place at the Sixth World Congress on Psychiatric Ge- netics from October 6th–10th, 1998 in Bonn, Germany. Aim of the workshop was to sum- marize the findings in psychiatric genetics on chromosome 22. Four reports concerning a susceptibility locus for schizophrenia and one report on bipolar disorder were given. A potential locus for nocturnal enuresis has been suggested to reside on chromosome 22. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:276–278, 1999. © Wiley-Liss, Inc. INTRODUCTION The aim of this workshop was to summarize and map new findings in psychiatric disorders on chromosome 22. There have been four reports on findings in schizo- phrenia, one report on affective disorder, and one on nocturnal enuresis on chromosome 22. Reports of non- replication or exclusion of findings on chromosome 22 were communicated neither for schizophrenia nor bi- polar disorder. Figure 1 shows the distribution of findings on chro- mosome 22 as reported at the 1997 and 1998 chromo- some 22 workshops. Details of the data of the 1997 workshop have been given by Levinson and Coon [1998]. Data communicated at the 1998 workshop is given in the following report. SCHIZOPHRENIA Most of the reports at the first chromosome 22 work- shop in 1997 have focused on findings in schizophrenia [Levinson and Coon, 1998]. Positive findings seemed to cluster in a region of 4–5 cM on 22q13.1. This year Gejman et al. [1998] reported results on 76 schizo- phrenic families, which included 96 affected sib-pairs and consisted of more than 90% Caucasians. He ob- tained a maximum lod score of 1.1 (ASPEX) and a mini- mum p-value of .011 (SIBPAL) for the marker D22S279. This marker maps into the region that was first reported by Pulver and colleagues [Pulver et al., 1994a]. Ekelund and colleagues [Hovatta et al., 1998] have studied linkage in 62 families with a total of 137 schizophrenic cases. Parametric linkage analysis re- vealed a lod score of .88 for the marker D22S427, which maps about 40 cM proximal to the most positive region in schizophrenia, and a lod score of .77 for the marker D22S272, which maps within the most positive region. D. Collier gave a summary of results obtained in a Chi- nese sample of 180 triads and 80 sibling pairs [Collier et al., 1998]. A DNA pooling technique was used in a first stage to identify markers that show linkage dis- equilibrium (LD). Statistically significant evidence for LD was observed for the marker D22S278 and also for polymorphic markers within the COMT gene. For the COMT gene, data for LD was still statistically signifi- cant when they analyzed the haplotypes. S. Schwab summarized the data of chromosome 22 from a genome scan of the Bonn group [Hallmayer et al., 1998]. Sev- enty-two families, including 87 affected sib-pairs, were used for nonparametric analysis, identity by descent. Genehunter analysis revealed a maximum NPL of 1.91 (p 4 .02) for the marker D22S280. This result is still consistent with their report of last year, where they reported a maximum lod score of 1.1 (ASPEX) with the same marker in a subsample of 54 families [Zill et al., 1997]. Negative reports have not been communicated at this year’s workshop. In the literature, we found four negative reports on schizophrenia and chromosome 22. Parsian et al. [1997] analyzed markers in the neigh- borhood of IL2RB and found no evidence for a suscep- *Correspodence to: Sibylle G. Schwab, Molecular Genetics Laboratory, Department of Psychiatry, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany. E-mail: schwab@ uni-bonn.de American Journal of Medical Genetics (Neuropsychiatric Genetics) 88:276–278 (1999) © 1999 Wiley-Liss, Inc.
Transcript of Chromosome 22 workshop report
Chromosome 22 Workshop Report
Chair: Sibylle G. Schwab;* Co-Chair: Dieter B. WildenauerDepartment of Psychiatry, University of Bonn, Germany
Participants:D.A. Collier (Institute of Psychiatry, London, U.K.)A. Ekelund (National Public Health Institute, Helsinki, Finland)P. Gejman (University of Chicago, Chicago, Illinois)J. Hallmayer (University of Western Australia, Perth, Australia)J.R. Kelsoe (University of California, San Diego, California)A. von Gontard (University of Cologne, Cologne, Germany)D.B. Wildenauer (University of Bonn, Bonn, Germany)
The chromosome 22 workshop took place atthe Sixth World Congress on Psychiatric Ge-netics from October 6th–10th, 1998 in Bonn,Germany. Aim of the workshop was to sum-marize the findings in psychiatric geneticson chromosome 22. Four reports concerninga susceptibility locus for schizophrenia andone report on bipolar disorder were given. Apotential locus for nocturnal enuresis hasbeen suggested to reside on chromosome 22.Am. J. Med. Genet. (Neuropsychiatr. Genet.)88:276–278, 1999. © Wiley-Liss, Inc.
INTRODUCTION
The aim of this workshop was to summarize and mapnew findings in psychiatric disorders on chromosome22. There have been four reports on findings in schizo-phrenia, one report on affective disorder, and one onnocturnal enuresis on chromosome 22. Reports of non-replication or exclusion of findings on chromosome 22were communicated neither for schizophrenia nor bi-polar disorder.
Figure 1 shows the distribution of findings on chro-mosome 22 as reported at the 1997 and 1998 chromo-some 22 workshops. Details of the data of the 1997workshop have been given by Levinson and Coon[1998]. Data communicated at the 1998 workshop isgiven in the following report.
SCHIZOPHRENIA
Most of the reports at the first chromosome 22 work-shop in 1997 have focused on findings in schizophrenia
[Levinson and Coon, 1998]. Positive findings seemed tocluster in a region of 4–5 cM on 22q13.1. This yearGejman et al. [1998] reported results on 76 schizo-phrenic families, which included 96 affected sib-pairsand consisted of more than 90% Caucasians. He ob-tained a maximum lod score of 1.1 (ASPEX) and a mini-mum p-value of .011 (SIBPAL) for the markerD22S279. This marker maps into the region that wasfirst reported by Pulver and colleagues [Pulver et al.,1994a]. Ekelund and colleagues [Hovatta et al., 1998]have studied linkage in 62 families with a total of 137schizophrenic cases. Parametric linkage analysis re-vealed a lod score of .88 for the marker D22S427, whichmaps about 40 cM proximal to the most positive regionin schizophrenia, and a lod score of .77 for the markerD22S272, which maps within the most positive region.D. Collier gave a summary of results obtained in a Chi-nese sample of 180 triads and 80 sibling pairs [Collieret al., 1998]. A DNA pooling technique was used in afirst stage to identify markers that show linkage dis-equilibrium (LD). Statistically significant evidence forLD was observed for the marker D22S278 and also forpolymorphic markers within the COMT gene. For theCOMT gene, data for LD was still statistically signifi-cant when they analyzed the haplotypes. S. Schwabsummarized the data of chromosome 22 from a genomescan of the Bonn group [Hallmayer et al., 1998]. Sev-enty-two families, including 87 affected sib-pairs, wereused for nonparametric analysis, identity by descent.Genehunter analysis revealed a maximum NPL of 1.91(p 4 .02) for the marker D22S280. This result is stillconsistent with their report of last year, where theyreported a maximum lod score of 1.1 (ASPEX) with thesame marker in a subsample of 54 families [Zill et al.,1997].
Negative reports have not been communicated atthis year’s workshop. In the literature, we found fournegative reports on schizophrenia and chromosome 22.Parsian et al. [1997] analyzed markers in the neigh-borhood of IL2RB and found no evidence for a suscep-
*Correspodence to: Sibylle G. Schwab, Molecular GeneticsLaboratory, Department of Psychiatry, University of Bonn,Wilhelmstrasse 31, D-53111 Bonn, Germany. E-mail: [email protected]
American Journal of Medical Genetics (Neuropsychiatric Genetics) 88:276–278 (1999)
© 1999 Wiley-Liss, Inc.
tibility gene for schizophrenia. Williams et al. [1997]found no allelic association between markers D22S278and D22S283 in a case control study using schizo-phrenic patients. Riley et al. [1996] obtained no evi-dence for linkage in Southern African Bantu-speakingfamilies with schizophrenia. The first negative reporton schizophrenia and chromosome 22 became availablein 1994, when Pulver and colleagues [1994b] reportedon a multicenter study with no linkage in the sameregion in which they first reported the positive linkage.
AFFECTIVE DISORDER
There has been only one report on chromosome 22and affective disorder. J. Kelsoe et al. [1998] studied 20families with a total of 164 subjects, 46 individualswith bipolar disorder and 38 with recurrent depression.A maximum lod score of 3.8 was obtained for themarker D22S278. This marker maps in exactly the
same region where most of the positive results inschizophrenia were reported and linkage disequilib-rium in schizophrenic subjects has been detected[Levinson and Coon, 1998]. Compared with their lastyear’s report on a subsample of 13 families [Lachmannet al., 1997], the maximum lod score has moved about15 cM distal. No negative reports have been communi-cated.
NOCTURNAL ENURESISA. von Gontard and colleagues have analyzed chro-
mosome 22 markers in 35 families including 42 chil-dren suffering from nocturnal enuresis [von Gontard etal., 1998]. Linkage analysis with the marker D22S446revealed a lod score of 3.52 in a subset of 11 families (14patients). The marker is located about 10 cM distal tothe COMT gene. Locus heterogeneity was assumedsince no positive linkage could be detected in the 24remaining families.
Fig. 1. Ideogram of chromosome 22 with markers that were reported positive in psychiatric disorders at the chromosome workshops of the Fifth andSixth International Congress of Psychiatric Genetics in Santa Fe, N. Mex. (1997), and in Bonn, Germany (1998). Map positions were taken from theMarshfield map (http://www.marshmed.org/genetics/). d lod score or NPL between 0 and 1, or p-value #.05 in schizophrenia; l lod score or NPL between1 and 2, or p-value #.01 in schizophrenia; j lod score or NPL >2 or p-value #.001 in schizophrenia; lod score >2 in bipolar disorder; lod score >2 innocturnal enuresis. References: (1) Pulver et al. [1994a]; (2) Lasseter et al. [1995]; (3) Gill et al. [1996]; (4) Vallada et al. [1997]; (5) Polymeropoulos etal. [1994]; (6) Zill et al. [1997]; (7) Murphy et al. [1997]; (8) Shaw et al. [1998]; (9) Levinson et al. [1998]; (10) Straub et al. [1997]; (11) Coon et al. [1994a,1994b]; (12) Coon at al. in Levinson and Coon [1998]; (13) Lachman et al. [1997]; (14) Gejman et al. [1998]; (15) Hovatta et al. [1998]; (16) Collier et al.[1998]; (17) Hallmayer et al. [1998]; (18) Kelsoe et al. [1998]; (19) von Gontard et al. [1998].
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CONCLUSION
Positive reports on schizophrenia seem to concen-trate in a region around the markers D22S278 toD22S279. Three groups provided additional evidencefor a susceptibility gene for schizophrenia in this areaby linkage analysis as well as by linkage disequilib-rium analysis. There was also some evidence for a sus-ceptibility locus for affective disorder in this region[Kelsoe et al., 1998]. One additional trait has beenmapped to chromosome 22: the trait for nocturnal en-uresis was mapped about 15 cM proximal to the region,that is the most positive in schizophrenia.
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