Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

被引:39
作者
Jorgensen, TH
Borglum, AD
Mors, O
Wang, AG
Pinaud, M
Flint, TJ
Dahl, HA
Vang, M
Kruse, TA
Ewald, H
机构
[1] Aarhus Univ Hosp, Psychiat Hosp Aarhus, Dept Psychiat Demog, Inst Basic Psychiat Res, DK-8240 Risskov, Denmark
[2] Aarhus Univ Hosp, Psychiat Hosp Aarhus, Dept Biol Psychiat, Inst Basic Psychiat Res, DK-8240 Risskov, Denmark
[3] Univ Aarhus, Inst Human Genet, Aarhus, Denmark
[4] Natl Hosp, Dept Psychiat, Torshavn, Faroe Islands, Denmark
[5] Copenhagen Univ Hosp, Copenhagen, Denmark
[6] Odense Univ Hosp, Dept Clin Biochem & Genet, DK-5000 Odense, Denmark
来源
AMERICAN JOURNAL OF MEDICAL GENETICS | 2002年 / 114卷 / 02期
关键词
genetic association; haplotype sharing; WKL1; chromosome; 22q;
D O I
10.1002/ajmg.10191
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring with different frequencies in patients compared to controls. Two segments were of most interest when the results of the association tests were combined with the probabilities of identity by descent of single haplotypes. For bipolar patients, the strongest evidence for a candidate region harboring a risk gene was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P = 0.0075). Patients were tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161-D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:245 / 252
页数:8
相关论文
共 44 条
[1]  
American Psychiatric Association, 2000, Diagnostic and statistical manual of mental disorders, V5th, DOI [10.1176/appi.books.9780890425596, DOI 10.1176/APPI.BOOKS.9780890425596]
[2]   Genetics of schizophrenia and the new millennium: Progress and pitfalls [J].
Baron, M .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (02) :299-312
[3]   22q11 deletion syndrome: A genetic subtype of schizophrenia [J].
Bassett, AS ;
Chow, EWC .
BIOLOGICAL PSYCHIATRY, 1999, 46 (07) :882-891
[4]   Are schizophrenic and bipolar disorders related? A review of family and molecular studies [J].
Berrettini, WH .
BIOLOGICAL PSYCHIATRY, 2000, 48 (06) :531-538
[5]   Affected sibling pair linkage analysis of qualitative and quantitative traits for schizophrenia on chromosome 22 in a Chinese population [J].
Cai, GQ ;
Li, T ;
Deng, D ;
Zhao, JH ;
Hu, X ;
Murray, RM ;
Liu, XH ;
Sham, PC ;
Collier, DA .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2001, 105 (04) :321-327
[6]   GENOMIC SCAN FOR GENES PREDISPOSING TO SCHIZOPHRENIA [J].
COON, H ;
JENSEN, S ;
HOLIK, J ;
HOFF, M ;
MYLESWORSLEY, M ;
REIMHERR, F ;
WENDER, P ;
WALDO, M ;
FREEDMAN, R ;
LEPPERT, M ;
BYERLEY, W .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1994, 54 (01) :59-71
[7]   Further evidence for a bipolar risk gene on chromosome 12q24 suggested by investigation of haplotype sharing and allelic association in patients from the Faroe Islands [J].
Degn, B ;
Lundorf, MD ;
Wang, A ;
Vang, M ;
Mors, O ;
Kruse, TA ;
Ewald, H .
MOLECULAR PSYCHIATRY, 2001, 6 (04) :450-455
[8]   Genome scanning for segments shared identical by descent among distant relatives in isolated populations [J].
Durham, LK ;
Feingold, E .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (04) :830-842
[9]  
Eaves IA, 2000, NAT GENET, V25, P320
[10]   A common molecular basis for rearrangement disorders on chromosome 22q11 [J].
Edelmann, L ;
Pandita, RK ;
Spiteri, E ;
Funke, B ;
Goldberg, R ;
Palanisamy, N ;
Chaganti, RSK ;
Magenis, E ;
Shprintzen, RJ ;
Morrow, BE .
HUMAN MOLECULAR GENETICS, 1999, 8 (07) :1157-1167