Linkage disequlibrium in the DTNBP1 (dysbindin) gene region and on chromosome 1p36 among psychotic patients from a genetic isolate in Israel: findings from identity by descent haplotype sharing analysis.
Several genes have been reported recently to be associated with schizophrenia and bipolar disorder. Because of the complexity of the inheritance of these disorders, there is an urgent need to replicate these findings and to search for additional candidate genes. The study of genetic isolates is a powerful technique that may overcome some of the obstacles caused by genetic heterogeneity and ambiguity of phenotype definition. Identity by descent (IBD) haplotype sharing analysis in these populations may be used to detect mutations within shared haplotypes in smaller samples of affected individuals. In this study, we used IBD haplotype sharing analysis to replicate positive linkage and association findings in psychotic disorders, and to identify other regions of interest. Fifty-two patients with major psychiatric disorders from a genetically isolated village in Israel were studied. By studying eight Y chromosome markers, we were able to confirm the oral tradition of members of this isolate regarding a common paternal origin. Three hundred fifty nine microsatellite markers on 9 candidate chromosomes were genotyped, and haplotypes were reconstructed using information from family members. Two highly significant (P < 0.0001) peaks of haplotype sharing were found. One was for psychotic patients with any diagnosis at the location of dysbindin, a gene previously associated with schizophrenia. The other peak was for patients with schizophrenia on chromosome 1p36. Thus, this study both replicates an earlier finding and points to a novel region of interest, which might be unique to this population.
Kohn
Yoav
Y
Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120. kohn@md2.huji.ac.il
Danilovich
Eduardo
E
Filon
Dvorah
D
Oppenheim
Ariella
A
Karni
Osnat
O
Kanyas
Kyra
K
Turetsky
Neil
N
Korner
Mira
M
Lerer
Bernard
B
D002352:Carrier Proteins / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D041322:Chromosomes, Human, Y; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D018703:Founder Effect; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D007557:Israel / Q000453:epidemiology; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008957:Models, Genetic; D011618:Psychotic Disorders / Q000235:genetics*
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers