Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree
- 1 March 2004
- journal article
- Published by Wolters Kluwer Health in Psychiatric Genetics
- Vol. 14 (1) , 1-8
- https://doi.org/10.1097/00041444-200403000-00001
Abstract
We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 10p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.Keywords
This publication has 25 references indexed in Scilit:
- Erratum: Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11Molecular Psychiatry, 2000
- Long Homozygous Chromosomal Segments in Reference Families from the Centre d'Étude du Polymorphisme HumainAmerican Journal of Human Genetics, 1999
- Linkage-Disequilibrium Mapping of Disease Genes by Reconstruction of Ancestral Haplotypes in Founder PopulationsAmerican Journal of Human Genetics, 1999
- Support for a possible schizophrenia vulnerability locus in region 5q22–31 in Irish familiesMolecular Psychiatry, 1997
- Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populationsHuman Genetics, 1997
- Linkage studies on chromosome 22 in familial schizophreniaAmerican Journal of Medical Genetics, 1995
- Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32Psychiatric Genetics, 1995
- Chromosome 22 markers demonstrate transmission disequilibrium with schizophreniaPsychiatric Genetics, 1995
- Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasisNature Genetics, 1994
- Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22Human Molecular Genetics, 1994