Journal article
Association of the HOPA12bp allele with a large X-chromosome haplotype and positive symptom schizophrenia
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.127B(1), pp.20-27
05/15/2004
DOI: 10.1002/ajmg.b.20175
PMID: 15108174
Abstract
HOPA is a X-chromosome gene that encodes an essential nuclear receptor co-activator. Previously, we have demonstrated that an exonic polymorphism, termed HOPA(12bp), in the Opa (Opposite Paired) domain of this gene that is critical for neuronal growth and differentiation is associated with a low risk for schizophrenia. But curiously, we have also noted that all HOPA(12bp) probands have the same haplotype immediately surrounding the HOPA(12bp), and other investigators have found evidence of population stratification with the HOPA(12bp) allele. Since deleterious alleles are weeded from the population, and the HOPA(12bp) allele is not rare, these prior findings suggest the possibility that positive selection may be occurring with respect to the HOPA(12bp) allele and that unique phenotypic features may be associated with this allele. To test these hypotheses, we analyzed symptom data collected from schizophrenic probands and conducted haplotyping studies around the HOPA(12bp) polymorphism. Consistent with our hypotheses, genotyping studies of 43 unrelated HOPA(12bp) males and 137 HOPA(wild) males demonstrated that the HOPA(12bp) allele is associated with a large conserved DNA haplotype that extends over several genes known to be critical for human survival. Furthermore, ANOVA analysis of symptom data demonstrated that HOPA(12bp) schizophrenic probands (n = 14) have significantly lower severity of negative symptoms (P < 0.002) and better attention (P < 0.002) than matched controls (n = 30). Taken together, these findings further refine the behavioral endophenotype associated with the HOPA(12bp) allele and suggest that the sequence surrounding HOPA may need to be considered to fully understand the molecular basis of the phenotype associated with the HOPA(12bp) allele.
Details
- Title: Subtitle
- Association of the HOPA12bp allele with a large X-chromosome haplotype and positive symptom schizophrenia
- Creators
- Ruth Spinks - Department of Psychiatry, The University of Iowa, Psychiatry Research/MEB, Iowa City, USAHarinder K SandhuNancy C AndreasenRobert A Philibert
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.127B(1), pp.20-27
- Publisher
- United States
- DOI
- 10.1002/ajmg.b.20175
- PMID
- 15108174
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- MH31593 / NIMH NIH HHS MH40856 / NIMH NIH HHS MH43271 / NIMH NIH HHS MH60990 / NIMH NIH HHS K08MH064714 / NIMH NIH HHS
- Language
- English
- Date published
- 05/15/2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003414002771
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