Genome Screen to Identify Susceptibility Genes for Parkinson Disease in a Sample without parkin Mutations
| Autor: | William C. Nichols, P. Michael Conneally, Tatiana Foroud, Alice Rudolph, Cheryl Halter, Cliff Shults, Sean K. Uniacke, Nathan Pankratz |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
X Chromosome
Genetic Linkage Ubiquitin-Protein Ligases Biology medicine.disease_cause Parkin Genetic determinism Ligases 03 medical and health sciences 0302 clinical medicine Genetic linkage medicine Genetics Humans Genetics(clinical) Genetic Testing Sibling 10. No inequality Genetics (clinical) X chromosome 030304 developmental biology Genetic testing 0303 health sciences Mutation Chromosomes Human Pair 13 Models Genetic medicine.diagnostic_test Genome Human Genetic heterogeneity Chromosome Mapping Parkinson Disease Articles nervous system diseases Chromosomes Human Pair 2 Chromosomes Human Pair 5 Chromosomes Human Pair 4 Lod Score 030217 neurology & neurosurgery |
| Zdroj: | The American Journal of Human Genetics. (1):124-135 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/341282 |
| Popis: | Parkinson disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity, and postural instability, as well as by a clinically significant response to treatment with levodopa. Mutations in the alpha-synuclein gene have been found to result in autosomal dominant PD, and mutations in the parkin gene produce autosomal recessive juvenile-onset PD. We have studied 203 sibling pairs with PD who were evaluated by a rigorous neurological assessment based on (a) inclusion criteria consisting of clinical features highly associated with autopsy-confirmed PD and (b) exclusion criteria highly associated with other, non-PD pathological diagnoses. Families with positive LOD scores for a marker in an intron of the parkin gene were prioritized for parkin-gene testing, and mutations in the parkin gene were identified in 22 families. To reduce genetic heterogeneity, these families were not included in subsequent genome-screen analysis. Thus, a total of 160 multiplex families without evidence of a parkin mutation were used in multipoint nonparametric linkage analysis to identify PD-susceptibility genes. Two models of PD affection status were considered: model I included only those individuals with a more stringent diagnosis of verified PD (96 sibling pairs from 90 families), whereas model II included all examined individuals as affected, regardless of their final diagnostic classification (170 sibling pairs from 160 families). Under model I, the highest LOD scores were observed on chromosome X (LOD score 2.1) and on chromosome 2 (LOD score 1.9). Analyses performed with all available sibling pairs (model II) found even greater evidence of linkage to chromosome X (LOD score 2.7) and to chromosome 2 (LOD score 2.5). Evidence of linkage was also found to chromosomes 4, 5, and 13 (LOD scores1.5). Our findings are consistent with those of other linkage studies that have reported linkage to chromosomes 5 and X. |
| Databáze: | OpenAIRE |
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