Document Detail


Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree by 500 K SNP arrays.
MedLine Citation:
PMID:  18513678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Robust SNP genotyping technologies and data analysis programs have encouraged researchers in recent years to use SNPs for linkage studies. Platforms used to date have been 10 K chip arrays, but the possible value of interrogating SNPs at higher densities has been considered. Here, we present a genome-wide linkage analysis by means of a 500 K SNP platform. The analysis was done on a large pedigree affected with Parkinsonian-pyramidal syndrome (PPS), and the results showed linkage to chromosome 22. Sequencing of candidate genes revealed a disease-associated homozygous variation (R378G) in FBXO7. FBXO7 codes for a member of the F-box family of proteins, all of which may have a role in the ubiquitin-proteosome protein-degradation pathway. This pathway has been implicated in various neurodegenerative diseases, and identification of FBXO7 as the causative gene of PPS is expected to shed new light on its role. The performance of the array was assessed and systematic analysis of effects of SNP density reduction was performed with the real experimental data. Our results suggest that linkage in our pedigree may have been missed had we used chips containing less than 100,000 SNPs across the genome.
Authors:
Seyedmehdi Shojaee; Farzad Sina; Setareh Sadat Banihosseini; Mohammad Hossein Kazemi; Reza Kalhor; Gholam-Ali Shahidi; Hossein Fakhrai-Rad; Mostafa Ronaghi; Elahe Elahi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of human genetics     Volume:  82     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-03     Completed Date:  2008-06-27     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1375-84     Citation Subset:  IM    
Affiliation:
Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Chromosomes, Human, Pair 22 / genetics
F-Box Proteins / genetics
Female
Genome, Human
Humans
Linkage (Genetics)
Lod Score
Male
Oligonucleotide Array Sequence Analysis
Parkinson Disease / genetics*
Pedigree
Phenotype
Point Mutation
Polymorphism, Single Nucleotide*
Pyramidal Tracts*
Synapsins / genetics
Syndrome
Chemical
Reg. No./Substance:
0/F-Box Proteins; 0/FBXO7 protein, human; 0/SYN3 protein, human; 0/Synapsins
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