Genome-wide Linkage Analysis of a Parkinsonian-Pyramidal Syndrome Pedigree by 500 K SNP Arrays

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 genom...

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Bibliographic Details
Published in:American journal of human genetics 2008-06, Vol.82 (6), p.1375-1384
Main Authors: Shojaee, Seyedmehdi, Sina, Farzad, Banihosseini, Setareh Sadat, Kazemi, Mohammad Hossein, Kalhor, Reza, Shahidi, Gholam-Ali, Fakhrai-Rad, Hossein, Ronaghi, Mostafa, Elahi, Elahe
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Chromosomes, Human, Pair 22 - genetics
F-Box Proteins - genetics
Female
Genetic Linkage
Genome, Human
Humans
Lod Score
Male
Oligonucleotide Array Sequence Analysis
Parkinson Disease - genetics
Pedigree
Phenotype
Point Mutation
Polymorphism, Single Nucleotide
Pyramidal Tracts
Synapsins - genetics
Syndrome
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2008.05.005