Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree by 500 KSNP arrays

被引：170

作者：

Shojaee, Seyedmehdi ^{[1
]}

Sina, Farzad ^{[4
]}

Banihosseini, Setareh Sadat ^{[5
]}

Kazemi, Mohammad Hossein ^{[5
]}

Kalhor, Reza ^{[6
]}

Shahidi, Gholam-Ali ^{[4
]}

Fakhrai-Rad, Hossein ^{[7
]}

Ronaghi, Mostafa ^{[7
]}

Elahi, Elahe ^{[2
,3
]}

机构：

[1] Univ Tehran, Coll Sci, Sch Biol, Tehran, Iran

[2] Univ Tehran, Coll Sci, Sch Math Stat & Comp Sci, Ctr Excellence Biomath, Tehran, Iran

[3] Univ Tehran, Coll Sci, Dept Biotechnol, Tehran, Iran

[4] Iran Univ Med Sci, Hazrat Rasool Hosp, Tehran, Iran

[5] Univ Tehran Med Sci, Tehran, Iran

[6] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA

[7] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2008年 / 82卷 / 06期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/j.ajhg.2008.05.005

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1375 / 1384

页数：10