Parallel Genotyping of Over 10,000 SNPs Using a One-Primer Assay on a High-Density Oligonucleotide Array

2005/1/3

生資所 陳孟均

Abstract

The study presents a high-throughput genotyping platform that uses a one-primer assay to genotype over 10,000 SNPs per individual on a single oligonucleotide array. This approach uses restriction digestion to fractionate the genome, followed by amplification of a specific fractionated subset of the genome. The resulting reduction in genome complexity enables allele-specific hybridization to the array. The selection of SNPs was primarily determined by computer-predicted lengths of restriction fragments containing the SNPs, and was further driven by strict empirical measurements of accuracy, reproducibility, and average call rate. With average heterozygosity of 0.38 and genome scan resolution of 0.31 cM, the SNP array is a viable alternative to panels of microsatellites (STRs). As a demonstration of the utility of the genotyping platform in whole-genome scans, this study have replicated and refined a linkage region on chromosome 2p for chronic mucocutaneous candidiasis and thyroid disease, previously identified using a panel of microsatellite (STR) markers

Author: Hajime Matsuzaki, Halina Loi, Shoulian Dong, Ya-Yu Tsai, Joy Fang, Jane Law, Xiaojun Di, Wei-Min Liu, Geoffrey Yang, Guoying Liu, Jing Huang, Giulia C. Kennedy, Thomas B. Ryde, Gregory A. Marcus, P. Sean Walsh, Mark D. Shriver, Jennifer M. Puck, Keith W. Jones and Rui Mei

Source: Genome Res., Mar 2004; 14: 414 - 425

Reference:

1. Atkinson, T.P., Schaffer, A.A., Grimbacher, B., Schroeder Jr., H.W., Woellner, C., Zerbe, C.S., and Puck, J.M. 2001. An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family. Am. J. Hum. Genet. 69: 791–803.[CrossRef][Medline]

2. Cutler, D.J., Zwick, M.E., Carrasquillo, M.M., Yohn, C.T., Tobin, K.P., Kashuk, C., Mathews, D.J., Shah, N.A., Eichler, E.E., Warrington, J.A., et al. 2001. High-throughput variation detection and genotyping using microarrays. Genome Res. 11: 1913–1925.[Abstract/Free Full Text]

3. Dong, S., Wang, E., Hsie, L., Cao, Y., Chen, X., and Gingeras, T.R. 2001. Flexible use of high-density oligonucleotide arrays for single-nucleotide polymorphism discovery and validation. Genome Res. 11: 1418–1424.[Abstract/Free Full Text]

4. Liu, W.-m., Di, X., Yang, G., Matsuzaki, H., Huang, J., Mei, R., Ryder, T.B., Webster, T.A., Dong, S., Liu, G., et al. 2003. Algorithms for large scale genotyping microarrays. Bioinformatics 19: 2397–2403.[Abstract/Free Full Text]

5. Tsuchihashi, Z. and Dracopoli, N.C. 2002. Progress in high throughput SNP genotyping methods. Pharmacogenomics J. 2: 103–110.[CrossRef][Medline]