High‐Throughput Single Nucleotide Polymorphisms Genotyping Technologies


Genome‐wide association studies have successfully identified many novel genetic loci for various human complex diseases and quantitative traits. There are several important factors contributing to the feasibility of this approach; one of them is the rapid advancement in high‐throughput single nucleotide polymorphisms (SNPs) genotyping technologies which has enabled researchers to comprehensively interrogate the entire human genome. Almost all the studies that have been published up to date used commercially available whole‐genome genotyping arrays from Illumina® and Affymetrix®. The most prominent feature of these high‐throughput genotyping platforms is the ability to interrogate several hundred thousands to one million SNPs simultaneously in a microarray. The application of genotyping arrays is not only limited to association studies, but it has also been applied to many other human genetic studies. However, the rapid developments of sequencing technologies have started replacing the microarray experiments for both structural and functional genomics studies.

Key concepts:

  • Over the past three years, GWAS have been playing an important role in identifying novel genetic loci for various human complex diseases and quantitative traits.

  • The paradigm shift in genetic approach to GWAS has been attributed to several important developments, notably the rapid advancement in high‐throughput SNPs genotyping technologies.

  • High‐throughput SNPs genotyping technologies had enabled researchers to interrogate several hundred thousands to one million SNPs simultaneously in a microarray.

  • GWAS is a comprehensive and agnostic approach in the search for unknown disease variants, as such; the ability to interrogate large number of SNPs covering the entire human genome is a prerequisite to this study design.

  • Currently, Illumina® and Affymetrix® are the only two companies in the market who design and provide whole‐genome genotyping arrays for human genetic studies.

  • There are two commonly adopted approaches in SNPs selection for whole‐genome genotyping arrays: direct and indirect. Direct approach focuses on selecting SNPs that are of putative functional importance. In contrast, indirect approach selects SNPs despite their functionality.

  • Genome coverage is an estimate of the proportion of SNPs (using the International HapMap data as reference) that can be captured by the SNPs which directly genotyped in an array with a preset r2 threshold.

  • Expeditious developments of sequencing technologies have started threatening the market of microarray.

  • Currently, the three next‐generation sequencing platforms are Illumina® Genome Analyzer, Roche® 454 GS‐FLX Sequencer and ABI® SOLiD Sequencer.

  • Sequencing approach has been quickly adopted for various applications in structural and functional genomic studies, for example, ChIP‐Seq, transcriptome profiling (RNA‐Seq) and paired‐end sequencing method to detect structural variations.

Keywords: single nucleotide polymorphisms; high‐throughput genotyping technologies; illumina; affymetrix; genome coverage

Figure 1.

Comparisons of genome coverage across several whole‐genome genotyping arrays from Illumina® and Affymetrix® in International HapMap populations. The y‐axis is the genome coverage in percentage. (see Li et al., ; Barrett and Cardon, ).



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Chee Seng, KU, Katherine, KASIMAN, and Kee Seng, CHIA(Sep 2009) High‐Throughput Single Nucleotide Polymorphisms Genotyping Technologies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021631]