Whole-Genome Genotyping Using DNA Microarrays for Population Genetics

Abstract

The field of population genetics has exploded in the last two decades following the sequencing of the human genome in 2001 (Green et al. Nature 526:29–31, 2015). Tools to measure genetic variation have matured significantly throughout this advancement in knowledge (Lenoir and Giannella. J Biomed Discov Collab 1:11, 2006; Marzancola et al. Methods Mol Biol 1368:161–178, 2016). In this chapter, the focus is on the laboratory methods developed to perform genome-wide genotyping utilizing DNA microarrays, which is one of the most commonly used molecular techniques to assess global genetic variation (Heller MJ, Annu Rev Biomed Eng 4:129-153, 2002). DNA microarrays allow for the interrogation of hundreds of thousands of SNPs (single nucleotide polymorphisms) at once utilizing array-based technology in conjunction with fluorescent molecular labels in a process referred to as genotyping (Marzancola et al. Methods Mol Biol 1368:161–178, 2016). Genotype data can be utilized to associate certain phenotypes in relation with specific genetic variants within a population in a process known as genome-wide association studies or GWAS (Charlesworth and Charlesworth. Heredity (Edinb) 118(1):2–9, 2017; Casillas and Barbadilla. Genetics 205(3):1003–1035, 2017). This experimental technique is a multiple-day process involving the combination of DNA extraction, amplification, fragmentation, binding, and staining (Illumina Infinium HTS Assay Protocol Guide, 2013). Many vendors supply platforms and products to assess global genetic variation using DNA microarrays (Illumina Infinium HTS Assay Protocol Guide, 2013). In this chapter, the focus is on the methods utilized to generate high-quality genotype data with the Illumina^® Infinium Global Screening Array. Although data analysis and quality control are not the focus for this chapter, they are also briefly addressed.