Genotyping and LOH Analysis on Archival Tissue using SNP Arrays

Genotyping is instrumental in the elucidation of the genetics underlying the cause of human diseases, such as cancer. Linkage analysis and association studies can improve our understanding of the relation between genetic information and disease phenotype and identify genomic loci that harbor disease-causing genes. Ultimately, this could result in the identification of the underlying genes. Linkage analysis, for example, led to the successful identification of genes that cause breast cancer, BRCA1 and 2 [1–3], and colorectal cancer, MLH1 and MSH2 [4–7]. Over the last few decades genotyping has evolved from time-consuming and low-throughput methods – such as the determination of restriction fragment length polymorphisms (RFLPs, [8]) or simple sequence length polymorphisms (SSLPs [9]) – to the high-throughput genotyping using single nucleotide polymorphism (SNP) arrays. In this chapter we will discuss methods and SNP array platforms for high-throughput genotyping with a focus on the use of DNA from formalin-fixed paraffin embedded (FFPE) tissue and the detection of loss of heterozygosity (LOH).