Biomedical Engineering Reference
In-Depth Information
Genotyping and LOH Analysis
on Archival Tissue Using
SNP Arrays
Ronald van Eijk, Anneke Middeldorp, Esther H. Lips, Marjo van Puijenbroek,
Hans Morreau, Jan Oosting and Tom van Wezel
Department of Pathology, Leiden University Medical Center, Leiden,
The Netherlands
3.1 Introduction
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 under-
standing of the relation between genetic information and disease phenotype and identify
genomic loci that harbor disease-causing genes. Ultimately, this could result in the iden-
tification 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 can-
cer,
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).
