ABSTRACT

The earliest of methods to be applied to the analysis of DNA sequence variation were renaturation studies, which were used for obtaining a global view of variation between species.1 Southern analysis2 and the Restriction Fragment Length Polymorphism (RFLP)3 enabled the analysis of specific polymorphisms and showed the power of molecular tests in genetics. The desire to explore the sequence variation underpinning genetic traits has brought a need to perform molecular tests on a large scale.4 Single nucleotide polymorphisms (SNPs) are the most abundant form of sequence variation. Where the number of SNPs to be analyzed is small, initial optimization of PCR and genotyping can be followed by high-throughput screening in

large populations. However, the study of complex traits5 by association studies requires analysis of sequence variation in both a large number of individuals and a large number of loci; here undertaking a prior optimization effort is too large a task.