Genotyping

Genetic studies in both haploid and diploid organisms rely on our ability to accurately interrogate polymorphic sites in the genome: that is single base positions or sequence segments in the genome that occur in two or more alleles in the population. Bi-allelic markers such as Single Nucleotide Polymorphisms (SNPs) and small insertion deletions (INDELS) have largely replaced microsatellites as they are amenable to automation and high level of multiplexing.

The aim of our facility is to implement a combination of robust genotyping platforms to undertake large-scale genetic analyses. The facility houses multiple high-throughput genotyping platforms including Illumina (Golden Gate and Infinium assays), Affymetrix (Gene Chip), Sequenom (iPLEX and homogeneous mass extend assays) and Taqman (ABI). In addition to accuracy, we select platforms on the basis of study design, throughput, cost efficiency, and DNA consumption. The latter is very important in studies with irreplaceable clinical samples available in finite quantities. Research activities focus on issues surrounding sample quality and optimisation of calling algorithms, both of paramount importance since the advent of genome-wide genotyping based on array technology developed by both Affymetrix and Illumina.

We have made substantial contributions to major International projects such as those undertaken by The SNP Consortium, the HapMap consortium and the Wellcome Trust Case Control Consortium in addition to participating in other collaborative genome wide association studies and replication studies.

Genotyping quality control

Disease association studies aim to identify variants with differences in frequency between cases and controls which are often small. Thus any bias in genotype calling introduced by either DNA quality and / or the calling algorithm used can lead to false positive associations. Our informatics team is developing tools for automating data handling and quality control as well as data storage and visualisation.

This document outlines aspects of the process and quality control implemented in the genotyping pipeline. Many details are given, but it should be noted that these may vary depending on the nature of each project.