Strategies for Genotyping in Large Scale Biobanks

Leaders: Leena Peltonen, Tom Hudson

Aims and objectives
PHOEBE and P3G plan to create an operational infrastructure for the evaluation of ongoing large-scale genotyping efforts in population cohorts, as well as provide a forum for expert opinions in regards to genotyping methods and quality assessment of these methods. We are collecting information from pre-existing genotyping projects involving large population cohorts. Ultimately, our activities will provide the international community with advice and standards that will promote harmonization in regards to selection of markers, genotyping quality control and cost, data collection and storage, and genotype database structures. Recent experience is resulting in new aim to generate and evaluate new approaches to integrate studies developed using different marker sets and/or technologies. Ultimately, our activities will provide the international community with advice and standards that will promote harmonization in regards to selection of markers, genotyping quality control and cost, data collection and storage, and genotype database structures.

Description of the work
The workpackage will consist of the following elements:
1) Exploration, integration and posting on the cyber site (www) of existing information about strategies for genotyping in large cohorts (derived both from publicly accessible databases/information sources and in the possession of individual experts in our research consortium);
2) Exploration, summary and posting of issues pertaining to standardization, quality control and cost of genotyping and related data storage and handling systems to assess pre-existing technologies and facilities; and
3) Provide on the cyber site the catalogue of genotyping methods and strategies both at the genome-wide level and on targeted genome regions (candidate genes, linkage peaks, promising regions based on genome-wide association studies).

For the purposes of 1), and in collaboration with other workpackages in this CA, we will establish a central web site for the European population genetic community that will provide information and links to genetic studies that involve large population cohorts in Europe. The web site will also contain links to the ever increasing number of databases relevant to population genetics (such as allele and haplotype freqencies in various populations). The web site will provide information on genotyping services that are available (location, technology, costs, etc.).
In relation to 2) we will establish a genotyping technology assessment centre. Given that genotyping technologies are evolving at a rapid pace, it is imperative that we not only be aware of developments, but that we be able to make objective comparisons between technologies, in regards to cost, throughput and accuracy.
For the purposes of 3) we realize that there is a growing insecurity among established genetics laboratories in the selection of SNPs from the newer resources generated by the HapMap, gene resequencing efforts, SNP databases (with over 9 million human SNPs). Using the expertise developed by our groups, we will combine and further develop existing web-based tools that extract information (functional characteristics, allele frequency, linkage disequilibrium, etc., technology-specific limitations) for every SNP in targeted regions, and propose efficient marker sets and priority scores to user labs. We will establish a genotype database group. This group will establish database structures, definitions, language for data exchange, etc. that will allow comparisons of data among population genetic projects, including both outbred populations and genetic isolates.

Deliverables
In collaboration with P3G and harmonizing the operations with it’s IWG2, genotyping data structures will be generated that are compatible with existing and new technologies for raw and processed genotyping data. These deliverables do vetail very naturally with the aims and deliverables of complementary workpackages in the GenomEUtwin project. See Leena Peltonen, form A2

D 1      Preliminary planning, strategy setting and identification of full expert groups for all
           workpackagesat Initial PHOEBE Conference
           Time: 6 months
D 2      Debriefing, presentation and discussion of final reports, and discussion of future
           strategy for all workpackages at the Concluding PHOEBE Conference
           Time: 35 months
D 3      Final report to be posted on the world wide web:
           Time 36 months
D 20    Genotyping data handling and reporting structures will be generated that are
           compatible with existing and new technologies for raw and processed
           genotyping data.
           Time: 36 months
D 21    Online catalogue will be produced of genotyping methods: protocols, QC results,
           genotype calling algorithms.
           Time: 36 months
D 22    Online repository of common marker sets will be produced (such as Affymetrix 500K,
           Illumina 550K, and future products):
           Time: 36 months
D 23    A special report will be produced on genotype data merging methods from different
           genome-wide platforms (performed by pdf with Dr. Peltonen, in collaboration with
           M. Daly at Harvard).
           Time: 36 months

Milestones
The sole ”decision point” will occur at the Initial PHOEBE Conference when we will determine the full composition of the expert groups. Time: 6 months

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