Rapid technological advances mean that the data used in human gene-mapping is changing rapidly. Technologies that allow 100,000s to 1,000,000s of SNPs to be characterized in each individual are now widely used, and whole genome re-sequencing technologies are emerging. Extracting the full benefits of these sequencing technologies will require new analytical models and tools, both because (a) approaches and implementations designed to handle more modest amounts of data can not always handle high-throughput data or provide only cumbersome ways for doing so and because (b) the nature of the data generated by re-sequencing studies will often by quite different from that generated by more conventional genotyping technologies. Here, we propose to develop statistical methods and software tools that can handle high-throughput re- sequencing data, including results from shotgun re-sequencing of whole genomes or candidate regions. Our proposed methods and tools will aid the analysis both of case-control samples and of mixed samples of pedigrees and unrelated individuals. We also propose to conduct simulation experiments to develop guidelines on how these new sequencing technologies can be deployed effectively in gene-mapping studies. We hope they will allow investigators to extract the benefits of new high-throughput data-sources in the genetic dissection of complex traits. Rapid technological advances mean the data used in human gene mapping is changing rapidly. New technologies for analyzing genetic variation on a large scale are being deployed in the dissection of complex multi-factorial traits such as asthma, diabetes, and obesity. Here, we propose to develop efficient methods for analyzing high-throughput sequence data and to distribute software tools that allow others to extract maximum benefit from our methods. ? ? ?
| Zhan, Xiaowei; Larson, David E; Wang, Chaolong et al. (2013) Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nat Genet 45:1375-9 |
| 1000 Genomes Project Consortium; Abecasis, Goncalo R; Auton, Adam et al. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56-65 |
| Jun, Goo; Flickinger, Matthew; Hetrick, Kurt N et al. (2012) Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data. Am J Hum Genet 91:839-48 |
| Howie, Bryan; Fuchsberger, Christian; Stephens, Matthew et al. (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 44:955-9 |
| Heid, Iris M (see original citation for additional authors) (2010) Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 42:949-60 |
| Speliotes, Elizabeth K (see original citation for additional authors) (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42:937-48 |
| 1000 Genomes Project Consortium; Abecasis, Gonçalo R; Altshuler, David et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061-73 |
| Lango Allen, Hana (see original citation for additional authors) (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467:832-8 |
| Willer, Cristen J; Li, Yun; Abecasis, Goncalo R (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26:2190-1 |
| Pruim, Randall J; Welch, Ryan P; Sanna, Serena et al. (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336-7 |
Showing the most recent 10 out of 14 publications
