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A second generation of exome arrays will be available in 2013, from both Illumina and Affymetrix. In addition to the original exome array content, each of these includes a grid of SNPs across the genome that facilitates analysis of common variants when a suitably large reference panel is available. These grids were selected both to ensure good coverage of the genome and to ensure that assays could be manufactured inexpensively, taking into account proprietary platform specific constraints.
A second generation of exome arrays will be available in 2013, from both Illumina and Affymetrix. In addition to the original exome array content, each of these includes a grid of SNPs across the genome that facilitates analysis of common variants when a suitably large reference panel is available. These grids were selected both to ensure good coverage of the genome and to ensure that assays could be manufactured inexpensively, taking into account proprietary platform specific constraints.
To evaluate the accuracy of these grids, we have used data from the Go T2D project (led by David Altshuler, Mike Boehnke and Mark McCarthy). The dataset includes ~2,650 individuals that have been whole genome sequenced (depth ~4x) and whole exome sequenced (depth ~80-100x). We focused on 600 samples from the UK and, for each of these in turn, tried to impute missing genotypes using the remaining sequenced individuals as a reference panel. The results show both the Affymetrix and Illumina arrays are expected to provide excellent coverage of the genome provided that a suitably large reference panel is available.
To evaluate the accuracy of these grids, we have used data from the Go T2D project (led by David Altshuler, Mike Boehnke and Mark McCarthy). The dataset includes ~2,650 individuals that have been whole genome sequenced (depth ~4x) and whole exome sequenced (depth ~80-100x). We focused on chr20 and 600 samples from the UK and, for each of these in turn, tried to impute missing genotypes using the remaining sequenced individuals as a reference panel. The results show both the Affymetrix and Illumina arrays are expected to provide excellent coverage of the genome provided that a suitably large reference panel is available.
The specific numbers are that:
The specific numbers are that:
* For variants with MAF >5%, 94.6% (Affymetrix) and 89.2% (Illumina)
* For variants with MAF >5%, 94.6% (Affymetrix) and 89.2% (Illumina)
The evaluation is based on imputation of ~600 UK samples that have been whole genome and whole exome sequenced (comparing imputed genotypes and the sequenced based calls) and using a panel of 2,500 sequenced individuals from the T2D-Go Project (Altshuler, Boehnke, McCarthy) as a reference.
The evaluation is based on imputation of ~600 UK samples that have been whole genome and whole exome sequenced (comparing imputed genotypes and the sequenced based calls) and using a panel of 2,650 sequenced individuals from the T2D-Go Project (Altshuler, Boehnke, McCarthy) as a reference.
All evaluations used [[Minimac]] and were carried out by [mailto:cfuchsb@umich.edu Christian Fuchsberger].
All evaluations used [[Minimac]] and were carried out by [mailto:cfuchsb@umich.edu Christian Fuchsberger].
== Cautious Sites ==
== Sites to be Careful About ==
333 exome chip variants sites should be treated cautiously.
Peter Chines, working with Francis Collins, provided a list of 333 exome chip variants sites that should be treated with caution. The sites include variants for which the SNP probe differs from the expected reference genome sequence, could not be mapped back to the reference, mapped to multiple places, or where neither allele matches the reference genome.
A plain text list of these sites [ftp://share.sph.umich.edu/exomeChip/IlluminaDesigns/cautiousSites/cautiousSite.sorted.sites list] and corresponding [ftp://share.sph.umich.edu/exomeChip/IlluminaDesigns/cautiousSites/cautiousSite.sorted.README descriptions] are available.
= Affymetrix Exome Arrays =
= Affymetrix Exome Arrays =
