Rapid genotype imputation from sequence without reference panels
Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human s...
| Main Authors: | , , , |
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1797090388159234048 |
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| author | Myers, S Davies, R Flint, J Mott, R |
| author_facet | Myers, S Davies, R Flint, J Mott, R |
| author_sort | Myers, S |
| collection | OXFORD |
| description | Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r2 of 0.98 in 2,073 outbred laboratory mice (0.15X sequencing coverage). In a sample of 11,670 Han Chinese (1.7X), we achieve accuracy similar to alternative approaches that require a reference panel, demonstrating that this approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans. |
| first_indexed | 2024-03-07T03:17:52Z |
| format | Journal article |
| id | oxford-uuid:b66a0727-fcdb-4dee-bc6a-8e408e43181e |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:17:52Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:b66a0727-fcdb-4dee-bc6a-8e408e43181e2022-03-27T04:40:50ZRapid genotype imputation from sequence without reference panelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b66a0727-fcdb-4dee-bc6a-8e408e43181eSymplectic Elements at OxfordNature Publishing Group2016Myers, SDavies, RFlint, JMott, RInexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r2 of 0.98 in 2,073 outbred laboratory mice (0.15X sequencing coverage). In a sample of 11,670 Han Chinese (1.7X), we achieve accuracy similar to alternative approaches that require a reference panel, demonstrating that this approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans. |
| spellingShingle | Myers, S Davies, R Flint, J Mott, R Rapid genotype imputation from sequence without reference panels |
| title | Rapid genotype imputation from sequence without reference panels |
| title_full | Rapid genotype imputation from sequence without reference panels |
| title_fullStr | Rapid genotype imputation from sequence without reference panels |
| title_full_unstemmed | Rapid genotype imputation from sequence without reference panels |
| title_short | Rapid genotype imputation from sequence without reference panels |
| title_sort | rapid genotype imputation from sequence without reference panels |
| work_keys_str_mv | AT myerss rapidgenotypeimputationfromsequencewithoutreferencepanels AT daviesr rapidgenotypeimputationfromsequencewithoutreferencepanels AT flintj rapidgenotypeimputationfromsequencewithoutreferencepanels AT mottr rapidgenotypeimputationfromsequencewithoutreferencepanels |