The statistics of bulk segregant analysis using next generation sequencing.
We describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard G statistic, and takes into account variation in allele frequency estimates due to sampling of...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-11-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002255&type=printable |
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| _version_ | 1850189909629861888 |
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| author | Paul M Magwene John H Willis John K Kelly |
| author_facet | Paul M Magwene John H Willis John K Kelly |
| author_sort | Paul M Magwene |
| collection | DOAJ |
| description | We describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard G statistic, and takes into account variation in allele frequency estimates due to sampling of segregants to form bulks as well as variation introduced during the sequencing of bulks. Using simulation, we explore the impact of key experimental variables such as bulk size and sequencing coverage on the ability to detect QTLs. Counterintuitively, we find that relatively large bulks maximize the power to detect QTLs even though this implies weaker selection and less extreme allele frequency differences. Our simulation studies suggest that with large bulks and sufficient sequencing depth, the methods we propose can be used to detect even weak effect QTLs and we demonstrate the utility of this framework by application to a BSA experiment in the budding yeast Saccharomyces cerevisiae. |
| format | Article |
| id | doaj-art-ba4055691f384cd6ad55eddc2872a3ab |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2011-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-ba4055691f384cd6ad55eddc2872a3ab2025-08-20T02:15:29ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-11-01711e100225510.1371/journal.pcbi.1002255The statistics of bulk segregant analysis using next generation sequencing.Paul M MagweneJohn H WillisJohn K KellyWe describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard G statistic, and takes into account variation in allele frequency estimates due to sampling of segregants to form bulks as well as variation introduced during the sequencing of bulks. Using simulation, we explore the impact of key experimental variables such as bulk size and sequencing coverage on the ability to detect QTLs. Counterintuitively, we find that relatively large bulks maximize the power to detect QTLs even though this implies weaker selection and less extreme allele frequency differences. Our simulation studies suggest that with large bulks and sufficient sequencing depth, the methods we propose can be used to detect even weak effect QTLs and we demonstrate the utility of this framework by application to a BSA experiment in the budding yeast Saccharomyces cerevisiae.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002255&type=printable |
| spellingShingle | Paul M Magwene John H Willis John K Kelly The statistics of bulk segregant analysis using next generation sequencing. PLoS Computational Biology |
| title | The statistics of bulk segregant analysis using next generation sequencing. |
| title_full | The statistics of bulk segregant analysis using next generation sequencing. |
| title_fullStr | The statistics of bulk segregant analysis using next generation sequencing. |
| title_full_unstemmed | The statistics of bulk segregant analysis using next generation sequencing. |
| title_short | The statistics of bulk segregant analysis using next generation sequencing. |
| title_sort | statistics of bulk segregant analysis using next generation sequencing |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002255&type=printable |
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