Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations
Abstract Background Polymorphic human Alu elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover Alu elements in human populations, and various sequencing...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-07-01
|
| Series: | Mobile DNA |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13100-017-0093-0 |
| _version_ | 1811226581808447488 |
|---|---|
| author | Julie Feusier David J. Witherspoon W. Scott Watkins Clément Goubert Thomas A. Sasani Lynn B. Jorde |
| author_facet | Julie Feusier David J. Witherspoon W. Scott Watkins Clément Goubert Thomas A. Sasani Lynn B. Jorde |
| author_sort | Julie Feusier |
| collection | DOAJ |
| description | Abstract Background Polymorphic human Alu elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover Alu elements in human populations, and various sequencing and bioinformatics methods have been designed to tackle the problem of detecting these highly repetitive elements. However, current techniques for Alu discovery may miss rare, polymorphic Alu elements. Combining multiple discovery approaches may provide a better profile of the polymorphic Alu mobilome. AluYb8/9 elements have been a focus of our recent studies as they are young subfamilies (~2.3 million years old) that contribute ~30% of recent polymorphic Alu retrotransposition events. Here, we update our ME-Scan methods for detecting Alu elements and apply these methods to discover new insertions in a large set of individuals with diverse ancestral backgrounds. Results We identified 5,288 putative Alu insertion events, including several hundred novel AluYb8/9 elements from 213 individuals from 18 diverse human populations. Hundreds of these loci were specific to continental populations, and 23 non-reference population-specific loci were validated by PCR. We provide high-quality sequence information for 68 rare AluYb8/9 elements, of which 11 have hallmarks of an active source element. Our subfamily distribution of rare AluYb8/9 elements is consistent with previous datasets, and may be representative of rare loci. We also find that while ME-Scan and low-coverage, whole-genome sequencing (WGS) detect different Alu elements in 41 1000 Genomes individuals, the two methods yield similar population structure results. Conclusion Current in-silico methods for Alu discovery may miss rare, polymorphic Alu elements. Therefore, using multiple techniques can provide a more accurate profile of Alu elements in individuals and populations. We improved our false-negative rate as an indicator of sample quality for future ME-Scan experiments. In conclusion, we demonstrate that ME-Scan is a good supplement for next-generation sequencing methods and is well-suited for population-level analyses. |
| first_indexed | 2024-04-12T09:27:32Z |
| format | Article |
| id | doaj.art-046ccbb1e3264f1ba464b90929820dbd |
| institution | Directory Open Access Journal |
| issn | 1759-8753 |
| language | English |
| last_indexed | 2024-04-12T09:27:32Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Mobile DNA |
| spelling | doaj.art-046ccbb1e3264f1ba464b90929820dbd2022-12-22T03:38:26ZengBMCMobile DNA1759-87532017-07-018111010.1186/s13100-017-0093-0Discovery of rare, diagnostic AluYb8/9 elements in diverse human populationsJulie Feusier0David J. Witherspoon1W. Scott Watkins2Clément Goubert3Thomas A. Sasani4Lynn B. Jorde5Department of Human Genetics, University of Utah School of MedicineDepartment of Human Genetics, University of Utah School of MedicineDepartment of Human Genetics, University of Utah School of MedicineDepartment of Human Genetics, University of Utah School of MedicineDepartment of Human Genetics, University of Utah School of MedicineDepartment of Human Genetics, University of Utah School of MedicineAbstract Background Polymorphic human Alu elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover Alu elements in human populations, and various sequencing and bioinformatics methods have been designed to tackle the problem of detecting these highly repetitive elements. However, current techniques for Alu discovery may miss rare, polymorphic Alu elements. Combining multiple discovery approaches may provide a better profile of the polymorphic Alu mobilome. AluYb8/9 elements have been a focus of our recent studies as they are young subfamilies (~2.3 million years old) that contribute ~30% of recent polymorphic Alu retrotransposition events. Here, we update our ME-Scan methods for detecting Alu elements and apply these methods to discover new insertions in a large set of individuals with diverse ancestral backgrounds. Results We identified 5,288 putative Alu insertion events, including several hundred novel AluYb8/9 elements from 213 individuals from 18 diverse human populations. Hundreds of these loci were specific to continental populations, and 23 non-reference population-specific loci were validated by PCR. We provide high-quality sequence information for 68 rare AluYb8/9 elements, of which 11 have hallmarks of an active source element. Our subfamily distribution of rare AluYb8/9 elements is consistent with previous datasets, and may be representative of rare loci. We also find that while ME-Scan and low-coverage, whole-genome sequencing (WGS) detect different Alu elements in 41 1000 Genomes individuals, the two methods yield similar population structure results. Conclusion Current in-silico methods for Alu discovery may miss rare, polymorphic Alu elements. Therefore, using multiple techniques can provide a more accurate profile of Alu elements in individuals and populations. We improved our false-negative rate as an indicator of sample quality for future ME-Scan experiments. In conclusion, we demonstrate that ME-Scan is a good supplement for next-generation sequencing methods and is well-suited for population-level analyses.http://link.springer.com/article/10.1186/s13100-017-0093-0RetrotransposonMobilomePolymorphismPopulation geneticsHuman ancestryAncestry informative markers |
| spellingShingle | Julie Feusier David J. Witherspoon W. Scott Watkins Clément Goubert Thomas A. Sasani Lynn B. Jorde Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations Mobile DNA Retrotransposon Mobilome Polymorphism Population genetics Human ancestry Ancestry informative markers |
| title | Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations |
| title_full | Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations |
| title_fullStr | Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations |
| title_full_unstemmed | Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations |
| title_short | Discovery of rare, diagnostic AluYb8/9 elements in diverse human populations |
| title_sort | discovery of rare diagnostic aluyb8 9 elements in diverse human populations |
| topic | Retrotransposon Mobilome Polymorphism Population genetics Human ancestry Ancestry informative markers |
| url | http://link.springer.com/article/10.1186/s13100-017-0093-0 |
| work_keys_str_mv | AT juliefeusier discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations AT davidjwitherspoon discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations AT wscottwatkins discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations AT clementgoubert discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations AT thomasasasani discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations AT lynnbjorde discoveryofrarediagnosticaluyb89elementsindiversehumanpopulations |