HLA diversity in the 1000 genomes dataset.
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most freque...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4079705?pdf=render |
| _version_ | 1818323644465545216 |
|---|---|
| author | Pierre-Antoine Gourraud Pouya Khankhanian Nezih Cereb Soo Young Yang Michael Feolo Martin Maiers John D Rioux Stephen Hauser Jorge Oksenberg |
| author_facet | Pierre-Antoine Gourraud Pouya Khankhanian Nezih Cereb Soo Young Yang Michael Feolo Martin Maiers John D Rioux Stephen Hauser Jorge Oksenberg |
| author_sort | Pierre-Antoine Gourraud |
| collection | DOAJ |
| description | The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies. |
| first_indexed | 2024-12-13T11:15:58Z |
| format | Article |
| id | doaj.art-0de66967ac2e48a5a361dcf4b683a074 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:15:58Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0de66967ac2e48a5a361dcf4b683a0742022-12-21T23:48:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e9728210.1371/journal.pone.0097282HLA diversity in the 1000 genomes dataset.Pierre-Antoine GourraudPouya KhankhanianNezih CerebSoo Young YangMichael FeoloMartin MaiersJohn D RiouxStephen HauserJorge OksenbergThe 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.http://europepmc.org/articles/PMC4079705?pdf=render |
| spellingShingle | Pierre-Antoine Gourraud Pouya Khankhanian Nezih Cereb Soo Young Yang Michael Feolo Martin Maiers John D Rioux Stephen Hauser Jorge Oksenberg HLA diversity in the 1000 genomes dataset. PLoS ONE |
| title | HLA diversity in the 1000 genomes dataset. |
| title_full | HLA diversity in the 1000 genomes dataset. |
| title_fullStr | HLA diversity in the 1000 genomes dataset. |
| title_full_unstemmed | HLA diversity in the 1000 genomes dataset. |
| title_short | HLA diversity in the 1000 genomes dataset. |
| title_sort | hla diversity in the 1000 genomes dataset |
| url | http://europepmc.org/articles/PMC4079705?pdf=render |
| work_keys_str_mv | AT pierreantoinegourraud hladiversityinthe1000genomesdataset AT pouyakhankhanian hladiversityinthe1000genomesdataset AT nezihcereb hladiversityinthe1000genomesdataset AT sooyoungyang hladiversityinthe1000genomesdataset AT michaelfeolo hladiversityinthe1000genomesdataset AT martinmaiers hladiversityinthe1000genomesdataset AT johndrioux hladiversityinthe1000genomesdataset AT stephenhauser hladiversityinthe1000genomesdataset AT jorgeoksenberg hladiversityinthe1000genomesdataset |