Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups
<p>Abstract</p> <p>Background</p> <p>A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, <it>ERCC1</it>, <it>ERCC2</it>, and <it>PPP1R13L </it>(aka <it>RAI</it>) are related to DNA rep...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-03-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/10/20 |
| _version_ | 1818560014000848896 |
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| author | Wang Jun Li Heng Mailund Thomas Schierup Mikkel H Tjønneland Anne Vogel Ulla Bolund Lars Nexø Bjørn A |
| author_facet | Wang Jun Li Heng Mailund Thomas Schierup Mikkel H Tjønneland Anne Vogel Ulla Bolund Lars Nexø Bjørn A |
| author_sort | Wang Jun |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, <it>ERCC1</it>, <it>ERCC2</it>, and <it>PPP1R13L </it>(aka <it>RAI</it>) are related to DNA repair and cell survival, and one, <it>CD3EAP</it>, aka <it>ASE1</it>, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers.</p> <p>Methods</p> <p>We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk.</p> <p>Results</p> <p>We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the F<sub>st </sub>value) closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping.</p> <p>Conclusion</p> <p>The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.</p> |
| first_indexed | 2024-12-14T00:32:56Z |
| format | Article |
| id | doaj.art-6c03077ed1ee4a6287c065030938b454 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T00:32:56Z |
| publishDate | 2009-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-6c03077ed1ee4a6287c065030938b4542022-12-21T23:24:47ZengBMCBMC Medical Genetics1471-23502009-03-011012010.1186/1471-2350-10-20Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groupsWang JunLi HengMailund ThomasSchierup Mikkel HTjønneland AnneVogel UllaBolund LarsNexø Bjørn A<p>Abstract</p> <p>Background</p> <p>A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, <it>ERCC1</it>, <it>ERCC2</it>, and <it>PPP1R13L </it>(aka <it>RAI</it>) are related to DNA repair and cell survival, and one, <it>CD3EAP</it>, aka <it>ASE1</it>, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers.</p> <p>Methods</p> <p>We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk.</p> <p>Results</p> <p>We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the F<sub>st </sub>value) closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping.</p> <p>Conclusion</p> <p>The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.</p>http://www.biomedcentral.com/1471-2350/10/20 |
| spellingShingle | Wang Jun Li Heng Mailund Thomas Schierup Mikkel H Tjønneland Anne Vogel Ulla Bolund Lars Nexø Bjørn A Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups BMC Medical Genetics |
| title | Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups |
| title_full | Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups |
| title_fullStr | Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups |
| title_full_unstemmed | Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups |
| title_short | Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups |
| title_sort | haplotype frequencies in a sub region of chromosome 19q13 3 related to risk and prognosis of cancer differ dramatically between ethnic groups |
| url | http://www.biomedcentral.com/1471-2350/10/20 |
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