Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection
The hemoglobin E variant (HbE; β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (...
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| Veröffentlicht in: | American journal of human genetics 2004-06, Vol.74 (6), p.1198-1208 |
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| container_title | American journal of human genetics |
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| creator | Ohashi, Jun Naka, Izumi Patarapotikul, Jintana Hananantachai, Hathairad Brittenham, Gary Looareesuwan, Sornchai Clark, Andrew G. Tokunaga, Katsushi |
| description | The hemoglobin E variant (HbE;
β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against
Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection. |
| doi_str_mv | 10.1086/421330 |
| format | Article |
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β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against
Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1086/421330</identifier><identifier>PMID: 15114532</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Chicago, IL: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Biological Evolution ; Computer Simulation ; Evolution, Molecular ; Gene Frequency ; Genetic Markers ; Genetic Predisposition to Disease ; Genetic Variation ; Haplotypes ; Hemoglobin A - genetics ; Hemoglobin E - genetics ; Heterozygote ; Homozygote ; Human protozoal diseases ; Humans ; Infectious diseases ; Linkage Disequilibrium - genetics ; Malaria ; Malaria, Falciparum - genetics ; Malaria, Falciparum - prevention & control ; Medical sciences ; Models, Genetic ; Mutation - genetics ; Parasitic diseases ; Polymorphism, Single Nucleotide ; Protozoal diseases ; Selection, Genetic ; Thailand</subject><ispartof>American journal of human genetics, 2004-06, Vol.74 (6), p.1198-1208</ispartof><rights>2004 The American Society of Human Genetics</rights><rights>2004 INIST-CNRS</rights><rights>2004 by The American Society of Human Genetics. All rights reserved. 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-5715e26d4a6fe29ad62b438d7e409450b1bf92554219b3f2615427af95251d3c3</citedby><cites>FETCH-LOGICAL-c433t-5715e26d4a6fe29ad62b438d7e409450b1bf92554219b3f2615427af95251d3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182083/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002929707628456$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15783870$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15114532$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohashi, Jun</creatorcontrib><creatorcontrib>Naka, Izumi</creatorcontrib><creatorcontrib>Patarapotikul, Jintana</creatorcontrib><creatorcontrib>Hananantachai, Hathairad</creatorcontrib><creatorcontrib>Brittenham, Gary</creatorcontrib><creatorcontrib>Looareesuwan, Sornchai</creatorcontrib><creatorcontrib>Clark, Andrew G.</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><title>Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>The hemoglobin E variant (HbE;
β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against
Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Evolution</subject><subject>Computer Simulation</subject><subject>Evolution, Molecular</subject><subject>Gene Frequency</subject><subject>Genetic Markers</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Haplotypes</subject><subject>Hemoglobin A - genetics</subject><subject>Hemoglobin E - genetics</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Malaria</subject><subject>Malaria, Falciparum - genetics</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Medical sciences</subject><subject>Models, Genetic</subject><subject>Mutation - genetics</subject><subject>Parasitic diseases</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protozoal diseases</subject><subject>Selection, Genetic</subject><subject>Thailand</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhi0EotsCPwH5AreAP-I4uSChdkuRFvVQ4Ijl2JPtgGO3dlLBv29Wu6KF04xmHr0z8w4hrzh7x1nbvK8Fl5I9ISuupK6ahqmnZMUYE1UnOn1Ejkv5yRjnLZPPyRFXnNdKihX5sf49QfTg6QbjL7sFeoYFbmcM2GecR3o155zm6DFu6XQN9ALGtA2px0jX9LvNaONEz2agU6JfbNgVAr2CAG7CFF-QZ4MNBV4e4gn5dr7-enpRbS4_fT79uKlcLeVUKc0ViMbXthlAdNY3oq9l6zXUrKsV63k_dEKp5cqul4No-JJqO3RKKO6lkyfkw173Zu5H8A7ilG0wNxlHm_-YZNH824l4bbbpziyOCNbKReDtQSCn2xnKZEYsDkKwEdJcjOYd14LrB9DlVEqG4e8QzszuFWb_igV8_XilB-zg_QK8OQC2OBuGbKPD8ojTrWz1TojtOVgMvEPIpjiE6MBjXlw2PuH_s-8BOzygaw</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Ohashi, Jun</creator><creator>Naka, Izumi</creator><creator>Patarapotikul, Jintana</creator><creator>Hananantachai, Hathairad</creator><creator>Brittenham, Gary</creator><creator>Looareesuwan, Sornchai</creator><creator>Clark, Andrew G.</creator><creator>Tokunaga, Katsushi</creator><general>Elsevier Inc</general><general>University of Chicago Press</general><general>American Society of Human Genetics</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040601</creationdate><title>Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection</title><author>Ohashi, Jun ; Naka, Izumi ; Patarapotikul, Jintana ; Hananantachai, Hathairad ; Brittenham, Gary ; Looareesuwan, Sornchai ; Clark, Andrew G. ; Tokunaga, Katsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-5715e26d4a6fe29ad62b438d7e409450b1bf92554219b3f2615427af95251d3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Evolution</topic><topic>Computer Simulation</topic><topic>Evolution, Molecular</topic><topic>Gene Frequency</topic><topic>Genetic Markers</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Haplotypes</topic><topic>Hemoglobin A - genetics</topic><topic>Hemoglobin E - genetics</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Malaria</topic><topic>Malaria, Falciparum - genetics</topic><topic>Malaria, Falciparum - prevention & control</topic><topic>Medical sciences</topic><topic>Models, Genetic</topic><topic>Mutation - genetics</topic><topic>Parasitic diseases</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protozoal diseases</topic><topic>Selection, Genetic</topic><topic>Thailand</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohashi, Jun</creatorcontrib><creatorcontrib>Naka, Izumi</creatorcontrib><creatorcontrib>Patarapotikul, Jintana</creatorcontrib><creatorcontrib>Hananantachai, Hathairad</creatorcontrib><creatorcontrib>Brittenham, Gary</creatorcontrib><creatorcontrib>Looareesuwan, Sornchai</creatorcontrib><creatorcontrib>Clark, Andrew G.</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohashi, Jun</au><au>Naka, Izumi</au><au>Patarapotikul, Jintana</au><au>Hananantachai, Hathairad</au><au>Brittenham, Gary</au><au>Looareesuwan, Sornchai</au><au>Clark, Andrew G.</au><au>Tokunaga, Katsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>74</volume><issue>6</issue><spage>1198</spage><epage>1208</epage><pages>1198-1208</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><coden>AJHGAG</coden><abstract>The hemoglobin E variant (HbE;
β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against
Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.</abstract><cop>Chicago, IL</cop><pub>Elsevier Inc</pub><pmid>15114532</pmid><doi>10.1086/421330</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Biological and medical sciences Biological Evolution Computer Simulation Evolution, Molecular Gene Frequency Genetic Markers Genetic Predisposition to Disease Genetic Variation Haplotypes Hemoglobin A - genetics Hemoglobin E - genetics Heterozygote Homozygote Human protozoal diseases Humans Infectious diseases Linkage Disequilibrium - genetics Malaria Malaria, Falciparum - genetics Malaria, Falciparum - prevention & control Medical sciences Models, Genetic Mutation - genetics Parasitic diseases Polymorphism, Single Nucleotide Protozoal diseases Selection, Genetic Thailand |
| title | Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection |
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