Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean
Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anaemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is u...
| Hoofdauteurs: | , , , |
|---|---|
| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
National Academy of Sciences of the United States
2009
|
| Onderwerpen: |
| _version_ | 1826276921779945472 |
|---|---|
| author | Penman, B Pybus, O Weatherall, D Gupta, S |
| author_facet | Penman, B Pybus, O Weatherall, D Gupta, S |
| author_sort | Penman, B |
| collection | OXFORD |
| description | Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anaemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of α- and β-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when α-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions. |
| first_indexed | 2024-03-06T23:21:07Z |
| format | Journal article |
| id | oxford-uuid:68c0d3da-e2af-477a-b125-b49f1150d95c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:21:07Z |
| publishDate | 2009 |
| publisher | National Academy of Sciences of the United States |
| record_format | dspace |
| spelling | oxford-uuid:68c0d3da-e2af-477a-b125-b49f1150d95c2022-03-26T18:47:03ZEpistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the MediterraneanJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:68c0d3da-e2af-477a-b125-b49f1150d95cZoological sciencesEnglishOxford University Research Archive - ValetNational Academy of Sciences of the United States2009Penman, BPybus, OWeatherall, DGupta, SSeveral human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anaemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of α- and β-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when α-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions. |
| spellingShingle | Zoological sciences Penman, B Pybus, O Weatherall, D Gupta, S Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title | Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title_full | Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title_fullStr | Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title_full_unstemmed | Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title_short | Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean |
| title_sort | epistatic interactions between genetic disorders of hemoglobin can explain why the sickle cell gene is uncommon in the mediterranean |
| topic | Zoological sciences |
| work_keys_str_mv | AT penmanb epistaticinteractionsbetweengeneticdisordersofhemoglobincanexplainwhythesicklecellgeneisuncommoninthemediterranean AT pybuso epistaticinteractionsbetweengeneticdisordersofhemoglobincanexplainwhythesicklecellgeneisuncommoninthemediterranean AT weatheralld epistaticinteractionsbetweengeneticdisordersofhemoglobincanexplainwhythesicklecellgeneisuncommoninthemediterranean AT guptas epistaticinteractionsbetweengeneticdisordersofhemoglobincanexplainwhythesicklecellgeneisuncommoninthemediterranean |