Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms
Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For th...
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description | Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data. |
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D. S. ; KAMGNO, J. ; GARDON, J. ; GARDON-WENDEL, N. ; DUKE, B. O. L. ; PRICHARD, R. K. ; BOUSSINESQ, M.</creator><creatorcontrib>BOURGUINAT, C. ; PION, S. D. S. ; KAMGNO, J. ; GARDON, J. ; GARDON-WENDEL, N. ; DUKE, B. O. L. ; PRICHARD, R. K. ; BOUSSINESQ, M.</creatorcontrib><description>Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.</description><identifier>ISSN: 0031-1820</identifier><identifier>EISSN: 1469-8161</identifier><identifier>DOI: 10.1017/S0031182005008899</identifier><identifier>PMID: 16197589</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Antiparasitic Agents - therapeutic use ; Cameroon ; Child ; Drug Resistance ; Female ; fertility ; Fertility - genetics ; Gene Frequency - genetics ; genetic polymorphism ; Genotype ; Humans ; Ivermectin - therapeutic use ; Male ; Middle Aged ; Odds Ratio ; Onchocerca volvulus ; Onchocerca volvulus - genetics ; Onchocerca volvulus - isolation & purification ; Onchocerca volvulus - physiology ; Onchocerciasis - drug therapy ; Onchocerciasis - parasitology ; Phenotype ; Polymerase Chain Reaction - methods ; Polymorphism, Genetic - genetics ; Polymorphism, Genetic - physiology ; Tubulin - genetics ; β-tubulin</subject><ispartof>Parasitology, 2006-02, Vol.132 (2), p.255-262</ispartof><rights>2005 Cambridge University Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-3c31c543b22ef9966775de2ea185670243d2c95ec15247449d6aef5c8ec01e623</citedby><cites>FETCH-LOGICAL-c412t-3c31c543b22ef9966775de2ea185670243d2c95ec15247449d6aef5c8ec01e623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0031182005008899/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,314,780,784,27924,27925,55628</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16197589$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BOURGUINAT, C.</creatorcontrib><creatorcontrib>PION, S. D. S.</creatorcontrib><creatorcontrib>KAMGNO, J.</creatorcontrib><creatorcontrib>GARDON, J.</creatorcontrib><creatorcontrib>GARDON-WENDEL, N.</creatorcontrib><creatorcontrib>DUKE, B. O. L.</creatorcontrib><creatorcontrib>PRICHARD, R. K.</creatorcontrib><creatorcontrib>BOUSSINESQ, M.</creatorcontrib><title>Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms</title><title>Parasitology</title><addtitle>Parasitology</addtitle><description>Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Antiparasitic Agents - therapeutic use</subject><subject>Cameroon</subject><subject>Child</subject><subject>Drug Resistance</subject><subject>Female</subject><subject>fertility</subject><subject>Fertility - genetics</subject><subject>Gene Frequency - genetics</subject><subject>genetic polymorphism</subject><subject>Genotype</subject><subject>Humans</subject><subject>Ivermectin - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Onchocerca volvulus</subject><subject>Onchocerca volvulus - genetics</subject><subject>Onchocerca volvulus - isolation & purification</subject><subject>Onchocerca volvulus - physiology</subject><subject>Onchocerciasis - drug therapy</subject><subject>Onchocerciasis - parasitology</subject><subject>Phenotype</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Polymorphism, Genetic - physiology</subject><subject>Tubulin - genetics</subject><subject>β-tubulin</subject><issn>0031-1820</issn><issn>1469-8161</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2O1DAUhCMEYpqBA7BBXrEi4J_YiZeoBQ3SiAHxo9lFbudl4iG2g-300LfhBkhcgT1nwlE3sECCla1X3yuXXEVxn-DHBJP6yVuMGSENxZhj3DRS3ihWpBKybIggN4vVIpeLflLcifEKYyyYoLeLkyzLmjdyVXzZgINkNJr8uLc-TIOJFvkepQHQj29lmrfzaBy6zNgyPnd68BqCVmjnx908zhFl2ewgWNApX536_nUHaFLJgEsR9cFbtFYWgvfuEVKuQyaPA4yZ8C4OZkLXJg2oh5DMaNL-1_PXPth4t7jVqzHCveN5Wrx__uzd-kV5dr55uX56VuqK0FQyzYjmFdtSCr2UQtQ174CCIg0XNaYV66iWHDThtKqrSnZCQc91AxoTEJSdFg8PvlPwn2aIqbUmahhH5cDPsRW14DWn7L8gkYyTplkcyQHUwccYoG-nYKwK-5bgdumv_au_vPPgaD5vLXR_No6FZaA8ACYm-PxbV-FjTshq3orNm5Z9eCVZdfG6vcg8O4ZQdhtMdwntlZ-Dy1_5jxg_AXbhuBs</recordid><startdate>200602</startdate><enddate>200602</enddate><creator>BOURGUINAT, C.</creator><creator>PION, S. 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K.</au><au>BOUSSINESQ, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms</atitle><jtitle>Parasitology</jtitle><addtitle>Parasitology</addtitle><date>2006-02</date><risdate>2006</risdate><volume>132</volume><issue>2</issue><spage>255</spage><epage>262</epage><pages>255-262</pages><issn>0031-1820</issn><eissn>1469-8161</eissn><abstract>Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>16197589</pmid><doi>10.1017/S0031182005008899</doi><tpages>8</tpages></addata></record> |
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subjects | Adolescent Adult Aged Animals Antiparasitic Agents - therapeutic use Cameroon Child Drug Resistance Female fertility Fertility - genetics Gene Frequency - genetics genetic polymorphism Genotype Humans Ivermectin - therapeutic use Male Middle Aged Odds Ratio Onchocerca volvulus Onchocerca volvulus - genetics Onchocerca volvulus - isolation & purification Onchocerca volvulus - physiology Onchocerciasis - drug therapy Onchocerciasis - parasitology Phenotype Polymerase Chain Reaction - methods Polymorphism, Genetic - genetics Polymorphism, Genetic - physiology Tubulin - genetics β-tubulin |
title | Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms |
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