Haplotype Diversity and Linkage Disequilibrium at Human G6PD: Recent Origin of Alleles That Confer Malarial Resistance

The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite...

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Published inScience (American Association for the Advancement of Science) Vol. 293; no. 5529; pp. 455 - 462
Main Authors Tishkoff, Sarah A., Varkonyi, Robert, Cahinhinan, Nelie, Abbes, Salem, Argyropoulos, George, Destro-Bisol, Giovanni, Drousiotou, Anthi, Dangerfield, Bruce, Lefranc, Gerard, Loiselet, Jacques, Piro, Anna, Stoneking, Mark, Tagarelli, Antonio, Tagarelli, Giuseppe, Touma, Elias H., Williams, Scott M., Clark, Andrew G.
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for the Advancement of Science 20.07.2001
American Association for the Advancement of Science
The American Association for the Advancement of Science
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Abstract The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.
AbstractList The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite.
The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.
The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support he hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.
The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These “deficiency” alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of “A−” and ”Med“ mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A− allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.
Audience Academic
Author Tagarelli, Giuseppe
Argyropoulos, George
Clark, Andrew G.
Lefranc, Gerard
Dangerfield, Bruce
Loiselet, Jacques
Cahinhinan, Nelie
Tagarelli, Antonio
Destro-Bisol, Giovanni
Williams, Scott M.
Drousiotou, Anthi
Varkonyi, Robert
Stoneking, Mark
Touma, Elias H.
Abbes, Salem
Tishkoff, Sarah A.
Piro, Anna
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https://www.ncbi.nlm.nih.gov/pubmed/11423617$$D View this record in MEDLINE/PubMed
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Issue 5529
Keywords Human
Protozoal disease
Glucose-6-phosphate 1-dehydrogenase
Malaria
Enzyme
Biological evolution
Genetic diversity
Parasitosis
Linkage equilibrium
Mechanism
Infection
Gene frequency
Gene
Oxidoreductases
Mutation
Haplotype
Protection
Geographical variation
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Snippet The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency"...
The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These “deficiency”...
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StartPage 455
SubjectTerms Africa - epidemiology
Agriculture
Alleles
Allelochemicals
Allelopathic agents
Animals
Biological and medical sciences
Chromosomes
Death
Electrons
Endemic Diseases
Evolution
Evolution, Molecular
Female
Genes
Genetic loci
Genetic mutation
Genetic Variation
Geographic regions
Glucose-6-phosphate dehydrogenase deficiency
Glucosephosphate Dehydrogenase - genetics
Glucosephosphate Dehydrogenase Deficiency - epidemiology
Glucosephosphate Dehydrogenase Deficiency - genetics
Haplotypes
Human protozoal diseases
Humans
Immune system
Immunity, Innate - genetics
Infectious diseases
Linkage Disequilibrium
Malaria
Malaria - enzymology
Malaria - epidemiology
Malaria - genetics
Malaria, Falciparum - enzymology
Malaria, Falciparum - epidemiology
Malaria, Falciparum - genetics
Male
Medical sciences
Mediterranean Region - epidemiology
Microsatellites
Mutation
Observation
Parasites
Parasitic diseases
Plasmodium falciparum
Plasmodium falciparum - genetics
Polymorphism, Restriction Fragment Length
Protozoal diseases
Selection, Genetic
Statistical Data
Statistical variance
Time
Tropical medicine
Title Haplotype Diversity and Linkage Disequilibrium at Human G6PD: Recent Origin of Alleles That Confer Malarial Resistance
URI https://www.jstor.org/stable/3084085
https://www.ncbi.nlm.nih.gov/pubmed/11423617
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https://search.proquest.com/docview/21429980
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https://search.proquest.com/docview/743080631
Volume 293
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