The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe

Frédérick Libert, Pascale Cochaux, Gunhild Beckman, Michel Samson, Marina Aksenova, Antonio Cao, Andrew Czeizel, Mireille Claustres, Concepción De La Rúa, Maurizio Ferrari, Claude Ferrec, Guillermo Glover, Bjorn Grinde, Sefik Güran, Vaidutis Kucinskas, Joao Lavinha, Bernard Mercier, Gönül Ogur, Leena Peltonen, Cristina Rosatelli & 6 others Marianne Schwartz, Victor Spitsyn, Laszlo Timar, Lars Beckman, Marc Parmentier, Gilbert Vassart

Research output: Contribution to journalArticle

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Abstract

The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Δccr5, was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Δccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Δccr5 variant. A strong linkage disequilibrium was found between Δccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: > 95% of the Δccr5 chromesomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Δccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the accr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Δccr5 allele.

Original languageEnglish
Pages (from-to)399-406
Number of pages8
JournalHuman Molecular Genetics
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 1998

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HIV-1
Alleles
Mutation
Population
Gene Frequency
Microsatellite Repeats
Chromosomes
Genes
Genetic Drift
Chromosomes, Human, Pair 3
Chemokine Receptors
Linkage Disequilibrium
Gene Deletion
Homozygote
Human Chromosomes
Haplotypes
Italy
HIV Infections
Macrophages

ASJC Scopus subject areas

  • Genetics

Cite this

The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. / Libert, Frédérick; Cochaux, Pascale; Beckman, Gunhild; Samson, Michel; Aksenova, Marina; Cao, Antonio; Czeizel, Andrew; Claustres, Mireille; De La Rúa, Concepción; Ferrari, Maurizio; Ferrec, Claude; Glover, Guillermo; Grinde, Bjorn; Güran, Sefik; Kucinskas, Vaidutis; Lavinha, Joao; Mercier, Bernard; Ogur, Gönül; Peltonen, Leena; Rosatelli, Cristina; Schwartz, Marianne; Spitsyn, Victor; Timar, Laszlo; Beckman, Lars; Parmentier, Marc; Vassart, Gilbert.

In: Human Molecular Genetics, Vol. 7, No. 3, 03.1998, p. 399-406.

Research output: Contribution to journalArticle

Libert, F, Cochaux, P, Beckman, G, Samson, M, Aksenova, M, Cao, A, Czeizel, A, Claustres, M, De La Rúa, C, Ferrari, M, Ferrec, C, Glover, G, Grinde, B, Güran, S, Kucinskas, V, Lavinha, J, Mercier, B, Ogur, G, Peltonen, L, Rosatelli, C, Schwartz, M, Spitsyn, V, Timar, L, Beckman, L, Parmentier, M & Vassart, G 1998, 'The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe', Human Molecular Genetics, vol. 7, no. 3, pp. 399-406. https://doi.org/10.1093/hmg/7.3.399
Libert, Frédérick ; Cochaux, Pascale ; Beckman, Gunhild ; Samson, Michel ; Aksenova, Marina ; Cao, Antonio ; Czeizel, Andrew ; Claustres, Mireille ; De La Rúa, Concepción ; Ferrari, Maurizio ; Ferrec, Claude ; Glover, Guillermo ; Grinde, Bjorn ; Güran, Sefik ; Kucinskas, Vaidutis ; Lavinha, Joao ; Mercier, Bernard ; Ogur, Gönül ; Peltonen, Leena ; Rosatelli, Cristina ; Schwartz, Marianne ; Spitsyn, Victor ; Timar, Laszlo ; Beckman, Lars ; Parmentier, Marc ; Vassart, Gilbert. / The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 3. pp. 399-406.
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T1 - The Δccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe

AU - Libert, Frédérick

AU - Cochaux, Pascale

AU - Beckman, Gunhild

AU - Samson, Michel

AU - Aksenova, Marina

AU - Cao, Antonio

AU - Czeizel, Andrew

AU - Claustres, Mireille

AU - De La Rúa, Concepción

AU - Ferrari, Maurizio

AU - Ferrec, Claude

AU - Glover, Guillermo

AU - Grinde, Bjorn

AU - Güran, Sefik

AU - Kucinskas, Vaidutis

AU - Lavinha, Joao

AU - Mercier, Bernard

AU - Ogur, Gönül

AU - Peltonen, Leena

AU - Rosatelli, Cristina

AU - Schwartz, Marianne

AU - Spitsyn, Victor

AU - Timar, Laszlo

AU - Beckman, Lars

AU - Parmentier, Marc

AU - Vassart, Gilbert

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N2 - The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Δccr5, was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Δccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Δccr5 variant. A strong linkage disequilibrium was found between Δccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: > 95% of the Δccr5 chromesomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Δccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the accr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Δccr5 allele.

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