The extent of linkage disequilibrium caused by selection on G6PD in humans

Matthew A. Saunders, Montgomery Slatkin, Chad Garner, Michael F Hammer, Michael W. Nachman

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The gene coding for glucose-6-phosphate dehydrogenase (G6PD) is subject to positive selection by malaria in some human populations. The G6PD A- allele, which is common in sub-Saharan Africa, is associated with deficient enzyme activity and protection from severe malaria. To delimit the impact of selection on patterns of linkage disequilibrium (LD) and nucleotide diversity, we resequenced 5.1 kb at G6PD and ∼2-3 kb at each of eight loci in a 2.5-Mb region roughly centered on G6PD in a diverse sub-Saharan African panel of 51 unrelated men (including 20 G6PD A-, 11 G6PD A+, and 20 G6PD B chromosomes). The signature of selection is evident in the absence of genetic variation at G6PD and at three neighboring loci within 0.9 Mb from G6PD among all individuals bearing G6PD A- alleles. A genomic region of ∼1.6 Mb around G6PD was characterized by long-range LD associated with the A- alleles. These patterns of nucleotide variability and LD suggest that G6PD A- is younger than previous age estimates and has increased in frequency in sub-Saharan Africa due to strong selection (0.1 < s < 0.2). These results also show that selection can lead to nonrandom associations among SNPs over great physical and genetic distances, even in African populations.

Original languageEnglish (US)
Pages (from-to)1219-1229
Number of pages11
JournalGenetics
Volume171
Issue number3
DOIs
StatePublished - Nov 2005

Fingerprint

Glucosephosphate Dehydrogenase
Linkage Disequilibrium
Africa South of the Sahara
Alleles
Malaria
Nucleotides
Chromosomes, Human, 4-5
Population
Single Nucleotide Polymorphism
glucose-6-phosphate dehydrogenase A-
Enzymes
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

The extent of linkage disequilibrium caused by selection on G6PD in humans. / Saunders, Matthew A.; Slatkin, Montgomery; Garner, Chad; Hammer, Michael F; Nachman, Michael W.

In: Genetics, Vol. 171, No. 3, 11.2005, p. 1219-1229.

Research output: Contribution to journalArticle

Saunders, MA, Slatkin, M, Garner, C, Hammer, MF & Nachman, MW 2005, 'The extent of linkage disequilibrium caused by selection on G6PD in humans', Genetics, vol. 171, no. 3, pp. 1219-1229. https://doi.org/10.1534/genetics.105.048140
Saunders, Matthew A. ; Slatkin, Montgomery ; Garner, Chad ; Hammer, Michael F ; Nachman, Michael W. / The extent of linkage disequilibrium caused by selection on G6PD in humans. In: Genetics. 2005 ; Vol. 171, No. 3. pp. 1219-1229.
@article{e5b5aad1b1f749a2ada487bdf3a03025,
title = "The extent of linkage disequilibrium caused by selection on G6PD in humans",
abstract = "The gene coding for glucose-6-phosphate dehydrogenase (G6PD) is subject to positive selection by malaria in some human populations. The G6PD A- allele, which is common in sub-Saharan Africa, is associated with deficient enzyme activity and protection from severe malaria. To delimit the impact of selection on patterns of linkage disequilibrium (LD) and nucleotide diversity, we resequenced 5.1 kb at G6PD and ∼2-3 kb at each of eight loci in a 2.5-Mb region roughly centered on G6PD in a diverse sub-Saharan African panel of 51 unrelated men (including 20 G6PD A-, 11 G6PD A+, and 20 G6PD B chromosomes). The signature of selection is evident in the absence of genetic variation at G6PD and at three neighboring loci within 0.9 Mb from G6PD among all individuals bearing G6PD A- alleles. A genomic region of ∼1.6 Mb around G6PD was characterized by long-range LD associated with the A- alleles. These patterns of nucleotide variability and LD suggest that G6PD A- is younger than previous age estimates and has increased in frequency in sub-Saharan Africa due to strong selection (0.1 < s < 0.2). These results also show that selection can lead to nonrandom associations among SNPs over great physical and genetic distances, even in African populations.",
author = "Saunders, {Matthew A.} and Montgomery Slatkin and Chad Garner and Hammer, {Michael F} and Nachman, {Michael W.}",
year = "2005",
month = "11",
doi = "10.1534/genetics.105.048140",
language = "English (US)",
volume = "171",
pages = "1219--1229",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "3",

}

TY - JOUR

T1 - The extent of linkage disequilibrium caused by selection on G6PD in humans

AU - Saunders, Matthew A.

AU - Slatkin, Montgomery

AU - Garner, Chad

AU - Hammer, Michael F

AU - Nachman, Michael W.

PY - 2005/11

Y1 - 2005/11

N2 - The gene coding for glucose-6-phosphate dehydrogenase (G6PD) is subject to positive selection by malaria in some human populations. The G6PD A- allele, which is common in sub-Saharan Africa, is associated with deficient enzyme activity and protection from severe malaria. To delimit the impact of selection on patterns of linkage disequilibrium (LD) and nucleotide diversity, we resequenced 5.1 kb at G6PD and ∼2-3 kb at each of eight loci in a 2.5-Mb region roughly centered on G6PD in a diverse sub-Saharan African panel of 51 unrelated men (including 20 G6PD A-, 11 G6PD A+, and 20 G6PD B chromosomes). The signature of selection is evident in the absence of genetic variation at G6PD and at three neighboring loci within 0.9 Mb from G6PD among all individuals bearing G6PD A- alleles. A genomic region of ∼1.6 Mb around G6PD was characterized by long-range LD associated with the A- alleles. These patterns of nucleotide variability and LD suggest that G6PD A- is younger than previous age estimates and has increased in frequency in sub-Saharan Africa due to strong selection (0.1 < s < 0.2). These results also show that selection can lead to nonrandom associations among SNPs over great physical and genetic distances, even in African populations.

AB - The gene coding for glucose-6-phosphate dehydrogenase (G6PD) is subject to positive selection by malaria in some human populations. The G6PD A- allele, which is common in sub-Saharan Africa, is associated with deficient enzyme activity and protection from severe malaria. To delimit the impact of selection on patterns of linkage disequilibrium (LD) and nucleotide diversity, we resequenced 5.1 kb at G6PD and ∼2-3 kb at each of eight loci in a 2.5-Mb region roughly centered on G6PD in a diverse sub-Saharan African panel of 51 unrelated men (including 20 G6PD A-, 11 G6PD A+, and 20 G6PD B chromosomes). The signature of selection is evident in the absence of genetic variation at G6PD and at three neighboring loci within 0.9 Mb from G6PD among all individuals bearing G6PD A- alleles. A genomic region of ∼1.6 Mb around G6PD was characterized by long-range LD associated with the A- alleles. These patterns of nucleotide variability and LD suggest that G6PD A- is younger than previous age estimates and has increased in frequency in sub-Saharan Africa due to strong selection (0.1 < s < 0.2). These results also show that selection can lead to nonrandom associations among SNPs over great physical and genetic distances, even in African populations.

UR - http://www.scopus.com/inward/record.url?scp=25444440354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444440354&partnerID=8YFLogxK

U2 - 10.1534/genetics.105.048140

DO - 10.1534/genetics.105.048140

M3 - Article

C2 - 16020776

AN - SCOPUS:25444440354

VL - 171

SP - 1219

EP - 1229

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 3

ER -