Genome-wide linkage analysis of malaria infection intensity and mild disease.
Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2...
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doaj-012bf775d8664a34810c10cc878260672020-11-24T21:37:05ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042007-03-0133e4810.1371/journal.pgen.0030048Genome-wide linkage analysis of malaria infection intensity and mild disease.Christian TimmannJennifer A EvansInke R KönigAndré KleensangFranz RüschendorfJulia LenzenJürgen SievertsenChristian BeckerYeetey EnuamehKingsley Osei KwakyeErnest OpokuEdmund N L BrowneAndreas ZieglerPeter NürnbergRolf D HorstmannAlthough balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (Hb)S, HbC, alpha(+) thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5), locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%). The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.http://europepmc.org/articles/PMC1829404?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christian Timmann Jennifer A Evans Inke R König André Kleensang Franz Rüschendorf Julia Lenzen Jürgen Sievertsen Christian Becker Yeetey Enuameh Kingsley Osei Kwakye Ernest Opoku Edmund N L Browne Andreas Ziegler Peter Nürnberg Rolf D Horstmann |
spellingShingle |
Christian Timmann Jennifer A Evans Inke R König André Kleensang Franz Rüschendorf Julia Lenzen Jürgen Sievertsen Christian Becker Yeetey Enuameh Kingsley Osei Kwakye Ernest Opoku Edmund N L Browne Andreas Ziegler Peter Nürnberg Rolf D Horstmann Genome-wide linkage analysis of malaria infection intensity and mild disease. PLoS Genetics |
author_facet |
Christian Timmann Jennifer A Evans Inke R König André Kleensang Franz Rüschendorf Julia Lenzen Jürgen Sievertsen Christian Becker Yeetey Enuameh Kingsley Osei Kwakye Ernest Opoku Edmund N L Browne Andreas Ziegler Peter Nürnberg Rolf D Horstmann |
author_sort |
Christian Timmann |
title |
Genome-wide linkage analysis of malaria infection intensity and mild disease. |
title_short |
Genome-wide linkage analysis of malaria infection intensity and mild disease. |
title_full |
Genome-wide linkage analysis of malaria infection intensity and mild disease. |
title_fullStr |
Genome-wide linkage analysis of malaria infection intensity and mild disease. |
title_full_unstemmed |
Genome-wide linkage analysis of malaria infection intensity and mild disease. |
title_sort |
genome-wide linkage analysis of malaria infection intensity and mild disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2007-03-01 |
description |
Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (Hb)S, HbC, alpha(+) thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5), locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%). The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria. |
url |
http://europepmc.org/articles/PMC1829404?pdf=render |
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