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Open AccessJournal ArticleDOI

Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31-q33.

TLDR
Sib-pair linkage analyses between blood infection levels and chromosome 5q31-q33, which contains numerous candidate genes encoding immunological molecules indicate that the locus plays a central role in the control of parasitemia, and the identification of the gene is of major interest in understanding the mechanisms controlling P. falciparum Parasitemia.
Abstract
Plasmodium falciparum malaria remains a major cause of morbidity and mortality in many tropical countries, especially those in sub-Saharan Africa. Human genetic control of malaria infection is poorly understood; in particular, genes controlling P. falciparum blood infection levels remain to be identified. We recently evidenced the existence of complex genetic factors controlling blood infection levels in an urban population living in Burkina Faso. We performed, on 153 sibs from 34 families, sib-pair linkage analyses between blood infection levels and chromosome 5q31-q33, which contains numerous candidate genes encoding immunological molecules. Our results, obtained by means of the two-point Haseman-Elston (HE) method and a nonparametric (NP) approach, show linkage of parasitemia to D5S393 (P=.002) and D5S658 (P=.0004). Multipoint analyses confirmed linkage, with a peak close to D5S658 (P=.0013 and P=.0007 with the HE and NP methods, respectively). The heritability of the locus was .48, according to the two-point results, and .43, according to the multipoint results; this indicates that its variation accounted for approximately 45% of the variance of blood infection levels and that the locus plays a central role in the control of parasitemia. The identification of the gene is, therefore, of major interest in understanding the mechanisms controlling P. falciparum parasitemia.

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How malaria has affected the human genome and what human genetics can teach us about malaria.

TL;DR: The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine.
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Genetics of susceptibility to human infectious disease

TL;DR: Developments in genetics have allowed a more systematic study of the impact that the human genome and infectious disease have on each other, and have confirmed heritability of susceptibility to several infectious diseases.
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A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control.

TL;DR: The model has potential applications for the development and implementation of transmission control measures and for public health education and the potential impacts of various control measures on malaria transmission intensity to be tested under a range of endemic conditions.
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A major susceptibility locus for leprosy in India maps to chromosome 10p13

TL;DR: A genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, finds significant linkage (maximum lod score (MLS)=4.09) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease.
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High Immunoglobulin G2 (IgG2) and Low IgG4 Levels Are Associated with Human Resistance to Plasmodium falciparum Malaria

TL;DR: Analyzing the isotypic distribution of the IgG response to conserved epitopes and P. falciparum blood-stage extract in 283 malaria-exposed individuals favors a protective role of IgG3 and IgG2, which may activate effector cells through FcγRIIA, and provides evidence for a blocking role for IgG4 in malarial infection and disease.
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