Genetic analysis of susceptibility to infection with Ascaris lumbricoides.

Williams‐Blangero, Sarah; Subedi, Janardan; Upadhayay, Ram Prasad; Manral, Deepak B.; R., Dev; Jha, Bharat; Robinson, Edward; Blangero, John

doi:10.4269/ajtmh.1999.60.921

Cited by 107 publications

(94 citation statements)

References 36 publications

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“…The immune system is no exception, and considerable insight may be gained from an ecological, adaptationist perspective. Correspondingly, anthropologists have become increasingly interested in field studies of immunity and their significance to the study of adaptation and human ecology (Barnes et al, 1999;Campbell et al, 2001;Flinn, 1999;Hoff, 1999;Hurtado et al, 1997Hurtado et al, , 2003Lubach et al, 1995;McDade et al, 2000bMcDade et al, , 2001aMcDade and Worthman, 1999;Shell-Duncan, 1993;Shell-Duncan and Wood, 1997;Ulijaszek, 1998;Williams-Blangero et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Life history theory and the immune system: Steps toward a human ecological immunology

McDade¹

2003

Am. J. Phys. Anthropol.

288

305

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KEY WORDSimmunology; human biology; growth and development; evolutionary theory; infectious disease ABSTRACTWithin anthropology and human biology, there is growing interest in immune function and its importance to the ecology of human health and development. Biomedical research currently dominates our understanding of immunology, and this paper seeks to highlight the potential contribution of a population-based, ecological approach to the study of human immune function. Concepts from life-history theory are applied to highlight the major challenges and demands that are likely to shape immune function in a range of ecological contexts. Immune function is a major component of maintenance effort, and since resources are limited, trade-offs are expected between investment in maintenance and other critical life-history functions involving growth and reproduction. An adaptationist, life-history perspective helps make sense of the unusual developmental trajectory of immune tissues, and emphasizes that this complex system is designed to incorporate information from the surrounding ecology to guide its development. As a result, there is substantial population variation in immune development and function that is not considered by current biomedical approaches. In an attempt to construct a framework for understanding this variation, immune development is considered in relation to the competing life-history demands that define gestation, infancy, childhood, adolescence, and adulthood. Each life stage poses a unique set of adaptive challenges, and a series of hypotheses is proposed regarding their implications for immune development and function. Research in human ecological immunology is in its earliest stages, but this is a promising area of exploration, and one in which anthropology is wellpositioned to make important contributions. Yrbk Phys Research on human immune function has proliferated in the past 25 years, leading to fundamental insights into basic physiology, as well as strategies for the prevention and treatment of a wide range of diseases. The complexity of the immune system is daunting, and current biomedical research elaborates this complexity by focusing almost exclusively on cellular-and molecular-level processes. The majority of this research uses animal models, with human research participants drawn primarily from clinical settings. Complementary population-based research in international health has observed consistent, bidirectional associations between undernutrition and infectious morbidity, sparking interest in immunocompetence as a potentially important mediator (Chandra, 1988;Gershwin et al., 2000;Hoffman-Goetz, 1986;Pelletier et al., 1995;Suskind and Tontisirin, 2001).The significance of these contributions should not be overlooked, but something is missing. Human physiological systems are products of natural selection, designed to develop and function in whole organisms that are integral components of surrounding social and physical environments (Oyama, 1985;Williams and Nesse, 1991). The immune s...

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Section: Introductionmentioning

confidence: 99%

Life history theory and the immune system: Steps toward a human ecological immunology

McDade¹

2003

Am. J. Phys. Anthropol.

288

305

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“…7 In the present study, we address these issues by (i) assembling the sample reported in our household study 7 into multihousehold extended pedigrees, and (ii) using a variance decomposition method to estimate the effect of shared residence, shared genes, and individual risk factors on variation in fecal egg excretion. The variance decomposition method has been applied successfully to other helminthic infections, notably Ascaris lumbricoides, 16 human hookworm infection, 17 and gastrointestinal nematodes in N'Dama cattle. 18 The current study is the first to use this method to estimate the relative importance of shared residence and additive genetic effects on fecal egg counts during S. mansoni infection.…”

Section: Introductionmentioning

confidence: 99%

Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil.

Bethony¹,

Williams²,

Blangero³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. This study quantifies the influence of shared household and kinship on egg counts during Schistosoma mansoni infection in a sample from rural Brazil. Detailed genealogic information allowed assignment of 597 individuals to 6 multihousehold pedigrees residing in 145 households. A variance component method was used to partition egg counts into shared household, additive genetic, and individual-specific environmental effects. Host additive genetic effects consistently accounted for a large proportion of the variation in egg counts: 43% in an unadjusted model and 40% in model adjusted for covariates. In a model that examined the confounding of shared household with kinship, additive genetic effects still accounted for 27% of the variation in egg counts and shared household only 12%. The consistently important role for host additive genetic factors on the variation in egg counts points to new ways of modeling and understanding the mechanisms that contribute to trait variation during infection with S. mansoni.

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“…Our previous studies have demonstrated that there is a substantial genetic component to susceptibility to Ascaris infection in humans (22). The focal population for these studies was the Jirel population of eastern Nepal, a Tibeto-Burman language speaking hybrid group derived from Sherpas and Sunwars approximately 10-11 generations ago (23,24).…”

mentioning

confidence: 99%

“…The focal population for these studies was the Jirel population of eastern Nepal, a Tibeto-Burman language speaking hybrid group derived from Sherpas and Sunwars approximately 10-11 generations ago (23,24). We used data on Ascaris egg counts in a single large pedigree comprising 1,261 members of the Jirel population to determine that genetic factors accounted for approximately 30% (h 2 ϭ 0.291, P Ͻ 0.0001) of the variation in eggs per gram of feces (EPG) as assessed by the Kato-Katz thick smear method (22). Systematic environmental factors accounted for an additional 6% of the variation.…”

mentioning

confidence: 99%

Genes on chromosomes 1 and 13 have significant effects on Ascaris infection

Williams‐Blangero

VandeBerg

Subedi

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

120

108

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Nematode parasites show a characteristic aggregated distribution among hosts. This observation has important implications for pathogenesis, immunology, and control of these infections, but the relative roles of environment and genetics in determining these patterns have remained uncertain. This paper presents the results of the first genome scan for susceptibility to infection with roundworm (Ascaris lumbricoides). Data on 375 genetic markers were generated for each of 444 members of a genetically isolated Nepalese population, the Jirels. Ascaris worm burden as assessed by egg counts was measured in these same individuals by using the Kato Katz thick smear method. The extensive genealogical data available for the population allowed assignment of all 444 individuals to a single pedigree that contained 6,209 pairs of relatives that were informative for genetic analysis. A variance components linkage analysis resulted in the unequivocal localization of two genes (one on chromosome 1 and another on chromosome 13) with clear, significant effects on susceptibility to Ascaris infection. This is the first evidence that individual quantitative trait loci influence variation in Ascaris burden in humans.

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Genetic analysis of susceptibility to infection with Ascaris lumbricoides.

Cited by 107 publications

References 36 publications

Life history theory and the immune system: Steps toward a human ecological immunology

Life history theory and the immune system: Steps toward a human ecological immunology

Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil.

Genes on chromosomes 1 and 13 have significant effects on Ascaris infection

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