Divergent patterns of linkage disequilibrium and haplotype structure across global populations at the interleukin-13 (IL13) locus

Tarazona‐Santos, Eduardo; Tishkoff, Sarah A.

doi:10.1038/sj.gene.6364149

Cited by 35 publications

(29 citation statements)

References 68 publications

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“…Additionally, 44% of all SNPs in this population were private (78). The high level of genetic diversity in African populations is also consistent with a larger long-term effective population size (N e ) compared to non-Africans (72,195,196,202,206 ; N e is estimated to be ~15,000 for Africans and ~7500 for non-Africans based on a resequencing analysis of several 10-kb regions (243) (see Supplemental Material).…”

Section: Nucleotide and Haplotype Variationmentioning

confidence: 84%

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

Campbell

Tishkoff

2008

Annu. Rev. Genom. Hum. Genet.

679

573

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Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility.

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Section: Nucleotide and Haplotype Variationmentioning

confidence: 84%

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

Campbell

Tishkoff

2008

Annu. Rev. Genom. Hum. Genet.

679

573

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“…This may be the case of IL-13/Ϫ1112, which has been extensively replicated as a determinant of higher total serum IgE levels and has been shown to protect against parasitic infections (24). There is also evidence of selective pressure in and around the IL-13 locus (25). Other polymorphisms in genes involved in T-helper 2-like responses, such as IL-13, may show similar, highly replicable associations with asthma-related traits.…”

Section: Assumptions Of Direct Studies Of the Genetic Associations Inmentioning

confidence: 85%

Gene-Environment Interactions in Asthma: With Apologies to William of Ockham

Martínez¹

2007

Proceedings of the American Thoracic Society

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Many environmental factors and a large number of genetic polymorphisms have been reported to be associated with asthma risk in different locales and at different ages. It seems that what we call asthma is a heterogeneous set of conditions for which the only common feature is recurrent airway obstruction that is at least partially responsive to usual asthma therapy. Recent studies in which environmental factors and genetic variants were studied concomitantly have suggested a potential unifying concept for the disease. It seems that asthma is a genetically mediated development dysregulation of diverse immune and airway responses to a variety of specific and nonspecific exposures. It thus seems improbable that most genetic variants associated with asthma influence the disease regardless of which environmental factors trigger it and at which lifetime phase they are present. More likely, the most important gene variants for asthma are polymorphisms that exert their influence on the network system controlling biological responses to asthma-related exposures.

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“…54 In humans, allergen-specific T-cell clones produce IL-13, 55 and IL-13 will elevate mast-cell proliferation; 56 experimental anti-Th2 strategies which do not address IL-13 have failed. 57 The IL-13 locus, which is ethnically very diverse, 58 is recognized as contributing to asthma susceptibility. 59,60 Thus, as elevated IL-13 is a recognized aspect of the Th2 response in asthma patients, it may be the case that the diminished IFN-l1 response in these patients 37 contributes directly to their elevated IL-13 levels via the mechanism suggested by the present data.…”

Section: Discussionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Divergent patterns of linkage disequilibrium and haplotype structure across global populations at the interleukin-13 (IL13) locus

Cited by 35 publications

References 68 publications

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

Gene-Environment Interactions in Asthma: With Apologies to William of Ockham

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

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