TY - JOUR
T1 - Human genetic resistance to Onchocerca volvulus
T2 - Evidence for linkage to chromosome 2p from an autosome-wide scan
AU - Timmann, Christian
AU - Van Der Kamp, Esther
AU - Kleensang, André
AU - König, Inke R.
AU - Thye, Thorsten
AU - Büttner, Dietrich W.
AU - Hamelmann, Christoph
AU - Marfo, Yeboah
AU - Vens, Maren
AU - Brattig, Norbert
AU - Ziegler, Andreas
AU - Horstmann, Rolf D.
N1 - Funding Information:
Received 25 September 2007; accepted 14 February 2008; electronically published 17 June 2008. Potential conflicts of interest: none reported. Financial support: Deutsche Forschungsgemeinschaft (grant HO 886/4-1); Volkswagen Foundation, Germany; National Center for Research Resources, National Institutes of Health (grant RR03655 for use of S.A.G.E). This work is part of the doctoral thesis of E.v.d.K. at the Faculty of Medicine, University of Hamburg. a Present affiliation: European Commission DG Joint Research Centre, Institute for Health and Consumer Protection, European Centre for the Validation of Alternative Methods, Ispra, Italy. Reprints or correspondence: Christian Timmann, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany (timmann@bni.uni-hamburg.de).
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Background. Human infections with the tissue nematode Onchocerca volvulus show strong interindividual variation in intensity, which cannot be explained by differences in exposure alone. Several lines of evidence suggest a relevant influence of human genetics. Methods. In a genome-wide search for genetic determinants of resistance, we studied 196 siblings from 51 families exposed to endemic O. volvulus transmission in the forest zone of Ghana, West Africa. The numbers of worm larvae in the skin (i.e., microfilariae), which are the established measure of O. volvulus infection intensity, were counted in 4 small skin biopsy specimens (i.e., skin snips), and the numbers of palpable subcutaneous worm nodules (i.e., onchocercomata) were assessed. Numbers were corrected for age and exposure and were analyzed for linkage to 377 autosomal microsatellite markers and additional markers in genomic regions of interest. Results. Linkage was detected between the numbers of microfilariae and chromosome 2p21-p14 (maximum multipoint log 10 of odds (LOD) score of 3.80 at marker position D2S2378; empirical P = 2.9 × 10 -5). Conclusions. This finding provides strong evidence that a human genetic factor influences the intensity of O. volvulus infection. The strength of the linkage signal may facilitate the identification of the decisive genetic variants.
AB - Background. Human infections with the tissue nematode Onchocerca volvulus show strong interindividual variation in intensity, which cannot be explained by differences in exposure alone. Several lines of evidence suggest a relevant influence of human genetics. Methods. In a genome-wide search for genetic determinants of resistance, we studied 196 siblings from 51 families exposed to endemic O. volvulus transmission in the forest zone of Ghana, West Africa. The numbers of worm larvae in the skin (i.e., microfilariae), which are the established measure of O. volvulus infection intensity, were counted in 4 small skin biopsy specimens (i.e., skin snips), and the numbers of palpable subcutaneous worm nodules (i.e., onchocercomata) were assessed. Numbers were corrected for age and exposure and were analyzed for linkage to 377 autosomal microsatellite markers and additional markers in genomic regions of interest. Results. Linkage was detected between the numbers of microfilariae and chromosome 2p21-p14 (maximum multipoint log 10 of odds (LOD) score of 3.80 at marker position D2S2378; empirical P = 2.9 × 10 -5). Conclusions. This finding provides strong evidence that a human genetic factor influences the intensity of O. volvulus infection. The strength of the linkage signal may facilitate the identification of the decisive genetic variants.
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U2 - 10.1086/589720
DO - 10.1086/589720
M3 - Article
C2 - 18558870
AN - SCOPUS:48749098503
SN - 0022-1899
VL - 198
SP - 427
EP - 433
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -