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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 104, No. 2, 2009, pp. 162-169
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Bioline Code: oc09029
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 104, No. 2, 2009, pp. 162-169
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Host genetic and epigenetic factors in toxoplasmosis
Jamieson, Sarra E.; Cordell, Heather; Petersen, Eskild; McLeod, Rima; Gilbert, Ruth E. & Blackwell, Jenefer M.
Abstract
Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma
gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in
brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis
could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis
that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or
juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North
America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with
polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated
with juvenile onset retinal dystrophies including Stargardt’s disease. Polymorphisms at COL2A1 encoding type II
collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis.
Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications
consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic
and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.
Keywords
congenital infection - toxoplasmosis - genetics - epigenetics
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