A key question too is how the parasite influences genetically-regulated, specifically imprinting, could be influencing these genetic associations. We found evidence of isoform-specific monoallelic expression of alleles at both genes, which for ABCA4 was also polymorphic. Isoform-specific and polymorphic imprinting patterns have also been reported in other genes. At ABCA4 it was the paternally-derived allele for the normally expressed exon 10-containing isoform that was silenced in the polyclonal EBV cell lines that we examined. Although consistent with imprinting, we could not formally rule out random choice autosomal mono-allelic expression. The patterns of monoallelic expression that we observed in EBV cells may not reflect precisely what occurs in the tissue-specific setting in vivo. However, if the data for EBV cell lines does parallel the in vivo situation, children homozygous for the disease allele will always have a disease allele expressed in the eye or brain during embryogenesis and postnatally, consistent with the high odds ratios for disease in children homozygous at SNP ABCA4 rs2297633 that contributes independent main effects in the EMSCOT cohort. For heterozygous children, expression of the disease allele will be dependent upon which parent it was derived from. At COL2A1, only the maternallyderived allele for isoform IIB was silenced in the polyclonal EBV cell lines examined. Skeletal anomalies are never associated with congenital toxoplasmosis. Possible explanations for the observed patterns of association between COL2A1 and clinical signs in congenital Chloroquine Phosphate toxoplasmosis are that the etiological variant only influences expression or function of the non-silenced exon 2containing IIA long-form allele; or the disease-causing variant is common to both isoforms but does not manifest as skeletal abnormalities due to the silencing of isoform IIB expressed in Ginsenoside-F2 cartilage. This could also explain why Stickler��s disease with ocular but no skeletal involvement is not confined to exon 2 variants. Re-sequencing is in progress to identify the etiological variant in our cohorts. Further work is required to clarify the mechanisms of epigenetic modifications at both COL2A1 and ABCA4, especially during development. Such research will benefit from further analysis of imprinting patterns in animal models of congenital toxoplasmosis, in addition to human cell lines and clinical samples.