PMC:4564992 / 46498-48544 JSONTXT

{"project":"2_test","denotations":[{"id":"26320892-15990197-2052552","span":{"begin":1385,"end":1387},"obj":"15990197"},{"id":"26320892-16381868-2052552","span":{"begin":1385,"end":1387},"obj":"16381868"},{"id":"26320892-11595025-2052553","span":{"begin":1650,"end":1652},"obj":"11595025"},{"id":"26320892-10951461-2052554","span":{"begin":1900,"end":1902},"obj":"10951461"}],"text":"Parent-of-origin effects, particularly if mediated through imprinting, represent a more complex, potentially functionally relevant mechanism than the genetic effects that are typically identified through large-scale case-control GWASs. The requirement for parental data necessarily limits the power of studies designed to detect such effects (except, perhaps, in special populations such as the Icelandic population), owing to the decreased sample sizes that are likely to be available; however, suitable cohorts (particularly of mother-child duos) are often collected, for example, when investigating traits related to pregnancy complications. An attraction of focusing on the detection of parent-of-origin effects (rather than on effects mediated primarily by the case subject’s own genotype) is the greater potential for immediate functional investigation and experimental validation. Our application of the new versions of PREMIM and EMIM to four genomic regions that have been postulated as harboring parent-of-origin effects (in cohorts with two separate disorders) found slightly decreased evidence in three of the four regions and considerably decreased evidence in one region, as a result of a larger number of parent-of-origin resolved transmissions than had previously been available. None of the SNPs investigated lie in regions already known to contain imprinted genes,37,38 so further investigation will be required to determine the underlying cause of the parent-of-origin effects observed. The parent-of-origin effect seen on 14q for SLI does, however, overlap with a region that has previously shown a hint toward genomic imprinting.39 A comparison of individuals with a paternal deletion of 14q11–13 and individuals with maternal uniparental disomy of that region showed that the two groups had some overlapping phenotypes, suggesting that the paternal allele is normally expressed.40 Together, these studies suggest that the region may be maternally imprinted, and thus paternal parent-of-origin effects may be operating there."}