Show simple item record

AuthorZaghlool, Shaza B
AuthorAl-Shafai, Mashael
AuthorAl Muftah, Wadha A
AuthorKumar, Pankaj
AuthorGieger, Christian
AuthorWaldenberger, Melanie
AuthorFalchi, Mario
AuthorSuhre, Karsten
Available date2017-12-10T08:04:04Z
Publication Date2016-11-22
Publication NameClinical Epigeneticsen_US
Identifierhttp://dx.doi.org/10.1186/s13148-016-0295-1
CitationZaghlool et al. Mendelian inheritance of trimodal CpG methylation sites suggests distal cis-acting genetic effects. Clinical Epigenetics (2016) 8:124
ISSN1868-7083
URIhttp://hdl.handle.net/10576/5932
AbstractEnvironmentally influenced phenotypes, such as obesity and insulin resistance, can be transmitted over multiple generations. Epigenetic modifications, such as methylation of DNA cytosine-guanine (CpG) pairs, may be carriers of inherited information. At the population level, the methylation state of such "heritable" CpG sites is expected to follow a trimodal distribution, and their mode of inheritance should be Mendelian. Using the Illumina Infinium 450 K DNA methylation array, we determined DNA CpG-methylation in blood cells from a family cohort 123 individuals of Arab ethnicity, including 18 elementary father-mother-child trios, we asked whether Mendelian inheritance of CpG methylation is observed, and most importantly, whether it is independent of any genetic signals. Using 40× whole genome sequencing, we therefore excluded all CpG sites with possibly confounding genetic variants (SNP) within the binding regions of the Illumina probes. We identified a total of 955 CpG sites that displayed a trimodal distribution and confirmed trimodality in a study of 1805 unrelated Caucasians. Of 955 CpG sites, 99.9% observed a strict Mendelian pattern of inheritance and had no SNP within +/-110 nucleotides of the CpG site by design. However, in 97% of these cases a distal cis-acting SNP within a +/-1 Mbp window was found that explained the observed CpG distribution, excluding the hypothesis of epigenetic inheritance for these clear-cut trimodal sites. Using power analysis, we showed that in 46% of all cases, the closest CpG-associated SNP was located more than 1000 bp from the CpG site. Our findings suggest that CpG methylation is maintained over larger genomic distances. Furthermore, nearly half of the SNPs associated with these trimodal sites were also associated with the expression of nearby genes (P = 4.08 × 10(-6)), implying a regulatory effect of these trimodal CpG sites.
Languageen
PublisherBioMed Central
SubjectCpG
SubjectDNA methylation
SubjectEpigenetics
SubjectGenetic variance
SubjectMendelian inheritance
SubjectTrimodal distribution
TitleMendelian inheritance of trimodal CpG methylation sites suggests distal cis-acting genetic effects.
TypeArticle
Volume Number8
dc.identifier.essn 1868-7083


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record