Novel parent-of-origin specific differentially methylated loci on chromosome 16

To identify parent-of-origin biased DNA methylation, we performed high-resolution bisulfite sequencing of chromosome 16 on peripheral blood and cultured skin fibroblasts from individuals with maternal and paternal UPD(16) as well as lung tissue from patients with 16q24.1 ACDMPV-causative deletions and a normal control. We identified 22 differentially methylated regions (DMRs) with =5 consecutive CpG methylation sites and varying tissue-specificity, including the known DMRs associated with the established imprinted gene ZNF597 and DMRs supporting maternal methylation of PRR25, thought to be paternally expressed in lymphoblastoid cells. Lastly, we found evidence of paternal methylation on 16q24.1 near LINC01082 mapping to the FOXF1 enhancer. Using high-resolution bisulfite sequencing to evaluate DNA methylation across chromosome 16, we found evidence of novel candidate imprinted loci on chromosome 16 that would not be evident in array-based assays and could contribute to the birth defects observed in association with UPD(16)mat and in ACDMPV. Overall design: Comparison of DNA methylation profiles between individuals with UPD(16)mat (n=2), UPD(16)pat (n=2), and normal controls in blood, juxtaposed with UPD(16)mat from fibroblast cultures (n=1), and lung tissue samples from ACDMPV individuals with maternal deletions (n=2) and normal control (n=1).