In:
Cytogenetic and Genome Research, S. Karger AG, Vol. 158, No. 2 ( 2019), p. 56-62
Abstract:
〈 i 〉 SHOX 〈 /i 〉 resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. 〈 i 〉 SHOX 〈 /i 〉 haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with 〈 i 〉 SHOX 〈 /i 〉 haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of 〈 i 〉 SHOX 〈 /i 〉 . Our previous study using peripheral blood samples showed that some CpG dinucleotides adjacent to 〈 i 〉 SHOX 〈 /i 〉 exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of 〈 i 〉 SHOX 〈 /i 〉 -flanking CpG islands. In this study, we examined the DNA methylation status of 〈 i 〉 SHOX 〈 /i 〉 -flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of 〈 i 〉 SHOX 〈 /i 〉 . Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of 〈 i 〉 SHOX 〈 /i 〉 -flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb 〈 i 〉 SHOX 〈 /i 〉 expression through DNA methylation-independent mechanisms, which need to be determined in future studies.
Type of Medium:
Online Resource
ISSN:
1424-8581
,
1424-859X
Language:
English
Publisher:
S. Karger AG
Publication Date:
2019
detail.hit.zdb_id:
2061918-2
SSG:
12
Permalink