Epigenetic analysis of the critical region I for premature ovarian failure: demonstration of a highly heterochromatic domain on the long arm of the mammalian X chromosome.
J Med Genet
; 46(9): 585-92, 2009 Sep.
Article
in En
| MEDLINE
| ID: mdl-18628312
ABSTRACT
BACKGROUND:
X chromosome rearrangements defined a critical region for premature ovarian failure (POF) that extended for >15 Mb in Xq. It has been shown previously that the region could be divided into two functionally distinct portions and suggested that balanced translocations interrupting its proximal part, critical region 1 (CR1), could be responsible for POF through downregulation of ovary expressed autosomal genes translocated to the X chromosome. RESULTS ANDCONCLUSION:
This study reports that such position effect can indeed be demonstrated by analysis of breakpoint regions in somatic cells of POF patients and by the finding that CR1 has a highly heterochromatic organisation, very different from that of the euchromatic autosomal regions involved in the rearrangements. The chromatin organisation of the POF CR1 is likely to be responsible for the epigenetic modifications observed in POF patients. The characteristics of CR1 and its downregulation in oocytes may very well explain its role in POF and the frequency of the POF phenotype in chromosomal rearrangements involving Xq. This study also demonstrates a large and evolutionary conserved domain of the long arm of the X chromosome, largely corresponding to CR1, that may have structural or functional roles, in oocyte maturation or in X chromosome inactivation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Heterochromatin
/
Primary Ovarian Insufficiency
/
Chromosomes, Human, X
/
Epigenesis, Genetic
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Med Genet
Year:
2009
Document type:
Article
Affiliation country:
Italy