Epigenetic control of the critical region for premature ovarian failure on autosomal genes translocated to the X chromosome: A hypothesis

Flavio Rizzolio, Cinzia Sala, Simone Alboresi, Silvia Bione, Serena Gilli, Mara Goegan, Tiziano Pramparo, Orsetta Zuffardi, Daniela Toniolo

Research output: Contribution to journalArticlepeer-review

Abstract

Chromosomal rearrangements in Xq are frequently associated to premature ovarian failure (POF) and have contributed to define a POF "critical region" from Xq13.3 to Xq26. Search for X-linked genes responsible for the phenotype has been elusive as most rearrangements did not interrupt genes and many were mapped to gene deserts. We now report that ovary-expressed genes flanked autosomal breakpoints in four POF cases analyzed whose X chromosome breakpoints interrupted a gene poor region in Xq21, where no ovary-expressed candidate genes could be found. We also show that the global down regulation in the oocyte and up regulation in the ovary of X-linked genes compared to the autosomes is mainly due to genes in the POF "critical region". We thus propose that POF, in X;autosome balanced translocations, may not only be caused by haploinsufficiency, but also by a oocyte-specific position effect on autosomal genes, dependent on dosage compensation mechanisms operating on the active X chromosome in mammals.

Original languageEnglish
Pages (from-to)441-450
Number of pages10
JournalHuman Genetics
Volume121
Issue number3-4
DOIs
Publication statusPublished - May 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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