Non-invasive pre-implantation genetic diagnosis of X-linked disorders

Abstract

Pre-implantation genetic diagnosis (PGD) is a powerful clinical tool to identify embryos with or at risk of specific genetic diseases before implantation in utero after in vitro fertilization (IVF). PGD is performed on embryo biopsies that are obtained by aspiration of one or two cells from pre-implantation embryos at day 3 or day 5/6 of culture. However this is a traumatic method that cannot be avoided because non-invasive procedures to assess the genetic status of pre-implantation embryos are not available yet. We hypothesize that cell-free nucleic acids, which are released by embryos in the culture medium during the IVF procedure, could be used for genetic screening. To test our hypothesis we will focus first on X-linked disorders because these single-gene diseases due to the presence of defective genes on the X chromosome are dominant in males. Therefore the objective here is to discriminate between female (XX) and male (XY) embryos by detecting Y chromosome-specific sequences in cell-free nucleic acids. Using culture medium from embryos we are able to discriminate between male and female embryos. This opens new avenues for the development of a non-invasive PGD method.