PRE-IMPLANTATION GENETIC DIAGNOSIS FOR β-THALASSEMIA, SICKLE CELL SYNDROMES AND CYSTIC FIBROSIS IN GREECE
Traeger-Synodinos J1,*, Vrettou C1, Tzetis M1, Palmer G2, Davis S3, Mastrominas M3, Kokali G4, Pandos K4, Kanavakis E1
*Corresponding Author: : Dr. Joanne Traeger-Synodinos, Medical Genetics, Athens University, Choremio Research Laboratory, St. Sophia’s Children’s Hospital, Thivon and Levadias Streets, Athens 11527, Greece; Tel.: +30-210-746-7461; Fax: +30-210-779-5553; E-mail: jtraeger@cc.uoa.gr
page: 25

INTRODUCTION

Pre-implantation genetic diagnosis (PGD) represents an alternative to prenatal diagnosis (PND), originally developed to allow selection of unaffected in vitro fertil­ized (IVF) embryos for establishing pregnancies in couples at risk for transmitting a genetic disorder, thus avoiding the need to terminate affected on-going pregnancies [1]. More than any other procedure in genetic diagnostic ser­vices PGD requires close collaboration with experts in reproductive medicine, as well as genetics, and standard assisted reproductive treatment is required prior to and following embryo biopsy and genetic diagnosis [2,3]. There are potentially three types of cells suitable for PGD analysis including polar bodies (PBs) from the oocyte/ zygote stage, blastomeres from cleavage-stage embryos, or trophectoderm cells from blastocysts, and the expertise of an embryologist is fundamental to ensure a successful biopsy while maintaining embryo viability [2]. Blastomere biopsy is the current method of choice of most centers offering clinical PGD cycles [4].
The β hemoglobinopathies and cystic fibrosis (CF) are the most common monogenic disorders in Greece, with a carrier incidence of approximately 10 and 5%, respec­tively [5-7]. Prevention programs involving PND are well established for both diseases, but for some couples PGD may be a more appropriate option. These include carrier couples with infertility who are resorting to assisted repro­duction to initiate a pregnancy, couples who have experi­enced termination of at least one affected pregnancy fol­lowing a prenatal diagnosis, and couples who have an ethical or religious objection to pregnancy termination [8].
Protocols for genotyping single-cells for monogenic disorders are based on the polymerase chain reaction (PCR). More than a decade of experience has highlighted several inherent pitfalls associated with single-cell DNA amplification [2,9] These include potential sample con­tamination, total PCR failure, and allelic drop-out (ADO) when one of the alleles fails to amplify to detectable lev­els, all of which should be minimized for any PGD PCR protocol prior to clinical application. In addition, the cho­sen method must reliably and accurately characterize the genotype of the embryo relative to the disorder under investigation. In Greece, both β-thal and CF are caused by a wide range of mutations [5-7]. Thus, for each disease, we elected to develop PGD analytical protocols applica­ble to a wide range of affected genotypes (outlined in this review), rather than having to develop case-specific proto­cols for each PGD performed. In addition, many practical aspects of applying PGD within the context of a preven­tive genetic service for common recessive diseases, are summarized, highlighting approaches for improvement, pitfalls and overall limitations.



Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Accepted articles
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Accepted articles
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006