Abstract
The term monogenic disorder describes inherited disease caused by a defect in a single gene and encompasses those inherited in an autosomal recessive pattern, autosomal dominant, and sex-linked. DNA from single cells provides an acceptable PGD starter material but requires a lot of initial and ongoing test optimisation. PGD tests using whole gene amplification (WGA) allows diagnosis with standard DNA-based tests. Haplotyping has the advantage over the disease-specific tests being applicable to all couples known to have a mutation in the disease gene. Developing PGD tests is now faster and more efficient, allowing more equity of access for couples with rare disorders.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Further Reading
Altarescu G, Eldar-Geva T, Varshower I, Brooks B, Haran EZ, Margalioth EJ, Levy-Lahad E, Renbaum PPI. Real-time reverse linkage using polar body analysis for preimplantation genetic diagnosis in female carriers of de novo mutations. Hum Reprod. 2009;24(12):3225–9.
Altarescu G, Beeri R, Eldar-Geva T, Varshaver I, Margalioth EJ, Levy-Lahad E, Renbaum P. PGD for germline mosaicism. Reprod Biomed Online. 2012;25(4):390–5.
Barat-Houari M, Nguyen K, Bernard R, Fernandez C, Vovan C, Bareil C, Khau Van Kien P, Thorel D, Tuffery-Giraud S, Vasseur F, Attarian S, Pouget J, Girardet A, Lévy N, Claustres M. New multiplex PCR-based protocol allowing indirect diagnosis of FSHD on single cells: can PGD be offered despite high risk of recombination? Eur J Hum Genet. 2010;18(5):533–8.
Fiorentino F, Magli MC, Podini D, Ferraretti AP, Nuccitelli A, Vitale N, Baldi M, Gianaroli L. The minisequencing method: an alternative strategy for preimplantation genetic diagnosis of single gene disorders. Mol Hum Reprod. 2003;9:399–410.
Goossens V, Traeger-Synodinos J, Coonen E, De Rycke M, Moutou C, Pehlivan T, Derks-Smeets IA, Harton G. ESHRE PGD consortium data collection XI: cycles from January to December 2008 with pregnancy follow-up to October 2009. Hum Reprod. 2012;27(7):1887–911.
Handyside AH, Robinson MD, Simpson RJ, Omar MB, Shaw MA, Grudzinskas JG, Rutherford A. Isothermal whole genome amplification from single and small numbers of cells: a new era for preimplantation genetic diagnosis of inherited disease. Mol Hum Reprod. 2004;10:767–72.
Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, Shaw MA, Griffin DK. Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J Med Genet. 2010;47(10):651–8.
Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, Pehlivan Budak T, Renwick P, De Rycke M, Geraedts JP, Harton G. The ESHRE PGD consortium: 10 years of data collection. Hum Reprod Update. 2012;18(3):234–47.
Harton GL, De Rycke M, Fiorentino F, Moutou C, SenGupta S, Traeger-Synodinos J, Harper JC, European Society for Human Reproduction and Embryology (ESHRE). PGD consortium. ESHRE PGD consortium best practice guidelines for amplification-based PGD. Hum Reprod. 2010;26(1):33–40.
Hellebrekers DMEI, Wolfe R, Hendrick ATM, de Coo IFM, de Die CE, Geraedts JPM, Chinnery PF, Smeets HJM. PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring. Hum Reprod Update. 2012;18(4):341–9.
Poulton J, Chiaratti MR, Meirelles FV, Kennedy S, Wells D, Holt IJ. Transmission of mitochondrial DNA diseases and ways to prevent them. PLoS Genet. 2010;6(8):pii: e1001066.
Rechitsky S, Pomerantseva E, Pakhalchuk T, Pauling D, Verlinsky O, Kuliev A. First systematic experience of preimplantation genetic diagnosis for de-novo mutations. Reprod Biomed Online. 2011;22(4):350–61. Epub 2011 Jan 20.
Renwick P, Ogilvie CM. Preimplantation genetic diagnosis for monogenic diseases: overview and emerging issues. Expert Rev Mol Diagn. 2007;7:33–43.
Renwick PJ, Trussler J, Ostad-Saffari E, Fassihi H, Black C, Braude P, Ogilvie CM, Abbs S. Proof of principle and first cases using preimplantation genetic haplotyping-a paradigm shift for embryo diagnosis. Reprod Biomed Online. 2006;13:110–9.
Renwick P, Trussler J, Lashwood A, Braude P, Ogilvie CM. Preimplantation genetic haplotyping: 127 diagnostic cycles demonstrating a robust, efficient alternative to direct mutation testing on single cells. Reprod Biomed Online. 2010;20(4):470–6.
Sermon K, De Rycke M. Single cell polymerase chain reaction for preimplantation genetic diagnosis: methods, strategies, and limitations. Methods Mol Med. 2007;132:31–42.
Wilton L, Thornhill A, Traeger-Synodinos J, Sermon KD, Harper JC. The causes of misdiagnosis and adverse outcomes in PGD. Hum Reprod. 2009;24(5):1221–8.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag London
About this chapter
Cite this chapter
Renwick, P., Altarescu, G. (2014). PGD Analysis of Embryos for Monogenic Disorders. In: El-Toukhy, T., Braude, P. (eds) Preimplantation Genetic Diagnosis in Clinical Practice. Springer, London. https://doi.org/10.1007/978-1-4471-2948-6_8
Download citation
DOI: https://doi.org/10.1007/978-1-4471-2948-6_8
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-2947-9
Online ISBN: 978-1-4471-2948-6
eBook Packages: MedicineMedicine (R0)