Next generation sequencing for preimplantation genetic diagnosis

19 02 2013

To the Editor:

We read with interest the editorial written by Simpson and colleagues regarding next-generation sequencing (NGS) for preimplantation genetic diagnosis (PGD) (1). While the authors provide their debatable opinion regarding the history, success, and failure of prior and existing methodologies for genetic analysis of the human embryo, here we will focus only on the major concern raised over allele dropout (ADO) after using NGS, and the proposed limitations of NGS in PGD, which are based upon inaccurate assumptions of the methodology and a misrepresentation of contemporary PGD.

First, the authors incorrectly suggest that NGS-based PGD cannot assess trinucleotide repeat disorders such as Fragile X syndrome. For instance, some NGS methods with longer read length capability (2) may provide enhanced ability and more accurate direct analysis of repeat size and expansion (3). Also, given that these types of disorders are often diagnosed indirectly through the evaluation of linked informative polymorphisms and not directly through repeat size analysis, NGS is even more capable than current methodologies. Specifically, NGS provides an opportunity for increased parallel analysis of multiple markers, and a unique opportunity for direct phasing (4), to predict inheritance of mutations and to reduce the risk of misdiagnosis from ADO. Read the rest of this entry »