Next generation sequencing of SNPs for non-invasive prenatal diagnosis: Challenges and feasibility as illustrated by an application to β-thalassaemia

50Citations
Citations of this article
114Readers
Mendeley users who have this article in their library.

Abstract

β-Thalassaemia is one of the most common autosomal recessive single-gene disorder worldwide, with a carrier frequency of 12% in Cyprus. Prenatal tests for at risk pregnancies use invasive methods and development of a non-invasive prenatal diagnostic (NIPD) method is of paramount importance to prevent unnecessary risks inherent to invasive methods. Here, we describe such a method by assessing a modified version of next generation sequencing (NGS) using the Illumina platform, called 'targeted sequencing', based on the detection of paternally inherited fetal alleles in maternal plasma. We selected four single-nucleotide polymorphisms (SNPs) located in the β-globin locus with a high degree of heterozygosity in the Cypriot population. Spiked genomic samples were used to determine the specificity of the platform. We could detect the minor alleles in the expected ratio, showing the specificity of the platform. We then developed a multiplexed format for the selected SNPs and analysed ten maternal plasma samples from pregnancies at risk. The presence or absence of the paternal mutant allele was correctly determined in 27 out of 34 samples analysed. With haplotype analysis, NIPD was possible on eight out of ten families. This is the first study carried out for the NIPD of β-thalassaemia using targeted NGS and haplotype analysis. Preliminary results show that NGS is effective in detecting paternally inherited alleles in the maternal plasma. © 2013 Macmillan Publishers Limited All rights reserved.

Cite

CITATION STYLE

APA

Papasavva, T., Van Ijcken, W. F. J., Kockx, C. E. M., Van Den Hout, M. C. G. N., Kountouris, P., Kythreotis, L., … Kleanthous, M. (2013). Next generation sequencing of SNPs for non-invasive prenatal diagnosis: Challenges and feasibility as illustrated by an application to β-thalassaemia. European Journal of Human Genetics, 21(12), 1403–1410. https://doi.org/10.1038/ejhg.2013.47

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free