Diagnostic utility of novel combined arrays for genome-wide simultaneous detection of aneuploidy and uniparental isodisomy in losses of pregnancy.

Stefanie Bug,Andrew Craig,Jana Pricelius,Claudia Nevinny-Stickel-Hinzpeter,Marc Botcherby,Beate Solfrank,Mona Stecher,Felizitas Schmitz

doi:10.1186/1755-8166-7-43

Abstract

BackgroundThis proof-of-principle study demonstrates the usefulness and robustness of a novel array based method for the elucidation of genetic causes underlying early pregnancy loss. A combined microarray utilizing comparative genomic hybridization and single nucleotide polymorphism detection (CGH + SNP) was used for parallel genome-wide identification of copy number and heterozygosity status of 70 products of conception. Results of samples with previously determined aneuploidies were juxtaposed to those of a second cohort appearing normal after routine genetic diagnostics.ResultsAll chromosomal imbalances were confirmed, in one sample of the aneuploid panel additional monosomy X was discovered. Genome-wide uniparental disomy causing a complete hydatidiform mole was identified in another sample. No specimen featured microaberrations of obvious clinical relevance. Among cases with presumable euploidy, one microdeletion and a single region of homozygosity were assigned unclear clinical significance.ConclusionsThe results prove the utility of combined imbalance and homozygosity mapping for routine workup of these challenging specimens. Moreover parallel screening at submicroscopic resolution facilitates the detection of novel genetic alterations underlying spontaneous abortion.

Highlights

This proof-of-principle study demonstrates the usefulness and robustness of a novel array based method for the elucidation of genetic causes underlying early pregnancy loss
uniparental disomy (UPD) comprises the concepts of uniparental heterodisomy (UPHD) and isodisomy (UPID)
High molecular weight genomic Deoxyribonucleic acid (DNA) was successfully extracted from all 70 Product of conception (POC)-samples

Summary

Introduction

This proof-of-principle study demonstrates the usefulness and robustness of a novel array based method for the elucidation of genetic causes underlying early pregnancy loss. About 8 to 20% of clinically confirmed pregnancies abort spontaneously in the first trimester [1,2] About half of these early abortions can be explained by chromosome aneuploidy. In order to determine the best medical treatment for all possible causes underlying embryonic demise, genetic analyses of products of conception (POCs) were introduced to diagnostic genome-wide profiling at even higher resolution [11,12,13,14,15,16,17,18,19]. Most often distal gains or losses arise from the presence of chromosome derivatives from a balanced translocation carrier parent In this clinical context, the introduction of precise imbalance mapping meant significant progress. The occurrence of either in POCs is unknown [28]

Methods

Results

Conclusion