Genome-wide array-based copy number profiling in human placentas from unexplained stillbirths
Article first published online: 5 JUL 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Volume 31, Issue 10, pages 932–944, October 2011
How to Cite
Harris, R. A., Ferrari, F., Ben-Shachar, S., Wang, X., Saade, G., Van Den Veyver, I., Facchinetti, F. and Aagaard-Tillery, K. (2011), Genome-wide array-based copy number profiling in human placentas from unexplained stillbirths. Prenat. Diagn., 31: 932–944. doi: 10.1002/pd.2817
- Issue published online: 28 SEP 2011
- Article first published online: 5 JUL 2011
- Manuscript Accepted: 1 JUN 2011
- Manuscript Revised: 29 MAY 2011
- Manuscript Received: 7 MAR 2011
- NIH New Innovator Award
- copy number variants;
- deletion syndromes;
- duplication syndromes;
- fetal death
Accumulating evidence suggests that genomic structural variations, particularly copy number variations (CNV), are a common occurrence in humans that may bear phenotypic consequences for living individuals possessing the variant. While precise estimates vary, large-scale karyotypic abnormalities are present in 6–12% of stillbirths (SB). However, due to inherent limitations of conventional cytogenetics, the contribution of genomic aberrations to stillbirth is likely underrepresented. High-resolution copy number variant analysis by genomic array-based profiling may overcome such limitations.
Prospectively acquired SB cases > 22 weeks underwent classification of ‘unexplained’ stillbirth by Wigglesworth and Aberdeen criteria after extensive testing and rigorous multidisciplinary audit. Genome-wide analysis was conducted using high-resolution Illumina single nucleotide polymorphism (SNP) arrays (Human CNV370-Duo) on placental and fetal samples. Potential alternate detection methods were completed by one or more of three independent means (quantitative PCR, Illumina1M, or Agilent105K comparative genomic hybridization arrays).
In our cohort of 54 stillbirths, 29 met strict unexplained criteria. Among these, we identified 24 putative novel CNVs. Subsequent interrogation detected 18 of 24 CNVs (75%) in placental samples, 8 of which were also confirmed in available fetal samples; none were present in maternal blood.
We describe the potential of whole-genome placental profiling to identify small genomic imbalances, which might contribute to a small proportion of well-characterized, unexplained stillbirths. Copyright © 2011 John Wiley & Sons, Ltd.