title: Genome-wide array-based copy number profiling in human placentas from unexplained stillbirths.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors: R Alan
authors: RA
authors: Harris
authors: Francesca
authors: F
authors: Ferrari
authors: Shay
authors: S
authors: Ben-Shachar
authors: Xiaoling
authors: X
authors: Wang
authors: George
authors: G
authors: Saade
authors: Ignatia
authors: I
authors: Van Den Veyver
authors: Fabio
authors: F
authors: Facchinetti
authors: Kjersti
authors: K
authors: Aagaard-Tillery
mesh_terms: D000328:Adult; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010920:Placenta; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011446:Prospective Studies; D050497:Stillbirth / Q000235:genetics*