Molecular inversion probe array for the genetic evaluation of stillbirth using formalin-fixed, paraffin-embedded
Leslie R Rowe1, Harshwardhan M Thaker, John M Opitz
1Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, UT 84108-1221, USA.
The Journal of Molecular Diagnostics : JMD
|May 14, 2013
Summary
Molecular inversion probe (MIP) array analysis effectively identifies genomic alterations in formalin-fixed paraffin-embedded (FFPE) stillbirth samples. This method requires minimal DNA and overcomes limitations of traditional cytogenetics for fetal loss evaluation.
Area of Science:
- Genomics
- Reproductive Medicine
- Pathology
Background:
- Array comparative hybridization (ACH) is limited by high DNA requirements for stillbirth analysis.
- Traditional cytogenetic methods and short-term fetal cell culture present challenges for FFPE stillbirth autopsy samples.
Purpose of the Study:
- To evaluate the utility of Molecular Inversion Probe (MIP) array analysis for detecting genomic alterations in FFPE stillbirth autopsy tissue.
- To identify genetic abnormalities missed by conventional cytogenetic methods in archival stillbirth cases.
Main Methods:
- MIP array analysis was performed on genomic DNA extracted from 29 archival FFPE stillbirth autopsy samples (≥20 weeks gestation).
- Samples were selected based on phenotypic suspicion of genomic alterations, normal/unavailable karyotype, or lack of prior microarray testing.
- A 330,000-feature MIP array was used with 75 ng of genomic DNA per sample.
Main Results:
- MIP analysis achieved passing quality control scores in 93.1% (27/29) of FFPE samples.
- Genomic abnormalities were detected in 11% (3/27) of analyzed samples, including a 17q12 deletion, trisomy 18, and a 4qter duplication/13qter deletion from an unbalanced translocation.
- These findings represent genetic abnormalities not identified by previous traditional cytogenetic methods.
Conclusions:
- MIP array analysis is a valuable tool for identifying genomic alterations in FFPE stillbirth autopsy tissue.
- This technique circumvents DNA quantity and quality limitations associated with other methods, enabling retrospective analysis of fetal loss.
- Early identification of these genomic alterations could potentially alter medical management.
