Single nucleotide polymorphism (SNP) based
chromosomal microarray (CMA) is a powerful cytogenomic tool for detecting both
copy number variation (deletions or duplications) and copy-neutral structural
variants such as regions of homozygosity (ROH) and uniparental disomy (UPD).
Detection of submicroscopic abnormalities, including microdeletions and microduplications,
may be missed by standard and high resolution chromosome analysis.
Features of the Infinium® CytoSNP-850K BeadChip Array
- High resolution array containing 850,000 SNPs with ~15x redundancy of each
- Follows the International Standard Cytogenomic Arrays (ISCA) consortium guidelines for chip design
- Features are spaced ~16 kb along the backbone of the genome
- Probes spaced ~1.8 kb along genome for a resolution of ~10kb
- Targets microdeletion/microduplication syndrome regions with enriched coverage for more than 3,200 known disease genes
- Regions of homozygosity (ROH) evaluated for possible
uniparental disomy (UPD) and recent shared ancestry
- Spontaneous fetal loss at any gestational age
- Induced termination due to fetal anomalies
- Fetal loss with abnormal karyotype requiring further characterization
- Fetal loss when conventional chromosome analysis cannot be obtained (due to cultulre failure)
If clinically relevant, common aneuploidies,
such as Down syndrome or Trisomy 18, should be ruled out by chromosome analysis
or fluorescence in situ hybridization before CMA testing is
DNA is obtained by extraction from
fetal tissue, products of conception and/or placenta. The CytoSNP-850K
assay utilizes an amplification step for the DNA and hybridizes this to the
BeadChip. The assay then uses a labeling process to provide allele and
intensity data. BeadChips are scanned using a two-channel high-resolution laser
imager and analyzed using Illumina software.
For reporting of copy number
variations (CNVs), thresholds are ≥1 Mb for deletions and ≥2 Mb for
duplications with reporting of smaller findings in clinically significant
regions. Common CNVs listed in the Database of Genomic Variants are not
reported. While NOT diagnostic, SNP data allows for detection of regions of
homozygosity (ROH) suggestive of UPD (isodisomy) or shared ancestry
(consanguinity) with possible implications in the context of recessive
disorders. ROH is evaluated at ≥5 Mb with a reporting threshold of ~10 MB.
Total percentage of ROH is reported when ≥5%.
CMA will not detect balanced
rearrangements (i.e., inversions, translocations), heterodisomy, or very low
level mosaicism. It will not detect single gene mutations, such as single
nucleotide mutations/polymorphisms. Abnormalities that are smaller than the
resolution of the array may not be detected.
SNP CMA can detect whole genome
mosaicism suggestive of two different genomic cell lines, as in the case of
maternal cell contamination. The
presence of maternal cell contamination may limit the interpretation of CMA
Fetal tissue is preferred in order to minimize the possibility of maternal cell contamination.
Fetal tissue (preferred)
Products of conception or placenta
Submit 0.5 cm3 products of conception or placenta in a sterile, plastic, screw-top tube filled with sterile transport media. CGL can provide
- Label specimen tubes with patient’s name and a second identifier.
- Hold specimen at room temperature and transport to the Colorado Genetics Laboratory as soon as possible. Refrigerate if held overnight.
Detailed written report provided with genetic counseling phone consultation available to medical providers.
Colorado Genetics Laboratory recommends that parental/familial testing be considered when a genomic imbalance is detected by chromosomal microarray. Please see current policy – Familial Follow-up After Abnormal Microarray Effective June 1, 2014.
Microarray Billing Policy Effective June 1, 2014
When the new molecular CPT codes became effective January 1, 2013, insurance companies subsequently revised their medical policies regarding medical necessity for chromosomal microarray. Because of the variability among these policies, waivers for microarray testing have been implemented for all insurance carriers, except Colorado Medicaid.
Please have your patient complete and sign the Waiver for CytoSNP-850K Microarray form below, and submit it with the specimen for microarray testing. If the patient’s insurance denies the charges, the patient will be billed at a discounted rate.
Reddy UM, et al., Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth. The New England Journal of Medicine 367:23:2185-2193, 2013.