Whole-genome microarray analysis in prenatal specimens identifies clinically significant chromosome alterations without increase in results of unclear significance compared to targeted microarray.
OBJECTIVE
To determine the detection rates of whole-genome microarray technology compared to targeted microarray analysis for chromosome abnormalities in prenatal samples submitted for diagnostic testing.


METHODS
Microarray analysis using either whole-genome bacterial artificial chromosome (BAC)-based and oligonucleotide (oligo)-based microarrays or targeted BAC microarrays was performed on 182 and 62 prenatal cases, respectively, from North American healthcare providers without previously known chromosome abnormalities or family history of a parent with a known chromosome rearrangement.


RESULTS
Microarray analysis identified clinically significant chromosome alterations in 7 out of 182 (3.8%) prenatal specimens, two of which each had two unrelated abnormalities. After excluding two of the cases in which the abnormality would have been identified by routine karyotyping, the diagnostic yield of clinically significant findings was 5 out of 182 (2.7%). One case had a finding of unclear significance (0.5%) and 16 cases had benign copy number variants (CNVs) (8.8%). Targeted microarray analysis combined with previously published data demonstrated detection rates of 0.9% for clinically significant results, 0.5% for results of unclear significance, and 8.0% for benign CNVs.


CONCLUSIONS
Whole-genome prenatal aCGH detected clinically significant submicroscopic chromosome abnormalities in addition to chromosome abnormalities that could be identified by concurrent karyotyping without an increase in unclear results or benign CNVs compared to targeted aCGH.
Coppinger
Justine
J
Signature Genomic Laboratories, Spokane, WA, USA.
Alliman
Sarah
S
Lamb
Allen N
AN
Torchia
Beth S
BS
Bejjani
Bassem A
BA
Shaffer
Lisa G
LG
D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D055815:Young Adult