Test Code: 6798

Chromosomal Microarray: SNP
Test Code: 6798
Turnaround time: 3 to 4 weeks

What is Chromosomal microarray: SNP test ?
This test utilizes an array which consists of 2.6 million markers (including 750,000 SNPs) which allows for the detection of both copy number variation (CNV) and large stretches [>10 Megabases (Mb)] of absence of heterozygosity (AOH), which can result from uniparental disomy (UPD) or common descent. The design is based on recommendations from the International Standards for Cytogenomic Arrays (ISCA) Consortium (Baldwin et al. (2008) Genet Med 10(6):415-429).

Why Choose the Chromosomal microarray: SNP test ?
When compared to conventional cytogenetic testing by G-banded chromosome analysis, this Chromosomal microarray: SNP test detects more than twice as many clinically significant imbalances. The literature supports offering whole genome chromosomal microarray testing as the first tier test for all genetic evaluations for developmental disabilities for developmental disabilities including birth defects, developmental delay, dysmorphic features, growth deficiency and intellectual disability (Miller et al. (2010) Am J Hum Genet 86(5):749-764; Manning and Hudgins (2010) Genet Med 12(11):742-745). Testing for chromosomal imbalances by microarray is cost effective given the greater capability to detect imbalances when compared to conventional methods. This test is roughly equivalent to the cost of chromosome analysis by G- banded analysis plus one targeted FISH study.

By combining SNP analysis with copy number detection, the Chromosomal microarray: SNP test provides one assay for the detection of genomic imbalances and UPD or homozygosity due to apparent common descent. This can help identify recessive risk alleles.

References
Baldwin et al. (2008) Genet Med 10(6):415-429
Miller et al. (2010) Am J Hum Genet 86(5):749-764
Manning and Hudgins (2010) Genet Med 12(11):742-745

INDICATIONS
Chromosomal microarray is indicated for the following reasons:

• Unexplained developmental delay or intellectual disability
• Autism spectrum disorders
• Epilepsy or seizures
• Dysmorphic features, congenital anomalies or birth defects
• Normal chromosome analysis and an abnormal phenotype
• Apparently balanced chromosome rearrangements and an abnormal phenotype to look for cryptic imbalances at the breakpoints
• Characterization of a previously identified chromosome abnormality
• Suspected UPD
• Autosomal recessive condition due to suspected common ancestry

METHODOLOGY
DNA isolated from peripheral blood is hybridized to an array containing oligonucleotide and SNP probes across the genome to detect copy number imbalances and regions of homozygosity. FISH analysis or another method, such as G-banding, is used to confirm any abnormal findings either at the time of initial testing or upon receipt of parental samples, depending on the abnormality. Suspected UPD of chromosome 6, 7, 14 or 15 will be confirmed by methylation analysis.

DETECTION

The detection of deletions and duplications of 400 kb or greater is expected to be very high. Deletions and duplications of 400 kb or greater are reported. Smaller deletions or duplications in regions of known microdeletion/microduplication syndromes or in clinically relevant genes will also be reported. The clinical sensitivity for known microdeletion or microduplication syndromes is available in our detection rate chart. The clinical sensitivity for other disorders is dependent on the proportion of cases caused by deletions/duplications compared with other mutations not detectable by array analysis. Microarray will not detect balanced translocations, balanced inversions, imbalances smaller than the resolution of this array, point mutations or low level mosaicism (usually less than 25%) that may underlie the clinical presentation of the patient.

This test is designed to detect whole and partial chromosome UPD, multiple long stretches of absence of heterozygosity (AOH) greater than 3 Mb and AOH in clinically relevant regions. Possible UPD will be reported when a chromosome has at least one homozygous regions >10 kb. Homozygosity due to apparent common descent will be reported when >5% of the genome is homozygous. These regions of AOH will be specified, allowing for the identification of recessive risk alleles.

SPECIMEN REQUIREMENTS

Additional Specimen Collection/Handling Instructions Required for this Test
Both tube types are required for this test.

Type: Whole Blood
Specimen Requirements:

In EDTA (purple top) AND sodium heparin (green top) tubes: Infants (2 years): 3-5 ml in both tubes
Older Children & Adults: 7-10 ml in both tubes

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

SPECIAL INSTRUCTIONS
Parental samples may be requested to interpret the clinical significance of some findings.