High Resolution Deletion/Duplication Array

Test Background

Claritas Genomics offers a high resolution array that can be used alone or as an add-on companion deletion/duplication analysis for its Claritas Clinical Exome (CCE) and Region of Interest (ROI) tests. When ordered with a CCE or ROI, results will be included with the CCE/ROI Report. When ordered after a CCE/ROI test is completed, results will be reported in 4-5 weeks.

Technical Details

  • An Agilent 1x1M™ custom oligonucleotide whole genome array covering more than 6000 medically-relevant genes with enhanced probe coverage on all exons within those genes. Most other arrays contain far fewer probes and thus cannot achieve the resolution of this array.
  • The inter-probe spacing for exonic regions is less than 100 bp for >100K probes and less than 200 bp for >200K probes. To ensure good coverage in intergenic regions, there are >700K probes with spacing less than 15 Kbp.
  • Each exon of the targeted genes is covered by at least 5 probes. For exons that are too small, probes are included in the flanking intronic regions.
  • This high resolution array is designed to detect CNVs as small as exon-level resolution. Clinical sensitivity, specificity, and reproducibility were measured against well characterized HapMap samples (CNVs ranging from 3-20 kb in targeted genes) with 100% detection. It is possible to detect much smaller CNVs in most exonic regions but the exact resolution varies by gene.
  • To the extent allowed by the nature of the sequence, there are no gaps in genomic sequence >50Kb. This allows superior resolution for detecting CNVs in non-genic regions. See Table 2 for a comparison of gap sizes for our standard whole genome array versus this high resolution array.
  • >100K SNPs are also included in the array to detect regions with loss of heterozygosity (LOH) or uniparental disomy (UPD). These SNPs are spread relatively evenly across the genome and the large number of SNPs provides higher resolution than other arrays. Minimal resolution is 4 Mb but regions as small as 0.5 Mb may also be detected.
  • This assay does not detect balanced alterations (reciprocal translocations, Robertsonian translocations, inversions, and balanced insertions), low level mosaicism, sequence variants, or methylation abnormalities.
  • Note that saliva is not an accepted sample type for deletion/duplication analyses.

The new high resolution array is a custom Agilent 1x1M™ array with an increased number of probes to cover more genes and more exons. Probe selection has been focused on regions of known disease relevance for improved clinical sensitivity. See Table 1 for a coverage summary. Coverage for any gene/exon is available on request. Probes have been selected for optimal performance to ensure exon coverage. Each probe pair is separated by at least 20bp to avoid artifacts.

While the new array has been designed to maximize coverage around disease-relevant genes, whole genome coverage is also improved. All well-behaved probes from previous arrays are included in the new array and intergenic regions not well covered in older versions of the array have been supplemented with new probes for better resolution of non-genic CNVs.

 

Table 1

≥5 Probes within:         # Genes with % exon coverage
100% 95% 90% 80%
1 kb 3751 4215 5024 6028
2 kb 6272 6477 6702 6876
5 kb 7326 7358 7404 7518
10 kb 8162 8175 8210 8391

 

Table 2

Gap Size         # V2 Gaps         V2 Total Gap Bases         # CGH Gaps         CGH Total Gap Bases        
>50kb 795 198,569,660 5746  590,411,843
>100kb 156 157,817,127 758  272,892,369
>250kb 28 139,516,219 118  185,185,867
>500kb 24 138,003,434 50  162,801,516
>1Mb 22 136,637,668 26  146,783,245

 

 

Region of Interest Companion Deletion/Duplication Analysis

If a deletion/duplication analysis is ordered for a Region of Interest test, only those genes that are analyzed in the sequencing portion of the assay will be analyzed for copy number variants. The test codes for individual companion deletion/duplication analyses are listed below.

  • Claritas Clinical Exome Deletion/Duplication Analysis: C0164 (CPT code 81228x1)
  • Bone Marrow Failure Region of Interest Deletion/Duplication Analysis: C0974 (CPT code 81479x1)
  • Comprehensive Immunology Region of Interest Deletion/Duplication Analysis: C0892 (CPT code 81479x1)
  • HLH Region of Interest Deletion/Duplication Analysis: N0659 (CPT code 81479x1)
  • Nephrotic Syndrome Region of Interest Deletion/Duplication Analysis: C0573 (CPT code 81479x1)
  • Pediatric Neurology Region of Interest Deletion/Duplication Analysis: C0598 (CPT code 81479x1)
  • SCID Region of Interest Deletion/Duplication Analysis: C0959 (CPT code 81479x1)
  • Expand ROI Deletion/Duplication Analysis to Claritas Clinical Exome Deletion/Duplication Analysis: C0796 (81228x1)

About Claritas

Claritas Genomics serves children affected with complex genetic disorders by providing timely and accurate results, resolving families’ long search for answers. By combining clinical expertise of the world’s best pediatric specialists with innovative platform solutions, Claritas is working to improve patient care and enable new discoveries. We are committed to the highest quality and accessibility of information and our interpretive services and unique approach to reporting set the standard for reliably and clearly communicating genetic information.

Now is the time to integrate genomics into clinical practice to inform, guide and improve medical treatment for kids around the world.