Table 1.
Genomic technologies for chromosomal and molecular syndromes.
| Types of aberrations | Resolution | Clinical indication examples | |
|---|---|---|---|
| Karyotyping | Large structural changes: aneuploidies, translocations, isochromosomes, rings, CNVs >5–10 Mb, etc. Balanced changes (translocations, insertions, inversions, rings) | 5–10 Mb* *depends on region and banding level |
- Suspicion of chromosome syndrome - Infertility or recurrent miscarriage - Rule out structural variant after microarray finding |
| FISH | Aneuploidies, CNVs, translocations, inversions, insertions Probes must be designed for specific aberration | 50 kb−1 Mb; most 200–400 kb | - Prenatal aneuploidy - Parental studies for proband with structural rearrangement (balanced or imbalanced) or CNV - Follow-up studies after abnormal karyotype (e.g., SRY FISH on abnormal Y) |
| SNP array | Copy number changes associated with unbalanced structural changes; Regions of homozygosity/Uniparental disomy; Mosaicism | 10–100 kb *depends on probe density and reporting criteria may be significantly larger |
- Congenital anomalies - Intellectual disability |
| aCGH | Gene or exon level copy number changes associated with unbalanced structural changes | Based on designed, clinical grade typically single-exon resolution for genes of interest | - As part of a phenotype-specific panel test - A complement to exome sequencing |
| MLPA, real-time PCR | Deletions or duplications | Exon-level | - SMA - Thalassemia - Imprinting disorders |
| NGS panel or exome | SNVs, indels, copy number changes Mitochondrial DNA if long-range PCR used first | SNVs: single-nucleotide CNVs: exon-level unless breakpoint within exon, then nucleotide-level as most panels only cover exonic regions | - Phenotype-specific gene panel |
| NIPS | Chromosomal aneuploidies and recurrent deletion/duplication syndromes | Variable depending on methodology. Some designed to detect recurrent CNVs | -Prenatal aneuploidy screening |
| Sanger sequencing | Sequence variants including SNVs, small indels; CNVs smaller than the amplicon size can also be detected but not typical usage | 1 bp | - Specific phenotype known to be caused by sequence variants in a single gene - Targeted testing for familial variant |
| Repeat-primed PCR | Repeat expansions | Quantify 1–220 repeats; Detect up to 1,000 repeats | Repeat expansion disorders |
| MS-MLPA and MS-qPCR | Deletion, UPD and imprinting center defect in the imprinted regions | Exon level | Imprinting disorders such as Prader-Willi Syndrome |