Fast Facts - Array Comparative Genome Hybridisation (Array CGH)

PATHCHAT Edition
Published: 2024
Please contact your local Ampath pathologist for more information.

What is Array CGH?

✅ Overview of Chromosomal Abnormalities

• Chromosomal abnormalities are a major cause of:
  • Congenital malformations.
  • Intellectual disability (IQ <70).
  • First-trimester miscarriages (over 50% due to chromosomal defects).
  • Recognisable chromosome abnormalities in 0.5–1% of live births.

✅ Evolution of Cytogenetic Testing

• The human chromosome number (46) was established in 1956.
• Lejeune (1959) identified trisomy 21 as the cause of Down syndrome.
• Advances in cell culturing and banding techniques in the 1970s improved chromosome analysis.

📌 Standard karyotyping is limited in resolution (detects abnormalities >5–10Mb), while fluorescence in situ hybridisation (FISH) allows targeted analysis of specific chromosomal regions.

What is Chromosomal Microarray (CMA)?

✅ Definition and Function of CMA

• CMA is a molecular cytogenetic test that detects copy number variants (CNVs), including deletions and duplications.
• CNVs can be:
  • Benign (normal variants).
  • Pathogenic (linked to disease).
  • Of uncertain clinical significance.

✅ Types of CMA

• Oligonucleotide array comparative genomic hybridisation (Array CGH).
• Single nucleotide polymorphism (SNP) arrays.
• Combination of both.

📌 CMA is used in tumour genetics, gene expression studies, and constitutional (hereditary) genetic testing.

Clinical Use of CMA in Developmental Disorders

✅ CMA as a Diagnostic Tool

• First used in clinical settings in 2004.
• Since 2011, recommended as the first-tier test for:
  • Developmental delay/intellectual disability (DD/ID).
  • Autism spectrum disorder (ASD).
  • Multiple congenital anomalies (MCA).

✅ Diagnostic Yield of CMA vs. Karyotyping

• Conventional karyotyping has a diagnostic yield of ~3% for unexplained DD/ID, ASD, or MCA.
• CMA increases diagnostic yield to 15–20%.

📌 CMA provides a higher-resolution method for identifying chromosomal imbalances compared to traditional karyotyping.

How Array CGH Works

✅ Comparison of Patient vs. Control DNA

1. Patient and control DNA are labelled and mixed.
2. Both are applied to a slide containing multiple DNA targets (probes).
3. Hybridisation occurs at oligonucleotide target sites.
4. Imbalances are detected based on fluorescence intensity:
   • Deletions → Reduced patient DNA signal.
   • Duplications → Increased patient DNA signal.
5. A scanner converts this information into a karyogram for clinical interpretation.

📌 Array CGH provides high-resolution analysis of chromosomal copy number variations across the genome.

Limitations of Array CGH

✅ What Array CGH Cannot Detect

• Balanced chromosomal rearrangements (e.g., inversions, balanced translocations).
• Small CNVs below the array’s resolution threshold.
• Low-level mosaicism.
• Uniparental disomy (requires SNP array testing).

✅ When Additional Testing is Needed

• Parental studies (CMA, karyotyping, or FISH) may be required to assess inheritance of detected variants.
• Standard karyotyping remains useful for:
  • Common trisomies (e.g., Down syndrome).
  • Sex chromosome aneuploidies.
  • Disorders of sexual differentiation.
  • Recurrent miscarriages.
  • Confirming the mechanism of structural chromosomal findings.

📌 Array CGH is highly effective for detecting unbalanced chromosomal abnormalities but requires complementary tests for structural rearrangements.

Array CGH at Ampath Genetics

✅ Technology and Resolution

• Ampath Genetics has offered array CGH since 2016.
• Uses Signature Genomics’ CGX Oligo Arrays (Agilent platform).
• 60,000 oligonucleotide probes provide:
  • 200kb resolution across the genome.
  • 30kb resolution in targeted clinically relevant regions.
• Probes cover over 200 recognised syndromes, functionally significant genes, and pericentromeric/subtelomeric regions.

✅ Specimen Requirements & Test Details

• Sample Type: 3–5 mL EDTA blood (sent at room temperature).
• Mnemonic for Test Request: ACGHGENO.
• Turnaround Time: 4 weeks from sample receipt.

📌 Ampath’s array CGH service provides a high-resolution approach to identifying chromosomal imbalances in the postnatal setting.

Contact Information

✅ For Test Enquiries:

• Ampath Genetics: 012 678 1350.

✅ For Genetic Counselling Appointments:

• Phone: 012 678 0645.
• Email: geneticsclinic@ampath.co.za.

📌 Array CGH is a powerful tool for diagnosing unexplained developmental disorders, increasing diagnostic accuracy and improving patient care.