CHROMOSOMAL MICROARRAY VS. WHOLE EXOME SEQUENCING

“𝓜𝓲𝓬𝓻𝓸𝓪𝓻𝓻𝓪𝔂𝓼 𝓱𝓮𝓵𝓹 𝓾𝓼 𝓯𝓲𝓷𝓭 𝓶𝓲𝓼𝓼𝓲𝓷𝓰 𝓸𝓻 𝓮𝔁𝓽𝓻𝓪 𝓬𝓱𝓻𝓸𝓶𝓸𝓼𝓸𝓶𝓪𝓵 𝓹𝓲𝓮𝓬𝓮𝓼; 𝓦𝓔𝓢 𝓽𝓪𝓴𝓮𝓼 𝓾𝓼 𝓭𝓮𝓮𝓹𝓮𝓻, 𝓲𝓷𝓽𝓸 𝓽𝓱𝓮 𝓬𝓸𝓭𝓲𝓷𝓰 𝓻𝓮𝓰𝓲𝓸𝓷𝓼 𝔀𝓱𝓮𝓻𝓮 𝓻𝓪𝓻𝓮 𝓿𝓪𝓻𝓲𝓪𝓷𝓽𝓼 𝓱𝓲𝓭𝓮.” — Ellen Matloff

🧬 Chromosomal Microarray (CMA) and Whole Exome Sequencing (WES) are cornerstones of modern genomic diagnostics. Each offers unique insights: CMA identifies large-scale structural changes like copy number variations (CNVs), while WES investigates the exome; the protein-coding portion where most pathogenic mutations reside.

🔹 CMA is a first-line tool for neurodevelopmental disorders, intellectual disability, and congenital anomalies. It scans for chromosomal imbalances missed by karyotyping, offering ~15–20% diagnostic yield in such cases. Its speed and cost-effectiveness make it a go-to for initial evaluations.

🔹 WES, by contrast, dives into the exonic 1–2% of the genome that harbors ~85% of known disease-causing variants. WES is particularly useful in cases where CMA results are negative, especially when a monogenic disorder is suspected. It excels in detecting single nucleotide variants (SNVs), indels, and gene-disrupting mutations, but may miss structural rearrangements or low-level mosaicism.

🔹 Comparison & Clinical Use:

CMA → Strong for CNVs; limited for point mutations.

WES → Strong for sequence variants; complex interpretation.

WES is best used after CMA in unresolved syndromic cases. The combined use improves yield, informing diagnosis, genetic counseling, and treatment.

          ➡️ WES presents challenges around incidental findings and variant uncertainty, requiring robust genetic counseling. CMA, though more targeted, may still identify risk alleles with familial or reproductive implications.

⚠️ In an Oystershell, CMA and WES are not rivals; they are complementary technologies. Together, they represent a genomic toolkit that supports precision diagnostics, enhances personalized medicine, and shapes the future of ethical, patient-centered care.

Abubakar Abubakar ✍️

• Serey-Gaut, Margaux et al.
The American Journal of Human Genetics, Volume 110, Issue 3, 499 - 515

• Rodriguez, Isabel et al.
The American Journal of Human Genetics, Volume 111, Issue 3, 544 - 561

#Genomics #GeneticTesting #WholeExomeSequencing #CMA #PrecisionMedicine #AJHG #ClinicalGenetics #RareDiseases #Bioethics #HumanGenetics #PersonalizedMedicine #SNV #CNV #WES #MolecularDiagnostics #GeneCounsel #ART #IVF

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