Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples...

Area of Science:

• Genetics
• Molecular Biology
• Clinical Diagnostics

Background:

• Single nucleotide polymorphism (SNP) arrays are increasingly used to investigate developmental disorders.
• These arrays provide copy number and genotyping data for various genetic analyses.
• The clinical utility of SNP genotyping data beyond copy number variations remains underexplored.

Purpose of the Study:

• To evaluate the clinical utility of SNP genotyping data in a large cohort of clinical samples.
• To identify clinically significant abnormalities detected by SNP genotyping beyond copy number analysis.

Main Methods:

• Molecular karyotyping using SNP arrays was performed on 5000 clinical samples.
• Analysis focused on SNP genotyping data, including autozygosity mapping and long continuous stretches of homozygosity (LCSH).

Main Results:

• Clinically significant genotyping abnormalities were found in 0.5% of cases.
• Detected abnormalities included chimerism, low-level chromosome mosaicism, and LCSH associated with uniparental disomy.
• LCSH linked to clinically relevant recessive genetic defects were also identified.

Conclusions:

• SNP genotyping data is valuable for detecting chimerism, mosaicism, and recessive Mendelian disorders.
• The incidence of clinically significant low-level mosaicism may be underestimated.
• Interpreting LCSH presents challenges, especially without detailed phenotypic information, and raises ethical considerations regarding consanguinity.