Utilization of a SNP microarray to detect uniparental disomy: Implications and outcomes

Area of Science:

• Genetics
• Genomic analysis
• Molecular diagnostics

Background:

• Uniparental disomy (UPD) is a condition where an individual inherits two copies of a chromosome from only one parent.
• Accurate detection of UPD is crucial for diagnosing various genetic disorders.
• Single-nucleotide polymorphism (SNP) microarray analysis offers a potential method for UPD detection.

Purpose of the Study:

• To evaluate the effectiveness of SNP microarray analysis in identifying UPD.
• To assess the utility of SNP microarray in both trio and duo family study designs.
• To establish diagnostic criteria for UPD detection using SNP microarray data.

Main Methods:

• Established Mendelian Inheritance Error (MIE) values to differentiate UPD from biparental inheritance in 124 patients.
• Utilized trio data (proband and both parents) and duo data (proband and one parent).
• Calculated the percentage of heterozygous (AB) SNPs contributed by the parent in duo analyses.

Main Results:

• In trios, distinct MIE ranges identified UPD (MIE ≈ 0.02) versus biparental inheritance (MIE ≈ 8.76).
• In duos, a heterozygous SNP percentage (AB%) of approximately 52.0% indicated biparental inheritance.
• In duos, an AB% of approximately 97.2% was consistent with UPD, demonstrating the method's utility.

Conclusions:

• SNP microarray analysis is a valuable tool for detecting UPD.
• Specific MIE ranges and AB% calculations reliably distinguish UPD from biparental inheritance.
• The diagnostic yield for UPD testing can be limited by the detection of large homozygous regions in routine microarray analysis, impacting clinical practice.