Uniparental disomy: can SNP array data be used for diagnosis?

Area of Science:

• Genetics
• Molecular Biology
• Clinical Diagnostics

Background:

• Single-nucleotide polymorphism (SNP) microarray analysis is a tool for detecting copy-number variants and homozygosity.
• These findings can indicate consanguinity or uniparental disomy (UPD).
• Validation of SNP microarray for UPD identification in clinical settings is crucial.

Purpose of the Study:

• To validate the use of chromosomal microarray analysis (CMA) for identifying uniparental disomy (UPD) in a clinical laboratory setting.
• To assess the efficacy of CMA in detecting different types of UPD.

Main Methods:

• Retrospective analysis of nine UPD cases (chromosomes 7, 14, 15) using SNP microarray (Affymetrix 6.0).
• Analysis of four additional chromosome 15 UPD cases with pre-existing microsatellite marker data.
• Comparison of CMA results with conventional polymorphic microsatellite marker analysis.

Main Results:

• CMA detected blocks of homozygosity in eight out of nine UPD cases in the initial phase.
• In the second phase, CMA failed to detect blocks of homozygosity in three out of four cases of chromosome 15 heterodisomy.
• All undetected cases involved chromosome 15, suggesting a potential failure of recombination.

Conclusions:

• A failure to recombine might increase the risk of nondisjunction and subsequent UPD.
• Standard CMA may not detect all instances of uniparental disomy 15 (UPD15), specifically heterodisomy.
• A normal CMA result for chromosome 15 does not exclude UPD, necessitating further investigation and potentially alternative diagnostic methods.