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

Purpose: To examine the utility of single-nucleotide polymorphisms (SNP) microarray analysis to detect uniparental disomy (UPD) by utilizing trios and duos (for which only 1 parent is available). Methods: We established Mendelian Inheritance Error (MIE) values associated with either UPD or biparental inheritance in a cohort of 124 patients. In duos, the percentage of proband heterozygous (AB) SNPs contributed from the parent submitted was also used to detect UPD. Results: Examination of 25 trios revealed UPD with a MIE = 0.02 +/- 0.02 and a range of 0.01 to 0.23 for the contributing parent and a MIE = 8.76 +/- 1.68 with a range of 5.96 to 11.14 for the noncontributing parent. Detailed examination of 13 duos (involving 16 chromosomes) showed an AB% = 52.0% +/- 4.85% consistent with biparental origin of the chromosome of interest. In 6 duos (6 chromosomes), the AB% = 97.2% +/- 2.6% and a range of 92.9% to 99.4% were consistent with UPD. Conclusion: Our results demonstrate utility of a SNP microarray to detect UPD. Distinct MIE ranges were observed that defined UPD or biparental inheritance. In duos, the AB% calculation effectively detected UPD. The diagnostic yield for UPD testing is significantly decreased when large regions of homozygosity are not detected by routine microarray analysis, which has implications for UPD test ordering practices. (c) 2024 Published by Elsevier Inc. on behalf of American College of Medical Genetics and