Regions of Homozygosity Identified with a Chromosomal Microarray in a Korean Population: Distribution, Frequency, and...

Single nucleotide polymorphism-based chromosomal microarray analysis (CMA) can detect regions of homozygosity (ROHs), which may be associated with medical conditions; however, limited ROH data, especially in East Asians, complicates clinical interpretations. We characterized ROH distributions and frequencies in a Korean population using CMA, highlighting clinically relevant findings, including suspected uniparental disomy (UPD), using standardized criteria.

We analyzed ROHs in 1,731 individuals who underwent postnatal CMA at a Korean medical center. ROHs ≥ 3 Mb long were detected using the CytoScan Dx platform and Chromosome Analysis Suite Dx. Suspected UPD and consanguinity were assessed per the American College of Medical Genetics and Genomics technical standards.

We identified 3,962 ROHs, with 76.7% of patients carrying at least one. Common "hotspot" regions included 3p21.31p21.1 (20.3%), 11p11.2 (18.2%), 1q21.1q21.3 (17.7%), and 1p33p32.3 (12.0%). Almost all ROHs observed in >1% of patients had a median size of <5 Mb. ROH frequencies correlated negatively with chromosomal recombination rates and positively with gene densities. Additionally, 1.2% (N = 21) of patients exhibited ROH patterns suggestive of UPD or consanguinity (13 suspected UPDs on imprinted chromosomes, 6 on non-imprinted chromosomes, and 2 consanguinities); 8 of 13 patients with suspected UPD were diagnosed as having imprinting disorders, with no pathogenic copy number variations detected.

Our population-specific ROH data for Koreans improve clinical interpretations by minimizing the risk of overinterpreting benign variants and highlight the value of standardized criteria for reliably detecting UPD and consanguinity and integrating ROH analysis into routine CMA interpretations.