biostudies-literatureDong ZHealth and Medical Research FundNHGRI NIH HHSNIGMS NIH HHS1225-1233https://www.ebi.ac.uk/biostudies/studies/S-EPMC8522200biostudies-literatureUnknown23(7)<h4>Purpose</h4>Absence of heterozygosity (AOH) is a genetic characteristic known to cause human genetic disorders through autosomal recessive or imprinting mechanisms. However, the analysis of AOH via low-pass genome sequencing (GS) is not yet clinically available.<h4>Methods</h4>Low-pass GS (fourfold) with different types of libraries was performed on 17 clinical samples with previously ascertained AOH by chromosomal microarray analysis (CMA). In addition, AOH detection was performed with low-pass GS data in 1,639 cases that had both GS and high-probe density CMA data available from the 1000 Genomes Project. Cases with multiple AOHs (coefficient of inbreeding F ≥ 1/32) or terminal AOHs ≥5 Mb (suspected uniparental disomy [UPD]) were reported based on the guidelines of the American CollegGenetics in medicine : official journal of the American College of Medical GeneticsLow-pass genome sequencing-based detection of absence of heterozygosity: validation in clinical cytogenetics.PMC852220004152666UM1 HG008901P01 GM061354T32 GM007748Choy KWYang ZMorton CCShi MLeung TYChau MHKZhang YDong ZWah YMKwok YKfalseLow-pass genome sequencing-based detection of absence of heterozygosity: validation in clinical cytogenetics.<h4>Purpose</h4>Absence of heterozygosity (AOH) is a genetic characteristic known to cause human genetic disorders through autosomal recessive or imprinting mechanisms. However, the analysis of AOH via low-pass genome sequencing (GS) is not yet clinically available.<h4>Methods</h4>Low-pass GS (fourfold) with different types of libraries was performed on 17 clinical samples with previously ascertained AOH by chromosomal microarray analysis (CMA). In addition, AOH detection was performed with low-pass GS data in 1,639 cases that had both GS and high-probe density CMA data available from the 1000 Genomes Project. Cases with multiple AOHs (coefficient of inbreeding F ≥ 1/32) or terminal AOHs ≥5 Mb (suspected uniparental disomy [UPD]) were reported based on the guidelines of the American Colleg2021-01-01T00:00:00Z2021 Jul2026-05-28T07:08:41.667Z2025-04-19T08:23:57.545ZS-EPMC85222003377222110.1038/s41436-021-01128-7