DOI: 10.18413/2658-6533-2023-9-3-0-2

Outcomes of ROHs (runs of homozygosity)/LCSHs (long contiguous stretches of homozygosity) spanning the imprinted loci of chromosomes 7, 11 and 15 among children with neurodevelopmental disorders

Oksana S. Kurinnaia
Kirill S. Vasin
Maria A. Zelenova
Yuri B. Yurov
Victoria Y. Voinova
Svetlana G. Vorsanova
Ivan Y. Iourov

Background: Runs of homozygosity or long contiguous stretches of homozygosity (ROHs/LCSHs) are common in the human genome. ROHs/LCSHs spanning the imprinted loci have been previously associated with neurodevelopmental disorders. However, the outcomes of these epigenomic variations remain enigmatic. Accordingly, there is a need to evaluate the ROHs/LCSHs outcomes covering the imprinted loci. The aim of the study: To describe the outcomes of ROHs/LCSHs spanning the imprinted loci of chromosomes 7, 11 and 15 among children with neurodevelopmental disorders. Materials and methods: Using molecular karyotyping by high-resolution SNP array, we obtained data on ROHs/LCSHs from 772 children with neurodevelopmental disorders and congenital malformations. ROHs/LCSHs spanning the imprinted loci of chromosomes 7, 11 and 15 were additionally analyzed by original bioinformatic approaches to uncover the pathogenic value. Results: ROHs/LCSHs spanning the imprinted loci of chromosomes 7, 11 and 15 were detected in 67 (8.7%) individuals. Bioinformatic analyses demonstrated that ROHs/LCSHs affecting imprinted loci of chromosome 7 are not associated with clearly recognizable outcomes. Alternatively, ROHs/LCSHs affecting imprinted loci of chromosome 11 (11p15.5p15.4; Beckwith-Wiedemann syndrome) and chromosome 15 (15q11.2; Prader-Willi/Angelman syndromes) were associated with distinct outcomes as shown by bioinformatics approaches. Prader-Willi/Angelman syndrome loci were affected in 18 cases (2.3%), whereas Beckwith-Wiedemann syndrome loci were affected in 10 cases (1.3%). Conclusion: Analysis of the outcomes of ROHs/LCSHs spanning the imprinted loci of chromosomes 7, 11 and 15 has demonstrated that the epigenomic changes affecting 11p15.5p15.4, and 15q11.2 (28 cases; 3.6%) are associated with atypical forms of Beckwith-Wiedemann and Prader-Willi/Angelman syndromes, respectively. The outcomesof ROHs/LCSHs in chromosome 7 have not been found convincing for a definitive conclusion about the phenotypic effects. Molecular karyotyping by SNP array is a valuable diagnostic technique offering opportunities for detecting these common but underestimated epigenetic causes for neurodevelopmental disorders and congenital malformations.

Keywords: chromosome, runs of homozygosity, long contiguous stretches of homozygosity, neurodevelopmental disorders, SNP array, bioinformatics, cytogenomics.

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Kurinnaia OS, Vasin KS, Zelenova MA, et al. Outcomes of ROHs (runs of homozygosity)/LCSHs (long contiguous stretches of homozygosity) spanning the imprinted loci of chromosomes 7, 11 and 15 among children with neurodevelopmental disorders. Research Results in Biomedicine. 2023;9(3):312-321. DOI: 10.18413/2658-6533-2023-9-3-0-2

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