{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kohailan M"],"funding":["Qatar National Research Fund","Qatar National Research Fund (QNRF)"],"pagination":["579-588"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9510050"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(10)"],"pubmed_abstract":["While de novo mutations (DNMs) are key to genetic diversity, they are also responsible for a high number of rare disorders. To date, no study has systematically examined the rate and distribution of DNMs in multiplex families in highly consanguineous populations. Leveraging WGS profiles of 645 individuals in 146 families, we implemented a combinatorial approach using 3 complementary tools for DNM discovery in 353 unique trio combinations. We found a total of 27,168 DNMs (median: 70 single-nucleotide and 6 insertion-deletions per individual). Phasing revealed around 80% of DNMs were paternal in origin. Notably, using whole-genome methylation data of spermatogonial stem cells, these DNMs were significantly more likely to occur at highly methylated CpGs (OR: 2.03; p value = 6.62 × 10<sup>-11<"],"journal":["Journal of human genetics"],"pubmed_title":["Patterns and distribution of de novo mutations in multiplex Middle Eastern families."],"pmcid":["PMC9510050"],"funding_grant_id":["NPRP10-0202-170320","NPRP11S-0110-180250"],"pubmed_authors":["Padmajeya S","Palaniswamy S","Janardhanan J","Hussein S","Fakhro KA","Sayed A","Kohailan M","Syed N","Aamer W","Al-Shabeeb Akil A","El Hajj N"],"additional_accession":[]},"is_claimable":false,"name":"Patterns and distribution of de novo mutations in multiplex Middle Eastern families.","description":"While de novo mutations (DNMs) are key to genetic diversity, they are also responsible for a high number of rare disorders. To date, no study has systematically examined the rate and distribution of DNMs in multiplex families in highly consanguineous populations. Leveraging WGS profiles of 645 individuals in 146 families, we implemented a combinatorial approach using 3 complementary tools for DNM discovery in 353 unique trio combinations. We found a total of 27,168 DNMs (median: 70 single-nucleotide and 6 insertion-deletions per individual). Phasing revealed around 80% of DNMs were paternal in origin. Notably, using whole-genome methylation data of spermatogonial stem cells, these DNMs were significantly more likely to occur at highly methylated CpGs (OR: 2.03; p value = 6.62 × 10<sup>-11<","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-04-18T20:58:48.631Z","creation":"2025-04-07T08:58:43.797Z"},"accession":"S-EPMC9510050","cross_references":{"pubmed":["35718832"],"doi":["10.1038/s10038-022-01054-9"]}}