{"doi":"10.1101/2020.10.14.339796","title":"Temporal stability of human sperm mosaic mutations results in life-long threat of transmission to offspring","abstract":"Summary Every newborn harbors scores of new single nucleotide variants (SNVs) that may impact health and disease 1–4 ; the majority of these are contributed by the paternal germ cells 5 . In some cases, these mutations are identifiable in a subset of the parents’ cells—a phenomenon called mosaicism, which is capable of producing disease recurrence 6–8 . Here, we provide a comprehensive analysis of male gonadal mosaic mutations, employing 300× whole genome sequencing (WGS) of blood and sperm in 17 healthy individuals, including assessment across multiple samples and age groups. Approximately 1 in 15 healthy males is predicted to harbor a transmissible, likely pathogenic exonic variant that is mosaic in his sperm. In general, only a third of sperm mosaic mutations were detectable in blood cells, all were remarkably stable over the course of months to years, and 23% were present in 5% or more of sperm cells. There was no evidence of age-dependent clonal expansion or collapse, as seen in hematopoiesis. Thus, despite the observed increase of mutations in offspring of men with advanced paternal age, detectable sperm mosaicism remains stable, represents a life-long transmission risk to offspring, and suggests a testis stem cell niche that prevents widespread clonality.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124122,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322760,"name":"Martin W. Breuss","orcid":"0000-0003-2200-8604","position":1,"is_corresponding":false},{"id":565779,"name":"Xin Xu","orcid":"0000-0003-3973-2236","position":2,"is_corresponding":false},{"id":2971,"name":"Danny Antaki","orcid":"0000-0003-0381-7801","position":3,"is_corresponding":false},{"id":249083,"name":"Kiely N. James","orcid":"0000-0001-8409-4363","position":4,"is_corresponding":false},{"id":291288,"name":"Valentina Stanley","orcid":"0000-0002-2212-7796","position":5,"is_corresponding":false},{"id":566520,"name":"Laurel Ball","orcid":null,"position":6,"is_corresponding":false},{"id":342945,"name":"Renee D. George","orcid":"0000-0003-0733-9691","position":7,"is_corresponding":false},{"id":568405,"name":"Sara A. Wirth","orcid":"0000-0002-8159-8344","position":8,"is_corresponding":false},{"id":568406,"name":"Beibei Cao","orcid":"0000-0003-3920-5823","position":9,"is_corresponding":false},{"id":440026,"name":"An Nguyen","orcid":"0000-0003-0456-3866","position":10,"is_corresponding":false},{"id":384497,"name":"Jennifer McEvoy‐Venneri","orcid":null,"position":11,"is_corresponding":false},{"id":322756,"name":"Guoliang Chai","orcid":"0000-0001-9658-6381","position":12,"is_corresponding":false},{"id":249089,"name":"Shareef Nahas","orcid":"0000-0003-4494-0320","position":13,"is_corresponding":false},{"id":252537,"name":"Lucitia Van Der Kraan","orcid":null,"position":14,"is_corresponding":false},{"id":249078,"name":"Yan Ding","orcid":"0000-0002-9914-9352","position":15,"is_corresponding":false},{"id":3004,"name":"Jonathan Sebat","orcid":"0000-0002-9087-526X","position":16,"is_corresponding":false},{"id":286444,"name":"Joseph G. Gleeson","orcid":"0000-0002-0889-9220","position":17,"is_corresponding":false},{"id":322763,"name":"Xiaoxu Yang","orcid":"0000-0003-0219-0023","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}