{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:13:41Z","timestamp":1789614821193,"version":"build-2803163510"},"reference-count":22,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,6,19]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>De novo mutations underlie individually rare but collectively common pediatric congenital disorders. Some of these mutations can also be detected in tissues and from cells in a parent, where their abundance and tissue distribution can be measured. We previously reported that a subset of these mutations is detectable in sperm from the father, predicted to impact the health of offspring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>As a cohort study, in three independent couples undergoing in vitro fertilization, we first identified male gonadal mosaicism through deep whole genome sequencing. We then confirmed variants and assessed their transmission to preimplantation blastocysts (32 total) through targeted ultra-deep genotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Across 55 gonadal mosaic variants, 15 were transmitted to blastocysts for a total of 19 transmission events. This represented an overall predictable but slight undertransmission based upon the measured mutational abundance in sperm. We replicated this conclusion in an independent, previously published family-based cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Unbiased preimplantation genetic testing for gonadal mosaicism may represent a feasible approach to reduce the transmission of potentially harmful de novo mutations. This\u2014in turn\u2014could help to reduce their impact on miscarriages and pediatric disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>No external funding was received for this work.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.78459","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T06:15:40Z","timestamp":1655705740000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.78459","source":"Crossref","is-referenced-by-count":14,"title":["Unbiased mosaic variant assessment in sperm: a cohort study to test predictability of transmission"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-8604","authenticated-orcid":true,"given":"Martin W","family":"Breuss","sequence":"first","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]},{"name":"Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine","place":["Aurora, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-0023","authenticated-orcid":true,"given":"Xiaoxu","family":"Yang","sequence":"first","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Stanley","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McEvoy-Venneri","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene J","family":"Morales","sequence":"additional","affiliation":[{"name":"Fertility Specialists Medical Group","place":["San Diego, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-9220","authenticated-orcid":true,"given":"Joseph G","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Institute for Genomic Medicine","place":["San Diego, United States"]},{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurosciences, University of California, San Diego","place":["La Jolla, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrg3424","article-title":"A genomic view of mosaicism and human disease","volume":"14","author":"Biesecker","year":"2013","journal-title":"Nature Reviews. 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