{"id":"https://openalex.org/W7215824432","doi":"https://doi.org/10.64898/2026.09.30.755673","title":"Functional modelling of human infertility-associated genetic variants using C. elegans and mice","display_name":"Functional modelling of human infertility-associated genetic variants using C. elegans and mice","publication_year":2026,"publication_date":"2026-10-02","ids":{"openalex":"https://openalex.org/W7215824432","doi":"https://doi.org/10.64898/2026.09.30.755673"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.30.755673","doi":"https://doi.org/10.64898/2026.09.30.755673","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755673","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755673.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755673.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5002747635","display_name":"Omar El Tokhy","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210161592","display_name":"MRC London Institute of Medical Sciences","ror":"https://ror.org/05p1n6x86","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210161592","https://openalex.org/I47508984"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Omar El Tokhy","raw_affiliation_strings":["MRC Laboratory of Medical Sciences, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC Laboratory of Medical Sciences, London, United Kingdom","institution_ids":["https://openalex.org/I4210161592"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003639217","display_name":"Euan Mitchell","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210158898","display_name":"Institute of Genetics and Cancer","ror":"https://ror.org/05hygey35","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4210158898","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I4387154614","display_name":"MRC Human Genetics Unit","ror":"https://ror.org/011jsc803","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4387154614","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I98677209","display_name":"University of Edinburgh","ror":"https://ror.org/01nrxwf90","country_code":"GB","type":"education","lineage":["https://openalex.org/I98677209"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Euan Mitchell","raw_affiliation_strings":["MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom","institution_ids":["https://openalex.org/I4210158898","https://openalex.org/I4387154614","https://openalex.org/I98677209"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023042647","display_name":"Consuelo Barroso","orcid":"https://orcid.org/0000-0002-0661-3460","observed_orcids":["https://orcid.org/0000-0002-0661-3460"]},"institutions":[{"id":"https://openalex.org/I4210161592","display_name":"MRC London Institute of Medical Sciences","ror":"https://ror.org/05p1n6x86","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210161592","https://openalex.org/I47508984"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Consuelo Barroso","raw_affiliation_strings":["MRC Laboratory of Medical Sciences, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC Laboratory of Medical Sciences, London, United Kingdom","institution_ids":["https://openalex.org/I4210161592"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063560061","display_name":"Jennifer Lawson","orcid":"https://orcid.org/0000-0003-2637-7546","observed_orcids":["https://orcid.org/0000-0003-2637-7546"]},"institutions":[{"id":"https://openalex.org/I4210158898","display_name":"Institute of Genetics and Cancer","ror":"https://ror.org/05hygey35","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4210158898","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I4387154614","display_name":"MRC Human Genetics Unit","ror":"https://ror.org/011jsc803","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4387154614","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I98677209","display_name":"University of Edinburgh","ror":"https://ror.org/01nrxwf90","country_code":"GB","type":"education","lineage":["https://openalex.org/I98677209"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Jennifer Lawson","raw_affiliation_strings":["MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom","institution_ids":["https://openalex.org/I4210158898","https://openalex.org/I4387154614","https://openalex.org/I98677209"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085342571","display_name":"Owen Richard Davies","orcid":"https://orcid.org/0000-0002-3806-5403","observed_orcids":["https://orcid.org/0000-0002-3806-5403"]},"institutions":[{"id":"https://openalex.org/I4210134627","display_name":"Wellcome Centre for Cell Biology","ror":"https://ror.org/03xbccz06","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210134627","https://openalex.org/I87048295","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I98677209","display_name":"University of Edinburgh","ror":"https://ror.org/01nrxwf90","country_code":"GB","type":"education","lineage":["https://openalex.org/I98677209"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Owen R. Davies","raw_affiliation_strings":["Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, United Kingdom"],"raw_orcid":"https://orcid.org/0000-0002-3806-5403","affiliations":[{"raw_affiliation_string":"Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, United Kingdom","institution_ids":["https://openalex.org/I4210134627","https://openalex.org/I98677209"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072694814","display_name":"Channa Nalin Jayasena","orcid":"https://orcid.org/0000-0002-2578-8223","observed_orcids":["https://orcid.org/0000-0002-2578-8223"]},"institutions":[{"id":"https://openalex.org/I47508984","display_name":"Imperial College London","ror":"https://ror.org/041kmwe10","country_code":"GB","type":"education","lineage":["https://openalex.org/I47508984"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Channa N. Jayasena","raw_affiliation_strings":["Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom","institution_ids":["https://openalex.org/I47508984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024404524","display_name":"Joris A. Veltman","orcid":"https://orcid.org/0000-0002-3218-8250","observed_orcids":["https://orcid.org/0000-0002-3218-8250"]},"institutions":[{"id":"https://openalex.org/I4210158898","display_name":"Institute of Genetics and Cancer","ror":"https://ror.org/05hygey35","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4210158898","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I98677209","display_name":"University of Edinburgh","ror":"https://ror.org/01nrxwf90","country_code":"GB","type":"education","lineage":["https://openalex.org/I98677209"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Joris A. Veltman","raw_affiliation_strings":["Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom","institution_ids":["https://openalex.org/I4210158898","https://openalex.org/I98677209"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024926457","display_name":"Ian R. Adams","orcid":"https://orcid.org/0000-0001-8838-1271","observed_orcids":["https://orcid.org/0000-0001-8838-1271"]},"institutions":[{"id":"https://openalex.org/I133960621","display_name":"Roslin Institute","ror":"https://ror.org/01920rj20","country_code":"GB","type":"facility","lineage":["https://openalex.org/I133960621","https://openalex.org/I2799693246","https://openalex.org/I4210087105","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I4210158898","display_name":"Institute of Genetics and Cancer","ror":"https://ror.org/05hygey35","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4210158898","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I4387154614","display_name":"MRC Human Genetics Unit","ror":"https://ror.org/011jsc803","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210087105","https://openalex.org/I4387154614","https://openalex.org/I90344618","https://openalex.org/I98677209"]},{"id":"https://openalex.org/I98677209","display_name":"University of Edinburgh","ror":"https://ror.org/01nrxwf90","country_code":"GB","type":"education","lineage":["https://openalex.org/I98677209"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Ian R. Adams","raw_affiliation_strings":["MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom","Roslin Institute and the Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK"],"raw_orcid":"https://orcid.org/0000-0001-8838-1271","affiliations":[{"raw_affiliation_string":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom","institution_ids":["https://openalex.org/I4210158898","https://openalex.org/I4387154614","https://openalex.org/I98677209"]},{"raw_affiliation_string":"Roslin Institute and the Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK","institution_ids":["https://openalex.org/I133960621","https://openalex.org/I98677209"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5081365587","display_name":"Enrique Mart\u00ednez-P\u00e9rez","orcid":"https://orcid.org/0000-0001-5813-0383","observed_orcids":["https://orcid.org/0000-0001-5813-0383"]},"institutions":[{"id":"https://openalex.org/I4210161592","display_name":"MRC London Institute of Medical Sciences","ror":"https://ror.org/05p1n6x86","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210161592","https://openalex.org/I47508984"]},{"id":"https://openalex.org/I47508984","display_name":"Imperial College London","ror":"https://ror.org/041kmwe10","country_code":"GB","type":"education","lineage":["https://openalex.org/I47508984"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Enrique Martinez-Perez","raw_affiliation_strings":["Institute of Clinical Sciences, Imperial College London, London, United Kingdom","MRC Laboratory of Medical Sciences, London, United Kingdom"],"raw_orcid":"https://orcid.org/0000-0001-5813-0383","affiliations":[{"raw_affiliation_string":"Institute of Clinical Sciences, Imperial College London, London, United Kingdom","institution_ids":["https://openalex.org/I47508984"]},{"raw_affiliation_string":"MRC Laboratory of Medical Sciences, London, United Kingdom","institution_ids":["https://openalex.org/I4210161592"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5081365587"],"corresponding_institution_ids":["https://openalex.org/I4210161592","https://openalex.org/I47508984"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10116","display_name":"Sperm and Testicular Function","score":0.03929999843239784,"subfield":{"id":"https://openalex.org/subfields/2743","display_name":"Reproductive Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10123","display_name":"DNA Repair Mechanisms","score":0.021299999207258224,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/infertility","display_name":"infertility","score":0.7179999947547913},{"id":"https://openalex.org/keywords/msh4","display_name":"MSH4","score":0.9399999976158142},{"id":"https://openalex.org/keywords/non-obstructive-azoospermia","display_name":"non-obstructive azoospermia","score":0.9110000133514404},{"id":"https://openalex.org/keywords/primary-ovarian-insufficiency","display_name":"primary ovarian insufficiency","score":0.828000009059906},{"id":"https://openalex.org/keywords/meiotic-recombination","display_name":"meiotic recombination","score":0.8180000185966492},{"id":"https://openalex.org/keywords/crossover-formation","display_name":"crossover formation","score":0.7699999809265137},{"id":"https://openalex.org/keywords/dna-mismatch-repair","display_name":"DNA mismatch repair","score":0.7229999899864197},{"id":"https://openalex.org/keywords/missense-mutations","display_name":"missense mutations","score":0.6629999876022339},{"id":"https://openalex.org/keywords/variant-pathogenicity","display_name":"variant pathogenicity","score":0.8799999952316284},{"id":"https://openalex.org/keywords/functional-validation","display_name":"functional validation","score":0.4869999885559082},{"id":"https://openalex.org/keywords/c-elegans-model","display_name":"C. elegans model","score":0.6740000247955322},{"id":"https://openalex.org/keywords/mouse-model","display_name":"mouse model","score":0.9779999852180481},{"id":"https://openalex.org/keywords/crispr-cas9","display_name":"CRISPR/Cas9","score":0.8339999914169312},{"id":"https://openalex.org/keywords/chiasmata","display_name":"chiasmata","score":0.6660000085830688},{"id":"https://openalex.org/keywords/dna-damage","display_name":"DNA damage","score":0.7419999837875366}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8149999976158142},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.6873000264167786},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.6646999716758728},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.6496000289916992},{"id":"https://openalex.org/C19843653","wikidata":"https://www.wikidata.org/wiki/Q213907","display_name":"Model organism","level":3,"score":0.6164000034332275},{"id":"https://openalex.org/C148196450","wikidata":"https://www.wikidata.org/wiki/Q21100485","display_name":"Meiosis","level":3,"score":0.5752000212669373},{"id":"https://openalex.org/C143589142","wikidata":"https://www.wikidata.org/wiki/Q2617554","display_name":"Loss of heterozygosity","level":4,"score":0.48539999127388},{"id":"https://openalex.org/C2777338322","wikidata":"https://www.wikidata.org/wiki/Q280156","display_name":"Male infertility","level":4,"score":0.4571000039577484},{"id":"https://openalex.org/C2777688143","wikidata":"https://www.wikidata.org/wiki/Q179399","display_name":"Infertility","level":3,"score":0.44190001487731934},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.44020000100135803},{"id":"https://openalex.org/C102744134","wikidata":"https://www.wikidata.org/wiki/Q22280388","display_name":"Homologous recombination","level":3,"score":0.4307999908924103},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3605000078678131},{"id":"https://openalex.org/C47042493","wikidata":"https://www.wikidata.org/wiki/Q265799","display_name":"Human genetics","level":3,"score":0.3544999957084656},{"id":"https://openalex.org/C2777420699","wikidata":"https://www.wikidata.org/wiki/Q794026","display_name":"Azoospermia","level":4,"score":0.35120001435279846},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.3449999988079071},{"id":"https://openalex.org/C68873052","wikidata":"https://www.wikidata.org/wiki/Q349856","display_name":"Genetic variation","level":3,"score":0.34470000863075256},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.32670000195503235},{"id":"https://openalex.org/C64502627","wikidata":"https://www.wikidata.org/wiki/Q170065","display_name":"Pathogenicity","level":2,"score":0.3061999976634979},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.30379998683929443},{"id":"https://openalex.org/C2992519594","wikidata":"https://www.wikidata.org/wiki/Q870433","display_name":"Genetic model","level":3,"score":0.28360000252723694},{"id":"https://openalex.org/C2780673598","wikidata":"https://www.wikidata.org/wiki/Q285223","display_name":"Genetic testing","level":2,"score":0.2799000144004822},{"id":"https://openalex.org/C197077220","wikidata":"https://www.wikidata.org/wiki/Q720988","display_name":"Human genome","level":4,"score":0.2775000035762787},{"id":"https://openalex.org/C16671776","wikidata":"https://www.wikidata.org/wiki/Q5420592","display_name":"Exome sequencing","level":4,"score":0.27390000224113464},{"id":"https://openalex.org/C24432333","wikidata":"https://www.wikidata.org/wiki/Q2068526","display_name":"Whole genome sequencing","level":4,"score":0.27230000495910645},{"id":"https://openalex.org/C64894306","wikidata":"https://www.wikidata.org/wiki/Q849622","display_name":"Homologous chromosome","level":3,"score":0.2662999927997589},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.26269999146461487},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.2603999972343445},{"id":"https://openalex.org/C207177822","wikidata":"https://www.wikidata.org/wiki/Q5050812","display_name":"Genetic screen","level":4,"score":0.2590999901294708},{"id":"https://openalex.org/C2776116246","wikidata":"https://www.wikidata.org/wiki/Q21067469","display_name":"Runs of Homozygosity","level":5,"score":0.25699999928474426},{"id":"https://openalex.org/C23085057","wikidata":"https://www.wikidata.org/wiki/Q5532877","display_name":"Genetic analysis","level":3,"score":0.2515000104904175}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.30.755673","doi":"https://doi.org/10.64898/2026.09.30.755673","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755673","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755673.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.30.755673","doi":"https://doi.org/10.64898/2026.09.30.755673","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.30.755673","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755673.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9537000060081482,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G276069791","display_name":null,"funder_award_id":"MC_A652_5PY60","funder_id":"https://openalex.org/F4320334626","funder_display_name":"Medical Research Council"},{"id":"https://openalex.org/G3777724969","display_name":"Mechanism and regulation of chromosome replication","funder_award_id":"MC_UU_00035/3","funder_id":"https://openalex.org/F4320334626","funder_display_name":"Medical Research Council"}],"funders":[{"id":"https://openalex.org/F4320334626","display_name":"Medical Research Council","ror":"https://ror.org/03x94j517"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7215824432.pdf","grobid_xml":"https://content.openalex.org/works/W7215824432.grobid-xml"},"referenced_works_count":68,"referenced_works":["https://openalex.org/W1532143905","https://openalex.org/W1876047377","https://openalex.org/W1969575610","https://openalex.org/W1969664012","https://openalex.org/W1979291624","https://openalex.org/W1984895636","https://openalex.org/W1990699200","https://openalex.org/W2001341582","https://openalex.org/W2004007221","https://openalex.org/W2006160555","https://openalex.org/W2012212160","https://openalex.org/W2012334640","https://openalex.org/W2032071761","https://openalex.org/W2036395605","https://openalex.org/W2067331893","https://openalex.org/W2069050874","https://openalex.org/W2071103790","https://openalex.org/W2086347537","https://openalex.org/W2101650794","https://openalex.org/W2116537939","https://openalex.org/W2120239133","https://openalex.org/W2124026197","https://openalex.org/W2124620607","https://openalex.org/W2130884140","https://openalex.org/W2136672186","https://openalex.org/W2138919235","https://openalex.org/W2141322090","https://openalex.org/W2143817569","https://openalex.org/W2147125910","https://openalex.org/W2151268228","https://openalex.org/W2155789458","https://openalex.org/W2156632388","https://openalex.org/W2160762623","https://openalex.org/W2166523005","https://openalex.org/W2171960324","https://openalex.org/W2326112268","https://openalex.org/W2410840366","https://openalex.org/W2614850398","https://openalex.org/W2619677561","https://openalex.org/W2735598737","https://openalex.org/W2749069611","https://openalex.org/W2762823924","https://openalex.org/W2915049380","https://openalex.org/W2997344773","https://openalex.org/W3010116705","https://openalex.org/W3029661147","https://openalex.org/W3040562670","https://openalex.org/W3046805499","https://openalex.org/W3063215485","https://openalex.org/W3123280312","https://openalex.org/W3167549442","https://openalex.org/W3189079727","https://openalex.org/W3200516517","https://openalex.org/W3213984151","https://openalex.org/W4206457317","https://openalex.org/W4210805416","https://openalex.org/W4284970556","https://openalex.org/W4315707269","https://openalex.org/W4375947398","https://openalex.org/W4386861232","https://openalex.org/W4389367121","https://openalex.org/W4390590145","https://openalex.org/W4396721167","https://openalex.org/W4401483510","https://openalex.org/W4402494646","https://openalex.org/W4411728731","https://openalex.org/W4414245384","https://openalex.org/W4416949547"],"related_works":["https://openalex.org/W3205121197","https://openalex.org/W3213984151","https://openalex.org/W2790109279","https://openalex.org/W4391103774","https://openalex.org/W4221040877","https://openalex.org/W2968347299","https://openalex.org/W2157603578","https://openalex.org/W3014858428","https://openalex.org/W4411750707","https://openalex.org/W4417211828"],"abstract_inverted_index":{"Abstract":[0],"Infertility":[1],"affects":[2],"one":[3],"in":[4,26,58,62,88,99,132,152,161,179,185,197,202,218,222],"six":[5],"couples":[6],"worldwide":[7],"and":[8,44,56,79,123,181,244],"has":[9],"a":[10,37,83,90,100,159,234],"significant":[11],"genetic":[12,193,240],"component.":[13],"Genome":[14],"sequencing":[15],"efforts":[16],"have":[17],"identified":[18,98,195],"increasing":[19],"numbers":[20],"of":[21,33,82,117,120,125,134,170,190,208,215,242,249],"potentially":[22,70],"pathogenic":[23,71],"variants,":[24],"including":[25,114],"conserved":[27],"meiotic":[28,96,112,219],"genes.":[29],"However,":[30],"the":[31,163,168,206,213,223,239,246],"lack":[32],"functional":[34],"validation":[35],"remains":[36],"major":[38],"barrier":[39],"to":[40,67,177,211],"establishing":[41],"variant":[42,86,149],"pathogenicity":[43,214],"clinical":[45,247],"diagnoses.":[46],"Here,":[47],"we":[48,76],"establish":[49],"an":[50,115],"experimental":[51],"pipeline":[52,232],"integrating":[53],"C.":[54],"elegans":[55],"mouse":[57,80],"vivo":[59],"models":[60,81,210],"with":[61,102],"silico":[63],"protein":[64,93],"structure":[65],"predictions":[66],"functionally":[68],"validate":[69],"infertility-associated":[72],"variants.":[73],"Using":[74],"CRISPR-Cas9":[75],"generated":[77],"worm":[78,188,209],"homozygous":[84,135],"missense":[85,216],"(P638L)":[87],"MSH4,":[89],"mismatch":[91],"repair":[92],"essential":[94],"for":[95,237],"recombination,":[97],"patient":[101],"non-obstructive":[103],"azoospermia":[104],"(NOA).":[105],"Homozygous":[106],"msh-4":[107],"P546L":[108],"worms":[109],"exhibited":[110],"severe":[111],"defects":[113,129],"absence":[116],"chiasmata,":[118],"accumulation":[119],"DNA":[121],"damage,":[122],"loss":[124],"crossover":[126],"markers.":[127],"Comparable":[128],"were":[130],"observed":[131],"spermatocytes":[133],"Msh4":[136,140],"P660L/P660L":[137,141],"mice,":[138],"while":[139],"ovaries":[142],"lacked":[143],"oocyte-containing":[144],"follicles,":[145],"demonstrating":[146],"that":[147,228],"this":[148,229],"causes":[150],"infertility":[151,243],"both":[153],"sexes.":[154],"Together,":[155],"these":[156],"findings":[157],"support":[158],"model":[160],"which":[162],"MSH4":[164,192],"P638L":[165],"substitution":[166],"disrupts":[167],"conversion":[169],"early":[171],"recombination":[172],"events":[173],"into":[174],"crossovers,":[175],"leading":[176],"NOA":[178],"men":[180],"primary":[182],"ovarian":[183],"insufficiency":[184],"women.":[186],"Further":[187],"modelling":[189],"human":[191,224],"variants":[194,217],"exclusively":[196],"heterozygosity":[198],"(G649R)":[199],"or":[200],"also":[201],"homozygosity":[203],"(Y589C)":[204],"demonstrates":[205],"potential":[207],"predict":[212],"proteins":[220],"found":[221],"population.":[225],"We":[226],"propose":[227],"integrated":[230],"worm-mouse":[231],"provides":[233],"powerful":[235],"framework":[236],"accelerating":[238],"diagnosis":[241],"informing":[245],"management":[248],"affected":[250],"individuals.":[251]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-10-03T00:00:00"}