{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:36:45Z","timestamp":1791902205450,"version":"4.3.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T00:00:00Z","timestamp":1651968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31890780"],"award-info":[{"award-number":["31890780"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070850"],"award-info":[{"award-number":["32070850"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32061143006"],"award-info":[{"award-number":["32061143006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32000587"],"award-info":[{"award-number":["32000587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900398"],"award-info":[{"award-number":["31900398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Universities","award":["YD2070002007"],"award-info":[{"award-number":["YD2070002007"]}]},{"name":"Central Universities","award":["YD2070002012"],"award-info":[{"award-number":["YD2070002012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>STUDY QUESTION<\/jats:title><jats:p>Do variants in helicase for meiosis 1 (HFM1) account for male infertility in humans?<\/jats:p><\/jats:sec><jats:sec><jats:title>SUMMARY ANSWER<\/jats:title><jats:p>Biallelic variants in HFM1 cause human male infertility owing to non-obstructive azoospermia (NOA) with impaired crossover formation and meiotic metaphase I (MMI) arrest.<\/jats:p><\/jats:sec><jats:sec><jats:title>WHAT IS KNOWN ALREADY<\/jats:title><jats:p>HFM1 encodes an evolutionarily conserved DNA helicase that is essential for crossover formation and completion of meiosis. The null mutants of Hfm1 or its ortholog in multiple organisms displayed spermatogenic arrest at the MMI owing to deficiencies in synapsis and severe defects in crossover formation. Although HFM1 variants were found in infertile men with azoospermia or oligozoospermia, the causal relationship has not yet been established with functional evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title><jats:p>A Pakistani family, having two infertile brothers born to consanguineous parents, and three unrelated Chinese men diagnosed with NOA were recruited for pathogenic variants screening.<\/jats:p><\/jats:sec><jats:sec><jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title><jats:p>All the patients were diagnosed with idiopathic NOA and, for the Chinese patients, meiotic defects were confirmed by histological analyses and\/or immunofluorescence staining on testicular sections. Exome sequencing and subsequent bioinformatic analyses were performed to screen for candidate pathogenic variants. The pathogenicity of identified variants was assessed and studied in vivo in mice carrying the equivalent mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title><jats:p>Six variants (homozygous or compound heterozygous) in HFM1 were identified in the three Chinese patients with NOA and two brothers with NOA from the Pakistani family. Testicular histological analysis revealed that spermatogenesis is arrested at MMI in patients carrying the variants. Mice modeling the HFM1 variants identified in patients recapitulated the meiotic defects of patients, confirming the pathogenicity of the identified variants. These Hfm1 variants led to various reductions of HFM1 foci on chromosome axes and resulted in varying degrees of synapsis and crossover formation defects in the mutant male mice. In addition, Hfm1 mutant female mice displayed infertility or subfertility with oogenesis variously affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title><jats:p>A limitation of the current study is the small sample size. Owing to the unavailability of fresh testicular samples, the defects of synapsis and crossover formation could not be detected in spermatocytes of patients. Owing to the unavailability of antibodies, we could not quantify the impact of these variants on HFM1 protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title><jats:p>Our findings provide direct clinical and in vivo functional evidence that HFM1 variants cause male infertility in humans and also suggest that HFM1 may regulate meiotic crossover formation in a dose-dependent manner. Noticeably, our findings from mouse models showed that HFM1 variants could impair spermatogenesis and oogenesis with a varying degree of severity and might also be compatible with the production of a few spermatozoa in men and subfertility in women, extending the phenotypic spectrum of patients with HFM1 variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title><jats:p>This work was supported by the National Natural Science Foundation of China (31890780, 32070850, 32061143006, 32000587 and 31900398) and the Fundamental Research Funds for the Central Universities (YD2070002007 and YD2070002012). The authors declare no potential conflicts of interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>TRIAL REGISTRATION NUMBER<\/jats:title><jats:p>N\/A.<\/jats:p><\/jats:sec>","DOI":"10.1093\/humrep\/deac092","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T11:11:38Z","timestamp":1650021098000},"page":"1664-1677","source":"Crossref","is-referenced-by-count":34,"title":["Biallelic<i>HFM1<\/i>variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees"],"prefix":"10.1093","volume":"37","author":[{"given":"Xuefeng","family":"Xie","sequence":"first","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Murtaza","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianteng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjha","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zubair","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-4300","authenticated-orcid":false,"given":"Baolu","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjia","family":"Gong","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suixing","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-0689","authenticated-orcid":false,"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-2345","authenticated-orcid":false,"given":"Hui","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1180-9799","authenticated-orcid":false,"given":"Qinghua","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Reproduction and Genetics, First Affiliated Hospital of USTC, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China , Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,8]]},"reference":[{"key":"2022070318262909200_deac092-B1","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1038\/s41436-020-0916-0","article-title":"A genomics approach to male infertility","volume":"22","author":"Alhathal","year":"2020","journal-title":"Genet Med"},{"key":"2022070318262909200_deac092-B2","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nrg3573","article-title":"Meiotic recombination in mammals: localization and regulation","volume":"14","author":"Baudat","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2022070318262909200_deac092-B3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0092-8674(04)00292-2","article-title":"Crossover\/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene\/zygotene transition of meiosis","volume":"117","author":"B\u00f6rner","year":"2004","journal-title":"Cell"},{"key":"2022070318262909200_deac092-B4","doi-asserted-by":"crossref","first-page":"E10041","DOI":"10.1073\/pnas.1810457115","article-title":"Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase","volume":"115","author":"Crickard","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022070318262909200_deac092-B5","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1126\/science.1220381","article-title":"FANCM limits meiotic crossovers","volume":"336","author":"Crismani","year":"2012","journal-title":"Science"},{"key":"2022070318262909200_deac092-B6","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1093\/humrep\/dex307","article-title":"Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences","volume":"32","author":"Donker","year":"2017","journal-title":"Hum Reprod"},{"key":"2022070318262909200_deac092-B7","doi-asserted-by":"crossref","first-page":"e21900","DOI":"10.7554\/eLife.21900","article-title":"Concerted action of the MutL\u03b2 heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion","volume":"6","author":"Duroc","year":"2017","journal-title":"Elife"},{"key":"2022070318262909200_deac092-B8","doi-asserted-by":"crossref","first-page":"459","DOI":"10.4103\/1008-682X.148719","article-title":"Clinical management of infertile men with nonobstructive azoospermia","volume":"17","author":"Esteves","year":"2015","journal-title":"Asian J Androl"},{"key":"2022070318262909200_deac092-B9","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"2022070318262909200_deac092-B10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ajhg.2021.01.010","article-title":"Homozygous mutations in C14orf39\/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans","volume":"108","author":"Fan","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2022070318262909200_deac092-B11","doi-asserted-by":"crossref","first-page":"13298","DOI":"10.1038\/ncomms13298","article-title":"C14ORF39\/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility","volume":"7","author":"Gomez","year":"2016","journal-title":"Nat Commun"},{"key":"2022070318262909200_deac092-B12","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1101\/gad.503108","article-title":"DNA helicases Sgs1 and BLM promote DNA double-strand break resection","volume":"22","author":"Gravel","year":"2008","journal-title":"Genes Dev"},{"key":"2022070318262909200_deac092-B13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev-genet-120215-035111","article-title":"Control of meiotic crossovers: from double-strand break formation to designation","volume":"50","author":"Gray","year":"2016","journal-title":"Annu Rev Genet"},{"key":"2022070318262909200_deac092-B14","doi-asserted-by":"crossref","first-page":"e1003383","DOI":"10.1371\/journal.pgen.1003383","article-title":"Mouse HFM1\/Mer3 is required for crossover formation and complete synapsis of homologous chromosomes during meiosis","volume":"9","author":"Guiraldelli","year":"2013","journal-title":"PLoS Genet"},{"key":"2022070318262909200_deac092-B15","doi-asserted-by":"crossref","first-page":"1700073","DOI":"10.1002\/bies.201700073","article-title":"Bloom syndrome helicase in meiosis: pro-crossover functions of an anti-crossover protein","volume":"39","author":"Hatkevich","year":"2017","journal-title":"Bioessays"},{"key":"2022070318262909200_deac092-B16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s004120050256","article-title":"Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation","volume":"106","author":"Hendzel","year":"1997","journal-title":"Chromosoma"},{"key":"2022070318262909200_deac092-B17","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.devcel.2020.01.010","article-title":"MEIOSIN directs the switch from mitosis to meiosis in mammalian germ cells","volume":"52","author":"Ishiguro","year":"2020","journal-title":"Dev Cell"},{"key":"2022070318262909200_deac092-B18","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.cub.2017.04.017","article-title":"RPL10L is required for male meiotic division by compensating for RPL10 during meiotic sex chromosome inactivation in mice","volume":"27","author":"Jiang","year":"2017","journal-title":"Curr Biol"},{"key":"2022070318262909200_deac092-B19","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/j.scib.2020.08.026","article-title":"A TOP6BL mutation abolishes meiotic DNA double-strand break formation and causes human infertility","volume":"65","author":"Jiao","year":"2020","journal-title":"Sci Bull"},{"key":"2022070318262909200_deac092-B20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12920-020-00813-x","article-title":"Identification of potential causal variants for premature ovarian failure by whole exome sequencing","volume":"13","author":"Jin","year":"2020","journal-title":"BMC Med Genomics"},{"key":"2022070318262909200_deac092-B21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00439-020-02112-y","article-title":"Monogenic causes of non-obstructive azoospermia: challenges, established knowledge, limitations and perspectives","volume":"140","author":"Kasak","year":"2021","journal-title":"Hum Genet"},{"key":"2022070318262909200_deac092-B22","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/humrep\/deab046","article-title":"A recurrent ZSWIM7 mutation causes male infertility resulting from decreased meiotic recombination","volume":"36","author":"Li","year":"2021","journal-title":"Hum Reprod"},{"key":"2022070318262909200_deac092-B23","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1126\/science.1220111","article-title":"The fission yeast FANCM ortholog directs non-crossover recombination during meiosis","volume":"336","author":"Lorenz","year":"2012","journal-title":"Science"},{"key":"2022070318262909200_deac092-B24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.molcel.2012.05.048","article-title":"MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination","volume":"47","author":"Lutzmann","year":"2012","journal-title":"Mol Cell"},{"key":"2022070318262909200_deac092-B25","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/nm.f.1895","article-title":"The biology of infertility: research advances and clinical challenges","volume":"14","author":"Matzuk","year":"2008","journal-title":"Nat Med"},{"key":"2022070318262909200_deac092-B26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0092-8674(04)00294-6","article-title":"Saccharomyces cerevisiae Mer3 helicase stimulates 3\u2032\u20135\u2032 heteroduplex extension by Rad51: implications for crossover control in meiotic recombination","volume":"117","author":"Mazina","year":"2004","journal-title":"Cell"},{"key":"2022070318262909200_deac092-B27","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.cub.2005.02.056","article-title":"Two meiotic crossover classes cohabit in Arabidopsis: one is dependent on MER3,whereas the other one is not","volume":"15","author":"Mercier","year":"2005","journal-title":"Curr Biol"},{"key":"2022070318262909200_deac092-B28","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature07312","article-title":"Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing","volume":"455","author":"Mimitou","year":"2008","journal-title":"Nature"},{"key":"2022070318262909200_deac092-B29","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJMoa2028973","article-title":"Variant PNLDC1, defective piRNA processing, and azoospermia","volume":"385","author":"Nagirnaja","year":"2021","journal-title":"N Engl J Med"},{"key":"2022070318262909200_deac092-B30","doi-asserted-by":"crossref","first-page":"31487","DOI":"10.1074\/jbc.M104003200","article-title":"The MER3 helicase involved in meiotic crossing over is stimulated by single-stranded DNA-binding proteins and unwinds DNA in the 3\u2032 to 5\u2032 direction","volume":"276","author":"Nakagawa","year":"2001","journal-title":"J Biol Chem"},{"key":"2022070318262909200_deac092-B31","doi-asserted-by":"crossref","first-page":"28019","DOI":"10.1074\/jbc.M204165200","article-title":"The MER3 DNA helicase catalyzes the unwinding of holliday junctions","volume":"277","author":"Nakagawa","year":"2002","journal-title":"J Biol Chem"},{"key":"2022070318262909200_deac092-B32","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1128\/MCB.22.10.3281-3291.2002","article-title":"Saccharomyces cerevisiae Mer3 is a DNA helicase involved in meiotic crossing over","volume":"22","author":"Nakagawa","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2022070318262909200_deac092-B33","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.1093\/emboj\/18.20.5714","article-title":"The Saccharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis","volume":"18","author":"Nakagawa","year":"1999","journal-title":"EMBO J"},{"key":"2022070318262909200_deac092-B34","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/bioinformatics\/btw044","article-title":"BCFtools\/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data","volume":"32","author":"Narasimhan","year":"2016","journal-title":"Bioinformatics"},{"key":"2022070318262909200_deac092-B35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cell.2007.05.035","article-title":"BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules","volume":"130","author":"Oh","year":"2007","journal-title":"Cell"},{"key":"2022070318262909200_deac092-B36","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/humrep\/dez022","article-title":"A systematic review and standardized clinical validity assessment of male infertility genes","volume":"34","author":"Oud","year":"2019","journal-title":"Hum Reprod"},{"key":"2022070318262909200_deac092-B37","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1023\/A:1018445520117","article-title":"A drying-down technique for the spreading of mammalian meiocytes from the male and female germline","volume":"5","author":"Peters","year":"1997","journal-title":"Chromosome Res"},{"key":"2022070318262909200_deac092-B38","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/cge.12718","article-title":"Association analysis between HFM1 variation and primary ovarian insufficiency in Chinese women","volume":"89","author":"Pu","year":"2016","journal-title":"Clin Genet"},{"key":"2022070318262909200_deac092-B39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00412-019-00714-8","article-title":"Crossing and zipping: molecular duties of the ZMM proteins in meiosis","volume":"128","author":"Pyatnitskaya","year":"2019","journal-title":"Chromosoma"},{"key":"2022070318262909200_deac092-B40","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ng.2858","article-title":"Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination","volume":"46","author":"Qiao","year":"2014","journal-title":"Nat Genet"},{"key":"2022070318262909200_deac092-B41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.2541","article-title":"RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis","volume":"45","author":"Reynolds","year":"2013","journal-title":"Nat Genet"},{"key":"2022070318262909200_deac092-B42","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.devcel.2020.04.010","article-title":"DNA Helicase Mph1FANCM ensures meiotic recombination between parental chromosomes by dissociating precocious displacement loops","volume":"53","author":"Sandhu","year":"2020","journal-title":"Dev Cell"},{"key":"2022070318262909200_deac092-B43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ajhg.2019.11.013","article-title":"SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility","volume":"106","author":"Schilit","year":"2020","journal-title":"Am J Hum Genet"},{"key":"2022070318262909200_deac092-B44","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cell.2010.02.041","article-title":"Recombination proteins mediate meiotic spatial chromosome organization and pairing","volume":"141","author":"Storlazzi","year":"2010","journal-title":"Cell"},{"key":"2022070318262909200_deac092-B45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00412-008-0185-1","article-title":"Coprinus cinereus Mer3 is required for synaptonemal complex formation during meiosis","volume":"118","author":"Sugawara","year":"2009","journal-title":"Chromosoma"},{"key":"2022070318262909200_deac092-B46","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12958-021-00815-z","article-title":"Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia","volume":"19","author":"Tang","year":"2021","journal-title":"Reprod Biol Endocrinol"},{"key":"2022070318262909200_deac092-B47","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2022070318262909200_deac092-B48","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"2022070318262909200_deac092-B49","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.1093\/nar\/gkab232","article-title":"The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length","volume":"49","author":"Vernekar","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2022070318262909200_deac092-B50","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1056\/NEJMc1310150","article-title":"Mutations in HFM1 in recessive primary ovarian insufficiency","volume":"370","author":"Wang","year":"2014","journal-title":"N Engl J Med"},{"key":"2022070318262909200_deac092-B51","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1242\/jcs.049080","article-title":"MER3 is required for normal meiotic crossover formation, but not for presynaptic alignment in rice","volume":"122","author":"Wang","year":"2009","journal-title":"J Cell Sci"},{"key":"2022070318262909200_deac092-B52","author":"WHO","year":"2010"},{"key":"2022070318262909200_deac092-B53","doi-asserted-by":"crossref","first-page":"e1000702","DOI":"10.1371\/journal.pgen.1000702","article-title":"Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase","volume":"5","author":"Wojtasz","year":"2009","journal-title":"PLoS Genet"},{"key":"2022070318262909200_deac092-B54","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ajhg.2020.06.010","article-title":"Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility","volume":"107","author":"Wyrwoll","year":"2020","journal-title":"Am J Hum Genet"},{"key":"2022070318262909200_deac092-B55","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.15252\/emmm.201404967","article-title":"TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse","volume":"7","author":"Yang","year":"2015","journal-title":"EMBO Mol Med"},{"key":"2022070318262909200_deac092-B56","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1406192","article-title":"X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men","volume":"372","author":"Yatsenko","year":"2015","journal-title":"N Engl J Med"},{"key":"2022070318262909200_deac092-B57","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41436-018-0015-7","article-title":"A homozygous FANCM frameshift pathogenic variant causes male infertility","volume":"21","author":"Yin","year":"2019","journal-title":"Genet Med"},{"key":"2022070318262909200_deac092-B58","doi-asserted-by":"crossref","first-page":"e20182365","DOI":"10.1084\/jem.20182365","article-title":"A DNAH17 missense variant causes flagella destabilization and asthenozoospermia","volume":"217","author":"Zhang","year":"2019","journal-title":"J Exp Med"},{"key":"2022070318262909200_deac092-B59","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11427-016-0274-9","article-title":"Association analysis between HFM1 variations and idiopathic azoospermia or severe oligozoospermia in Chinese Men","volume":"60","author":"Zhang","year":"2017","journal-title":"Sci China Life Sci"},{"key":"2022070318262909200_deac092-B60","doi-asserted-by":"crossref","first-page":"D1055","DOI":"10.1093\/nar\/gks1186","article-title":"SpermatogenesisOnline 1.0: a resource for spermatogenesis based on manual literature curation and genome-wide data mining","volume":"41","author":"Zhang","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2022070318262909200_deac092-B61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13048-019-0537-x","article-title":"A novel heterozygous splice-altering mutation in HFM1 may be a cause of premature ovarian insufficiency","volume":"12","author":"Zhe","year":"2019","journal-title":"J Ovarian Res"},{"key":"2022070318262909200_deac092-B62","doi-asserted-by":"crossref","first-page":"bbaa077","DOI":"10.1093\/bib\/bbaa077","article-title":"PedMiner: a tool for linkage analysis-based identification of disease-associated variants using family based whole-exome sequencing data","volume":"22","author":"Zhou","year":"2021","journal-title":"Brief Bioinform"},{"key":"2022070318262909200_deac092-B63","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cell.2008.08.037","article-title":"Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends","volume":"134","author":"Zhu","year":"2008","journal-title":"Cell"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/37\/7\/1664\/44386063\/deac092.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/37\/7\/1664\/44386063\/deac092.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:41:31Z","timestamp":1675312891000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/37\/7\/1664\/6582350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,8]]},"references-count":63,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,5,8]]},"published-print":{"date-parts":[[2022,6,30]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deac092","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2022,5,8]]}}}