Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency
Purpose The etiology of premature ovarian insufficiency (POI) is heterogeneous, and genetic factors account for 20–25% of the patients. The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. The...
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| Veröffentlicht in: | Genetics in medicine 2021-12, Vol.23 (12), p.2309-2315 |
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| creator | Wang, Yiyang Guo, Ting Ke, Hanni Zhang, Qian Li, Shan Luo, Wei Qin, Yingying |
| description | Purpose
The etiology of premature ovarian insufficiency (POI) is heterogeneous, and genetic factors account for 20–25% of the patients. The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. The objective of the study is to explore the role of DSB formation genes in POI pathogenesis.
Methods
Variants in DSB formation genes were analyzed from a database of exome sequencing in 1,030 patients with POI. The pathogenic effects of the potentially causative variants were verified by further functional studies.
Results
Three pathogenic heterozygous variants in
PRDM9
and two in
ANKRD31
were identified in seven patients. Functional studies showed the variants in
PRDM9
impaired its methyltransferase activity, and the
ANKRD31
variations disturbed its interaction with another DSB formation factor REC114 by haploinsufficiency effect, indicating the pathogenic effects of the two genes on ovarian function were dosage dependent.
Conclusion
Our study identified pathogenic variants of
PRDM9
and
ANKRD31
in POI patients, shedding new light on the contribution of meiotic DSB formation genes in ovarian development, further expanding the genetic architecture of POI. |
| doi_str_mv | 10.1038/s41436-021-01266-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8629753</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2551574454</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-b4de4f77665914bcf706fc9f560a5b12c1c4376a2022f0c994967cd27544625e3</originalsourceid><addsrcrecordid>eNp9kUtv1TAQhSMEoqXwB1ggS2zKIjB-X2-QSi8vUaAqsLYcx751SeyLnVS6C_47LinlsWBla-abMz4-TfMQw1MMdPWsMMyoaIHgFjARot3davYxp9ACFeJ2vYNatVQA7DX3SrkAwJISuNvsUUa4ZFjtN99PzXSeNi4Giy5NDiZOBSWPRhfSVGt9mrvBoTJlE3vUZWe-osP1pxdPkE95NFNIEdVpV9Dp2fq9QlfU0Yd3Z2uKUYhom12F5uxQWtRrsczeBxtctLv7zR1vhuIeXJ8HzZdXLz8fv2lPPr5-e3x00lom2dR2rHfMSykEV5h11ksQ3irPBRjeYWKxZVQKQ4AQD1YppoS0PZGcMUG4owfN80V3O3ej662L1c-gtzmMJu90MkH_3YnhXG_SpV4JoiSnVeDwWiCnb7Mrkx5DsW4YTHRpLppwjuuPMs4q-vgf9CLNOVZ7mghgpDIrqBRZKJtTKdn5m8dg0Ffp6iVdXdPVP9PVuzr06E8bNyO_4qwAXYBSW3Hj8u_d_5H9AaxHsHg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2604245480</pqid></control><display><type>article</type><title>Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>ProQuest Central UK/Ireland</source><source>Alma/SFX Local Collection</source><creator>Wang, Yiyang ; Guo, Ting ; Ke, Hanni ; Zhang, Qian ; Li, Shan ; Luo, Wei ; Qin, Yingying</creator><creatorcontrib>Wang, Yiyang ; Guo, Ting ; Ke, Hanni ; Zhang, Qian ; Li, Shan ; Luo, Wei ; Qin, Yingying</creatorcontrib><description>Purpose
The etiology of premature ovarian insufficiency (POI) is heterogeneous, and genetic factors account for 20–25% of the patients. The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. The objective of the study is to explore the role of DSB formation genes in POI pathogenesis.
Methods
Variants in DSB formation genes were analyzed from a database of exome sequencing in 1,030 patients with POI. The pathogenic effects of the potentially causative variants were verified by further functional studies.
Results
Three pathogenic heterozygous variants in
PRDM9
and two in
ANKRD31
were identified in seven patients. Functional studies showed the variants in
PRDM9
impaired its methyltransferase activity, and the
ANKRD31
variations disturbed its interaction with another DSB formation factor REC114 by haploinsufficiency effect, indicating the pathogenic effects of the two genes on ovarian function were dosage dependent.
Conclusion
Our study identified pathogenic variants of
PRDM9
and
ANKRD31
in POI patients, shedding new light on the contribution of meiotic DSB formation genes in ovarian development, further expanding the genetic architecture of POI.</description><identifier>ISSN: 1098-3600</identifier><identifier>EISSN: 1530-0366</identifier><identifier>DOI: 10.1038/s41436-021-01266-y</identifier><identifier>PMID: 34257419</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cell Cycle Proteins - genetics ; DNA Breaks, Double-Stranded ; Female ; Histone-Lysine N-Methyltransferase - genetics ; Human Genetics ; Humans ; Laboratory Medicine ; Meiosis - genetics ; Menopause, Premature ; Ovaries ; Primary Ovarian Insufficiency - genetics ; Yeast</subject><ispartof>Genetics in medicine, 2021-12, Vol.23 (12), p.2309-2315</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b4de4f77665914bcf706fc9f560a5b12c1c4376a2022f0c994967cd27544625e3</citedby><cites>FETCH-LOGICAL-c474t-b4de4f77665914bcf706fc9f560a5b12c1c4376a2022f0c994967cd27544625e3</cites><orcidid>0000-0002-0319-7799</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2604245480?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34257419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yiyang</creatorcontrib><creatorcontrib>Guo, Ting</creatorcontrib><creatorcontrib>Ke, Hanni</creatorcontrib><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Luo, Wei</creatorcontrib><creatorcontrib>Qin, Yingying</creatorcontrib><title>Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency</title><title>Genetics in medicine</title><addtitle>Genet Med</addtitle><addtitle>Genet Med</addtitle><description>Purpose
The etiology of premature ovarian insufficiency (POI) is heterogeneous, and genetic factors account for 20–25% of the patients. The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. The objective of the study is to explore the role of DSB formation genes in POI pathogenesis.
Methods
Variants in DSB formation genes were analyzed from a database of exome sequencing in 1,030 patients with POI. The pathogenic effects of the potentially causative variants were verified by further functional studies.
Results
Three pathogenic heterozygous variants in
PRDM9
and two in
ANKRD31
were identified in seven patients. Functional studies showed the variants in
PRDM9
impaired its methyltransferase activity, and the
ANKRD31
variations disturbed its interaction with another DSB formation factor REC114 by haploinsufficiency effect, indicating the pathogenic effects of the two genes on ovarian function were dosage dependent.
Conclusion
Our study identified pathogenic variants of
PRDM9
and
ANKRD31
in POI patients, shedding new light on the contribution of meiotic DSB formation genes in ovarian development, further expanding the genetic architecture of POI.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Cycle Proteins - genetics</subject><subject>DNA Breaks, Double-Stranded</subject><subject>Female</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Meiosis - genetics</subject><subject>Menopause, Premature</subject><subject>Ovaries</subject><subject>Primary Ovarian Insufficiency - genetics</subject><subject>Yeast</subject><issn>1098-3600</issn><issn>1530-0366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtv1TAQhSMEoqXwB1ggS2zKIjB-X2-QSi8vUaAqsLYcx751SeyLnVS6C_47LinlsWBla-abMz4-TfMQw1MMdPWsMMyoaIHgFjARot3davYxp9ACFeJ2vYNatVQA7DX3SrkAwJISuNvsUUa4ZFjtN99PzXSeNi4Giy5NDiZOBSWPRhfSVGt9mrvBoTJlE3vUZWe-osP1pxdPkE95NFNIEdVpV9Dp2fq9QlfU0Yd3Z2uKUYhom12F5uxQWtRrsczeBxtctLv7zR1vhuIeXJ8HzZdXLz8fv2lPPr5-e3x00lom2dR2rHfMSykEV5h11ksQ3irPBRjeYWKxZVQKQ4AQD1YppoS0PZGcMUG4owfN80V3O3ej662L1c-gtzmMJu90MkH_3YnhXG_SpV4JoiSnVeDwWiCnb7Mrkx5DsW4YTHRpLppwjuuPMs4q-vgf9CLNOVZ7mghgpDIrqBRZKJtTKdn5m8dg0Ffp6iVdXdPVP9PVuzr06E8bNyO_4qwAXYBSW3Hj8u_d_5H9AaxHsHg</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Wang, Yiyang</creator><creator>Guo, Ting</creator><creator>Ke, Hanni</creator><creator>Zhang, Qian</creator><creator>Li, Shan</creator><creator>Luo, Wei</creator><creator>Qin, Yingying</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0319-7799</orcidid></search><sort><creationdate>20211201</creationdate><title>Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency</title><author>Wang, Yiyang ; Guo, Ting ; Ke, Hanni ; Zhang, Qian ; Li, Shan ; Luo, Wei ; Qin, Yingying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-b4de4f77665914bcf706fc9f560a5b12c1c4376a2022f0c994967cd27544625e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Cycle Proteins - genetics</topic><topic>DNA Breaks, Double-Stranded</topic><topic>Female</topic><topic>Histone-Lysine N-Methyltransferase - genetics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Meiosis - genetics</topic><topic>Menopause, Premature</topic><topic>Ovaries</topic><topic>Primary Ovarian Insufficiency - genetics</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yiyang</creatorcontrib><creatorcontrib>Guo, Ting</creatorcontrib><creatorcontrib>Ke, Hanni</creatorcontrib><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Luo, Wei</creatorcontrib><creatorcontrib>Qin, Yingying</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genetics in medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yiyang</au><au>Guo, Ting</au><au>Ke, Hanni</au><au>Zhang, Qian</au><au>Li, Shan</au><au>Luo, Wei</au><au>Qin, Yingying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency</atitle><jtitle>Genetics in medicine</jtitle><stitle>Genet Med</stitle><addtitle>Genet Med</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>23</volume><issue>12</issue><spage>2309</spage><epage>2315</epage><pages>2309-2315</pages><issn>1098-3600</issn><eissn>1530-0366</eissn><abstract>Purpose
The etiology of premature ovarian insufficiency (POI) is heterogeneous, and genetic factors account for 20–25% of the patients. The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. The objective of the study is to explore the role of DSB formation genes in POI pathogenesis.
Methods
Variants in DSB formation genes were analyzed from a database of exome sequencing in 1,030 patients with POI. The pathogenic effects of the potentially causative variants were verified by further functional studies.
Results
Three pathogenic heterozygous variants in
PRDM9
and two in
ANKRD31
were identified in seven patients. Functional studies showed the variants in
PRDM9
impaired its methyltransferase activity, and the
ANKRD31
variations disturbed its interaction with another DSB formation factor REC114 by haploinsufficiency effect, indicating the pathogenic effects of the two genes on ovarian function were dosage dependent.
Conclusion
Our study identified pathogenic variants of
PRDM9
and
ANKRD31
in POI patients, shedding new light on the contribution of meiotic DSB formation genes in ovarian development, further expanding the genetic architecture of POI.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>34257419</pmid><doi>10.1038/s41436-021-01266-y</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-0319-7799</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Genetics in medicine, 2021-12, Vol.23 (12), p.2309-2315 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | Biomedical and Life Sciences Biomedicine Cell Cycle Proteins - genetics DNA Breaks, Double-Stranded Female Histone-Lysine N-Methyltransferase - genetics Human Genetics Humans Laboratory Medicine Meiosis - genetics Menopause, Premature Ovaries Primary Ovarian Insufficiency - genetics Yeast |
| title | Pathogenic variants of meiotic double strand break (DSB) formation genes PRDM9 and ANKRD31 in premature ovarian insufficiency |
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