Propensity for somatic expansion increases over the course of life in Huntington disease
Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD...
Saved in:
| Published in | eLife Vol. 10 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
eLife Sciences Publications Ltd
13.05.2021
eLife Sciences Publication eLife Sciences Publications, Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2050-084X 2050-084X |
| DOI | 10.7554/eLife.64674 |
Cover
Loading…
| Abstract | Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease. |
|---|---|
| AbstractList | Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease. Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease.Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical outcomes better than the length of the inherited allele. Here, we measured somatic expansion in blood samples collected from the same 50 HD mutation carriers over a twenty-year period, along with post-mortem tissue from 15 adults and 7 fetal mutation carriers, to examine somatic expansions at different stages of life. Post-mortem brains, as previously reported, had the greatest expansions, but fetal cortex had virtually none. Somatic instability in blood increased with age, despite blood cells being short-lived compared to neurons, and was driven mostly by CAG repeat length, then by age at sampling and by interaction between these two variables. Expansion rates were higher in symptomatic subjects. These data lend support to a previously proposed computational model of somatic instability-driven disease. |
| Author | Noël, Sandrine Cazeneuve, Cécile Humbert, Sandrine Durr, Alexandra Brice, Alexis Lejeune, François-Xavier Kacher, Radhia |
| Author_xml | – sequence: 1 givenname: Radhia orcidid: 0000-0003-4679-7361 surname: Kacher fullname: Kacher, Radhia organization: Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France, Univ. Grenoble Alpes, INSERM, U 1216, Grenoble Institut Neurosciences, Grenoble, France – sequence: 2 givenname: François-Xavier surname: Lejeune fullname: Lejeune, François-Xavier organization: Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France, Paris Brain Institute’s Data and Analysis Core, University Hospital Pitié-Salpêtrière, Paris, France – sequence: 3 givenname: Sandrine surname: Noël fullname: Noël, Sandrine organization: Neurogenetics Laboratory, Department of Genetics, Assistance Publique–Hôpitaux de Paris, University Hospital Pitié-Salpêtrière, Paris, France – sequence: 4 givenname: Cécile surname: Cazeneuve fullname: Cazeneuve, Cécile organization: Neurogenetics Laboratory, Department of Genetics, Assistance Publique–Hôpitaux de Paris, University Hospital Pitié-Salpêtrière, Paris, France – sequence: 5 givenname: Alexis surname: Brice fullname: Brice, Alexis organization: Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France – sequence: 6 givenname: Sandrine orcidid: 0000-0002-9501-2658 surname: Humbert fullname: Humbert, Sandrine organization: Univ. Grenoble Alpes, INSERM, U 1216, Grenoble Institut Neurosciences, Grenoble, France – sequence: 7 givenname: Alexandra orcidid: 0000-0002-8921-7104 surname: Durr fullname: Durr, Alexandra organization: Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France, Neurogenetics Laboratory, Department of Genetics, Assistance Publique–Hôpitaux de Paris, University Hospital Pitié-Salpêtrière, Paris, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33983118$$D View this record in MEDLINE/PubMed https://hal.sorbonne-universite.fr/hal-03230958$$DView record in HAL |
| BookMark | eNptkt9rWyEUxy-jY-26Pu19CHvZGOnUq1d9KZSyLYXA9rBB38Srx8Rwo5nehPW_n0na0Yb5ohw_53t-vm5OYorQNG8JvhScs88wCx4uO9YJ9qI5o5jjCZbs7uTJ-7S5KGWJ6xFMSqJeNadtq2RLiDxr7n7ktIZYwniPfMqopJUZg0XwZ22qNUUUos1gChSUtpDRuABk0yYXQMmjoUavBJpu4hjifKy8C2WHv2leejMUuHi4z5tfX7_8vJlOZt-_3d5czyaWCz5OeuIsJ0o47qmUmELPiOXGeSylIsKC6Y1ymHLVO0UYBWGJMV60mBNHvGzPm9uDrktmqdc5rEy-18kEvTekPNcm14oG0KK3Xghrvesow5Ia20nWMtkLIEQ5VrWuDlrrTb8CZyGO2QzPRJ__xLDQ87TVsvay420V-HgQWBy5Ta9nemfDLW2x4nJLKvvhIVhOvzdQRr0KxcIwmAhpUzTltKtVdlJV9P0RuqwTiLWtlVK1fVQQXql3T7P_F_9x2BUgB8DmVEoGr20Y67TTrpgwaIL1bqf0fqf0fqeqz6cjn0fZ_9F_ATexzbI |
| CitedBy_id | crossref_primary_10_1093_brain_awad275 crossref_primary_10_3390_ijms242216154 crossref_primary_10_1038_s41598_022_18848_8 crossref_primary_10_1042_ETLS20230074 crossref_primary_10_1111_nyas_14786 crossref_primary_10_1080_14737175_2022_2029703 crossref_primary_10_1167_iovs_64_5_16 crossref_primary_10_1038_s41598_023_33528_x crossref_primary_10_1016_j_neurol_2022_03_009 crossref_primary_10_1038_s41431_024_01546_6 crossref_primary_10_1016_j_jmoldx_2024_02_007 crossref_primary_10_1002_mds_29605 crossref_primary_10_3233_JHD_231516 crossref_primary_10_1016_S1474_4422_25_00071_7 crossref_primary_10_1016_j_tig_2022_03_016 crossref_primary_10_3390_biomedicines11082275 crossref_primary_10_1038_s41431_024_01587_x crossref_primary_10_3390_ijms25084354 crossref_primary_10_1093_brain_awad128 crossref_primary_10_1016_j_cell_2023_09_008 crossref_primary_10_1016_j_ajhg_2024_04_015 crossref_primary_10_1038_s41398_023_02689_8 crossref_primary_10_1093_brain_awae312 crossref_primary_10_7554_eLife_89782 crossref_primary_10_7554_eLife_70217 crossref_primary_10_1016_j_ebiom_2023_104720 crossref_primary_10_1038_s41598_022_14183_0 crossref_primary_10_1093_hmg_ddae137 crossref_primary_10_1038_s41598_023_32630_4 crossref_primary_10_3390_cells11030517 crossref_primary_10_1016_j_ajhg_2024_03_015 crossref_primary_10_1038_s41593_024_01850_w crossref_primary_10_1242_dmm_049453 crossref_primary_10_1038_s41598_023_46852_z crossref_primary_10_1111_jeb_14106 crossref_primary_10_7554_eLife_89782_2 crossref_primary_10_1016_j_cell_2025_01_031 crossref_primary_10_1093_gbe_evae153 crossref_primary_10_1007_s11910_024_01400_8 crossref_primary_10_1093_hmg_ddae087 crossref_primary_10_3390_ijms23105411 crossref_primary_10_1007_s00415_023_11572_x crossref_primary_10_1016_j_bpr_2022_100070 |
| Cites_doi | 10.1038/nrdp.2015.5 10.1007/s12035-015-9662-8 10.1016/j.bbr.2021.113230 10.1371/journal.pcbi.0030235 10.1126/science.aax3338 10.1073/pnas.1525564113 10.1093/nar/gkaa036 10.1074/jbc.REV119.007678 10.1093/hmg/ddy375 10.1038/s41582-020-0389-4 10.1016/j.ajhg.2020.05.012 10.1111/j.1750-3639.1997.tb00894.x 10.1038/s41588-019-0575-8 10.1093/brain/awz115 10.1016/j.neuron.2010.01.008 10.1073/pnas.94.8.3872 10.1002/ana.24656 10.1002/1531-8249(199901)45:1<25::AID-ART6>3.0.CO;2-E 10.1016/j.nbd.2015.01.004 10.1073/pnas.0308679101 10.1073/pnas.0800048105 10.1186/1752-0509-4-29 10.1016/j.ajhg.2019.04.007 10.1093/hmg/9.17.2539 10.1093/hmg/ddaa139 10.1016/S1097-2765(00)00146-5 10.1038/263517a0 10.1172/JCI45691 10.1016/j.ebiom.2019.09.020 10.1097/WCO.0b013e328304b692 10.1074/jbc.M111.309849 10.1038/263244a0 10.1093/nar/gkm756 10.1371/journal.pgen.1001242 10.1093/hmg/ddm054 10.1016/j.ygeno.2007.04.001 10.1111/j.1399-0004.2004.00241.x 10.1007/978-0-387-98141-3 10.1093/hmg/ddg352 10.1038/ng0494-409 10.1016/j.arcmed.2007.11.011 10.1038/ng0893-398 10.1371/journal.pgen.1003280 10.1111/j.1468-1331.2006.01264.x 10.3233/JHD-200438 10.1016/j.nbd.2008.09.014 10.1371/journal.pgen.1003930 10.1093/hmg/6.6.877 10.1212/WNL.0000000000009364 10.1126/scitranslmed.3010523 10.1093/hmg/ddp242 10.1016/j.cell.2019.06.036 10.1093/hmg/ddaa196 10.18637/jss.v067.i01 10.1111/nan.12465 |
| ContentType | Journal Article |
| Copyright | 2021, Kacher et al. 2021, Kacher et al. This work is published under https://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. Distributed under a Creative Commons Attribution 4.0 International License 2021, Kacher et al 2021 Kacher et al |
| Copyright_xml | – notice: 2021, Kacher et al. – notice: 2021, Kacher et al. This work is published under https://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. – notice: Distributed under a Creative Commons Attribution 4.0 International License – notice: 2021, Kacher et al 2021 Kacher et al |
| DBID | AAYXX CITATION NPM 3V. 7X7 7XB 88E 88I 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. LK8 M0S M1P M2P M7P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS Q9U 7X8 1XC VOOES 5PM DOA |
| DOI | 10.7554/eLife.64674 |
| DatabaseName | CrossRef PubMed ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Science Database (Alumni Edition) ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection PML(ProQuest Medical Library) Science Database (ProQuest) Biological Science Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) PubMed Central (Full Participant titles) Directory of Open Access Journals |
| DatabaseTitle | CrossRef PubMed Publicly Available Content Database ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Science Journals (Alumni Edition) ProQuest Biological Science Collection ProQuest Central Basic ProQuest Science Journals ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | PubMed CrossRef MEDLINE - Academic Publicly Available Content Database |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 2050-084X |
| ExternalDocumentID | oai_doaj_org_article_7bcf77ccfd624082ac684348b7e119d4 PMC8118653 oai_HAL_hal_03230958v1 33983118 10_7554_eLife_64674 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: Agence Nationale de la Recherche grantid: ANR-16-COEN-0006-02 – fundername: Fondation pour la Recherche Médicale grantid: DEQ20170336752 – fundername: ; grantid: ANR-16-COEN-0006-02 – fundername: ; grantid: DEQ20170336752 |
| GroupedDBID | 53G 5VS 7X7 88E 88I 8FE 8FH 8FI 8FJ AAFWJ AAKDD AAYXX ABUWG ACGFO ACGOD ACPRK ADBBV ADRAZ AENEX AFKRA AFPKN ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BBNVY BCNDV BENPR BHPHI BPHCQ BVXVI CCPQU CITATION DIK DWQXO EMOBN FYUFA GNUQQ GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IEA IHR INH INR ISR ITC KQ8 LK8 M1P M2P M48 M7P M~E NQS OK1 PGMZT PHGZM PHGZT PIMPY PQQKQ PROAC PSQYO RHI RNS RPM UKHRP NPM PJZUB PPXIY PQGLB 3V. 7XB 8FK K9. PKEHL PQEST PQUKI PRINS Q9U 7X8 1XC H13 VOOES 5PM PUEGO |
| ID | FETCH-LOGICAL-c575t-b1dc5197d5f28802eb41c5adf088917ceaba9d0259bd9142e7c1aaf73051d1f83 |
| IEDL.DBID | M48 |
| ISSN | 2050-084X |
| IngestDate | Wed Aug 27 00:55:51 EDT 2025 Thu Aug 21 18:45:37 EDT 2025 Fri May 09 12:20:51 EDT 2025 Fri Jul 11 12:17:08 EDT 2025 Fri Jul 25 11:49:40 EDT 2025 Mon Jul 21 05:55:47 EDT 2025 Tue Jul 01 04:13:13 EDT 2025 Thu Apr 24 23:12:48 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | genetics neuroscience Huntington disease genomics somatic instability CAG expansion longitudinal study human human data HD mutation carrier |
| Language | English |
| License | 2021, Kacher et al. Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0 This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c575t-b1dc5197d5f28802eb41c5adf088917ceaba9d0259bd9142e7c1aaf73051d1f83 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0002-8921-7104 0000-0003-4679-7361 0000-0002-9501-2658 0000-0002-0941-3990 0000-0002-6229-5364 0000-0002-5195-9348 |
| OpenAccessLink | https://www.proquest.com/docview/2595192715?pq-origsite=%requestingapplication% |
| PMID | 33983118 |
| PQID | 2595192715 |
| PQPubID | 2045579 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_7bcf77ccfd624082ac684348b7e119d4 pubmedcentral_primary_oai_pubmedcentral_nih_gov_8118653 hal_primary_oai_HAL_hal_03230958v1 proquest_miscellaneous_2526305689 proquest_journals_2595192715 pubmed_primary_33983118 crossref_citationtrail_10_7554_eLife_64674 crossref_primary_10_7554_eLife_64674 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-05-13 |
| PublicationDateYYYYMMDD | 2021-05-13 |
| PublicationDate_xml | – month: 05 year: 2021 text: 2021-05-13 day: 13 |
| PublicationDecade | 2020 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: Cambridge |
| PublicationTitle | eLife |
| PublicationTitleAlternate | Elife |
| PublicationYear | 2021 |
| Publisher | eLife Sciences Publications Ltd eLife Sciences Publication eLife Sciences Publications, Ltd |
| Publisher_xml | – name: eLife Sciences Publications Ltd – name: eLife Sciences Publication – name: eLife Sciences Publications, Ltd |
| References | Goold (bib14) 2019; 28 Xu (bib56) 2020; 48 Swami (bib47) 2009; 18 Leija-Salazar (bib27) 2018; 44 Wright (bib55) 2019; 104 Bates (bib4) 2015; 67 Tabrizi (bib49) 2020; 16 Kennedy (bib18) 2003; 12 Andrew (bib1) 1993; 4 Barnat (bib3) 2020; 369 Larson (bib24) 2015; 76 Møllersen (bib35) 2010; 6 Mochel (bib33) 2012; 287 Wexler (bib53) 2004; 101 Kaplan (bib17) 2007; 3 Squitieri (bib45) 2006; 13 Wickham (bib54) 2009 Tereshchenko (bib51) 2020; 94 Lee (bib25) 2010; 4 Gorbunova (bib15) 2007; 35 Schwer (bib43) 2016; 113 Loupe (bib28) 2020; 29 Koshy (bib22) 1997; 7 Tomé (bib52) 2013; 9 Lee (bib26) 2019; 178 Bettencourt (bib6) 2016; 79 Coyle (bib8) 1976; 263 De Biase (bib9) 2007; 90 Langbehn (bib23) 2004; 65 Dragileva (bib10) 2009; 33 Mochel (bib34) 2011; 121 Tabrizi (bib48) 1999; 45 Estrada Sánchez (bib11) 2008; 39 Sun (bib46) 2017; 54 Angeles-López (bib2) 2021; 408 Bates (bib5) 2015; 1 Nakamori (bib37) 2020; 52 Pinto (bib38) 2013; 9 Mouro Pinto (bib36) 2020; 29 Mcgeer (bib31) 1976; 263 Flower (bib12) 2019; 142 Milnerwood (bib32) 2010; 65 Khristich (bib20) 2020; 295 Rubinsztein (bib42) 1997; 94 Kennedy (bib19) 2000; 9 Shelbourne (bib44) 2007; 16 Lu (bib29) 2014; 6 R Development Core Team (bib39) 2019 Ciosi (bib7) 2019; 48 Iyer (bib16) 2021; 10 Roze (bib41) 2008; 21 Kim (bib21) 2020; 107 Gonitel (bib13) 2008; 105 Telenius (bib50) 1994; 6 Rolfsmeier (bib40) 2000; 6 Martorell (bib30) 1997; 6 |
| References_xml | – volume: 1 start-page: 1 year: 2015 ident: bib5 article-title: Huntington disease publication-title: Nature Reviews Disease Primers doi: 10.1038/nrdp.2015.5 – volume: 54 start-page: 342 year: 2017 ident: bib46 article-title: Huntington’s Disease: Relationship Between Phenotype and Genotype publication-title: Molecular Neurobiology doi: 10.1007/s12035-015-9662-8 – volume: 408 year: 2021 ident: bib2 article-title: The absence of the aryl hydrocarbon receptor in the R6/1 transgenic mouse model of Huntington's disease improves the neurological phenotype publication-title: Behavioural Brain Research doi: 10.1016/j.bbr.2021.113230 – volume: 3 year: 2007 ident: bib17 article-title: A Universal Mechanism Ties Genotype to Phenotype in Trinucleotide Diseases publication-title: PLOS Computational Biology doi: 10.1371/journal.pcbi.0030235 – volume: 369 start-page: 787 year: 2020 ident: bib3 article-title: Huntington’s disease alters human neurodevelopment publication-title: Science doi: 10.1126/science.aax3338 – volume: 113 start-page: 2258 year: 2016 ident: bib43 article-title: Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells publication-title: PNAS doi: 10.1073/pnas.1525564113 – volume: 48 start-page: 2232 year: 2020 ident: bib56 article-title: Dynamics of strand slippage in DNA hairpins formed by CAG repeats: roles of sequence parity and trinucleotide interrupts publication-title: Nucleic Acids Research doi: 10.1093/nar/gkaa036 – volume: 295 start-page: 4134 year: 2020 ident: bib20 article-title: On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability publication-title: Journal of Biological Chemistry doi: 10.1074/jbc.REV119.007678 – volume: 28 start-page: 650 year: 2019 ident: bib14 article-title: FAN1 modifies Huntington’s disease progression by stabilizing the expanded HTT CAG repeat publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddy375 – volume: 16 start-page: 529 year: 2020 ident: bib49 article-title: Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities publication-title: Nature Reviews Neurology doi: 10.1038/s41582-020-0389-4 – volume: 107 start-page: 96 year: 2020 ident: bib21 article-title: Genetic and Functional Analyses Point to FAN1 as the Source of Multiple Huntington Disease Modifier Effects publication-title: The American Journal of Human Genetics doi: 10.1016/j.ajhg.2020.05.012 – volume: 7 start-page: 927 year: 1997 ident: bib22 article-title: The CAG/Polyglutamine Tract Diseases: Gene Products and Molecular Pathogenesis publication-title: Brain Pathology doi: 10.1111/j.1750-3639.1997.tb00894.x – volume: 52 start-page: 146 year: 2020 ident: bib37 article-title: A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo publication-title: Nature Genetics doi: 10.1038/s41588-019-0575-8 – volume: 142 start-page: 1876 year: 2019 ident: bib12 article-title: MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1 publication-title: Brain doi: 10.1093/brain/awz115 – volume: 65 start-page: 178 year: 2010 ident: bib32 article-title: Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice publication-title: Neuron doi: 10.1016/j.neuron.2010.01.008 – volume: 94 start-page: 3872 year: 1997 ident: bib42 article-title: Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease publication-title: PNAS doi: 10.1073/pnas.94.8.3872 – year: 2019 ident: bib39 article-title: R: A Language and Environment for Statistical Computing – volume: 79 start-page: 983 year: 2016 ident: bib6 article-title: DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases publication-title: Annals of Neurology doi: 10.1002/ana.24656 – volume: 45 start-page: 25 year: 1999 ident: bib48 article-title: Biochemical abnormalities and excitotoxicity in Huntington's disease brain publication-title: Annals of Neurology doi: 10.1002/1531-8249(199901)45:1<25::AID-ART6>3.0.CO;2-E – volume: 76 start-page: 98 year: 2015 ident: bib24 article-title: Age-, tissue- and length-dependent bidirectional somatic CAG•CTG repeat instability in an allelic series of R6/2 Huntington disease mice publication-title: Neurobiology of Disease doi: 10.1016/j.nbd.2015.01.004 – volume: 101 start-page: 3498 year: 2004 ident: bib53 article-title: Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset publication-title: PNAS doi: 10.1073/pnas.0308679101 – volume: 105 start-page: 3467 year: 2008 ident: bib13 article-title: DNA instability in postmitotic neurons publication-title: PNAS doi: 10.1073/pnas.0800048105 – volume: 4 year: 2010 ident: bib25 article-title: A novel approach to investigate tissue-specific trinucleotide repeat instability publication-title: BMC Systems Biology doi: 10.1186/1752-0509-4-29 – volume: 104 start-page: 1116 year: 2019 ident: bib55 article-title: Length of Uninterrupted CAG, Independent of Polyglutamine Size, Results in Increased Somatic Instability, Hastening Onset of Huntington Disease publication-title: The American Journal of Human Genetics doi: 10.1016/j.ajhg.2019.04.007 – volume: 9 start-page: 2539 year: 2000 ident: bib19 article-title: Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease? publication-title: Human Molecular Genetics doi: 10.1093/hmg/9.17.2539 – volume: 29 start-page: 2551 year: 2020 ident: bib36 article-title: Patterns of CAG repeat instability in the central nervous system and periphery in Huntington’s disease and in spinocerebellar ataxia type 1 publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddaa139 – volume: 6 start-page: 1501 year: 2000 ident: bib40 article-title: Mismatch Repair Blocks Expansions of Interrupted Trinucleotide Repeats in Yeast publication-title: Molecular Cell doi: 10.1016/S1097-2765(00)00146-5 – volume: 263 start-page: 517 year: 1976 ident: bib31 article-title: Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids publication-title: Nature doi: 10.1038/263517a0 – volume: 121 start-page: 493 year: 2011 ident: bib34 article-title: Energy deficit in Huntington disease: why it matters publication-title: Journal of Clinical Investigation doi: 10.1172/JCI45691 – volume: 48 start-page: 568 year: 2019 ident: bib7 article-title: A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes publication-title: EBioMedicine doi: 10.1016/j.ebiom.2019.09.020 – volume: 21 start-page: 497 year: 2008 ident: bib41 article-title: Pathophysiology of Huntington’s disease: from huntingtin functions to potential treatments publication-title: Current Opinion in Neurology doi: 10.1097/WCO.0b013e328304b692 – volume: 287 start-page: 1361 year: 2012 ident: bib33 article-title: Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models* publication-title: Journal of Biological Chemistry doi: 10.1074/jbc.M111.309849 – volume: 263 start-page: 244 year: 1976 ident: bib8 article-title: Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea publication-title: Nature doi: 10.1038/263244a0 – volume: 35 start-page: 7466 year: 2007 ident: bib15 article-title: Changes in DNA repair during aging publication-title: Nucleic Acids Research doi: 10.1093/nar/gkm756 – volume: 6 year: 2010 ident: bib35 article-title: Continuous and Periodic Expansion of CAG Repeats in Huntington's Disease R6/1 Mice publication-title: PLOS Genetics doi: 10.1371/journal.pgen.1001242 – volume: 16 start-page: 1133 year: 2007 ident: bib44 article-title: Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddm054 – volume: 90 start-page: 1 year: 2007 ident: bib9 article-title: Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life publication-title: Genomics doi: 10.1016/j.ygeno.2007.04.001 – volume: 65 start-page: 267 year: 2004 ident: bib23 article-title: A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length publication-title: Clinical Genetics doi: 10.1111/j.1399-0004.2004.00241.x – volume-title: Ggplot2: Elegant Graphics for Data Analysis Use R! year: 2009 ident: bib54 doi: 10.1007/978-0-387-98141-3 – volume: 12 start-page: 3359 year: 2003 ident: bib18 article-title: Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddg352 – volume: 6 start-page: 409 year: 1994 ident: bib50 article-title: Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm publication-title: Nature Genetics doi: 10.1038/ng0494-409 – volume: 39 start-page: 265 year: 2008 ident: bib11 article-title: Excitotoxic Neuronal Death and the Pathogenesis of Huntington's Disease publication-title: Archives of Medical Research doi: 10.1016/j.arcmed.2007.11.011 – volume: 4 start-page: 398 year: 1993 ident: bib1 article-title: The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease publication-title: Nature Genetics doi: 10.1038/ng0893-398 – volume: 9 year: 2013 ident: bib52 article-title: MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice publication-title: PLOS Genetics doi: 10.1371/journal.pgen.1003280 – volume: 13 start-page: 408 year: 2006 ident: bib45 article-title: The search for cerebral biomarkers of Huntington's disease: a review of genetic models of age at onset prediction publication-title: European Journal of Neurology doi: 10.1111/j.1468-1331.2006.01264.x – volume: 10 start-page: 75 year: 2021 ident: bib16 article-title: DNA Mismatch Repair and its Role in Huntington’s Disease publication-title: Journal of Huntington's Disease doi: 10.3233/JHD-200438 – volume: 33 start-page: 37 year: 2009 ident: bib10 article-title: Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes publication-title: Neurobiology of Disease doi: 10.1016/j.nbd.2008.09.014 – volume: 9 year: 2013 ident: bib38 article-title: Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches publication-title: PLOS Genetics doi: 10.1371/journal.pgen.1003930 – volume: 6 start-page: 877 year: 1997 ident: bib30 article-title: Somatic Instability of the Myotonic Dystrophy (CTG)n Repeat during Human Fetal Development publication-title: Human Molecular Genetics doi: 10.1093/hmg/6.6.877 – volume: 94 start-page: e1908 year: 2020 ident: bib51 article-title: Abnormal development of cerebellar-striatal circuitry in Huntington disease publication-title: Neurology doi: 10.1212/WNL.0000000000009364 – volume: 6 year: 2014 ident: bib29 article-title: Targeting ATM ameliorates mutant huntingtin toxicity in cell and animal models of Huntington's disease publication-title: Science Translational Medicine doi: 10.1126/scitranslmed.3010523 – volume: 18 start-page: 3039 year: 2009 ident: bib47 article-title: Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddp242 – volume: 178 start-page: 887 year: 2019 ident: bib26 article-title: CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset publication-title: Cell doi: 10.1016/j.cell.2019.06.036 – volume: 29 start-page: 3044 year: 2020 ident: bib28 article-title: Promotion of somatic CAG repeat expansion by Fan1 knock-out in Huntington’s disease knock-in mice is blocked by Mlh1 knock-out publication-title: Human Molecular Genetics doi: 10.1093/hmg/ddaa196 – volume: 67 start-page: 1 year: 2015 ident: bib4 article-title: Fitting linear Mixed-Effects models using lme4 publication-title: Journal of Statistical Software doi: 10.18637/jss.v067.i01 – volume: 44 start-page: 267 year: 2018 ident: bib27 article-title: Review: Somatic mutations in neurodegeneration publication-title: Neuropathology and Applied Neurobiology doi: 10.1111/nan.12465 |
| SSID | ssj0000748819 |
| Score | 2.4780254 |
| Snippet | Recent work on Huntington disease (HD) suggests that somatic instability of CAG repeat tracts, which can expand into the hundreds in neurons, explains clinical... |
| SourceID | doaj pubmedcentral hal proquest pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| SubjectTerms | Age Blood cells Brain CAG expansion Computational neuroscience Disease Fetuses Genetics and Genomics HD mutation carrier human data Human health and pathology Huntington disease Huntington's disease Huntingtons disease Instability Life Sciences Longitudinal studies longitudinal study Mutation Neurons and Cognition Neuroscience Polyglutamine somatic instability Trinucleotide repeat diseases Trinucleotide repeats |
| SummonAdditionalLinks | – databaseName: Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Na9VAEF-kUPAiWr9Sq6zSkxDr7ma_jlUsD6niwcK7LftJH5REfK9F_3tnNunjRQUvXncnyTI7k_nNZvIbQo6FitZyPHHPSbSd56wNMoaWKaM94GvjK1n1p89qcdF9XMrlTqsvrAkb6YFHxZ3oEIvWMZakkI2L-6hMJzoTdGbMpsoECjFvJ5mq72ANhsns-EOehpB5ks9XJb9R2FxjFoIqUz8Elkusg_wTZP5eK7kTfM7uk3sTaqSn42ofkDu5PyD7Yx_Jnw_J8gseqfdYXkEBhNL1UIlYaf4Bvo7HYXTVIzpc5zXFkk0KqI_GAes36FDoFawZJOhibBsBaJBO320ekYuzD1_fL9qpZUIbAXdt2sBSxF9RkywcPJPn0LEofSpYzcR0zD54mwDn2JAs63jWkXlfwM0lS6wY8Zjs9UOfnxIKorqwEHNXTJeM9yxZ7gFtFCWt0rEhr2-16OLEJ45tLa4c5BWocldV7qrKG3K8Ff420mj8XewdbsdWBLmv6wBYhJsswv3LIhryCjZzdo_F6bnDsbcCMi4rzQ1ryNHtXrvJa9cO1ALK45rJhrzcToO_4UcU3-fhGmW4wrTL2IY8GU1j-yghrBGQsTVEz4xmtpb5TL-6rJzeBi5TUhz-DwU8I3c5Vt4gx6w4Inub79f5OUCnTXhRveQX4fQZOw priority: 102 providerName: Directory of Open Access Journals – databaseName: Health & Medical Collection dbid: 7X7 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lb9QwELagCIkL4k3aggzqCSkU24kfJ9QiqhUqiAOV9hb5SVeqktJsUfvvO5N4AwHENZkklj2T-WY8_oaQPSG9MRwz7jGIsrKcla72rmRSKwv4WtuBrPrzF7k4qT4t62VOuPW5rHLzTxx-1KHzmCPfB5gOYIMrVr8__1Fi1yjcXc0tNG6TO0hdhsGXWqopxwLuUYPHG4_lKXCc-_F4leJbiS02Zo5o4OsH93KK1ZB_Q80_KyZ_c0FHD8j9jB3pwbjYD8mt2D4id8duktePyfIrJtZbLLKgAEVp3w10rDRegcVjUoyuWsSIfewpFm5SwH7Ud1jFQbtEz2DMIEEXY_MIwIQ07948ISdHH799WJS5cULpAX2tS8eCxwOpoU4c7JNHVzFf25CwpokpH62zJgDaMS4YVvGoPLM2gbHXLLCkxVOy1XZtfE4oiKrEnI9V0lXQ1rJguAXMkWRtpPIFebOZxcZnVnFsbnHWQHSBU94MU94MU16QvUn4fCTT-LfYIS7HJIIM2MOF7uJ7kw2qUc4npbxPQSJLG7de6kpU2qkIqhDgJa9hMWfvWBwcN3jtnYC4y9T6JyvI7matm2y7ffNL0wryaroNVodbKbaN3SXKcInBlzYFeTaqxvQpIYwWELcVRM2UZjaW-Z12dTowe2t4TNZi-__D2iH3OFbWIIes2CVb64vL-AKg0dq9HPT_BsucEJk priority: 102 providerName: ProQuest |
| Title | Propensity for somatic expansion increases over the course of life in Huntington disease |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33983118 https://www.proquest.com/docview/2595192715 https://www.proquest.com/docview/2526305689 https://hal.sorbonne-universite.fr/hal-03230958 https://pubmed.ncbi.nlm.nih.gov/PMC8118653 https://doaj.org/article/7bcf77ccfd624082ac684348b7e119d4 |
| Volume | 10 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwdV3da9swED_6wUZfxr7nrQva6NPA2WTZ-nga7WgJoy1lLJA3I-ujDQR7S9LR_ve7s53QdN2rdZbF6U73k3S-H8CBkM6YjE7cgxdpbjOeVoWrUi61soivtW2LVZ-dy9E4_z4pJluwIuPsFbh4cGtHfFLj-Wx48_v2Kzo84tehwmj4OZxOYxhK4s3Yhl0MSYo4HM56nN8uyQrtlJvu_7z77-zBYyGMFpyIP-4Ep7aGP4acK8qQ_Bd-3s-ivBOWTp7Ckx5PssPOAJ7BVqifw6OOYfL2BUwu6LC9psQLhvCULZq2RCsLN7gK0EEZm9aEGxdhwSiZkyEeZK6hzA7WRDbD4aMEG3WEEogTWX-j8xLGJ8c_v43SnkwhdYjIlmnFvaOfVH0RM_TZLFQ5d4X1kfKcuHLBVtZ4RECm8obnWVCOWxtxASi451GLV7BTN3V4AwxFVeSVC3nUudfWcm8yizgkysJI5RL4tNJi6fpK40R4MStxx0HaL1vtl632EzhYC__qCmw8LHZE07EWoarY7YNmfln2TlaqykWlnIteUuW2zDqpc5HrSgXOjcdOPuJkbvQxOjwt6dkXgXsxU-g_PIH91VyXK3MsUS2ovEzxIoEP62b0RLpesXVorkkmk7Qh0yaB151prD-1MrAE1IbRbIxls6WeXrXVvjW-Jgvx9r99voO9jBJtqKSs2Ied5fw6vEektKwGsK0magC7R8fnFz8G7XnDoPWMv_H-Fl4 |
| linkProvider | Scholars Portal |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB6VIgQXxJtAAYPKBSm0dh62DwiVR7Wl24pDK-0tOH7QlaqkNFugf4rfyEweCwHErddk4ljjGc834_EMwHqSW60FRdy9S-LUCB6XmS1jnitpEF8r0xar3tvPJ4fph1k2W4Efw10YSqsc9sR2o3a1pRj5BsJ0BBtC8uz1yZeYukbR6erQQqMTi11__g1dtubVzjtc3-dCbL8_eDuJ-64CsUVosohL7izd1nRZECi8wpcpt5lxgRJ-uLTelEY7hAK6dJqnwkvLjQmoCRl3PKgEx70El9HwblIKoZzJZUwHzbFCC9tdA5RoqDf8dB78y5xaeowMX9sfAM3ZEWVf_g1t_8zQ_M3kbd-A6z1WZVudcN2EFV_dgitd98rz2zD7SIH8ipI6GEJf1tRt-Vfmv-MOQ0E4Nq8Ikza-YZQoyhBrMltT1girAzvGOSMFm3TNKhCDsv606A4cXghL78JqVVf-PjAklYGX1qdBpU4Zw50WBjFOyDOdSxvBi4GLhe2rmFMzjeMCvRliedGyvGhZHsH6kvikK97xb7I3tBxLEqq43T6oTz8XvQIXsrRBSmuDy6kqnDA2V2mSqlJ6zrXDQZ7hYo7GmGxNC3q2maCfpzP1lUewNqx10e8VTfFLsiN4unyNWk5HN6by9RnRiJycPaUjuNeJxvJXSaJVgn5iBHIkNKO5jN9U86O2krjCz_IsefD_aT2Bq5ODvWkx3dnffQjXBGX1UP3aZA1WF6dn_hHCskX5uNUFBp8uWvl-AotzTfI |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9QwDLfGEIgXxDeFAQGNF6RyJGmb5AGhwTjd2DHtgUn31qX5YCdN7djdgP1r_HXYbe_gAPG219ZNI8eOf3YcG2BTFs4YQRH34GWaWcHTKndVygutLOJrbdti1R_3itFB9mGST9bgx-IuDKVVLvbEdqP2jaMY-QBhOoINoXg-iH1axP728M3Jl5Q6SNFJ66KdRiciu-H8G7pvs9c727jWz4UYvv_0bpT2HQZShzBlnlbcO7q56fMoUJBFqDLucusjJf9w5YKtrPEIC0zlDc9EUI5bG1Ercu551BLHvQSXlUSzibqkJmoZ30HTrNHadlcCFRrtQRhPY3hZUHuPFSPY9gpA03ZEmZh_w9w_szV_M3_DG3C9x61sqxO0m7AW6ltwpetkeX4bJvsU1K8pwYMhDGazpi0Fy8J33G0oIMemNeHTWZgxShpliDuZayiDhDWRHeOckYKNusYViEdZf3J0Bw4uhKV3Yb1u6nAfGJKqyCsXsqgzr63l3giLeCcWuSmUS-DFgoul6yuaU2ON4xI9G2J52bK8bFmewOaS-KQr5PFvsre0HEsSqr7dPmhOP5e9MpeqclEp56IvqEKcsK7Qmcx0pQLnxuMgz3AxV8YYbY1LevZKos9ncv2VJ7CxWOuy3zdm5S8pT-Dp8jVqPB3j2Do0Z0QjCnL8tEngXicay19JabREnzEBtSI0K3NZfVNPj9qq4ho_K3L54P_TegJXUe3K8c7e7kO4JijBh0rZyg1Yn5-ehUeI0ObV41YVGBxetO79BNhQUig |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Propensity+for+somatic+expansion+increases+over+the+course+of+life+in+Huntington+disease&rft.jtitle=eLife&rft.au=Kacher%2C+Radhia&rft.au=Lejeune%2C+Fran%C3%A7ois-Xavier&rft.au=No%C3%ABl%2C+Sandrine&rft.au=Cazeneuve%2C+C%C3%A9cile&rft.date=2021-05-13&rft.eissn=2050-084X&rft.volume=10&rft_id=info:doi/10.7554%2FeLife.64674&rft_id=info%3Apmid%2F33983118&rft.externalDocID=33983118 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2050-084X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2050-084X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2050-084X&client=summon |