A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2.
Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (...
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2015-02-01
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| Series: | PLoS Genetics |
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| author | John P Didion Andrew P Morgan Amelia M-F Clayshulte Rachel C Mcmullan Liran Yadgary Petko M Petkov Timothy A Bell Daniel M Gatti James J Crowley Kunjie Hua David L Aylor Ling Bai Mark Calaway Elissa J Chesler John E French Thomas R Geiger Terry J Gooch Theodore Garland Alison H Harrill Kent Hunter Leonard McMillan Matt Holt Darla R Miller Deborah A O'Brien Kenneth Paigen Wenqi Pan Lucy B Rowe Ginger D Shaw Petr Simecek Patrick F Sullivan Karen L Svenson George M Weinstock David W Threadgill Daniel Pomp Gary A Churchill Fernando Pardo-Manuel de Villena |
| author_facet | John P Didion Andrew P Morgan Amelia M-F Clayshulte Rachel C Mcmullan Liran Yadgary Petko M Petkov Timothy A Bell Daniel M Gatti James J Crowley Kunjie Hua David L Aylor Ling Bai Mark Calaway Elissa J Chesler John E French Thomas R Geiger Terry J Gooch Theodore Garland Alison H Harrill Kent Hunter Leonard McMillan Matt Holt Darla R Miller Deborah A O'Brien Kenneth Paigen Wenqi Pan Lucy B Rowe Ginger D Shaw Petr Simecek Patrick F Sullivan Karen L Svenson George M Weinstock David W Threadgill Daniel Pomp Gary A Churchill Fernando Pardo-Manuel de Villena |
| author_sort | John P Didion |
| collection | DOAJ |
| description | Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 - 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2WSBdel1) that eliminates the majority of the R2d2WSB copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2WSBdel1, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2WSBdel1, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2WSB heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2WSB transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system. |
| format | Article |
| id | doaj-art-53c2f98bb98349e2a1907e6090291e44 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2015-02-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-53c2f98bb98349e2a1907e6090291e442025-08-20T02:23:18ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-02-01112e100485010.1371/journal.pgen.1004850A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2.John P DidionAndrew P MorganAmelia M-F ClayshulteRachel C McmullanLiran YadgaryPetko M PetkovTimothy A BellDaniel M GattiJames J CrowleyKunjie HuaDavid L AylorLing BaiMark CalawayElissa J CheslerJohn E FrenchThomas R GeigerTerry J GoochTheodore GarlandAlison H HarrillKent HunterLeonard McMillanMatt HoltDarla R MillerDeborah A O'BrienKenneth PaigenWenqi PanLucy B RoweGinger D ShawPetr SimecekPatrick F SullivanKaren L SvensonGeorge M WeinstockDavid W ThreadgillDaniel PompGary A ChurchillFernando Pardo-Manuel de VillenaSignificant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 - 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2WSBdel1) that eliminates the majority of the R2d2WSB copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2WSBdel1, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2WSBdel1, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2WSB heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2WSB transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004850&type=printable |
| spellingShingle | John P Didion Andrew P Morgan Amelia M-F Clayshulte Rachel C Mcmullan Liran Yadgary Petko M Petkov Timothy A Bell Daniel M Gatti James J Crowley Kunjie Hua David L Aylor Ling Bai Mark Calaway Elissa J Chesler John E French Thomas R Geiger Terry J Gooch Theodore Garland Alison H Harrill Kent Hunter Leonard McMillan Matt Holt Darla R Miller Deborah A O'Brien Kenneth Paigen Wenqi Pan Lucy B Rowe Ginger D Shaw Petr Simecek Patrick F Sullivan Karen L Svenson George M Weinstock David W Threadgill Daniel Pomp Gary A Churchill Fernando Pardo-Manuel de Villena A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. PLoS Genetics |
| title | A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. |
| title_full | A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. |
| title_fullStr | A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. |
| title_full_unstemmed | A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. |
| title_short | A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. |
| title_sort | multi megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2 |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004850&type=printable |
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