A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2
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{"title"=>"A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2", "type"=>"journal", "authors"=>[{"first_name"=>"John P.", "last_name"=>"Didion", "scopus_author_id"=>"36052312600"}, {"first_name"=>"Andrew P.", "last_name"=>"Morgan", "scopus_author_id"=>"56019771200"}, {"first_name"=>"Amelia M.F.", "last_name"=>"Clayshulte", "scopus_author_id"=>"56543714400"}, {"first_name"=>"Rachel C.", "last_name"=>"Mcmullan", "scopus_author_id"=>"10839205700"}, {"first_name"=>"Liran", "last_name"=>"Yadgary", "scopus_author_id"=>"36624570100"}, {"first_name"=>"Petko M.", "last_name"=>"Petkov", "scopus_author_id"=>"7101686301"}, {"first_name"=>"Timothy A.", "last_name"=>"Bell", "scopus_author_id"=>"7402501547"}, {"first_name"=>"Daniel M.", "last_name"=>"Gatti", "scopus_author_id"=>"20435755300"}, {"first_name"=>"James J.", "last_name"=>"Crowley", "scopus_author_id"=>"55826872700"}, {"first_name"=>"Kunjie", "last_name"=>"Hua", "scopus_author_id"=>"7006679696"}, {"first_name"=>"David L.", "last_name"=>"Aylor", "scopus_author_id"=>"14027999800"}, {"first_name"=>"Ling", "last_name"=>"Bai", "scopus_author_id"=>"55839015300"}, {"first_name"=>"Mark", "last_name"=>"Calaway", "scopus_author_id"=>"55271961700"}, {"first_name"=>"Elissa J.", "last_name"=>"Chesler", "scopus_author_id"=>"7006626258"}, {"first_name"=>"John E.", "last_name"=>"French", "scopus_author_id"=>"7403331091"}, {"first_name"=>"Thomas R.", "last_name"=>"Geiger", "scopus_author_id"=>"7006107454"}, {"first_name"=>"Terry J.", "last_name"=>"Gooch", "scopus_author_id"=>"55271684500"}, {"first_name"=>"Theodore", "last_name"=>"Garland", "scopus_author_id"=>"7006148472"}, {"first_name"=>"Alison H.", "last_name"=>"Harrill", "scopus_author_id"=>"25654858400"}, {"first_name"=>"Kent", "last_name"=>"Hunter", "scopus_author_id"=>"7201417377"}, {"first_name"=>"Leonard", "last_name"=>"McMillan", "scopus_author_id"=>"7006461052"}, {"first_name"=>"Matt", "last_name"=>"Holt", "scopus_author_id"=>"56542741400"}, {"first_name"=>"Darla R.", "last_name"=>"Miller", "scopus_author_id"=>"12243071300"}, {"first_name"=>"Deborah A.", "last_name"=>"O'Brien", "scopus_author_id"=>"7402739020"}, {"first_name"=>"Kenneth", "last_name"=>"Paigen", "scopus_author_id"=>"7003443101"}, {"first_name"=>"Wenqi", "last_name"=>"Pan", "scopus_author_id"=>"45261465900"}, {"first_name"=>"Lucy B.", "last_name"=>"Rowe", "scopus_author_id"=>"7102018279"}, {"first_name"=>"Ginger D.", "last_name"=>"Shaw", "scopus_author_id"=>"55272770000"}, {"first_name"=>"Petr", "last_name"=>"Simecek", "scopus_author_id"=>"24537974500"}, {"first_name"=>"Patrick F.", "last_name"=>"Sullivan", "scopus_author_id"=>"7402033718"}, {"first_name"=>"Karen L.", "last_name"=>"Svenson", "scopus_author_id"=>"6701832977"}, {"first_name"=>"George M.", "last_name"=>"Weinstock", "scopus_author_id"=>"7005387907"}, {"first_name"=>"David W.", "last_name"=>"Threadgill", "scopus_author_id"=>"7004449326"}, {"first_name"=>"Daniel", "last_name"=>"Pomp", "scopus_author_id"=>"7007181890"}, {"first_name"=>"Gary A.", "last_name"=>"Churchill", "scopus_author_id"=>"7006762387"}, {"first_name"=>"Fernando", "last_name"=>"Pardo-Manuel de Villena", "scopus_author_id"=>"6601922831"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"602902008", "sgr"=>"84924417008", "pmid"=>"25679959", "scopus"=>"2-s2.0-84924417008", "isbn"=>"1553-7404 (Electronic)\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1004850", "issn"=>"15537404"}, "id"=>"221f3008-015d-36e5-b2d3-1d8dcc57e74d", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/multimegabase-copy-number-gain-causes-maternal-transmission-ratio-distortion-mouse-chromosome-2", "reader_count"=>45, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>5, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>5, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "United Kingdom"=>1, "Switzerland"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1906681"], "description"=>"<p>A) Distribution of sum-intensity for the 34 probes in <i>R2d</i> present on the Mouse Diversity Array (MDA) for mice with a non-recombinant CAST/EiJ haplotype (green), a non-recombinant WSB/EiJ haplotype (purple) and non-CAST/EiJ/non-WSB/EiJ haplotypes (grey) is shown at the top of the panel. The sum intensity and recombinant haplotypes in six mice defining the boundaries of copy-number gain in the CAST/EiJ strain are shown below. B) Distribution of sum-intensity across three probes in <i>R2d</i> on the MegaMUGA array for mice with non-recombinant CAST/EiJ haplotype (green), a non-recombinant WSB/EiJ haplotype (purple) and non-CAST/EiJ/non-WSB/EiJ haplotypes (grey) is shown at the top of the panel. The sum intensity and recombinant haplotypes in six mice defining the boundaries of copy-number gain in the WSB/EiJ strain are shown below. C) QTL scan for the <i>R2d2</i> copy number gain using MDA sum-intensity as the phenotype in 330 CC G2:F<sub>1</sub> mice. D) QTL scan for the <i>R2d2</i> copy number gain using MegaMUGA sum-intensity as the phenotype in 96 (FVB/NJx(WSB/EiJxPWK/PhJ)F1)G2 offspring. E) Superposition of LOD curves from panels (C) and (D) on chromosome 2. The <i>R2d2</i> candidate interval is shaded in yellow.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309280, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.g003", "stats"=>{"downloads"=>2, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linkage_mapping_localizes_R2d2_to_a_900_kb_region_in_Chr_2_/1309280", "title"=>"Linkage mapping localizes <i>R2d2</i> to a 900 kb region in Chr 2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906682"], "description"=>"<p>A) Pedigree of DO-G13–44xCC cross. Female DO-G13–44, mother of the G3 dams phenotyped for TR, is segregating for a copy-number variant at <i>R2d2</i>. G3 dams inheriting the maternal WSB/EiJ haplotype associated with the high-copy allele (<i>R2d2</i><sup><i>WSB</i></sup>) are colored black; those inheriting the WSB/EiJ haplotype associated with the low-copy allele (<i>R2d2</i><sup><i>WSBdel1</i></sup>) are colored red. Genotypes at marker chr2:85.65Mbp is denoted -/- (homozygous non-WSB), +/- (heterozygous WSB/EiJ) or +/+ (homozygous WSB/EiJ). ΔC<sub>t</sub>, normalized cycle threshold by TaqMan qPCR assay; TR, transmission ratio, denoted as count of progeny inheriting a WSB/EiJ allele: count of progeny not inheriting a WSB allele; the paternal haplotype at chr2:83.6 Mb as determined by genotypes from the MegaMUGA array using the standard CC abbreviations is shown, A = A/J, E = NZO/HILtJ, ? = haplotype unknown. B) Distribution of ΔC<sub>t</sub> values among 27 G3 dams. Points are colored as in panel A. C) TR among 27 G3 dams partitioned according to copy-number (CN) haplotype at <i>R2d2</i>. Points are colored as in panel A. D) QTL scan for TRD, treated as a binary phenotype, in 25 G3 dams genotyped with MegaMUGA. Only the maternal signal from Chr 2 is shown. Grey dashed line indicates threshold for significance at <i>α</i> = 0.01 obtained by unrestricted permutation. Candidate interval for <i>R2d</i> is shaded yellow. E) Empirical cumulative distribution of both maternal and paternal LOD scores genome-wide, with <i>α</i> = 0.01 significance threshold indicated by grey dashed line.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309281, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.g004", "stats"=>{"downloads"=>1, "page_views"=>60, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_the_causal_locus_for_maternal_TRD_in_a_family_segregating_for_a_copy_number_variant_at_R2d2_/1309281", "title"=>"Mapping the causal locus for maternal TRD in a family segregating for a copy-number variant at <i>R2d2</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906683"], "description"=>"<p>Relationship between maternal TR and average litter size (top panels) and average number of offspring inheriting alternative alleles at R2d2 (bottom panels) for A) DO G13 dams, B) DO G16 dams, C) G3 dams in the D0-G13–44 pedigree and D) (NZO/HILtJxWSB/EiJ)F1 dams. Top panels: gray circles are dams without TRD (A, B, D) or having the low-copy allele (C); blue circles are dams with TRD (A, B, D) or having the high-copy allele (C). For each point, bars show standard error for TR (horizontal) and average litter size (vertical). Dotted lines show mean litter sizes for each type of female. Red line shows a linear fit to TR and average litter size. Bottom panels: left and right pairs of boxplots show average number of offspring per litter in females without and with TRD (A, B, D) or having the low- and high-copy allele (C) that inherit a WSB/EiJ (purple) or non-WSB/EiJ (gray) allele. Females with a mutant <i>R2d2</i><sup><i>WSB</i></sup> allele are excluded. Note that there are significantly more WSB/EiJ offspring of dams with TRD in F1 hybrid dams than in DO without TRD.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309282, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.g005", "stats"=>{"downloads"=>3, "page_views"=>73, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TRD_at_R2d2_requires_the_combined_action_of_meiotic_drive_and_embryonic_lethality_/1309282", "title"=>"TRD at <i>R2d2</i> requires the combined action of meiotic drive and embryonic lethality.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906684"], "description"=>"<p>Transmission ratios in the progeny of <i>R2d2</i><sup><i>WSB/notWSB</i></sup> heterozygous F1 hybrid sires and dams.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309283, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.t001", "stats"=>{"downloads"=>3, "page_views"=>62, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_ratios_in_the_progeny_of_R2d2_WSB_notWSB_heterozygous_F1_hybrid_sires_and_dams_/1309283", "title"=>"Transmission ratios in the progeny of <i>R2d2</i><sup><i>WSB/notWSB</i></sup> heterozygous F1 hybrid sires and dams.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906685", "https://ndownloader.figshare.com/files/1906686", "https://ndownloader.figshare.com/files/1906687", "https://ndownloader.figshare.com/files/1906688", "https://ndownloader.figshare.com/files/1906689", "https://ndownloader.figshare.com/files/1906690", "https://ndownloader.figshare.com/files/1906691", "https://ndownloader.figshare.com/files/1906692", "https://ndownloader.figshare.com/files/1906693", "https://ndownloader.figshare.com/files/1906694", "https://ndownloader.figshare.com/files/1906695", "https://ndownloader.figshare.com/files/1906696", "https://ndownloader.figshare.com/files/1906697", "https://ndownloader.figshare.com/files/1906698", "https://ndownloader.figshare.com/files/1906699", "https://ndownloader.figshare.com/files/1906700", "https://ndownloader.figshare.com/files/1906701", "https://ndownloader.figshare.com/files/1906702"], "description"=>"<div><p>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, <i>R2d</i>) emerged as the strongest candidate for the causative allele. We mapped <i>R2d</i> sequences to two loci within the candidate interval. <i>R2d1</i> is located near the proximal boundary, and contains a single copy of <i>R2d</i> in all strains tested. <i>R2d2</i> maps to a 900 kb interval, and the number of <i>R2d</i> 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 (<i>R2d2<sup>WSBdel1</sup></i>) that eliminates the majority of the <i>R2d2<sup>WSB</sup></i> copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for <i>R2d2<sup>WSBdel1</sup></i>, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for <i>R2d2<sup>WSBdel1</sup></i>, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in <i>R2d2<sup>WSB</sup></i> 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 <i>R2d2<sup>WSB</sup></i> 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.</p></div>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309284, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004850.s001", "https://dx.doi.org/10.1371/journal.pgen.1004850.s002", "https://dx.doi.org/10.1371/journal.pgen.1004850.s003", "https://dx.doi.org/10.1371/journal.pgen.1004850.s004", "https://dx.doi.org/10.1371/journal.pgen.1004850.s005", "https://dx.doi.org/10.1371/journal.pgen.1004850.s006", "https://dx.doi.org/10.1371/journal.pgen.1004850.s007", "https://dx.doi.org/10.1371/journal.pgen.1004850.s008", "https://dx.doi.org/10.1371/journal.pgen.1004850.s009", "https://dx.doi.org/10.1371/journal.pgen.1004850.s010", "https://dx.doi.org/10.1371/journal.pgen.1004850.s011", "https://dx.doi.org/10.1371/journal.pgen.1004850.s012", "https://dx.doi.org/10.1371/journal.pgen.1004850.s013", "https://dx.doi.org/10.1371/journal.pgen.1004850.s014", "https://dx.doi.org/10.1371/journal.pgen.1004850.s015", "https://dx.doi.org/10.1371/journal.pgen.1004850.s016", "https://dx.doi.org/10.1371/journal.pgen.1004850.s017", "https://dx.doi.org/10.1371/journal.pgen.1004850.s018"], "stats"=>{"downloads"=>83, "page_views"=>77, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Multi_Megabase_Copy_Number_Gain_Causes_Maternal_Transmission_Ratio_Distortion_on_Mouse_Chromosome_2_/1309284", "title"=>"A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906679"], "description"=>"<p>CC and DO mice were crossed to generate G1 dams, which were then crossed to FVB/NJ sires to determine the TR in their progeny. Each G1 dam carries a chromosome that is recombinant for the WSB/EiJ haplotype (shown under the heading <i>cis</i>) and a non-WSB/EiJ chromosome (the haplotype on the homologue is shown at far right under the heading <i>trans</i>). Dams with the same diplotype in the central region of Chr 2 were grouped together to define ten unique diplotypes. The aggregate number of WSB/EiJ and non-WSB/EiJ alleles transmitted by dams of each diplotype are shown for dams A) with TRD and B) without TRD. Significance of TR deviation from Mendelian expectation of 0.5 was computed using one-sided binomial exact test (<i>p</i>-value). The contribution from the eight founders of the CC and DO are shown in different colors. Thick purple bars indicate the extent of WSB/EiJ contributions, and thin bars indicate the extent of contributions from all other strains. The black box indicates the boundaries of the <i>R2d</i> candidate interval as determined by the region that is WSB/EiJ in all dams with TRD.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309278, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.g001", "stats"=>{"downloads"=>2, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_R2d_maps_to_a_9_3_Mb_candidate_interval_/1309278", "title"=>"<i>R2d</i> maps to a 9.3 Mb candidate interval.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-13 02:45:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/1906680"], "description"=>"<p>A) Read depth in 100 bp windows, normalized by the genome-wide mean read depth for each strain, for <i>R2d1</i>, a 158 kb region within the 9.3 Mb candidate interval defined in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004850#pgen.1004850.g001\" target=\"_blank\">Fig. 1</a>. <i>R2d1</i> includes a single (non-contiguous) copy of <i>R2d</i>. Strains are represented by the colors shown in the inset. Inbred strains included under the heading “classical” are A/J, 129S1/SvImJ, C57BL/6JN, NOD/ShiLtJ and NZO/HILtJ. The four large gaps represent LINEs that were inserted in the unique copy found in the reference genome after initial duplication. B) <i>R2d</i> copy number estimated by TaqMan assays for <i>Cwc22</i>. Normalized cycle threshold (ΔC<sub>t</sub>; see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004850#sec018\" target=\"_blank\">Methods</a>) is proportional to absolute copy number on the log scale. Strains are colored as in panel A. The (M16ixL6)F2 samples shown are known to be homozygous for the M16i allele based on genotypes from the MegaMUGA array. C-F) The yellow boxes highlight the 158 kb region depicted in panel A (<i>R2d1</i>) and the 900 kb <i>R2d2</i> locus mapping interval. Vertical dashed lines indicate the boundaries of the 9.3 Mb candidate interval. C) Locations of Ensembl genes in the NCBI/37 reference genome within the interval. The locations of the <i>Cwc22</i> gene and of seven <i>Cwc22</i> pseudogenes (<i>Gm13695</i>), are shown. D) Recombination frequency based on Liu et al. (2014), normalized by physical distance (Mb) and log10-transformed. The red line indicates the mean recombination frequency for Chr 2. E) Frequency distribution measured in 1 kb windows of SNPs with shared alleles among the three strains with TRD (WSB/EiJ, SPRET/EiJ and HR8; gray line), and with alleles perfectly consistent between strains with TRD and strains without TRD (A/J, 129S1/SvImJ, C57BL/6JN, NOD/ShiLtJ, NZO/HILt, CAST/EiJ and PWK/PhJ; red line). Lines are smoothed. Black circles indicate windows in which the strains with TRD share an allele for at least 90% of SNPs. F) Frequency distribution of reported SNPs in the candidate interval. G) The location and the number of copies of <i>R2d</i> that are present in <i>R2d1</i> and <i>R2d2</i>.</p>", "links"=>[], "tags"=>["CC founder inbred strains", "novel meiotic drive system", "900 kb interval", "Mendelian segregation", "R 2d sequences", "R 2d", "pcr", "copy number gain", "mouse reference genome", "transmission ratio distortion", "R 2d maps", "Mendelian inheritance ratios", "dna", "9.3 Mb region", "wsb", "R 2d transmission ratio", "Mouse Chromosome 2", "Chr 2 TRD", "R 2d copies"], "article_id"=>1309279, "categories"=>["Biological Sciences"], "users"=>["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 Jr.", "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"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004850.g002", "stats"=>{"downloads"=>2, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_large_copy_number_gain_is_present_in_strains_with_maternal_TRD_/1309279", "title"=>"A large copy number gain is present in strains with maternal TRD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-13 02:45:47"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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