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Genomic Networks of Hybrid Sterility


Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci (“Dobzhansky-Muller incompatibilities”). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL—but not cis eQTL—were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.


Vyšlo v časopise: Genomic Networks of Hybrid Sterility. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004162
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004162

Souhrn

Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci (“Dobzhansky-Muller incompatibilities”). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL—but not cis eQTL—were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.


Zdroje

1. WhiteMA, SteffyB, WiltshireT, PayseurBA (2011) Genetic dissection of a key reproductive barrier between nascent species of house mice. Genetics 189: 289–304 doi:10.1534/genetics.111.129171

2. WhiteMA, StubbingsM, DumontBL, PayseurBA (2012) Genetics and evolution of hybrid male sterility in house mice. Genetics 191: 917–934 doi:10.1534/genetics.112.140251

3. MoyleLC, NakazatoT (2008) Comparative genetics of hybrid incompatibility: sterility in two Solanum species crosses. Genetics 179: 1437–1453 doi:10.1534/genetics.107.083618

4. Dzur-GejdosovaM, SimecekP, GregorovaS, BhattacharyyaT, ForejtJ (2012) Dissecting the genetic architecture of F1 hybrid sterility in house mice. Evolution 66: 3321–3335 doi:10.1111/j.1558-5646.2012.01684.x

5. GoodJM, HandelMA, NachmanMW (2008) Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice. Evolution 62: 50–65.

6. MaheshwariS, BarbashDA (2011) The genetics of hybrid incompatibilities. Annu Rev Genet 45: 331–355 doi:10.1146/annurev-genet-110410-132514

7. RiesebergLH, WhittonJ, GardnerK (1999) Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species. Genetics 152: 713–727.

8. HaertyW, SinghRS (2006) Gene regulation divergence is a major contributor to the evolution of Dobzhansky-Muller incompatibilities between species of Drosophila. Mol Biol Evol 23: 1707–1714 doi:10.1093/molbev/msl033

9. RottscheidtR, HarrB (2007) Extensive additivity of gene expression differentiates subspecies of the house mouse. Genetics 177: 1553–1567.

10. GoodJM, GigerT, DeanMD, NachmanMW (2010) Widespread over-expression of the X chromosome in sterile F1 hybrid mice. PLoS Genet 6: 1–13.

11. VoolstraC, TautzD, FarbrotherP, EichingerL, HarrB (2007) Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse. Genome Res 17: 42–49.

12. MichalakP, NoorMAF (2004) Association of misexpression with sterility in hybrids of Drosophila simulans and D. mauritiana. J Mol Evol 59: 277–282 doi:10.1007/s00239-004-2622-y

13. MaloneJH, ChrzanowskiTH, MichalakP (2007) Sterility and gene expression in hybrid males of Xenopus laevis and X. muelleri. PLoS ONE 2: e781 doi:10.1371/journal.pone.0000781.s008

14. Dobzhansky T (1937) Genetics and the origin of species. New York: Columbia University Press.

15. MullerHJ (1942) Isolating mechanisms, evolution and temperature. Biol Symp 6: 71–125.

16. Coyne JA, Orr HA (2004) Speciation. Sunderland, Mass.: Sinauer Associates.

17. MatzukMM, LambDJ (2008) The biology of infertility: research advances and clinical challenges. Nat Med 14: 1197–1213 doi:10.1038/nm.f.1895

18. ForejtJ, IvanyiP (1974) Genetic studies on male sterility of hybrids between laboratory and wild mice (Mus musculus). Genet Res 24: 189–206.

19. OkaA, MitaA, Sakurai-YamataniN, YamamotoH, TakagiN, et al. (2004) Hybrid breakdown caused by substitution of the X chromosome between two mouse subspecies. Genetics 166: 913–924.

20. VyskocilovaM, TrachtulecZ, ForejtvJ, PialekJ (2005) Does geography matter in hybrid sterility in house mice? Biol J Linn Soc 84: 663–674.

21. Britton-DavidianJ, Fel-ClairF, LopezJ, AlibertP, BoursotP (2005) Postzygotic isolation between the two European subspecies of the house mouse: estimates from fertility patterns in wild and laboratory-bred hybrids. Biol J Linn Soc 84: 379–393.

22. VanlerbergheF, DodB, BoursotP, BellisM, BonhommeF (1986) Absence of Y-chromosome introgression across the hybrid zone between Mus musculus domesticus and Mus musculus musculus. Genet Res 48: 191–197.

23. TurnerLM, SchwahnDJ, HarrB (2012) Reduced male fertility is common but highly variable in form and severity in a natural house mouse hybrid zone. Evolution 66: 443–458 doi:10.1111/j.1558-5646.2011.01445.x

24. AlbrechtováJ, AlbrechtT, BairdSJ, MacholanM, RudolfsenG, et al. (2012) Sperm-related phenotypes implicated in both maintenance and breakdown of a natural species barrier in the house mouse. P Roy Soc B-Biol Sci 279: 4803–4810 doi:10.1371/journal.pbio.1000244

25. GoodJM, DeanMD, NachmanMW (2008) A complex genetic basis to X-linked hybrid male sterility between two species of house mice. Genetics 179: 2213–2228 doi:10.1534/genetics.107.085340

26. BhattacharyyaT, GregorovaS, MiholaO, AngerM, SebestovaJ, et al. (2013) Mechanistic basis of infertility of mouse intersubspecific hybrids. Proc Natl Acad Sci USA 110: E468–E477 doi:10.1073/pnas.1219126110

27. MiholaO, TrachtulecZ, VlcekC, SchimentiJC, ForejtJ (2009) A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323: 373–375 doi:10.1126/science.1163601

28. ChalmelF, RollandAD, Niederhauser-WiederkehrC, ChungSSW, DemouginP, et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proc Natl Acad Sci USA 104: 8346–8351 doi:10.1073/pnas.0701883104

29. HandelMA, SchimentiJC (2010) Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet 11: 124–136 doi:10.1038/nrg2723

30. TurnerJMA (2007) Meiotic sex chromosome inactivation. Development 134: 1823–1831 doi:10.1242/dev.000018

31. CampbellP, GoodJM, NachmanMW (2013) Meiotic sex chromosome inactivation is disrupted in sterile hybrid male house mice. Genetics 193: 819–828 doi:10.1534/genetics.112.148635

32. WestMAL, KimK, KliebensteinDJ, van LeeuwenH, MichelmoreRW, et al. (2006) Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis. Genetics 175: 1441–1450 doi:10.1534/genetics.106.064972

33. RockmanMV, KruglyakL (2006) Genetics of global gene expression. Nat Rev Genet 7: 862–872.

34. LanH, ChenM, FlowersJB, YandellBS, StapletonDS, et al. (2006) Combined expression trait correlations and expression quantitative trait locus mapping. PLoS Genet 2: e6 doi:10.1371/journal.pgen.0020006.eor

35. GiladY, RifkinSA, PritchardJK (2008) Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet 24: 408–415 doi:10.1016/j.tig.2008.06.001

36. BremRB, YvertG, ClintonR, KruglyakL (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296: 752–755 doi:10.1126/science.1069516

37. DixonAL, LiangL, MoffattMF, ChenW, HeathS, et al. (2007) A genome-wide association study of global gene expression. Nat Genet 39: 1202–1207 doi:10.1038/ng2109

38. EmilssonV, ThorleifssonG, ZhangB, LeonardsonAS, ZinkF, et al. (2008) Genetics of gene expression and its effect on disease. Nature 452: 423–U2 doi:10.1038/nature06758

39. PetrettoE, MangionJ, DickensNJ, CookSA, KumaranMK, et al. (2006) Heritability and tissue specificity of expression quantitative trait loci. PLoS Genet 2: e172 doi:10.1371/journal.pgen.0020172.st001

40. BremRB, KruglyakL (2005) The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proc Natl Acad Sci USA 102: 1572–1577 doi:10.1073/pnas.0408709102

41. LiY, ÁlvarezOA, GuttelingEW, TijstermanM, FuJ, et al. (2006) Mapping determinants of gene expression plasticity by genetical genomics in C. elegans. PLoS Genet 2: e222 doi:10.1371/journal.pgen.0020222.st004

42. MehrabianM, AllayeeH, StocktonJ, LumPY, DrakeTA, et al. (2005) Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Nat Genet 37: 1224–1233 doi:10.1038/ng1619

43. HuangDW, ShermanBT, LempickiRA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1–13 doi:10.1093/nar/gkn923

44. HuangDW, ShermanBT, LempickiRA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57 doi:10.1038/nprot.2008.211

45. JohnsonNA, PorterAH (2007) Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift. Genetica 129: 57–70 doi:10.1007/s10709-006-0033-2

46. JohnsonNA, PorterAH (2000) Rapid speciation via parallel, directional selection on regulatory genetic pathways. J Theor Biol 205: 527–542 doi:10.1006/jtbi.2000.2070

47. PalmerME, FeldmanMW (2009) Dynamics of hybrid incompatibility in gene networks in a constant environment. Evolution 63: 418–431 doi:10.1111/j.1558-5646.2008.00577.x

48. AyrolesJF, CarboneMA, StoneEA, JordanKW, LymanRF, et al. (2009) Systems genetics of complex traits in Drosophila melanogaster. Nat Genet 41: 299–307 doi:10.1038/ng.332

49. HarbisonST, CarboneMA, AyrolesJF, StoneEA, LymanRF, et al. (2009) Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep. Nat Genet 41: 371–375 doi:10.1038/ng.330

50. CarrollSB (2000) Endless forms: the evolution of gene regulation and morphological diversity. Cell 101: 577–580.

51. KingMC, WilsonAC (1975) Evolution at two levels in humans and chimpanzees. Science 188: 107–116.

52. WrayGA, HahnMW, AbouheifE, BalhoffJP, PizerM, et al. (2003) The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20: 1377–1419.

53. WrayGA (2007) The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 8: 206–216 doi:10.1038/nrg2063

54. MoehringAJ, TeeterKC, NoorMAF (2006) Genome-wide patterns of expression in Drosophila pure species and hybrid males. ii. examination of multiple-species hybridizations, platforms, and life cycle stages. Mol Biol Evol 24: 137–145 doi:10.1093/molbev/msl142

55. L'HôteD, SerresC, VeitiaRA, MontagutelliX, OulmoudenA, et al. (2008) Gene expression regulation in the context of mouse interspecific mosaic genomes. Genome Biol 9: R133 doi:10.1186/gb-2008-9-8-r133

56. MaloneJH, MichalakP (2008) Gene expression analysis of the ovary of hybrid females of Xenopus laevis and X. muelleri. BMC Evol Biol 8: 82 doi:10.1186/1471-2148-8-82

57. RenautS, NolteAW, BernatchezL (2009) Gene expression divergence and hybrid misexpression between lake whitefish species pairs (Coregonus spp. Salmonidae). Mol Biol Evol 26: 925–936 doi:10.1093/molbev/msp017

58. EllisonCK, BurtonRS (2008) Genotype-dependent variation of mitochondrial transcriptional profiles in interpopulation hybrids. Proc Natl Acad Sci USA 105: 15831–15836 doi:10.1073/pnas.0804253105

59. AugerDL (2004) Nonadditive gene expression in diploid and triploid hybrids of maize. Genetics 169: 389–397 doi:10.1534/genetics.104.032987

60. HegartyMJ, BarkerGL, BrennanAC, EdwardsKJ, AbbottRJ, et al. (2009) Extreme changes to gene expression associated with homoploid hybrid speciation. Mol Ecol 18: 877–889 doi:10.1111/j.1365-294X.2008.04054.x

61. JosefssonC, DilkesB, ComaiL (2006) Parent-dependent loss of gene silencing during interspecies hybridization. Curr Biol 16: 1322–1328 doi:10.1016/j.cub.2006.05.045

62. PayseurBA, KrenzJG, NachmanMW (2004) Differential patterns of introgression across the X chromosome in a hybrid zone between two species of house mice. Evolution 58: 2064–2078.

63. TeeterKC, PayseurBA, HarrisLW, BakewellMA, ThibodeauLM, et al. (2008) Genome-wide patterns of gene flow across a house mouse hybrid zone. Genome Res 18: 67–76.

64. TeeterKC, ThibodeauLM, GompertZ, BuerkleCA, NachmanMW, et al. (2010) The variable genomic architecture of isolation between hybridizing species of house mouse. Evolution 64: 472–485.

65. MacholanM, MunclingerP, SugerkovaM, DufkovaP, BimovaB, et al. (2007) Genetic analysis of autosomal and X-linked markers across a mouse hybrid zone. Evolution 61: 746–771.

66. StorchovaR, GregorovaS, BuckiovaD, KyselovaV, DivinaP, et al. (2004) Genetic analysis of X-linked hybrid sterility in the house mouse. Mamm Genome 15: 515–524.

67. FlachsP, MiholaO, SimecekP, GregorovaS, SchimentiJC, et al. (2012) Interallelic and intergenic incompatibilities of the Prdm9 (Hst1) gene in mouse hybrid sterility. PLoS Genet 8: e1003044 doi:10.1371/journal.pgen.1003044.s007

68. CampbellP, GoodJM, DeanMD, TuckerPK, NachmanMW (2012) The contribution of the Y chromosome to hybrid male sterility in house mice. Genetics 191: 1271–1281 doi:10.1534/genetics.112.141804

69. JonesGH (1984) The control of chiasma distribution. Symp Soc Exp Biol 38: 293–320.

70. EllisPJI, ClementeEJ, BallP, ToureA, FergusonL, et al. (2005) Deletions on mouse Yq lead to upregulation of multiple X- and Y-linked transcripts in spermatids. Hum Mol Genet 14: 2705–2715 doi:10.1093/hmg/ddi304

71. CocquetJ, EllisPJI, YamauchiY, MahadevaiahSK, AffaraNA, et al. (2009) The multicopy gene Sly represses the sex chromosomes in the male mouse germline after meiosis. PLoS Biol 7: e1000244 doi:10.1371/journal.pbio.1000244.s014

72. ScavettaRJ, TautzD (2010) Copy number changes of CNV regions in intersubspecific crosses of the house mouse. Mol Biol Evol 27: 1845–1856 doi:10.1093/molbev/msq064

73. BaudatF, BuardJ, GreyC, Fledel-AlonA, OberC, et al. (2010) PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327: 836–840 doi:10.1126/science.1183439

74. BergIL, NeumannR, LamKWG, SarbajnaS, Odenthal-HesseL, et al. (2010) PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat Genet 42: 859–863 doi:10.1038/ng.658

75. BlendyJA, KaestnerKH, WeinbauerGF, NieschlagE, SchützG (1996) Severe impairment of spermatogenesis in mice lacking the CREM gene. Nature 380: 162–165 doi:10.1038/380162a0

76. AlsheimerM (2004) Disruption of spermatogenesis in mice lacking A-type lamins. J Cell Sci 117: 1173–1178 doi:10.1242/jcs.00975

77. TurnerLM, ChuongEB, HoekstraHE (2008) Comparative analysis of testis protein evolution in rodents. Genetics 179: 2075–2089 doi:10.1534/genetics.107.085902

78. KuznetsovS, PellegriniM, ShudaK, Fernandez-CapetilloO, LiuY, et al. (2007) RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol 176: 581–592 doi:10.1083/jcb.200608130

79. KanedaM, OkanoM, HataK, SadoT, TsujimotoN, et al. (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429: 900–903 doi:10.1038/nature02633

80. WebsterKE, O'BryanMK, FletcherS, CrewtherPE, AapolaU, et al. (2005) Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis. Proc Natl Acad Sci USA 102: 4068–4073 doi:10.1073/pnas.0500702102

81. Bourc'hisD, BestorTH (2004) Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3l. Nature 431: 96–99 doi:10.1038/nature02886

82. ZamudioNM, ScottHS, WolskiK, LoC-Y, LawC, et al. (2011) Dnmt3l is a regulator of X chromosome compaction and post-meiotic gene transcription. PLoS ONE 6: e18276 doi:10.1371/journal.pone.0018276.s001

83. LiaoH-F, TaiK-Y, ChenWSC, ChengLCW, HoH-N, et al. (2012) Functions of DNA methyltransferase 3-like in germ cells and beyond. Biol Cell 104: 571–587 doi:10.1111/boc.201100109

84. BayesJJ, MalikHS (2009) Altered heterochromatin binding by a hybrid sterility protein in Drosophila sibling species. Science 326: 1538–1541 doi:10.1126/science.1181756

85. OrrHA (1995) The population genetics of speciation: the evolution of hybrid incompatibilities. Genetics 139: 1805–1813.

86. OrrHAH, TurelliMM (2001) The evolution of postzygotic isolation: accumulating Dobzhansky-Muller incompatibilities. Evolution 55: 1085–1094 doi:10.2307/2680275

87. PorterAH, JohnsonNA (2002) Speciation despite gene flow when developmental pathways evolve. Evolution 56: 2103–2111.

88. PetersonBK, WeberJN, KayEH, FisherHS, HoekstraHE (2012) Double digest RADseq: an inexpensive method for de novo SNP discovery and genotyping in model and non-model species. PLoS ONE 7: e37135 doi:10.1371/journal.pone.0037135.s003

89. VijayN, PoelstraJW, KünstnerA, WolfJBW (2012) Challenges and strategies in transcriptome assembly and differential gene expression quantification. A comprehensive in silicoassessment of RNA-seq experiments. Mol Ecol 22: 620–634 doi:10.1111/mec.12014

90. KentWJ (2002) BLAT—The BLAST-Like Alignment Tool. Genome Res 12: 656–664 doi:10.1101/gr.229202

91. Lopez-Romero P (2009) Agi4x44PreProcess: PreProcessing of Agilent 4x44 array data. R package version 1.10.0.

92. StoreyJD, TibshiraniR (2003) Statistical Significance for Genome-Wide Experiments. Proc Natl Acad Sci USA 100: 9440–9445.

93. YangH, BellTA, ChurchillGA, de VillenaFPM (2007) On the subspecific origin of the laboratory mouse. Nat Genet 39: 1100–1107.

94. YangH, WangJR, DidionJP, BuusRJ, BellTA, et al. (2011) Subspecific origin and haplotype diversity in the laboratory mouse. Nat Genet 43: 648–655 doi:10.1038/ng.847

95. KeaneTM, GoodstadtL, DanecekP, WhiteMA, WongK, et al. (2012) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477: 289–294 doi:10.1038/nature10413

96. FrazerKA, EskinE, KangHM, BogueMA, HindsDA, et al. (2007) A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature 448: 1050–1053.

97. Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. Current protocols in human genetics/editorial board, Jonathan L Haines [et al] Chapter 2.

98. DumontBL, PayseurBA (2011) Genetic analysis of genome-scale recombination rate evolution in house mice. PLoS Genet 7: e1002116 doi:10.1371/journal.pgen.1002116

99. BromanKW, RoweLB, ChurchillGA, PaigenK (2002) Crossover interference in the mouse. Genetics 160: 1123–1131.

100. BromanKW, WuH, SenS, ChurchillGA (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19: 889–890 doi:10.1093/bioinformatics/btg112

101. Broman KW, Sen S (2009) A Guide to QTL Mapping with R/qtl. New York: Springer.

102. FeenstraB (2006) Mapping quantitative trait loci by an extension of the Haley-Knott regression method using estimating equations. Genetics 173: 2269–2282 doi:10.1534/genetics.106.058537

103. ChurchillGA, DoergeRW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138: 963–971.

104. BromanKW, SenS, OwensSE, ManichaikulA, Southard-SmithEM, et al. (2006) The X chromosome in quantitative trait locus mapping. Genetics 174: 2151–2158 doi:10.1534/genetics.106.061176

105. Bolcun-FilasE, SchimentiJC (2012) Genetics of meiosis and recombination in mice. Int Rev Cell Mol Biol 298: 179–227 doi:10.1016/B978-0-12-394309-5.00005-5

106. KrzywinskiM, ScheinJ, BirolI, ConnorsJ, GascoyneR, et al. (2009) Circos: An information aesthetic for comparative genomics. Genome Res 19: 1639–1645 doi:10.1101/gr.092759.109

107. SchultzN, HamraFK, GarbersDL (2003) A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc Natl Acad Sci USA 100: 12201–12206 doi:10.1073/pnas.1635054100

108. ShimaJE, McLeanDJ, McCarreyJR, GriswoldMD (2004) The murine testicular transcriptome: Characterizing gene expression in the testis during the progression of spermatogenesis. Biology of reproduction 71: 319–330 doi:10.1095/biolreprod.103.026880

109. SmithLB, MilneL, NelsonN, EddieS, BrownP, et al. (2012) KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility. PLoS Genet 8: e1002697 doi:10.1371/journal.pgen.1002697.s002

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