A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock

English version České info

In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated.

Vyšlo v časopise: A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004049
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004049

Souhrn

Zdroje

1. DekkersJC, HospitalF (2002) The use of molecular genetics in the improvement of agricultural populations. Nat Rev Genet 3: 22–32.

2. GrisartB, CoppietersW, FarnirF, KarimL, FordC, et al. (2002) Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res 12: 222–231.

3. HayesBJ, PryceJ, ChamberlainAJ, BowmanPJ, GoddardME (2010) Genetic architecture of complex traits and accuracy of genomic prediction: coat colour, milk-fat percentage, and type in Holstein cattle as contrasting model traits. PLoS Genet 6: e1001139.

4. KemperKE, GoddardME (2012) Understanding and predicting complex traits: knowledge from cattle. Hum Mol Genet 21: R45–51.

5. WashburnSP, SilviaWJ, BrownCH, McDanielBT, McAllisterAJ (2002) Trends in reproductive performance in Southeastern Holstein and Jersey DHI herds. J Dairy Sci 85: 244–251.

6. LucyMC (2001) Reproductive loss in high-producing dairy cattle: where will it end? J Dairy Sci 84: 1277–1293.

7. SilviaW (1998) Changes in reproductive performance of Holstein dairy cows in Kentucky from 1972 to 1996. J Dairy Sci 81 (Suppl. 1) 244.

8. SunC, MadsenP, LundMS, ZhangY, NielsenUS, et al. (2010) Improvement in genetic evaluation of female fertility in dairy cattle using multiple-trait models including milk production traits. J Anim Sci 88: 871–878.

9. MacArthurDG, BalasubramanianS, FrankishA, HuangN, MorrisJ, et al. (2012) A systematic survey of loss-of-function variants in human protein-coding genes. Science 335: 823–828.

10. BittlesAH, NeelJV (1994) The costs of human inbreeding and their implications for variations at the DNA level. Nat Genet 8: 117–121.

11. CharlierC, AgerholmJS, CoppietersW, Karlskov-MortensenP, LiW, et al. (2012) A deletion in the bovine FANCI gene compromises fertility by causing fetal death and brachyspina. PLoS One 7: e43085.

12. ThomsenB, HornP, PanitzF, BendixenE, PetersenAH, et al. (2006) A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation. Genome Res 16: 97–105.

13. VanRadenPM, OlsonKM, NullDJ, HutchisonJL (2011) Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94: 6153–6161.

14. SonstegardTS, ColeJB, VanRadenPM, Van TassellCP, NullDJ, et al. (2013) Identification of a nonsense mutation in CWC15 associated with decreased reproductive efficiency in Jersey cattle. PLoS One 8: e54872.

15. FritzS, CapitanA, DjariA, RodriguezSC, BarbatA, et al. (2013) Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2. PLoS One 8: e65550.

16. SchulmanNF, SahanaG, LundMS, ViitalaSM, VilkkiJH (2008) Quantitative trait loci for fertility traits in Finnish Ayrshire cattle. Genet Sel Evol 40: 195–214.

17. SchulmanNF, SahanaG, Iso-TouruT, McKaySD, SchnabelRD, et al. (2011) Mapping of fertility traits in Finnish Ayrshire by genome-wide association analysis. Anim Genet 42: 263–269.

18. OlsenHG, HayesBJ, KentMP, NomeT, SvendsenM, et al. (2011) Genome-wide association mapping in Norwegian Red cattle identifies quantitative trait loci for fertility and milk production on BTA12. Anim Genet 42: 466–474.

19. DruetT, GeorgesM (2010) A hidden markov model combining linkage and linkage disequilibrium information for haplotype reconstruction and quantitative trait locus fine mapping. Genetics 184: 789–798.

20. HouY, BickhartDM, HvindenML, LiC, SongJ, et al. (2012) Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array. BMC Genomics 13: 376.

21. ReijnsMA, RabeB, RigbyRE, MillP, AstellKR, et al. (2012) Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Cell 149: 1008–1022.

22. WhiteJK, GerdinAK, KarpNA, RyderE, BuljanM, et al. (2013) Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes. Cell 154: 452–464.

23. FujiiJ, OtsuK, ZorzatoF, de LeonS, KhannaVK, et al. (1991) Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253: 448–451.

24. Georges M (2012) Impact of high-throughput genotyping and sequencing on the identification of genes and variants underlying phenotypic variation in domestic cattle. In: Womack J, editor. Bovine Genomics. Oxford (UK): Wiley-Blackwell.

25. GallowaySM, McNattyKP, CambridgeLM, LaitinenMP, JuengelJL, et al. (2000) Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 25: 279–283.

26. HanrahanJP, GreganSM, MulsantP, MullenM, DavisGH, et al. (2004) Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod 70: 900–909.

27. CockettNE, ShayTL, BeeverJE, NielsenD, AlbretsenJ, et al. (1999) Localization of the locus causing Spider Lamb Syndrome to the distal end of ovine Chromosome 6. Mamm Genome 10: 35–38.

28. BeeverJE, SmitMA, MeyersSN, HadfieldTS, BottemaC, et al. (2006) A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep. Anim Genet 37: 66–71.

29. SmithLB, DallyMR, SainzRD, RodrigueKL, OberbauerAM (2006) Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast growth factor receptor 3. J Anim Sci 84: 2942–2949.

30. FasquelleC, SarteletA, LiW, DiveM, TammaN, et al. (2009) Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle. PLoS Genet 5: e1000666.

31. SarteletA, KlingbeilP, FranklinCK, FasquelleC, GeronS, et al. (2012) Allelic heterogeneity of Crooked Tail Syndrome: result of balancing selection? Anim Genet 43: 604–607.

32. SironenA, UimariP, Iso-TouruT, VilkkiJ (2012) L1 insertion within SPEF2 gene is associated with increased litter size in the Finnish Yorkshire population. J Anim Breed Genet 129: 92–97.

33. UhlenM, OksvoldP, FagerbergL, LundbergE, JonassonK, et al. (2010) Towards a knowledge-based Human Protein Atlas. Nat Biotechnol 28: 1248–1250.

34. ZiminAV, DelcherAL, FloreaL, KelleyDR, SchatzMC, et al. (2009) A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol 10: R42.

35. PriceAL, PattersonNJ, PlengeRM, WeinblattME, ShadickNA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38: 904–909.

36. Madsen P, Jensen J (2010) DMU, A package for analysing Multivariate Mixed Models. http://dmuagrscidk/dmuv6_guide50pdf Version 6, release 5.0.

37. BrowningBL, YuZ (2009) Simultaneous genotype calling and haplotype phasing improves genotype accuracy and reduces false-positive associations for genome-wide association studies. Am J Hum Genet 85: 847–861.

38. Andersson-EklundL, DanellB (1993) Associations of breeding values for disease traits and genetic markers in dairy cattle estimated with a mixed model. J Dairy Sci 76: 3785–3791.

39. LiH, RuanJ, DurbinR (2008) Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res 18: 1851–1858.

40. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.

41. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079.

42. McKennaA, HannaM, BanksE, SivachenkoA, CibulskisK, et al. (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297–1303.

43. SherryST, WardM, SirotkinK (2000) Use of molecular variation in the NCBI dbSNP database. Hum Mutat 15: 68–75.

44. TrapnellC, RobertsA, GoffL, PerteaG, KimD, et al. (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7: 562–578.