Copy Number Variation Is a Fundamental Aspect of the Placental Genome


Generally, every mammalian cell has the same complement of each part of its genome. However, copy number variation (CNV) can occur, where, compared to the rest of its genome, a cell has either more or less of a specific genomic region. It is unknown whether CNVs cause disease, or whether they are a normal aspect of cell biology. We investigated CNVs in polyploid trophoblast giant cells (TGCs) of the mouse placenta, which have up to 1,000 copies of the genome in each cell. We found that there are 47 regions with decreased copy number in TGCs, which we call underrepresented (UR) domains. These domains are marked in the TGC progenitor cells and we suggest that they gradually form during gestation due to slow replication versus fast replication of the rest of the genome. While UR domains contain cell adhesion and neuronal genes, they also contain significantly fewer genes than other genomic regions. Our results demonstrate that CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during pregnancy.


Vyšlo v časopise: Copy Number Variation Is a Fundamental Aspect of the Placental Genome. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004290
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004290

Souhrn

Generally, every mammalian cell has the same complement of each part of its genome. However, copy number variation (CNV) can occur, where, compared to the rest of its genome, a cell has either more or less of a specific genomic region. It is unknown whether CNVs cause disease, or whether they are a normal aspect of cell biology. We investigated CNVs in polyploid trophoblast giant cells (TGCs) of the mouse placenta, which have up to 1,000 copies of the genome in each cell. We found that there are 47 regions with decreased copy number in TGCs, which we call underrepresented (UR) domains. These domains are marked in the TGC progenitor cells and we suggest that they gradually form during gestation due to slow replication versus fast replication of the rest of the genome. While UR domains contain cell adhesion and neuronal genes, they also contain significantly fewer genes than other genomic regions. Our results demonstrate that CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during pregnancy.


Zdroje

1. LupskiJR (2013) One Human, Multiple Genomes—Genome Mosaicism. Science 341: 358–359 doi:10.1126/science.1239503

2. PoduriA, EvronyGD, CaiX, WalshCA (2013) Somatic mutation, genomic variation, and neurological disease. Science 341: 1237758 doi:10.1126/science.1237758

3. JacksonKJL, KiddMJ, WangY, CollinsAM (2013) The shape of the lymphocyte receptor repertoire: lessons from the B cell receptor. Front Immunol 4: 263 doi:10.3389/fimmu.2013.00263

4. AbyzovA, MarianiJ, PalejevD, ZhangY, HaneyMS, et al. (2012) Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492: 438–442 doi:10.1038/nature11629

5. O'HuallachainM, KarczewskiKJ, WeissmanSM, UrbanAE, SnyderMP (2012) Extensive genetic variation in somatic human tissues. Proc Natl Acad Sci U S A 109: 18018–18023 doi:10.1073/pnas.1213736109

6. EdgarBA, Orr-WeaverTL (2001) Endoreplication cell cycles: more for less. Cell 105: 297 doi:10.1016/S0092-8674(01)00334-8

7. KimJC, NordmanJ, XieF, KashevskyH, EngT, et al. (2011) Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression. Genes Dev 25: 1384–1398 doi:10.1101/gad.2043111

8. Orr-WeaverTL (1991) Drosophila chorion genes: cracking the eggshell's secrets. Bioessays 13: 97–105 doi:10.1002/bies.950130302

9. BelyakinSN, ChristophidesGK, AlekseyenkoAA, KriventsevaEV, BelyaevaES, et al. (2005) Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. Proc Natl Acad Sci U S A 102: 8269–8274 doi:10.1073/pnas.0502702102

10. HammondMP, LairdCD (1985) Chromosome structure and DNA replication in nurse and follicle cells of Drosophila melanogaster. Chromosoma 91: 267–278 doi:10.1007/BF00328222

11. HammondMP, LairdCD (1985) Control of DNA replication and spatial distribution of defined DNA sequences in salivary gland cells of Drosophila melanogaster. Chromosoma 91: 279–286 doi:10.1007/BF00328223

12. NordmanJ, LiS, EngT, MacAlpineD, Orr-WeaverTL (2011) Developmental control of the DNA replication and transcription programs. Genome Res 21: 175–181 doi:10.1101/gr.114611.110

13. SherN, BellGW, LiS, NordmanJ, EngT, et al. (2012) Developmental control of gene copy number by repression of replication initiation and fork progression. Genome Res 22: 64–75 doi:10.1101/gr.126003.111

14. BridgesCB (1935) Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. J Hered 26: 60–64.

15. HuD, CrossJC (2010) Development and function of trophoblast giant cells in the rodent placenta. Int J Dev Biol 54: 341–354 doi:10.1387/ijdb.082768dh

16. GengY, YuQ, SicinskaE, DasM, SchneiderJE, et al. (2003) Cyclin E ablation in the mouse. Cell 114: 431–443 doi:10.1016/S0092-8674(03)00645-7

17. ParisiT, BeckAR, RougierN, McNeilT, LucianL, et al. (2003) Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells. EMBO J 22: 4794–4803 doi:10.1093/emboj/cdg482

18. OhganeJ, AikawaJ, OguraA, HattoriN, OgawaT, et al. (1998) Analysis of CpG islands of trophoblast giant cells by restriction landmark genomic scanning. Dev Genet 22: 132–140 doi:10.1002/(SICI)1520-6408(1998)22:2<132::AID-DVG3>3.0.CO;2-7

19. SherN, Von StetinaJR, BellGW, MatsuuraS, RavidK, et al. (2013) Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells. Proc Natl Acad Sci U S A 110: 9368–9373 doi:10.1073/pnas.1304889110

20. Sakaue-SawanoA, HoshidaT, YoM, TakahashiR, OhtawaK, et al. (2013) Visualizing developmentally programmed endoreplication in mammals using ubiquitin oscillators. Development 140: 4624–4632 doi:10.1242/dev.099226

21. TibshiraniR, WangP (2008) Spatial smoothing and hot spot detection for CGH data using the fused lasso. Biostatistics 9: 18–29 doi:10.1093/biostatistics/kxm013

22. GrandelaC, WolvetangE (2007) hESC adaptation, selection and stability. Stem Cell Rev 3: 183–191 doi:10.1007/s12015-007-0008-4

23. SkvortsovD, AbduevaD, CurtisC, SchaubB, TavaréS (2007) Explaining differences in saturation levels for Affymetrix GeneChip® arrays. Nucleic Acids Res 35: 4154–4163 doi:10.1093/nar/gkm348

24. AbyzovA, UrbanAE, SnyderM, GersteinM (2011) CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res 21: 974–984 doi:10.1101/gr.114876.110

25. ZhangY, HaraksinghR, GrubertF, AbyzovA, GersteinM, et al. (2013) Child development and structural variation in the human genome. Child Dev 84: 34–48 doi:10.1111/cdev.12051

26. CarneyEW, PrideauxV, LyeSJ, RossantJ (1993) Progressive expression of trophoblast-specific genes during formation of mouse trophoblast giant cells in vitro. Mol Reprod and Dev 34: 357–368 doi:10.1002/mrd.1080340403

27. ErlebacherA, PriceKA, GlimcherLH (2004) Maintenance of mouse trophoblast stem cell proliferation by TGF-ß/activin. Dev Biol 275: 158–169 doi:10.1016/j.ydbio.2004.07.032

28. YanJ, TanakaS, OdaM, MakinoT, OhganeJ, et al. (2001) Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate. Dev Biol 235: 422–432 doi:10.1006/dbio.2001.0300

29. BoyleEI, WengS, GollubJ, JinH, BotsteinD, et al. (2004) GO::TermFinder—open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics 20: 3710–3715 doi:10.1093/bioinformatics/bth456

30. BeckAH, WengZ, WittenDM, ZhuS, FoleyJW, et al. (2010) 3′-end sequencing for expression quantification (3SEQ) from archival tumor samples. PloS One 5: e8768 doi:10.1371/journal.pone.0008768

31. ChuongEB, RumiMAK, SoaresMJ, BakerJC (2013) Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nat Genet 45: 325–329 doi:10.1038/ng.2553

32. ZhangY, LiuT, MeyerCA, EeckhouteJ, JohnsonDS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137 doi:10.1186/gb-2008-9-9-r137

33. Rugg-GunnPJ, CoxBJ, RalstonA, RossantJ (2010) Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo. Proc Natl Acad Sci U S A 107: 10783–10790 doi:10.1073/pnas.0914507107

34. ValouevA, WengZ, SweeneyRT, VarmaS, LeQ-T, et al. (2013) Discovery of recurrent structural variants in nasopharyngeal carcinoma. Genome Res 24: 300–309 doi:10.1101/gr.156224.113

35. GilbertDM, TakebayashiSI, RybaT, LuJ, PopeBD, et al. (2010) Space and Time in the Nucleus Developmental Control of Replication Timing and Chromosome Architecture. Cold Spring Harb Symp Quant Biol 75: 143–153 doi:10.1101/sqb.2010.75.011

36. RybaT, BattagliaD, PopeBD, HirataniI, GilbertDM (2011) Genome-scale analysis of replication timing: from bench to bioinformatics. Nat Protoc 6: 870–895 doi:10.1038/nprot.2011.328

37. BelyaevaES, ZhimulevIF, VolkovaEI, AlekseyenkoAA, MoshkinYM, et al. (1998) Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric heterochromatin of Drosophila melanogaster polytene chromosomes. Proc Natl Acad Sci U S A 95: 7532–7537 doi:10.1073/pnas.95.13.7532

38. van HeeschS, MokryM, BoskovaV, JunkerW, MehonR, et al. (2013) Systematic biases in DNA copy number originate from isolation procedures. Genome Biol 14: R33 doi:10.1186/gb-2013-14-4-r33

39. ManukjanG, TauscherM, SteinemannD (2013) Replication timing influences DNA copy number determination by array-CGH. BioTechniques 55: 231–232 doi:10.2144/000114097

40. KokkinosMI, MurthiP, WafaiR, ThompsonEW, NewgreenDF (2010) Cadherins in the human placenta–epithelial–mesenchymal transition (EMT) and placental development. Placenta 31: 747–755 doi:10.1016/j.placenta.2010.06.017

41. El-HashashAHK, KimberSJ (2006) PTHrP induces changes in cell cytoskeleton and E-cadherin and regulates Eph/Ephrin kinases and RhoGTPases in murine secondary trophoblast cells. Dev Biol 290: 13–31 doi:10.1016/j.ydbio.2005.10.010

42. LiaoWX, LaurentL, AgentS, HodgesJ, ChenDB (2012) Human Placental Expression of SLIT/ROBO Signaling Cues: Effects of Preeclampsia and Hypoxia. Biol Reprod 86: 111 doi:10.1095/biolreprod.110.088138

43. BarlowPW (1978) Endopolyploidy: towards an understanding of its biological significance. Acta Biotheor 27: 1–18 doi:10.1007/BF00048400

44. RossantJ, CrossJC (2001) Placental development: lessons from mouse mutants. Nat Rev Genet 2: 538–548 doi:10.1038/35080570

45. NicholsJ, EvansEP, SmithAG (1990) Establishment of germ-line-competent embryonic stem (ES) cells using differentiation inhibiting activity. Development 110: 1341–1348.

46. ShivdasaniRA, SchulzeH (2005) Culture, expansion, and differentiation of murine megakaryocytes. Curr Protoc Immunol 22: 6.1–22F doi:10.1002/0471142735.im22f06s67

47. DNAnexus Inc (2010) RNA-Seq/3SEQ Transcriptome Based Quantification.

48. FoleyJW, SidowA (2013) Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines. BMC Genomics 14: 720 doi:10.1186/1471-2164-14-720

49. AndersS, HuberW (2010) Differential expression analysis for sequence count data. Genome Biol 11R: 106 doi:10.1186/gb-2010-11-10-r106

50. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25: 1754–1760 doi:10.1093/bioinformatics/btp324

51. LiuT, OrtizJA, TaingL, MeyerCA, LeeB, et al. (2011) Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol 12: R83 doi:10.1186/gb-2011-12-8-r83

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa