Display options
Cite
Dong Z, Yan J, Xu F, et al. Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. Am J Hum Genet. 2019;105(6):1102-1111doi: 10.1016/j.ajhg.2019.10.003.
Dong, Z., Yan, J., Xu, F., Yuan, J., Jiang, H., Wang, H., Chen, H., Zhang, L., Ye, L., Xu, J., Shi, Y., Yang, Z., Cao, Y., Chen, L., Li, Q., Zhao, X., Li, J., Chen, A., Zhang, W., Wong, H. G., Qin, Y., Zhao, H., Chen, Y., Li, P., Ma, T., Wang, W. J., Kwok, Y. K., Jiang, Y., Pursley, A. N., Chung, J. P. W., Hong, Y., Kristiansen, K., Yang, H., Piña-Aguilar, R. E., Leung, T. Y., Cheung, S. W., Morton, C. C., Choy, K. W., & Chen, Z. J. (2019). Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. American journal of human genetics, 105(6), 1102-1111. https://doi.org/10.1016/j.ajhg.2019.10.003
Dong, Zirui, et al. "Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage." American journal of human genetics vol. 105,6 (2019): 1102-1111. doi: https://doi.org/10.1016/j.ajhg.2019.10.003
Dong Z, Yan J, Xu F, Yuan J, Jiang H, Wang H, Chen H, Zhang L, Ye L, Xu J, Shi Y, Yang Z, Cao Y, Chen L, Li Q, Zhao X, Li J, Chen A, Zhang W, Wong HG, Qin Y, Zhao H, Chen Y, Li P, Ma T, Wang WJ, Kwok YK, Jiang Y, Pursley AN, Chung JPW, Hong Y, Kristiansen K, Yang H, Piña-Aguilar RE, Leung TY, Cheung SW, Morton CC, Choy KW, Chen ZJ. Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. Am J Hum Genet. 2019 Dec 05;105(6):1102-1111. doi: 10.1016/j.ajhg.2019.10.003. Epub 2019 Oct 31. PMID: 31679651; PMCID: PMC6904795.
Copy Download .nbib Format: NLM
Share it on

Am J Hum Genet. 2019 Dec 05;105(6):1102-1111. doi: 10.1016/j.ajhg.2019.10.003. Epub 2019 Oct 31.

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

American journal of human genetics

Zirui Dong, Junhao Yan, Fengping Xu, Jianying Yuan, Hui Jiang, Huilin Wang, Haixiao Chen, Lei Zhang, Lingfei Ye, Jinjin Xu, Yuhua Shi, Zhenjun Yang, Ye Cao, Lingyun Chen, Qiaoling Li, Xia Zhao, Jiguang Li, Ao Chen, Wenwei Zhang, Hoi Gin Wong, Yingying Qin, Han Zhao, Yuan Chen, Pei Li, Tao Ma, Wen-Jing Wang, Yvonne K Kwok, Yuan Jiang, Amber N Pursley, Jacqueline P W Chung, Yan Hong, Karsten Kristiansen, Huanming Yang, Raul E Piña-Aguilar, Tak Yeung Leung, Sau Wai Cheung, Cynthia C Morton, Kwong Wai Choy, Zi-Jiang Chen

Affiliations

  1. Centre for Reproductive Medicine, Shandong University, Jinan 250021, China; BGI-Shenzhen, Shenzhen 518083, China; Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
  2. Centre for Reproductive Medicine, Shandong University, Jinan 250021, China; The Key laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250021, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250021, China.
  3. BGI-Shenzhen, Shenzhen 518083, China; China National Genebank, BGI-Shenzhen, Shenzhen 518120, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
  4. BGI-Shenzhen, Shenzhen 518083, China; China National Genebank, BGI-Shenzhen, Shenzhen 518120, China.
  5. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China; Department of Central Laboratory, Bao'an Maternity and Child Healthcare Hospital Affiliated to Jinan University School of Medicine, Shenzhen, 518133, China.
  6. BGI-Shenzhen, Shenzhen 518083, China; Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518120, China.
  7. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
  8. BGI-Shenzhen, Shenzhen 518083, China.
  9. BGI-Shenzhen, Shenzhen 518083, China; Complete Genomics, Mountain View, CA 95134, USA.
  10. Department of Molecular and Cellar Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  11. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China.
  12. Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
  13. BGI-Shenzhen, Shenzhen 518083, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
  14. BGI-Shenzhen, Shenzhen 518083, China; China National Genebank, BGI-Shenzhen, Shenzhen 518120, China; James D. Watson Institute of Genome Sciences, Hangzhou 310008, China.
  15. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  16. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China; The Chinese University of Hong Kong-Baylor College of Medicine Joint Center For Medical Genetics, Hong Kong, China; Hong Kong Branches of Chinese National Engineering Research Centers - Center for Assisted Reproductive Technology and Reproductive Genetics, Hong Kong, China.
  17. Department of Molecular and Cellar Biology, Baylor College of Medicine, Houston, TX 77030, USA; The Chinese University of Hong Kong-Baylor College of Medicine Joint Center For Medical Genetics, Hong Kong, China.
  18. Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Manchester Centre for Audiology and Deafness, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
  19. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China; The Chinese University of Hong Kong-Baylor College of Medicine Joint Center For Medical Genetics, Hong Kong, China; Hong Kong Branches of Chinese National Engineering Research Centers - Center for Assisted Reproductive Technology and Reproductive Genetics, Hong Kong, China. Electronic address: [email protected].
  20. Centre for Reproductive Medicine, Shandong University, Jinan 250021, China; The Key laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250021, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250021, China; Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Hong Kong Branches of Chinese National Engineering Research Centers - Center for Assisted Reproductive Technology and Reproductive Genetics, Hong Kong, China. Electronic address: [email protected].

PMID: 31679651 PMCID: PMC6904795 DOI: 10.1016/j.ajhg.2019.10.003

Abstract

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.

Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Keywords: balanced translocation; chromosomal abnormality; chromothripsis and chomoplexy; copy number variants; cryptic structural rearrangements; genetics complexity; inversion; low-pass genome sequencing; preimplantation genetic testing; recurrent miscarriage

References

  1. Hum Reprod. 2018 Apr 1;33(4):579-587 - PubMed
  2. Hum Reprod Update. 2011 Jul-Aug;17(4):467-75 - PubMed
  3. J Chin Med Assoc. 2015 Jul;78(7):408-13 - PubMed
  4. Nat Genet. 2017 Jan;49(1):36-45 - PubMed
  5. Hum Reprod. 2019 Feb 1;34(2):380-387 - PubMed
  6. Genet Med. 2020 Mar;22(3):500-510 - PubMed
  7. PLoS Genet. 2015 Oct 22;11(10):e1005601 - PubMed
  8. Genet Med. 2016 Sep;18(9):940-8 - PubMed
  9. Eur J Obstet Gynecol Reprod Biol. 1998 Dec;81(2):171-6 - PubMed
  10. Am J Hum Genet. 2015 Apr 2;96(4):651-6 - PubMed
  11. Front Genet. 2019 Aug 16;10:761 - PubMed
  12. Nat Genet. 2012 Mar 04;44(4):390-7, S1 - PubMed
  13. N Engl J Med. 2012 Dec 6;367(23):2226-32 - PubMed
  14. Am J Hum Genet. 2019 Apr 4;104(4):565-577 - PubMed
  15. Fertil Steril. 2019 Feb;111(2):280-293 - PubMed
  16. Hum Mutat. 2014 May;35(5):625-36 - PubMed
  17. BJOG. 2010 Jun;117(7):885-8 - PubMed
  18. Lancet. 2019 Feb 23;393(10173):758-767 - PubMed
  19. Fertil Steril. 2013 Jan;99(1):63 - PubMed
  20. J Comput Biol. 2012 Mar;19(3):279-92 - PubMed
  21. Hum Mutat. 2017 Feb;38(2):180-192 - PubMed
  22. N Engl J Med. 2015 Nov 26;373(22):2141-8 - PubMed
  23. Reprod Biomed Online. 2019 May;38(5):669-675 - PubMed
  24. Am J Med Genet A. 2011 Oct;155A(10):2381-5 - PubMed
  25. Am J Hum Genet. 1994 Nov;55(5):960-7 - PubMed
  26. Reproduction. 2006 Jun;131(6):1025-35 - PubMed
  27. Mol Hum Reprod. 2015 Mar;21(3):271-80 - PubMed
  28. Mol Hum Reprod. 2016 May;22(5):364-72 - PubMed
  29. Clin Genet. 2010 Oct;78(4):299-309 - PubMed
  30. N Engl J Med. 2010 Apr 29;362(17):1586-96 - PubMed
  31. Hum Reprod. 1990 Jul;5(5):519-28 - PubMed
  32. Cytogenet Genome Res. 2014;142(2):145-9 - PubMed
  33. N Engl J Med. 2015 Nov 19;373(21):2089-90 - PubMed
  34. Reprod Biomed Online. 2017 Dec;35(6):693-700 - PubMed
  35. Obstet Gynecol. 2014 Aug;124(2 Pt 1):202-9 - PubMed
  36. Rev Obstet Gynecol. 2009 Spring;2(2):76-83 - PubMed
  37. Fertil Steril. 2012 Nov;98(5):1103-11 - PubMed
  38. Cell. 2011 Sep 16;146(6):889-903 - PubMed
  39. Science. 2010 Jan 1;327(5961):78-81 - PubMed
  40. Genet Med. 2011 Jul;13(7):680-5 - PubMed
  41. Eur J Hum Genet. 2015 Mar;23(3):401-4 - PubMed
  42. Reprod Biomed Online. 2018 Apr;36(4):442-449 - PubMed
  43. Genet Med. 2013 Nov;15(11):901-9 - PubMed
  44. Int J Androl. 2004 Aug;27(4):200-12 - PubMed
  45. Genet Med. 2018 Jul;20(7):697-707 - PubMed
  46. Fertil Steril. 2017 May;107(5):1122-1129 - PubMed
  47. Chromosome Res. 2014 Dec;22(4):517-32 - PubMed

MeSH terms

Publication Types

Grant support