Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage

Research output: Contribution to journalJournal articlepeer-review

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

In: American Journal of Human Genetics, Vol. 105, No. 6, 2019, p. 1102-1111.

Research output: Contribution to journalJournal articlepeer-review

Harvard

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, W-J, 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 2019, 'Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage', American Journal of Human Genetics, vol. 105, no. 6, pp. 1102-1111. https://doi.org/10.1016/j.ajhg.2019.10.003

APA

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., ... 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

Vancouver

Dong Z, Yan J, Xu F, Yuan J, Jiang H, Wang H et al. Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. American Journal of Human Genetics. 2019;105(6):1102-1111. https://doi.org/10.1016/j.ajhg.2019.10.003

Author

Dong, Zirui ; Yan, Junhao ; Xu, Fengping ; Yuan, Jianying ; Jiang, Hui ; Wang, Huilin ; Chen, Haixiao ; Zhang, Lei ; Ye, Lingfei ; Xu, Jinjin ; Shi, Yuhua ; Yang, Zhenjun ; Cao, Ye ; Chen, Lingyun ; Li, Qiaoling ; Zhao, Xia ; Li, Jiguang ; Chen, Ao ; Zhang, Wenwei ; Wong, Hoi Gin ; Qin, Yingying ; Zhao, Han ; Chen, Yuan ; Li, Pei ; Ma, Tao ; Wang, Wen-Jing ; Kwok, Yvonne K. ; Jiang, Yuan ; Pursley, Amber N. ; Chung, Jacqueline P.W. ; Hong, Yan ; Kristiansen, Karsten ; Yang, Huanming ; Piña-Aguilar, Raul E. ; Leung, Tak Yeung ; Cheung, Sau Wai ; Morton, Cynthia C ; Choy, Kwong Wai ; Chen, Zi Jiang. / Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. In: American Journal of Human Genetics. 2019 ; Vol. 105, No. 6. pp. 1102-1111.

Bibtex

@article{8e3c76be83b64f489dfa2812996ca6e2,
title = "Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage",
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.",
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",
author = "Zirui Dong and Junhao Yan and Fengping Xu and Jianying Yuan and Hui Jiang and Huilin Wang and Haixiao Chen and Lei Zhang and Lingfei Ye and Jinjin Xu and Yuhua Shi and Zhenjun Yang and Ye Cao and Lingyun Chen and Qiaoling Li and Xia Zhao and Jiguang Li and Ao Chen and Wenwei Zhang and Wong, {Hoi Gin} and Yingying Qin and Han Zhao and Yuan Chen and Pei Li and Tao Ma and Wen-Jing Wang and Kwok, {Yvonne K.} and Yuan Jiang and Pursley, {Amber N.} and Chung, {Jacqueline P.W.} and Yan Hong and Karsten Kristiansen and Huanming Yang and Pi{\~n}a-Aguilar, {Raul E.} and Leung, {Tak Yeung} and Cheung, {Sau Wai} and Morton, {Cynthia C} and Choy, {Kwong Wai} and Chen, {Zi Jiang}",
year = "2019",
doi = "10.1016/j.ajhg.2019.10.003",
language = "English",
volume = "105",
pages = "1102--1111",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage

AU - Dong, Zirui

AU - Yan, Junhao

AU - Xu, Fengping

AU - Yuan, Jianying

AU - Jiang, Hui

AU - Wang, Huilin

AU - Chen, Haixiao

AU - Zhang, Lei

AU - Ye, Lingfei

AU - Xu, Jinjin

AU - Shi, Yuhua

AU - Yang, Zhenjun

AU - Cao, Ye

AU - Chen, Lingyun

AU - Li, Qiaoling

AU - Zhao, Xia

AU - Li, Jiguang

AU - Chen, Ao

AU - Zhang, Wenwei

AU - Wong, Hoi Gin

AU - Qin, Yingying

AU - Zhao, Han

AU - Chen, Yuan

AU - Li, Pei

AU - Ma, Tao

AU - Wang, Wen-Jing

AU - Kwok, Yvonne K.

AU - Jiang, Yuan

AU - Pursley, Amber N.

AU - Chung, Jacqueline P.W.

AU - Hong, Yan

AU - Kristiansen, Karsten

AU - Yang, Huanming

AU - Piña-Aguilar, Raul E.

AU - Leung, Tak Yeung

AU - Cheung, Sau Wai

AU - Morton, Cynthia C

AU - Choy, Kwong Wai

AU - Chen, Zi Jiang

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - balanced translocation

KW - chromosomal abnormality

KW - chromothripsis and chomoplexy

KW - copy number variants

KW - cryptic structural rearrangements

KW - genetics complexity

KW - inversion

KW - low-pass genome sequencing

KW - preimplantation genetic testing

KW - recurrent miscarriage

U2 - 10.1016/j.ajhg.2019.10.003

DO - 10.1016/j.ajhg.2019.10.003

M3 - Journal article

C2 - 31679651

AN - SCOPUS:85075580234

VL - 105

SP - 1102

EP - 1111

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 6

ER -

ID: 234452431