The present and future of whole-exome sequencing in studying and treating human reproductive disorders

Wei Guo; Xiaohui Zhu; Liying Yan; Jie Qiao

doi:10.1016/j.jgg.2018.08.004

Volume 45 Issue 10

Oct. 2018

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The present and future of whole-exome sequencing in studying and treating human reproductive disorders

doi: 10.1016/j.jgg.2018.08.004

Wei Guo^{a, b, c},
Xiaohui Zhu^{a, b, c},
Liying Yan^{a, b, c},
Jie Qiao^{a, b, c, d, e}

a
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
b
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China
c
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing 100191, China
d
Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing 100871, China
e
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China

More Information

Corresponding author: E-mail address: yanliyingkind@aliyun.com (Liying Yan); E-mail address: jie.qiao@263.net (Jie Qiao)
Received Date: 2018-03-20
Accepted Date: 2018-08-24
Rev Recd Date: 2018-08-23

Available Online: 2018-10-22

Publish Date: 2018-10-20

Abstract

Abstract

The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.
- Whole exome sequencing (WES),
- Unexplained recurrent spontaneous abortion (URSA),
- Fetal malformations,
- Human reproduction

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References

[1]	ACMG Points to consider in the clinical application of genomic sequencing Genet. Med., 14 (2012),pp. 759-761
[2]	Alazami, A.M., Awad, S.M., Coskun, S. et al. Genome Biol., 16 (2015),p. 240
[3]	ASRM Definitions of infertility and recurrent pregnancy loss: a committee opinion Fertil. Steril., 99 (2013),p. 63
[4]	Asadollahi, R., Oneda, B., Joset, P. et al. The clinical significance of small copy number variants in neurodevelopmental disorders J. Med. Genet., 51 (2014),pp. 677-688
[5]	Asselta, R., Spena, S., Duga, S. et al. Molecular genetics of quantitative fibrinogen disorders Cardiovasc. Hematol. Agents Med. Chem., 5 (2007),pp. 163-173
[6]	Bamshad, M.J., Shendure, J.A., Valle, D. et al. The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions Am. J. Med. Genet., 158A (2012),pp. 1523-1525
[7]	Bao, R., Huang, L., Andrade, J. et al. Review of current methods, applications, and data management for the bioinformatics analysis of whole exome sequencing Cancer Inform., 13 (2014),pp. 67-82
[8]	Bhuiyan, Z.A., Momenah, T.S., Gong, Q. et al. Heart Rhythm., 5 (2008),pp. 553-561
[9]	Boycott, K.M., Rath, A., Chong, J.X. et al. International cooperation to enable the diagnosis of all rare genetic diseases Am. J. Hum. Genet., 100 (2017),pp. 695-705
[10]	Boycott, K.M., Vanstone, M.R., Bulman, D.E. et al. Rare-disease genetics in the era of next-generation sequencing: discovery to translation Nat. Rev. Genet., 14 (2013),pp. 681-691
[11]	Boyd, P.A., Tondi, F., Hicks, N.R. et al. Autopsy after termination of pregnancy for fetal anomaly: retrospective cohort study BMJ, 328 (2004),p. 137
[12]	Brown, T.L., Meloche, T.M. Exome sequencing a review of new strategies for rare genomic disease research Genomics, 108 (2016),pp. 109-114
[13]	Carss, K.J., Hillman, S.C., Parthiban, V. et al. Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound Hum. Mol. Genet., 23 (2014),pp. 3269-3277
[14]	CDC Update on overall prevalence of major birth defects--Atlanta, Georgia, 1978-2005 MMWR Morb. Mortal. Wkly. Rep., 57 (2008),pp. 1-5
[15]	Choi, M., Scholl, U.I., Ji, W. et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing Proc. Natl. Acad. Sci. U. S. A., 106 (2009),pp. 19096-19101
[16]	Chong, J.X., Buckingham, K.J., Jhangiani, S.N. et al. The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities Am. J. Hum. Genet., 97 (2015),pp. 199-215
[17]	Cobourne, M.T. The complex genetics of cleft lip and palate Eur. J. Orthod., 26 (2004),pp. 7-16
[18]	Dai, L., Zhu, J., Mao, M. et al. Time trends in oral clefts in Chinese newborns: data from the Chinese National Birth Defects Monitoring Network Birth Defects Res. A Clin. Mol. Teratol., 88 (2010),pp. 41-47
[19]	D'Amours, G., Kibar, Z., Mathonnet, G. et al. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype Clin. Genet., 81 (2012),pp. 128-141
[20]	Dickinson, M.E., Flenniken, A.M., Ji, X. et al. High-throughput discovery of novel developmental phenotypes Nature, 537 (2016),pp. 508-514
[21]	Dinwiddie, D.L., Smith, L.D., Miller, N.A. et al. Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome Genomics, 102 (2013),pp. 148-156
[22]	Dixon, M.J., Marazita, M.L., Beaty, T.H. et al. Cleft lip and palate: understanding genetic and environmental influences Nat. Rev. Genet., 12 (2011),pp. 167-178
[23]	Drury, S., Boustred, C., Tekman, M. et al. Am. J. Med. Genet., 164A (2014),pp. 1777-1783
[24]	Drury, S., Williams, H., Trump, N. et al. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities Prenat. Diagn., 35 (2015),pp. 1010-1017
[25]	Ellard, S., Kivuva, E., Turnpenny, P. et al. An exome sequencing strategy to diagnose lethal autosomal recessive disorders Eur. J. Hum. Genet., 23 (2015),pp. 401-404
[26]	Falardeau, F., Camurri, M.V., Campeau, P.M. Genomic approaches to diagnose rare bone disorders Bone, 102 (2017),pp. 5-14
[27]	Filges, I., Friedman, J.M. Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes Prenat. Diagn., 35 (2015),pp. 1005-1009
[28]	Filges, I., Manokhina, I., Penaherrera, M.S. et al. Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants Mol. Hum. Reprod., 21 (2015),pp. 339-346
[29]	Filges, I., Nosova, E., Bruder, E. et al. Clin. Genet., 86 (2014),pp. 220-228
[30]	FitzPatrick, D.R. Identification of SATB2 as the cleft palate gene on 2q32-q33 Hum. Mol. Genet., 12 (2003),pp. 2491-2501
[31]	Forlino, A., Marini, J.C. Osteogenesis imperfecta Lancet, 387 (2016),pp. 1657-1671
[32]	Geister, K.A., Camper, S.A. Advances in skeletal dysplasia genetics Annu. Rev. Genomics Hum. Genet., 16 (2015),pp. 199-227
[33]	Gelb, B., Brueckner, M., Chung, W. et al. The congenital heart disease genetic network study: rationale, design, and early results Circ. Res., 112 (2013),pp. 698-706
[34]	Giannandrea, M., Parks, W.C. Diverse functions of matrix metalloproteinases during fibrosis Dis. Model Mech., 7 (2014),pp. 193-203
[35]	Guo, C., Wang, Q., Wang, Y. et al. Mol. Med. Rep., 15 (2017),pp. 3193-3197
[36]	Handyside, A.H., Kontogianni, E.H., Hardy, K. et al. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification Nature, 344 (1990),pp. 768-770
[37]	Hiersch, L., Reches, A., Simchoni, S. et al.
[38]	Hyde, K.J., Schust, D.J. Genetic considerations in recurrent pregnancy loss Cold Spring Harb. Perspect. Med., 5 (2015),p. a023119
[39]	Itoh, T., Shirahama, S., Nakashima, E. et al. Comprehensive screening of multiple epiphyseal dysplasia mutations in Japanese population Am. J. Med. Genet., 140 (2006),pp. 1280-1284
[40]	Jia, Z., Fengbiao, M., Wang, L. et al. Int. J. Clin. Exp. Pathol., 10 (2017),pp. 5092-5104
[41]	Laurino, M.Y., Bennett, R.L., Saraiya, D.S. et al. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors J. Genet. Couns., 14 (2005),pp. 165-181
[42]	Lee, H., Deignan, J.L., Dorrani, N. et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders J. Am. Med. Assoc., 312 (2014),pp. 1880-1887
[43]	Lee, V., Chow, J., Yeung, W. et al. Preimplantation genetic diagnosis for monogenic diseases Best Pract. Res. Clin. Obstet. Gynaecol., 44 (2017),pp. 68-75
[44]	Lewis, A.J., Austin, E., Knapp, R. et al. Perinatal maternal mental health, fetal programming and child development Healthcare (Basel), 3 (2015),pp. 1212-1227
[45]	Li, T.C., Makris, M., Tomsu, M. et al. Recurrent miscarriage: aetiology, management and prognosis Hum. Reprod. Update, 8 (2002),pp. 463-481
[46]	Lohmann, K., Klein, C. Next generation sequencing and the future of genetic diagnosis Neurotherapeutics, 11 (2014),pp. 699-707
[47]	Mademont-Soler, I., Morales, C., Soler, A. et al. Prenatal diagnosis of chromosomal abnormalities in fetuses with abnormal cardiac ultrasound findings: evaluation of chromosomal microarray-based analysis Ultrasound Obstet. Gynecol., 41 (2013),pp. 375-382
[48]	Marazita, M.L., Mooney, M.P. Current concepts in the embryology and genetics of cleft lip and cleft palate Clin. Plast. Surg., 31 (2004 Apr),pp. 125-140
[49]	Marokakis, S., Kasparian, N.A., Kennedy, S.E. Prenatal counselling for congenital anomalies: a systematic review Prenat. Diagn., 36 (2016),pp. 662-671
[50]	McCulley, D.J.1, Black, et al. Transcription factor pathways and congenital heart disease Curr. Top Dev. Biol., 100 (2012),pp. 253-277
[51]	McInerney-Leo, A.M., Schmidts, M., Cortes, C.R. et al. Am. J. Hum. Genet., 93 (2013),pp. 515-523
[52]	Mills, J.L. Malformations in infants of diabetic mothers Teratology, 25 (2010),pp. 385-394
[53]	Mitchell, K., O'Sullivan, J., Missero, C. et al. Am. J. Hum. Genet., 90 (2012),pp. 69-75
[54]	Mossey, P.A., Little, J., Munger, R.G. et al. Cleft lip and palate Lancet, 374 (2009),pp. 1773-1785
[55]	Moyers, S., Bailey, L.B. Fetal malformations and folate metabolism: review of recent evidence Nutr. Rev., 59 (2001),pp. 215-224
[56]	Ng, S.B., Buckingham, K.J., Lee, C. et al. Exome sequencing identifies the cause of a mendelian disorder Nat. Genet., 42 (2010),pp. 30-35
[57]	Ng, S.B., Turner, E.H., Robertson, P.D. et al. Targeted capture and massively parallel sequencing of 12 human exomes Nature, 461 (2009),pp. 272-276
[58]	Ornoy, A., Ergaz, Z. Alcohol abuse in pregnant women: effects on the fetus and newborn, mode of action and maternal treatment Int. J. Environ. Res. Public Health, 7 (2010),pp. 364-379
[59]	Osoegawa, K., Vessere, G.M., Utami, K.H. et al. Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation J. Med. Genet., 45 (2008),pp. 81-86
[60]	Ottaviani, G., Buja, L.M. Update on congenital heart disease and sudden infant/perinatal death: from history to future trends J. Clin. Pathol., 70 (2017 Jul),pp. 555-562
[61]	Page, J.M., Silver, R.M. Genetic causes of recurrent pregnancy loss Clin. Obstet. Gynecol., 59 (2016),pp. 498-508
[62]	Pangalos, C., Hagnefelt, B., Lilakos, K. et al. First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects PeerJ, 4 (2016)
[63]	Pinto, A.M., Imperatore, V., Bianciardi, L. et al. Combined ultrasound and exome sequencing approach recognizes Opitz G/BBB syndrome in two malformed fetuses Clin. Dysmorphol., 26 (2017),pp. 18-25
[64]	Putoux, A., Thomas, S., Coene, K.L. et al. Nat. Genet., 43 (2011),pp. 601-606
[65]	Qiao, Y., Wen, J., Tang, F. et al. Whole exome sequencing in recurrent early pregnancy loss Mol. Hum. Reprod., 22 (2016),pp. 364-372
[66]	Quintero-Ronderos, P., Mercier, E., Fukuda, M. et al. Novel genes and mutations in patients affected by recurrent pregnancy loss PLoS One, 12 (2017)
[67]	Rabbani, B., Tekin, M., Mahdieh, N. The promise of whole-exome sequencing in medical genetics J. Hum. Genet., 59 (2014),pp. 5-15
[68]	Ramos, E.I., Bien-Willner, G.A., Li, J. et al. Clin. Genet., 85 (2014),pp. 423-432
[69]	Retterer, K., Juusola, J., Cho, M.T. et al. Clinical application of whole-exome sequencing across clinical indications Genet. Med., 18 (2016),pp. 696-704
[70]	Romani, M., Micalizzi, A., Valente, E.M. Joubert syndrome: congenital cerebellar ataxia with the molar tooth Lancet Neurol., 12 (2013),pp. 894-905
[71]	Roosing, S., Romani, M., Isrie, M. et al. J. Med. Genet., 53 (2016),pp. 608-615
[72]	Rossi, A.C., Prefumo, F. Accuracy of ultrasonography at 11-14 weeks of gestation for detection of fetal structural anomalies: a systematic review Obstet. Gynecol., 122 (2013),pp. 1160-1167
[73]	Sanders, A.A., de Vrieze, E., Alazami, A.M. et al. Genome Biol., 16 (2015),p. 293
[74]	Sawyer, S.L., Hartley, T., Dyment, D.A. et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care Clin. Genet., 89 (2016),pp. 275-284
[75]	Scapoli, L., Martinelli, M., Arlotti, M. et al. Genes causing clefting syndromes as candidates for non-syndromic cleft lip with or without cleft palate: a family-based association study Eur. J. Oral Sci., 116 (2008),pp. 507-511
[76]	Shamseldin, H.E., Swaid, A., Alkuraya, F.S. Lifting the lid on unborn lethal Mendelian phenotypes through exome sequencing Genet. Med., 15 (2013),pp. 307-309
[77]	Shamseldin, H.E., Kurdi, W., Almusafri, F. et al. Molecular autopsy in maternal-fetal medicine Genet. Med., 20 (2018 Apr),pp. 420-427
[78]	Shamseldin, H.E., Tulbah, M., Kurdi, W. et al. Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families Genome Biol., 16 (2015),p. 116
[79]	Sierra, S., Stephenson, M. Genetics of recurrent pregnancy loss Semin. Reprod. Med., 24 (2006),pp. 17-24
[80]	Silasi, M., Cardenas, I., Kwon, J.Y. et al. Viral infections during pregnancy Am. J. Reprod. Immunol., 73 (2015),pp. 199-213
[81]	Soden, S.E., Saunders, C.J., Willig, L.K. et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders Sci. Transl. Med., 6 (2014),p. 265ra168
[82]	Stals, K.L., Wakeling, M., Baptista, J. et al. Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing Prenat. Diagn., 38 (2018),pp. 33-43
[83]	Stark, Z., Tan, T.Y., Chong, B. et al. A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders Genet. Med., 18 (2016),pp. 1090-1096
[84]	Stern, H.J. Preimplantation genetic diagnosis: prenatal testing for embryos finally achieving its potential J. Clin. Med., 3 (2014),pp. 280-309
[85]	Stranneheim, H., Wedell, A. Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders J. Intern. Med., 279 (2016),pp. 3-15
[86]	Sumitha, E., Jayandharan, G.R., Arora, N. et al. Molecular basis of quantitative fibrinogen disorders in 27 patients from India Haemophilia, 19 (2013),pp. 611-618
[87]	Thomas, S., Legendre, M., Saunier, S. et al. Am. J. Hum. Genet., 91 (2012),pp. 372-378
[88]	Traboulsi, E.I. Congenital abnormalities of cranial nerve development: overview, molecular mechanisms, and further evidence of heterogeneity and complexity of syndromes with congenital limitation of eye movements Trans. Am. Ophthalmol. Soc., 102 (2004),pp. 373-389
[89]	Traeger-Synodinos, J. Pre-implantation genetic diagnosis Best Pract. Res. Clin. Obstet. Gynaecol., 39 (2017),pp. 74-88
[90]	Tsurusaki, Y., Yonezawa, R., Furuya, M. et al. Clin. Genet., 85 (2014),pp. 592-594
[91]	Tur-Torres, M.H., Garrido-Gimenez, C., Alijotas-Reig, J. Genetics of recurrent miscarriage and fetal loss Best Pract. Res. Clin. Obstet. Gynaecol., 42 (2017),pp. 11-25
[92]	Valente, E.M., Logan, C.V., Mougou-Zerelli, S. et al. Nat. Genet., 42 (2010),pp. 619-625
[93]	van den Berg, M.M., van Maarle, M.C., van Wely, M. et al. Genetics of early miscarriage Biochim. Biophys. Acta, 1822 (2012)
[94]	van den Boogaard, E., Kaandorp, S.P., Franssen, M.T. et al. Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier status? Hum. Reprod., 25 (2010),pp. 1411-1414
[95]	van den Veyver, I.B., Eng, C.M. Genome-wide sequencing for prenatal detection of fetal single-gene disorders Cold Spring Harb. Perspect. Med., 5 (2015),p. a023077
[96]	Vimercati, A., Grasso, S., Abruzzese, M. et al. Correlation between ultrasound diagnosis and autopsy findings of fetal malformations J. Prenat. Med., 6 (2012),pp. 13-17
[97]	Vora, N., Powell, B., Brandt, A. et al. Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges Genet. Med., 19 (2017),pp. 1207-1216
[98]	Walczak-Sztulpa, J., Eggenschwiler, J., Osborn, D. et al. Am. J. Hum. Genet., 86 (2010),pp. 949-956
[99]	Wang, Z., Yang, Z., Ke, Z. et al. J. Investig. Med., 57 (2009),pp. 662-667
[100]	Wieacker, P., Steinhard, J. The prenatal diagnosis of genetic diseases Dtsch. Arztebl. Int., 107 (2010),pp. 857-862
[101]	Witters, G., Van Robays, J., Willekes, C. et al. Trisomy 13, 18, 21, Triploidy and turner syndrome: the 5T's. Look at the hands Facts Views Vis. Obgyn., 3 (2011),pp. 15-21
[102]	Wright, C.F., FitzPatrick, D.R., Firth, H.V. Paediatric genomics: diagnosing rare disease in children Nat. Rev. Genet., 19 (2018 May),p. 325
[103]	Xu, Y., Shi, Y., Fu, J. et al. Am. J. Hum. Genet., 99 (2016),pp. 744-752
[104]	Yan, L., Huang, L., Xu, L. et al. Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses Proc. Natl. Acad. Sci. U. S. A., 112 (2015),pp. 15964-15969
[105]	Yang, Y., Muzny, D.M., Reid, J.G. et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders N. Engl. J. Med., 369 (2013),pp. 1502-1511
[106]	Yang, Y., Muzny, D.M., Xia, F. et al. Molecular findings among patients referred for clinical whole-exome sequencing J. Am. Med. Assoc., 312 (2014),pp. 1870-1879
[107]	Yates, C.L., Monaghan, K.G., Copenheaver, D. et al. Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development Genet. Med., 19 (2017),pp. 1171-1178