Clinical and Experimental Reproductive Medicine

  • 제51권2호
  • /
  • Pages.91-101
  • /
  • 2024
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Genomic aspects in reproductive medicine

  • Minyeon Go (Department of Biomedical Science, College of Life Science, CHA University) ;
  • Sung Han Shim (Department of Biomedical Science, College of Life Science, CHA University)
  • 투고 : 2023.06.16
  • 심사 : 2023.09.21
  • 발행 : 2024.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Infertility is a complex disease characterized by extreme genetic heterogeneity, compounded by various environmental factors. While there are exceptions, individual genetic and genomic variations related to infertility are typically rare, often family-specific, and may serve as susceptibility factors rather than direct causes of the disease. Consequently, identifying the cause of infertility and developing prevention and treatment strategies based on these factors remain challenging tasks, even in the modern genomic era. In this review, we first examine the genetic and genomic variations associated with infertility, and subsequently summarize the concepts and methods of preimplantation genetic testing in light of advances in genome analysis technology.

키워드

과제정보

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. NRF-2019R1A6A1A03032888).

참고문헌

  1. Ding X, Schimenti JC. Strategies to identify genetic variants causing infertility. Trends Mol Med 2021;27:792-806.
  2. Yatsenko SA, Rajkovic A. Chromosomal causes of infertility. In: Sermon K, Viville S, editors. Textbook of human reproductive genetics. Cambridge University Press; 2014. p. 97-112.
  3. Ando S, Koczok K, Bessenyei B, Balogh I, Ujfalusi A. Cytogenetic investigation of infertile patients in Hungary: a 10-year retrospective study. Genes (Basel) 2022;13:2086.
  4. Ford CE, Jones KW, Polani PE, De Almeida JC, Briggs JH. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet 1959;1:711-3.
  5. Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 1959;183:302-3.
  6. Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet 1991;87:81-3.
  7. Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod Biomed Online 2007;14:734-45.
  8. Mau-Holzmann UA. Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res 2005;111:317-36.
  9. Patel B, Parets S, Akana M, Kellogg G, Jansen M, Chang C, et al. Comprehensive genetic testing for female and male infertility using next-generation sequencing. J Assist Reprod Genet 2018;35:1489-96.
  10. Tunc E, Ilgaz S. Robertsonian translocation (13;14) and its clinical manifestations: a literature review. Reprod Biomed Online 2022;45:563-73.
  11. Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem 2018;62:2-10.
  12. Wasielak-Politowska M, Kordowitzki P. Chromosome segregation in the oocyte: what goes wrong during aging. Int J Mol Sci 2022;23:2880.
  13. Yun Y, Lane SI, Jones KT. Premature dyad separation in meiosis II is the major segregation error with maternal age in mouse oocytes. Development 2014;141:199-208.
  14. Wilch ES, Morton CC. Historical and clinical perspectives on chromosomal translocations. Adv Exp Med Biol 2018;1044:1-14.
  15. Neaves WB, Johnson L, Porter JC, Parker CR Jr, Petty CS. Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J Clin Endocrinol Metab 1984;59:756-63.
  16. Kaltsas A, Moustakli E, Zikopoulos A, Georgiou I, Dimitriadis F, Symeonidis EN, et al. Impact of advanced paternal age on fertility and risks of genetic disorders in offspring. Genes (Basel) 2023;14:486.
  17. Rodrigo L, Meseguer M, Mateu E, Mercader A, Peinado V, Bori L, et al. Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy. Biol Reprod 2019;101:1091-101.
  18. Sarrate Z, Vidal F, Blanco J. Role of sperm fluorescent in situ hybridization studies in infertile patients: indications, study approach, and clinical relevance. Fertil Steril 2010;93:1892-902.
  19. Mateu E, Rodrigo L, Prados N, Gil-Salom M, Remohi J, Pellicer A, et al. High incidence of chromosomal abnormalities in large-headed and multiple-tailed spermatozoa. J Androl 2006;27:6-10.
  20. Baart EB, Martini E, van den Berg I, Macklon NS, Galjaard RJ, Fauser BC, et al. Preimplantation genetic screening reveals a high incidence of aneuploidy and mosaicism in embryos from young women undergoing IVF. Hum Reprod 2006;21:223-33.
  21. Daphnis DD, Fragouli E, Economou K, Jerkovic S, Craft IL, Delhanty JD, et al. Analysis of the evolution of chromosome abnormalities in human embryos from day 3 to 5 using CGH and FISH. Mol Hum Reprod 2008;14:117-25.
  22. Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C, et al. Chromosome instability is common in human cleavage-stage embryos. Nat Med 2009;15:577-83.
  23. De Braekeleer M, Dao TN. Cytogenetic studies in male infertility: a review. Hum Reprod 1991;6:245-50.
  24. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992;340:17-8.
  25. Berntsen S, Laivuori H, la Cour Freiesleben N, Loft A, Soderstrom-Anttila V, Oldereid NB, et al. A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities. Hum Reprod Update 2021;27:801-47.
  26. In't Veld P, Brandenburg H, Verhoeff A, Dhont M, Los F. Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995;346:773.
  27. Van Opstal D, Los FJ, Ramlakhan S, Van Hemel JO, Van Den Ouweland AM, Brandenburg H, et al. Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection. Hum Reprod 1997;12:682-6.
  28. Kim JW, Lee WS, Yoon TK, Seok HH, Cho JH, Kim YS, et al. Chromosomal abnormalities in spontaneous abortion after assisted reproductive treatment. BMC Med Genet 2010;11:153.
  29. Chong S, Whitelaw E. Epigenetic germline inheritance. Curr Opin Genet Dev 2004;14:692-6.
  30. Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutat Res 2011;727:62-71.
  31. Gunes S, Esteves SC. Role of genetics and epigenetics in male infertility. Andrologia 2021;53:e13586.
  32. Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One 2007;2:e1289.
  33. Sonnack V, Failing K, Bergmann M, Steger K. Expression of hyper-acetylated histone H4 during normal and impaired human spermatogenesis. Andrologia 2002;34:384-90.
  34. Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, et al. Origins and functional impact of copy number variation in the human genome. Nature 2010;464:704-12.
  35. Sha Y, Zheng L, Ji Z, Mei L, Ding L, Lin S, et al. A novel TEX11 mutation induces azoospermia: a case report of infertile brothers and literature review. BMC Med Genet 2018;19:63.
  36. Chandley AC. Chromosome anomalies and Y chromosome microdeletions as causal factors in male infertility. Hum Reprod 1998;13 Suppl 1:45-50.
  37. Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 1996;5:933-43.
  38. Tsuiko O, Noukas M, Zilina O, Hensen K, Tapanainen JS, Magi R, et al. Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases. Hum Reprod 2016;31:1913-25.
  39. Schuettler J, Peng Z, Zimmer J, Sinn P, von Hagens C, Strowitzki T, et al. Variable expression of the fragile X mental retardation 1 (FMR1) gene in patients with premature ovarian failure syndrome is not dependent on number of (CGG)n triplets in exon 1. Hum Reprod 2011;26:1241-51.
  40. Rajcan-Separovic E. Chromosome microarrays in human reproduction. Hum Reprod Update 2012;18:555-67.
  41. Moosani N, Pattinson HA, Carter MD, Cox DM, Rademaker AW, Martin RH. Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization. Fertil Steril 1995;64:811-7.
  42. Schaeffer AJ, Chung J, Heretis K, Wong A, Ledbetter DH, Lese Martin C. Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet 2004;74:1168-74.
  43. Le Caignec C, Boceno M, Saugier-Veber P, Jacquemont S, Joubert M, David A, et al. Detection of genomic imbalances by array based comparative genomic hybridisation in fetuses with multiple malformations. J Med Genet 2005;42:121-8.
  44. Zhu Y, Hu L, Cao D, Ou X, Jiang M. Chromosomal microarray analysis of infertile men with azoospermia factor microdeletions. Gene 2020;735:144389.
  45. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med 2008;14:1197-213.
  46. Foresta C, Ferlin A, Gianaroli L, Dallapiccola B. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet 2002;10:303-12.
  47. Adashi EY, Hennebold JD. Single-gene mutations resulting in reproductive dysfunction in women. N Engl J Med 1999;340:709-18.
  48. Feng R, Sang Q, Kuang Y, Sun X, Yan Z, Zhang S, et al. Mutations in TUBB8 and human oocyte meiotic arrest. N Engl J Med 2016;374:223-32.
  49. Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 2001;27:159-66.
  50. Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet 2007;81:576-81.
  51. Zhao S, Li G, Dalgleish R, Vujovic S, Jiao X, Li J, et al. Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency. Fertil Steril 2015;103:548-53.
  52. Franca MM, Funari MFA, Nishi MY, Narcizo AM, Domenice S, Costa EMF, et al. Identification of the first homozygous 1-bp deletion in GDF9 gene leading to primary ovarian insufficiency by using targeted massively parallel sequencing. Clin Genet 2018;93:408-11.
  53. Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, et al. Mutant cohesin in premature ovarian failure. N Engl J Med 2014;370:943-9.
  54. Azziz R. Polycystic ovary syndrome. Obstet Gynecol 2018;132:321-36.
  55. Zore T, Joshi NV, Lizneva D, Azziz R. Polycystic ovarian syndrome: long-term health consequences. Semin Reprod Med 2017;35:271-81.
  56. Mykhalchenko K, Lizneva D, Trofimova T, Walker W, Suturina L, Diamond MP, et al. Genetics of polycystic ovary syndrome. Expert Rev Mol Diagn 2017;17:723-33.
  57. Fonseca DJ, Patino LC, Suarez YC, de Jesus Rodriguez A, Mateus HE, Jimenez KM, et al. Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations. Fertil Steril 2015;104:154-62.
  58. Jaillard S, Bell K, Akloul L, Walton K, McElreavy K, Stocker WA, et al. New insights into the genetic basis of premature ovarian insufficiency: novel causative variants and candidate genes revealed by genomic sequencing. Maturitas 2020;141:9-19.
  59. Volozonoka L, Miskova A, Kornejeva L, Kempa I, Bargatina V, Gailite L. A systematic review and standardized clinical validity assessment of genes involved in female reproductive failure. Reproduction 2022;163:351-63.
  60. Oud MS, Volozonoka L, Smits RM, Vissers LELM, Ramos L, Veltman JA. A systematic review and standardized clinical validity assessment of male infertility genes. Hum Reprod 2019;34:932-41.
  61. Bashamboo A, Ferraz-de-Souza B, Lourenco D, Lin L, Sebire NJ, Montjean D, et al. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet 2010;87:505-12.
  62. Yatsenko AN, Georgiadis AP, Ropke A, Berman AJ, Jaffe T, Olszewska M, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 2015;372:2097-107.
  63. Massart A, Lissens W, Tournaye H, Stouffs K. Genetic causes of spermatogenic failure. Asian J Androl 2012;14:40-8.
  64. Munne S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod 1993;8:2185-91.
  65. Viotti M. Preimplantation genetic testing for chromosomal abnormalities: aneuploidy, mosaicism, and structural rearrangements. Genes (Basel) 2020;11:602.
  66. Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril 2011;95:953-8.
  67. Wells D, Kaur K, Grifo J, Glassner M, Taylor JC, Fragouli E, et al. Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J Med Genet 2014;51:553-62.
  68. Kokkali G, Traeger-Synodinos J, Vrettou C, Stavrou D, Jones GM, Cram DS, et al. Blastocyst biopsy versus cleavage stage biopsy and blastocyst transfer for preimplantation genetic diagnosis of beta-thalassaemia: a pilot study. Hum Reprod 2007;22:1443-9.
  69. Cho EK, Tchinda J, Freeman JL, Chung YJ, Cai WW, Lee C. Array-based comparative genomic hybridization and copy number variation in cancer research. Cytogenet Genome Res 2006;115:262-72.
  70. Aradhya S, Cherry AM. Array-based comparative genomic hybridization: clinical contexts for targeted and whole-genome designs. Genet Med 2007;9:553-9.
  71. Wells D, Alfarawati S, Fragouli E. Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH. Mol Hum Reprod 2008;14:703-10.
  72. Treff NR, Levy B, Su J, Northrop LE, Tao X, Scott RT Jr. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH. Mol Hum Reprod 2010;16:583-9.
  73. Munne S, Blazek J, Large M, Martinez-Ortiz PA, Nisson H, Liu E, et al. Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing. Fertil Steril 2017;108:62-71.
  74. Barad DH, Albertini DF, Molinari E, Gleicher N. IVF outcomes of embryos with abnormal PGT-A biopsy previously refused transfer: a prospective cohort study. Hum Reprod 2022;37:1194-206.
  75. Gleicher N, Orvieto R. Is the hypothesis of preimplantation genetic screening (PGS) still supportable?: a review. J Ovarian Res 2017;10:21.
  76. Scriven PN. A tale of two studies: now is no longer the best of times for preimplantation genetic testing for aneuploidy (PGT-A). J Assist Reprod Genet 2020;37:673-6.
  77. Greco E, Minasi MG, Fiorentino F. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med 2015;373:2089-90.
  78. Yang M, Rito T, Metzger J, Naftaly J, Soman R, Hu J, et al. Depletion of aneuploid cells in human embryos and gastruloids. Nat Cell Biol 2021;23:314-21.
  79. Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768-70.
  80. Handyside AH, Lesko JG, Tarin JJ, Winston RM, Hughes MR. Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl J Med 1992;327:905-9.
  81. Wilton L, Thornhill A, Traeger-Synodinos J, Sermon KD, Harper JC. The causes of misdiagnosis and adverse outcomes in PGD. Hum Reprod 2009;24:1221-8.
  82. Hellani A, Coskun S, Benkhalifa M, Tbakhi A, Sakati N, Al-Odaib A, et al. Multiple displacement amplification on single cell and possible PGD applications. Mol Hum Reprod 2004;10:847-52.
  83. Fiorentino F, Biricik A, Nuccitelli A, De Palma R, Kahraman S, Iacobelli M, et al. Strategies and clinical outcome of 250 cycles of preimplantation genetic diagnosis for single gene disorders. Hum Reprod 2006;21:670-84.
  84. Chen SU, Su YN, Fang MY, Chang LJ, Tsai YY, Lin LT, et al. PGD of beta-thalassaemia and HLA haplotypes using OmniPlex whole genome amplification. Reprod Biomed Online 2008;17:699-705.
  85. Lukaszuk K, Pukszta S, Wells D, Cybulska C, Liss J, Plociennik L, et al. Routine use of next-generation sequencing for preimplantation genetic diagnosis of blastomeres obtained from embryos on day 3 in fresh in vitro fertilization cycles. Fertil Steril 2015;103:1031-6.
  86. Yan L, Huang L, Xu L, Huang J, Ma F, Zhu X, 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 2015;112:15964-9.
  87. Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, Shaw MA, et al. Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J Med Genet 2010;47:651-8.
  88. Turley P, Meyer MN, Wang N, Cesarini D, Hammonds E, Martin AR, et al. Problems with using polygenic scores to select embryos. N Engl J Med 2021;385:78-86.
  89. Lazaro-Munoz G, Pereira S, Carmi S, Lencz T. Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology. Genet Med 2021;23:432-4.
  90. Palini S, Galluzzi L, De Stefani S, Bianchi M, Wells D, Magnani M, et al. Genomic DNA in human blastocoele fluid. Reprod Biomed Online 2013;26:603-10.
  91. Magli MC, Pomante A, Cafueri G, Valerio M, Crippa A, Ferraretti AP, et al. Preimplantation genetic testing: polar bodies, blastomeres, trophectoderm cells, or blastocoelic fluid? Fertil Steril 2016;105:676-83.
  92. Kuznyetsov V, Madjunkova S, Antes R, Abramov R, Motamedi G, Ibarrientos Z, et al. Evaluation of a novel non-invasive preimplantation genetic screening approach. PLoS One 2018;13:e0197262.
  93. Zhang Y, Li N, Wang L, Sun H, Ma M, Wang H, et al. Molecular analysis of DNA in blastocoele fluid using next-generation sequencing. J Assist Reprod Genet 2016;33:637-45.
  94. Hammond ER, McGillivray BC, Wicker SM, Peek JC, Shelling AN, Stone P, et al. Characterizing nuclear and mitochondrial DNA in spent embryo culture media: genetic contamination identified. Fertil Steril 2017;107:220-8.
  95. Huang L, Bogale B, Tang Y, Lu S, Xie XS, Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci U S A 2019;116:14105-12.
  96. Chen J, Jia L, Li T, Guo Y, He S, Zhang Z, et al. Diagnostic efficiency of blastocyst culture medium in noninvasive preimplantation genetic testing. F S Rep 2020;2:88-94.
  97. Sonehara H, Matsumoto R, Nakayama N, Kobanawa M, Numata K, Kawasaki A, et al. Aneuploidy and sex concordance rate between cell-free DNA analysis from spent culture media of preimplantation embryo and DNA from whole embryo with respect to different morphological grading. Reprod Med Biol 2022;21:e12493.
  98. Tsai NC, Chang YC, Su YR, Lin YC, Weng PL, Cheng YH, et al. Validation of non-invasive preimplantation genetic screening using a routine IVF laboratory workflow. Biomedicines 2022;10:1386.
  99. Xu CL, Wei YQ, Tan QY, Huang Y, Wu JJ, Li CY, et al. Concordance of PGT for aneuploidies between blastocyst biopsies and spent blastocyst culture medium. Reprod Biomed Online 2023;46:483-90.
  100. Cai L, Zeng Q, Gao C, Wu W, Shen J, Wu BL, et al. Majority of transferred mosaic embryos developed healthy live births revealed by a preclinical study using embryonic morphology assessment and noninvasive PGT-A on cell-free DNA in blastocoel fluid. J Assist Reprod Genet 2022;39:2483-504.
  101. Liu W, Liu J, Du H, Ling J, Sun X, Chen D. Non-invasive pre-implantation aneuploidy screening and diagnosis of beta thalassemia IVSII654 mutation using spent embryo culture medium. Ann Med 2017;49:319-28.
  102. Capalbo A, Romanelli V, Patassini C, Poli M, Girardi L, Giancani A, et al. Diagnostic efficacy of blastocoel fluid and spent media as sources of DNA for preimplantation genetic testing in standard clinical conditions. Fertil Steril 2018;110:870-9.
  103. Huang J, Rong L, Zeng L, Hu L, Shi J, Cai L, et al. Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial. BMJ Open 2022;12:e057254.
  104. Capalbo A, Fabiani M, Caroselli S, Poli M, Girardi L, Patassini C, et al. Clinical validity and utility of preconception expanded carrier screening for the management of reproductive genetic risk in IVF and general population. Hum Reprod 2021;36:2050-61.
  105. Henneman L, Borry P, Chokoshvili D, Cornel MC, van El CG, Forzano F, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016;24:e1-12.
  106. Grody WW, Thompson BH, Gregg AR, Bean LH, Monaghan KG, Schneider A, et al. ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med 2013;15:482-3.
  107. de Wert G, Dondorp W, Clarke A, Dequeker EMC, Cordier C, Deans Z, et al. Opportunistic genomic screening: recommendations of the European Society of Human Genetics. Eur J Hum Genet 2021;29:365-77.
  108. Committee Opinion No. 690: carrier screening in the age of genomic medicine. Obstet Gynecol 2017;129:e35-40.
  109. Gregg AR, Aarabi M, Klugman S, Leach NT, Bashford MT, Goldwaser T, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021;23:1793-806.
  110. Veneruso I, Di Resta C, Tomaiuolo R, D'Argenio V. Current updates on expanded carrier screening: new insights in the Omics era. Medicina (Kaunas) 2022;58:455.
  111. Vassena R, Heindryckx B, Peco R, Pennings G, Raya A, Sermon K, et al. Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Hum Reprod Update 2016;22:411-9.
  112. Tang L, Zeng Y, Du H, Gong M, Peng J, Zhang B, et al. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein. Mol Genet Genomics 2017;292:525-33.