切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (02) : 132 -138. doi: 10.3877/cma.j.issn.1673-5250.2022.02.002

专题论坛

染色体嵌合体及单亲二体的研究现状
崔婉婷, 赵彦艳()   
  1. 中国医科大学附属盛京医院临床遗传科,沈阳 110004
  • 收稿日期:2021-10-30 修回日期:2022-02-09 出版日期:2022-04-01
  • 通信作者: 赵彦艳

Current research status on chromosomal mosaicism and uniparental disomy

Wanting Cui, Yanyan Zhao()   

  1. Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
  • Received:2021-10-30 Revised:2022-02-09 Published:2022-04-01
  • Corresponding author: Yanyan Zhao
  • Supported by:
    National Key Research and Development Program of " 13th Five-Year Plan"(2016YFC1000700, 2016YFC1000702)
引用本文:

崔婉婷, 赵彦艳. 染色体嵌合体及单亲二体的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(02): 132-138.

Wanting Cui, Yanyan Zhao. Current research status on chromosomal mosaicism and uniparental disomy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(02): 132-138.

染色体嵌合体(CM)和单亲二体(UPD)均与胚胎发育过程中的细胞分裂错误有关。目前多数研究认为,CM与胚胎细胞有丝分裂错误有关。利用辅助生殖技术结合单细胞高通量测序技术(NGST)进行研究发现,胚胎发育早期处于细胞分裂错误和自我纠正的动态变化中,其变化结果决定胚胎染色体的构成。染色体异常细胞可能以不同比例存在于不同组织和器官中,从而导致CM患者临床症状和染色体异常表型差异很大。UPD来源于发育过程中,胚胎对于细胞减数分裂错误或有丝分裂错误的"自救",其致病性与印迹基因有关,除明确的UPD相关疾病外,未含有印迹基因的UPD致病性尚有待进一步研究。在产前诊断中,对CM与UPD这2种染色体异常的检出率,随着NGST的发展而不断提高,但是有关其致病性判断及胎儿风险评估,则由于缺乏足够研究证据支持,而成为临床遗传咨询难点。笔者拟就上述2种染色体异常的发生机制、致病性及其产前诊断与遗传咨询的最新研究现状等进行阐述,旨在为临床对这2种染色体异常的研究提供参考。

Chromosomal mosaicism (CM) and uniparental disomy (UPD) arise from the chromosome mis-segregation in cell division of embryogenesis. Recent researches demonstrated the relationships between CM and mitosis errors of embryonic cell. By assisted reproductive technology and single cell next-generation sequencing technology (NGST), researchers found that the early embryo development accompanied with dynamic processes of chromosome segregation errors and self-correction, the result of which determined the chromosome constitutions of embryo. The abnormal cell lines with chromosome disorders could distribute in different tissues and organs with variable types and proportions, which could lead to a large variation in clinical symptoms and phenotypes of CM. UPD might result from the rescue of meiosis or mitosis errors. It was wide known that the UPD disorders related to imprinted genes, and the pathogenicities of UPD in other chromosomes without imprinted genes still need to be explored. The detection rate of these two chromosome abnormalities has been improved with the development of NGST, however, due to insufficient support of deficient research evidences, it is difficult to evaluate the pathogenicities of these two chromosome abnormalities and predict the risk of fetal involvement confidently in the genetic counseling. Thus, in order to provide references for clinical research of these two chromosome aberrations, we will demonstrate the latest research progresses of mechanism, pathogenicity, prenatal diagnosis and genetic counseling of these two chromosome abnormalities in this review.

[1]
Eggermann T, Soellner L, Buiting K, et al. Mosaicism and uniparental disomy in prenatal diagnosis[J]. Trends Mol Med, 201521(2): 77-87. DOI:10.1016/j.molmed.2014.11.010.
[2]
Taylor TH, Gitlin SA, Patrick JL, et al. The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans[J]. Hum Reprod Update, 2014, 20(4): 571-581. DOI: 10.1093/humupd/dmu016.
[3]
Conlin LK, Thiel BD, Bonnemann CG, et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis[J]. Hum Mol Genet, 201019(7): 1263-1275.DOI:10.1093/hmg/ddq003.
[4]
Robinson WP. Mechanisms leading to uniparental disomy and their clinical consequences[J]. Bioessays, 2000, 22(5): 452-459.
[5]
Butler MG. Imprinting disorders in humans: a review[J]. Curr Opin Pediatr, 2020, 32(6): 719-729. DOI: 10.1097/MOP.0000000000000965.
[6]
Chantot-Bastaraud S, Stratmann S, Brioude F, et al. Formation of upd(7)mat by trisomic rescue: SNP array typing provides new insights in chromosomal nondisjunction[J]. Mol Cytogenet, 2017, 10: 28. DOI: 10.1186/s13039-017-0329-1.
[7]
Popovic M, Dhaenens L, Boel A, et al. Chromosomal mosaicism in human blastocysts: the ultimate diagnostic dilemma[J]. Hum Reprod Update, 2020, 26(3): 313-334. DOI: 10.1093/humupd/dmz050.
[8]
Niida Y, Ozaki M, Shimizu M, et al. Classification of uniparental isodisomy patterns that cause autosomal recessive disorders: proposed mechanisms of different proportions and parental origin in each pattern[J]. Cytogenet Genome Res, 2018, 154(3): 137-146. DOI: 10.1159/000488572.
[9]
Lalou I, Gkrozou F, Meridis E, et al. Molecular investigation of uniparental disomy (UPD) in spontaneous abortions[J]. Eur J Obstet Gynecol Reprod Biol, 2019, 236: 116-120. DOI: 10.1016/j.ejogrb.2019.03.004.
[10]
Spinner NB, Conlin LK. Mosaicism and clinical genetics[J]. Am J Med Genet C Semin Med Genet, 2014, 166C(4): 397-405. DOI: 10.1002/ajmg.c.31421.
[11]
Schroeder C, Ekici AB, Moog U, et al. Genome-wide UPD screening in patients with intellectual disability[J]. Eur J Hum Genet, 2014, 22(10): 1233-1235. DOI: 10.1038/ejhg.2014.63.
[12]
Del Gaudio D, Shinawi M, Astbury C, et al. Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2020, 22(7): 1133-1141. DOI: 10.1038/s41436-020-0782-9.
[13]
Liu Y, Guo L, Chen H, et al. Discrepancy of QF-PCR, CMA and karyotyping on a de novo case of mosaic isodicentric Y chromosomes[J]. Mol Cytogenet, 2019, 12: 1. DOI: 10.1186/s13039-018-0413-1.
[14]
Vázquez-Diez C, FitzHarris G. Causes and consequences of chromosome segregation error in preimplantation embryos[J]. Reproduction, 2018, 155(1): R63-R76. DOI:10.1530/REP-17-05692018.
[15]
Macaulay IC, Haerty W, Kumar P, et al. G&T-seq: parallel sequencing of single-cell genomes and transcriptomes[J]. Nat Methods, 2015, 12(6): 519-522. DOI:10.1038/nmeth.3370.
[16]
Griffiths JA, Scialdone A, Marioni JC. Mosaic autosomal aneuploidies are detectable from single-cell RNAseq data[J]. BMC Genomics, 2017, 18(1): 904. DOI:10.1186/s12864-017-4253-x.
[17]
Starostik MR, Sosina OA, McCoy RC. Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism[J]. Genome Res, 2020, 30(6): 814-825. DOI: 10.1101/gr.262774.120.
[18]
Li X, Hao Y, Elshewy N, et al. The mechanisms and clinical application of mosaicism in preimplantation embryos[J]. J Assist Reprod Genet, 2020, 37(3): 497-508. DOI: 10.1007/s10815-019-01656-x.
[19]
Santos MA, Teklenburg G, Macklon NS, et al. The fate of the mosaic embryo: chromosomal constitution and development of day 4, 5 and 8 human embryos[J]. Hum Reprod, 2010, 25(8): 1916-1926. DOI: 10.1093/humrep/deq139.
[20]
Mantikou E, Wong KM, Repping S, et al. Molecular origin of mitotic aneuploidies in preimplantation embryos[J]. Biochim Biophys Acta, 2012, 1822(12): 1921-1930. DOI: 10.1016/j.bbadis.2012.06.013.
[21]
Singla S, Iwamoto-Stohl LK, Zhu M, et al. Autophagy-mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism[J]. Nat Commun, 2020, 11(1): 2958. DOI: 10.1038/s41467-020-16796-3.
[22]
Orvieto R, Shimon C, Rienstein S, et al. Do human embryos have the ability of self-correction[J]. Reprod Biol Endocrinol, 2020, 18(1): 98. DOI: 10.1186/s12958-020-00650-8.
[23]
Daughtry BL, Rosenkrantz JL, Lazar NH, et al. Single-cell sequencing of primate preimplantation embryos reveals chromosome elimination via cellular fragmentation and blastomere exclusion[J]. Genome Res, 2019, 29(3): 367-382. DOI: 10.1101/gr.239830.118.
[24]
Haouzi D, Boumela I, Chebli K, et al. Global, survival, and apoptotic transcriptome during mouse and human early embryonic development[J]. Biomed Res Int, 2018, 2018: 5895628. DOI: 10.1155/2018/5895628.
[25]
Chavez SL, Loewke KE, Han J, et al. Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage[J]. Nat Commun, 2012, 3: 1251. DOI: 10.1038/ncomms2249.
[26]
Kort DH, Chia G, Treff NR, et al. Human embryos commonly form abnormal nuclei during development: a mechanism of DNA damage, embryonic aneuploidy, and developmental arrest[J]. Hum Reprod, 2016, 31(2): 312-323. DOI: 10.1093/humrep/dev281.
[27]
McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm[J]. Trends Genet, 2017, 33(7): 448-463. DOI: 10.1016/j.tig.2017.04.001.
[28]
Webster A, Schuh M. Mechanisms of aneuploidy in human eggs[J]. Trends Cell Biol, 2017, 27(1): 55-68. DOI: 10.1016/j.tcb.2016.09.002.
[29]
Benn P. Uniparental disomy: origin, frequency, and clinical significance[J]. Prenat Diagn, 202141(5):564-572. DOI: 10.1002/pd.5837.
[30]
Ma J, Cram DS, Zhang J, et al. Birth of a child with trisomy 9 mosaicism syndrome associated with paternal isodisomy 9: case of a positive noninvasive prenatal test result unconfirmed by invasive prenatal diagnosis[J]. Mol Cytogenet, 2015, 8: 44. DOI: 10.1186/s13039-015-0145-4.
[31]
Liehr T, Ewers E, Hamid AB, et al. Small supernumerary marker chromosomes and uniparental disomy have a story to tell[J]. J Histochem Cytochem, 2011, 59(9): 842-848. DOI:10.1369/0022155411412780.
[32]
Wolstenholme J. Confined placental mosaicism for trisomies 2,3, 7, 8, 9, 16, and 22: their incidence, likely origins, and mechanisms for cell lineage compartmentalization[J]. Prenat Diagn, 199616(6):511-524. DOI:10.1002/(SICI)1097-0223(199606)16:6<511::AID-PD904>3.0.CO;2-8.
[33]
Del Gobbo GF, Konwar C, Robinson WP. The significance of the placental genome and methylome in fetal and maternal health[J]. Hum Genet, 2020, 139(9): 1183-1196. DOI: 10.1007/s00439-019-02058-w.
[34]
Cui W, Liu X, Zhang Y, et al. Evaluation of non-invasive prenatal testing to detect chromosomal aberrations in a Chinese cohort[J]. J Cell Mol Med, 2019, 23(11): 7873-7878. DOI:10.1111/jcmm.14614.
[35]
Hayata K, Hiramatsu Y, Masuyama H, et al. Discrepancy between non-invasive prenatal genetic testing (NIPT) and amniotic chromosomal test due to placental mosaicism: a case report and literature review[J]. Acta Med Okayama, 2017, 71(2): 181-185. DOI: 10.18926/AMO/54988.
[36]
Hook EB, Warburton D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss[J]. Hum Genet, 2014, 133(4): 417-424. DOI:10.1007/s00439-014-1420-x.
[37]
Karaman B, Kayserili H, Ghanbari A, et al. Pallister-Killian syndrome: clinical, cytogenetic and molecular findings in15 cases[J]. Mol Cytogenet, 2018, 11: 45. DOI: 10.1186/s13039-018-0395-z.
[38]
Yamazawa K, Ogata T, Ferguson-Smith AC. Uniparental disomy and human disease: an overview[J]. Am J Med Genet C Semin Med Genet, 2010, 154C(3): 329-334. DOI: 10.1002/ajmg.c.30270.
[39]
Liehr T. Cytogenetic contribution to uniparental disomy (UPD)[J]. Mol Cytogenet, 2010, 3: 8. DOI: 10.1186/1755-8166-3-8.
[40]
Nakka P, Pattillo Smith S, O′Donnell-Luria AH, et al. Characterization of prevalence and health consequences of uniparental disomy in four million individuals from the general population[J].Am J Hum Genet, 2019, 105(5): 921-932. DOI: 10.1016/j.ajhg.2019.09.016.
[41]
Vásquez Sotomayor F, Abarca-Barriga HH. Homozygous deletion of the CFTR gene caused by interstitial maternal isodisomy in a peruvian child with cystic fibrosis[J]. J Pediatr Genet, 2019, 8(3): 147-152. DOI: 10.1055/s-0039-1678682.
[42]
Quan F, Janas J, Toth-Fejel S, et al. Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy[J].Am J Hum Genet, 1997, 60(1): 160-165.
[43]
Grati FR, Grimi B, Frascoli G, et al. Confirmation of mosaicism and uniparental disomy in amniocytes, after detection of mosaic chromosome abnormalities in chorionic villi[J]. Eur J Hum Genet, 2006, 14(3): 282-288. DOI: 10.1038/sj.ejhg.5201564.
[44]
Grati FR. Chromosomal mosaicism in human feto-placental development: implications for prenatal diagnosis[J]. J Clin Med, 2014, 3(3): 809-837. DOI: 10.3390/jcm3030809.
[45]
Ballif BC, Rorem EA, Sundin K, et al. Detection of low-level mosaicism by array CGH in routine diagnostic specimens[J]. Am J Med Genet A, 2006, 140(24): 2757-2767. DOI: 10.1002/ajmg.a.31539.
[46]
Liang D, Peng Y, Lyu W, et al. Copy number variation sequencing for comprehensive diagnosis of chromosome disease syndromes[J]. J Mol Diagn, 2014, 16(5): 519-526. DOI: 10.1016/j.jmoldx.2014.05.002.
[47]
Robinson WP, McFadden DE, Barrett IJ, et al. Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism[J]. Prenat Diagn, 2002, 22(12): 1076-1085. DOI: 10.1002/pd.483.
[48]
Hsu LY, Benn PA. Revised guidelines for the diagnosis of mosaicism in amniocytes[J]. Prenat Diagn, 1999, 19(11): 1081-1082.
[49]
Nadesapillai S, van der Velden J, Smeets D, et al. Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary[J]. Fertil Steril, 2021, 115(5):1280-1287. DOI: 10.1016/j.fertnstert.2020.11.006.
[50]
Chen CP, Peng CR, Chern SR, et al. Interphase fluorescence in situ hybridization characterization of mosaicism using uncultured amniocytes and cultured stimulated cord blood lymphocytes in prenatally detected Pallister-Killian syndrome[J]. Taiwan J Obstet Gynecol, 2014, 53(4): 566-571. DOI: 10.1016/j.tjog.2014.09.004.
[51]
Zhang Y, Zhong M, Zheng D. Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis[J]. J Cell Mol Med, 2021, 25(1): 358-366. DOI: 10.1111/jcmm.16080.
[52]
Silva M, de Leeuw N, Mann K, et al. European guidelines for constitutional cytogenomic analysis[J]. Eur J Hum Genet, 2019, 27(1): 1-16. DOI: 10.1038/s41431-018-0244-x.
[53]
Schroeder C, Sturm M, Dufke A, et al. UPD tool: a tool for detection of iso- and heterodisomy in parent-child trios using SNP microarrays[J]. Bioinformatics, 2013, 29(12): 1562-1564. DOI: 10.1093/bioinformatics/btt174.
[54]
Moradkhani K, Cuisset L, Boisseau P, et al. Risk estimation of uniparental disomy of chromosome 14 or 15 in a fetus with a parent carrying a non-homologous Robertsonian translocation. Should we still perform prenatal diagnosis?[J]. Prenat Diagn, 2019, 39(11): 986-992. DOI: 10.1002/pd.5518.
[55]
Van Opstal D, Diderich KEM, Joosten M, et al. Unexpected finding of uniparental disomy mosaicism in term placentas: is it a common feature in trisomic placentas?[J]. Prenat Diagn, 2018, 38(12): 911-919. DOI: 10.1002/pd.5354.
[1] 刘镭, 杨昕, 许晓华, 林胜谋, 熊初琴, 农丽录, 董振宇, 李胜利. 中孕期胎儿鼻前皮肤厚度及鼻骨长度筛查胎儿染色体病的临床价值[J]. 中华医学超声杂志(电子版), 2023, 20(05): 506-510.
[2] 刘双, 董虹美, 张晓航, 冉茜, 冉素真. 妊娠11~13+6周超声诊断胎儿单脐动脉及其与染色体异常的相关性[J]. 中华医学超声杂志(电子版), 2022, 19(09): 908-914.
[3] 满婷婷, 郝晓艳, 刘晓伟, 孙海瑞, 何怡华. 法洛四联症常见心内合并畸形及遗传学异常分析[J]. 中华医学超声杂志(电子版), 2022, 19(08): 779-784.
[4] 刘磊, 王优, 黄锐斌, 张丽娜, 宋一丹, 雷婷缨. 染色体微阵列分析技术在股骨长度偏短胎儿遗传学诊断中的应用[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 437-445.
[5] 曾照敏, 余海燕. 超雌综合征的临床认知[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 145-150.
[6] 卞玉香, 王丽春, 蔡蓉. 胎儿超声软指标对胎儿染色体异常的预测价值[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(01): 85-92.
[7] 张禾璇, 宋咏刚, 杨雪. 孕妇无创产前检测结果的大样本分析[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(06): 685-691.
[8] 王珺, 张振强, 王茜怡, 苟兴庆, 何玉萍. 染色体相互易位携带者胚胎植入前染色体结构重排遗传学检测结果的影响因素分析[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(06): 652-659.
[9] 尤琳, 蔡振伟, 乔荆. Turner综合征临床研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(06): 634-639.
[10] 陈晶晶, 钱芳. 新疆地区不同民族育龄妇女胚胎停育与叶酸代谢酶基因多态性及染色体异常的相关性[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(05): 599-605.
[11] 骞佩, 包瑛, 黄惠梅, 韩艳, 索磊, 杨楠, 安小敏, 党佳文. 常染色体隐性遗传多囊肾病患儿PKHD1基因变异的临床表型及基因型[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(05): 540-547.
[12] 刘磊, 李颖思, 周航, 程肯, 霍颖, 雷婷缨. 单脐动脉合并其他先天性结构畸形胎儿预后的临床分析[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(04): 427-432.
[13] 张小康, 张伟, 赵彦宗, 李卫平, 常鹏程, 史志龙. 先天性肾上腺皮质增生症合并肾上腺肿瘤手术治疗一例报告[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 288-290.
[14] 袁英淇, 闫润芝, 范益民. ATRX丢失与胶质瘤患者预后及IDH突变相关性的Meta分析[J]. 中华神经创伤外科电子杂志, 2022, 08(03): 161-167.
[15] 李清鲜, 杜荷香, 陈帆, 吴永利, 乔杰, 耿丹, 栗二娇, 柴乐. 一例性染色体复杂变异合并性反转的病例分析[J]. 中华临床实验室管理电子杂志, 2023, 11(03): 186-191.
阅读次数
全文


摘要