Evaluation of Optical Genome Mapping for Detecting Chromosomal Translocation in Clinical Cytogenetics

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2022 Apr 6

PMID 35384386

Authors

Peng Dai

Xiaofan Zhu

Yanzheng Pei

Peng Chen

Jingjing Li

Zhi Gao

Yu Liang

Xiangdong Kong

Affiliations

Soon will be listed here.

Abstract

Background: Balanced reciprocal translocation is one of the most common chromosomal abnormalities in humans that may lead to infertility, recurrent pregnancy loss, or having children with physical or mental abnormalities. Karyotyping and FISH are traditional detection approaches with a low resolution. Bionano optical genome mapping (OGM) developed in recent years can be used to analyze chromosomal abnormalities at a higher resolution, providing the possibility of more in-depth analyses of balanced chromosome translocations.

Methods: To evaluate the feasibility of OGM to detect chromosome balanced translocations, 10 genetic outpatients were collected and detected simultaneously by karyotype analysis, FISH, CNV-seq, and Bionano OGM in this study.

Results: The results showed that the karyotypes of the patients were detected by karyotype analysis, FISH, and Bionano OGM, but one patient with karyotype t(Y,19) was not correctly detected by OGM. There were not find any chromosome abnormality by CNV-seq. More importantly, OGM allowed the location of the mutation to the gene level, which is important for aiding diagnoses, compared to karyotype analysis, and FISH.

Conclusions: This study shows that OGM can be a high adjunctive diagnostic method for detecting balanced chromosome translocations, but the accuracy and precision of OGM detecting mutations need to be gradually improved in telomere and centromere regions.

Citing Articles

OMKar: optical map based automated karyotyping of genomes to identify constitutional abnormalities.

Dehkordi S, Jia Z, Estabrook J, Hauenstein J, Miller N, Guleray-Lafci N medRxiv. 2025; .

PMID: 39990584 PMC: 11844600. DOI: 10.1101/2025.02.13.25322211.

Optical Genome Mapping Reveals Disruption of the Gene in a Patient with Developmental Delay Carrying a De Novo Balanced Reciprocal Translocation.

Lederbogen R, Hoffjan S, Thiels C, Mau-Holzmann U, Singer S, Yusenko M Genes (Basel). 2024; 15(6).

PMID: 38927744 PMC: 11203114. DOI: 10.3390/genes15060809.

Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease.

Record C, Pipis M, Skorupinska M, Blake J, Poh R, Polke J Brain. 2024; 147(9):3144-3156.

PMID: 38481354 PMC: 11370804. DOI: 10.1093/brain/awae064.

Optical Genome Mapping for Chromosomal Aberrations Detection-False-Negative Results and Contributing Factors.

Xu Y, Zhang Q, Wang Y, Zhou R, Ji X, Meng L Diagnostics (Basel). 2024; 14(2).

PMID: 38248042 PMC: 10814618. DOI: 10.3390/diagnostics14020165.

Confusing finding of quantitative fluorescent polymerase chain reaction analysis in invasive prenatal genetic diagnosis: A case report.

Chen C, Tang T, Song Q, He Y, Cai Y World J Clin Cases. 2023; 11(28):6895-6901.

PMID: 37901017 PMC: 10600840. DOI: 10.12998/wjcc.v11.i28.6895.

References

Jeffet J, Margalit S, Michaeli Y, Ebenstein Y . Single-molecule optical genome mapping in nanochannels: multidisciplinarity at the nanoscale. Essays Biochem. 2021; 65(1):51-66. PMC: 8056043. DOI: 10.1042/EBC20200021. View

Chow J, Cheng H, Lau E, Yeung W, Ng E . Distinguishing between carrier and noncarrier embryos with the use of long-read sequencing in preimplantation genetic testing for reciprocal translocations. Genomics. 2019; 112(1):494-500. DOI: 10.1016/j.ygeno.2019.04.001. View

Wang H, Jia Z, Mao A, Xu B, Wang S, Wang L . Analysis of balanced reciprocal translocations in patients with subfertility using single-molecule optical mapping. J Assist Reprod Genet. 2020; 37(3):509-516. PMC: 7125258. DOI: 10.1007/s10815-020-01702-z. View

Chantot-Bastaraud S, Ravel C, Siffroi J . Underlying karyotype abnormalities in IVF/ICSI patients. Reprod Biomed Online. 2008; 16(4):514-22. DOI: 10.1016/s1472-6483(10)60458-0. View

Mostovoy Y, Levy-Sakin M, Lam J, Lam E, Hastie A, Marks P . A hybrid approach for de novo human genome sequence assembly and phasing. Nat Methods. 2016; 13(7):587-90. PMC: 4927370. DOI: 10.1038/nmeth.3865. View

Liang D, Peng Y, Lv W, Deng L, Zhang Y, Li H . Copy number variation sequencing for comprehensive diagnosis of chromosome disease syndromes. J Mol Diagn. 2014; 16(5):519-526. DOI: 10.1016/j.jmoldx.2014.05.002. View

Miga K, Koren S, Rhie A, Vollger M, Gershman A, Bzikadze A . Telomere-to-telomere assembly of a complete human X chromosome. Nature. 2020; 585(7823):79-84. PMC: 7484160. DOI: 10.1038/s41586-020-2547-7. View

Dai P, Zhu X, Pei Y, Chen P, Li J, Gao Z . Evaluation of optical genome mapping for detecting chromosomal translocation in clinical cytogenetics. Mol Genet Genomic Med. 2022; 10(6):e1936. PMC: 9184658. DOI: 10.1002/mgg3.1936. View

Gilboa T, Garden P, Cohen L . Single-molecule analysis of nucleic acid biomarkers - A review. Anal Chim Acta. 2020; 1115:61-85. DOI: 10.1016/j.aca.2020.03.001. View

10.

Hofherr S, Wiktor A, Kipp B, Dawson D, Van Dyke D . Clinical diagnostic testing for the cytogenetic and molecular causes of male infertility: the Mayo Clinic experience. J Assist Reprod Genet. 2011; 28(11):1091-8. PMC: 3224174. DOI: 10.1007/s10815-011-9633-6. View

11.

Bates S . Classical cytogenetics: karyotyping techniques. Methods Mol Biol. 2011; 767:177-90. DOI: 10.1007/978-1-61779-201-4_13. View

12.

Chan S, Lam E, Saghbini M, Bocklandt S, Hastie A, Cao H . Structural Variation Detection and Analysis Using Bionano Optical Mapping. Methods Mol Biol. 2018; 1833:193-203. DOI: 10.1007/978-1-4939-8666-8_16. View

13.

Speicher M, Carter N . The new cytogenetics: blurring the boundaries with molecular biology. Nat Rev Genet. 2005; 6(10):782-92. DOI: 10.1038/nrg1692. View

14.

Ito S, Sakai A, Nomura T, Miki Y, Ouchida M, Sasaki J . A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner. Biochem Biophys Res Commun. 2001; 280(3):656-63. DOI: 10.1006/bbrc.2000.4163. View

15.

Schwartz D, Li X, Hernandez L, Ramnarain S, Huff E, Wang Y . Ordered restriction maps of Saccharomyces cerevisiae chromosomes constructed by optical mapping. Science. 1993; 262(5130):110-4. DOI: 10.1126/science.8211116. View

16.

Mantere T, Neveling K, Pebrel-Richard C, Benoist M, van der Zande G, Kater-Baats E . Optical genome mapping enables constitutional chromosomal aberration detection. Am J Hum Genet. 2021; 108(8):1409-1422. PMC: 8387289. DOI: 10.1016/j.ajhg.2021.05.012. View

17.

MacLeod R, Drexler H . Classical and molecular cytogenetic analysis. Methods Mol Biol. 2012; 946:39-60. DOI: 10.1007/978-1-62703-128-8_4. View

18.

Dremsek P, Schwarz T, Weil B, Malashka A, Laccone F, Neesen J . Optical Genome Mapping in Routine Human Genetic Diagnostics-Its Advantages and Limitations. Genes (Basel). 2021; 12(12). PMC: 8701374. DOI: 10.3390/genes12121958. View

19.

Jacobs P, Browne C, Gregson N, Joyce C, White H . Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet. 1992; 29(2):103-8. PMC: 1015848. DOI: 10.1136/jmg.29.2.103. View

20.

Swansbury J . Introduction to the analysis of the human G-banded karyotype. Methods Mol Biol. 2003; 220:259-69. DOI: 10.1385/1-59259-363-1:259. View