The Need for a Concert of Cytogenomic Methods in Chromosomic Research and Diagnostics
Abstract
:1. Introduction
2. The Concept of Chromosomics
3. The Core Technologies of Cytogenomics
4. Advantages and Restrictions of Available Cytogenomic Approaches
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- NGP can be useful in the diagnosis of congenital diseases by narrowing the number of preliminary diagnoses; accordingly, NGP can be extremely helpful in selecting the most appropriate confirmatory cytogenomic test(s) [27].
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- CAs (banding cytogenetics or FISH) are best for determining modal chromosome numbers and numerical or structural aberrations, or even polyploidy. Neither the structure of a balanced or unbalanced rearrangement nor the ploidy of a cell can be comprehensively assessed by cMAs or mMAs [2].
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- cMAs such as microsatellite analysis are still superior for detecting uniparental disomy (UPD). mMCs such as those based on single nucleotide polymorphisms (SNPs) miss at least 1/3 of cases with heterodisomy [34].
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- Optical mapping is blind to the heterochromatic regions of the genome (own unpublished observations), as are standard next-generation sequencing approaches [35]. These regions can still only be examined with CAs such as FISH. As recently shown, satellite DNA appears to play a role in advanced solid cancers [36].
5. Suggestions for the Sequence Cytogenomic Approaches Can Be Applied Most Efficiently in Diagnostics
- Infertile patients undergoing genetic diagnosis should be studied by cMAs or mMAs to exclude disease-causing mutations, e.g., in genes such as CFTR, AZF or FMR1 premutations [40]. In addition, CAs such as banding cytogenetics are indicated to exclude sex chromosome aneuploidies (even in small mosaics) or balanced translocations [40].
- Prenatal genetic diagnosis may include mMAs such as noninvasive prenatal testing (NIPT); however, the limitations of such methods must be considered. NIPT is a screening test that examines the placenta rather than the fetus and has a high rate of false positives [41]. Other screening tests, such as first trimester screening (including ultrasonography), may be easier. For invasive prenatal testing, CAs, cMAs, and mMAs may be indicated. For CMA as a first-line test, cytogenetics or FISH must be included in the testing scheme to understand the nature of the underlying unbalanced chromosomal rearrangement [42].
- Postnatal genetics is indicated if signs such as developmental delay, dysmorphisms, and/or delayed puberty are observed. Cytogenetics can be used first to find any gross genetic changes that may be causative. Subsequently, CMA should be performed. If no aberration is found, NGS approaches can be considered [28]. The use of AI-based tools such as NGP can also help to avoid costly whole genome analyses if a comparison of a patient’s facial phenotype with corresponding databases clearly indicates a chromosomal disorder, for example [27].
- In leukemia diagnostics, chromosome analysis should be the first test to be performed. FISH can complement these studies [43]. Large leukemia laboratories perform these tests together with panel diagnostics—knowledge of the chromosome constitution is still an important part of the WHO guidelines for leukemia classification [44].
6. Suggestions for the Sequence Cytogenomic Approaches Can Be Applied Most Efficiently in Research
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Wang, Y.; Liehr, T. The Need for a Concert of Cytogenomic Methods in Chromosomic Research and Diagnostics. Genes 2025, 16, 533. https://doi.org/10.3390/genes16050533
Wang Y, Liehr T. The Need for a Concert of Cytogenomic Methods in Chromosomic Research and Diagnostics. Genes. 2025; 16(5):533. https://doi.org/10.3390/genes16050533
Chicago/Turabian StyleWang, Yiping, and Thomas Liehr. 2025. "The Need for a Concert of Cytogenomic Methods in Chromosomic Research and Diagnostics" Genes 16, no. 5: 533. https://doi.org/10.3390/genes16050533
APA StyleWang, Y., & Liehr, T. (2025). The Need for a Concert of Cytogenomic Methods in Chromosomic Research and Diagnostics. Genes, 16(5), 533. https://doi.org/10.3390/genes16050533