Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method
Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potentia...
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| Veröffentlicht in: | Genes 2024-03, Vol.15 (3), p.342 |
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| creator | Barseghyan, Hayk Eisenreich, Doris Lindt, Evgenia Wendlandt, Martin Scharf, Florentine Benet-Pages, Anna Sendelbach, Kai Neuhann, Teresa Abicht, Angela Holinski-Feder, Elke Koehler, Udo |
| description | Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM's concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the
gene due to a balanced reciprocal translocation; (2) disruption of the
gene due to an inverted insertion; (3) disruption of the
gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions. |
| doi_str_mv | 10.3390/genes15030342 |
| format | Article |
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gene due to a balanced reciprocal translocation; (2) disruption of the
gene due to an inverted insertion; (3) disruption of the
gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes15030342</identifier><identifier>PMID: 38540401</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Breakpoints ; Carrier Proteins ; Centromere ; Chromosome Mapping ; Chromosomes ; Copy number ; Diagnostic equipment (Medical) ; DNA microarrays ; Gene deletion ; Gene mapping ; Genes ; Genetic disorders ; Genetic Markers ; Genomes ; Genomics ; Haplotypes ; Humans ; Labeling ; Methods ; Microarray Analysis ; Muscular dystrophy ; Nbea gene ; Nerve Tissue Proteins ; Patients ; Translocation, Genetic - genetics ; TSC2 gene</subject><ispartof>Genes, 2024-03, Vol.15 (3), p.342</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-f9f032d17deef7ac43f88f2ba3407547998356dae92a318c817490db0baf065a3</citedby><cites>FETCH-LOGICAL-c483t-f9f032d17deef7ac43f88f2ba3407547998356dae92a318c817490db0baf065a3</cites><orcidid>0000-0002-5172-2818</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10970541/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10970541/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38540401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barseghyan, Hayk</creatorcontrib><creatorcontrib>Eisenreich, Doris</creatorcontrib><creatorcontrib>Lindt, Evgenia</creatorcontrib><creatorcontrib>Wendlandt, Martin</creatorcontrib><creatorcontrib>Scharf, Florentine</creatorcontrib><creatorcontrib>Benet-Pages, Anna</creatorcontrib><creatorcontrib>Sendelbach, Kai</creatorcontrib><creatorcontrib>Neuhann, Teresa</creatorcontrib><creatorcontrib>Abicht, Angela</creatorcontrib><creatorcontrib>Holinski-Feder, Elke</creatorcontrib><creatorcontrib>Koehler, Udo</creatorcontrib><title>Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><description>Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM's concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the
gene due to a balanced reciprocal translocation; (2) disruption of the
gene due to an inverted insertion; (3) disruption of the
gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.</description><subject>Breakpoints</subject><subject>Carrier Proteins</subject><subject>Centromere</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Copy number</subject><subject>Diagnostic equipment (Medical)</subject><subject>DNA microarrays</subject><subject>Gene deletion</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic disorders</subject><subject>Genetic Markers</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Labeling</subject><subject>Methods</subject><subject>Microarray Analysis</subject><subject>Muscular dystrophy</subject><subject>Nbea gene</subject><subject>Nerve Tissue Proteins</subject><subject>Patients</subject><subject>Translocation, Genetic - genetics</subject><subject>TSC2 gene</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkU1v1DAQhiMEolXpkSuKxIVLythj184JVVtokVoVIThbXmecukrsECdI_HtcWlZdhH3wxzzz2jNvVb1mcILYwvueImUmAQEFf1YdclDYCMHl8yf7g-o45zsoQwAHkC-rA9RSlBM7rC5vpiU4O9QXFNNI9bWdphD72uba1l_SQnEJJfo1rUuIVG-GEP_g58H2MeWSW1_Tcpu6V9ULb4dMx4_rUfX908dvm8vm6ubi8-bsqnFC49L41gPyjqmOyCvrBHqtPd9aFKCkUG2rUZ52llpukWmnmRItdFvYWg-n0uJR9eFBd1q3I3WufHC2g5nmMNr5l0k2mP1IDLemTz8Ng1aBFKwovHtUmNOPlfJixpAdDYONlNZsEFhpDaJqC_r2H_QurXMs9RUKmOTIC7ijejuQCdGn8rC7FzVnSmsuVHGoUCf_ocrsaAwuRfKh3O8lNA8Jbk45z-R3RTIw9_abPfsL_-ZpZ3b0X7PxNyHoqO4</recordid><startdate>20240307</startdate><enddate>20240307</enddate><creator>Barseghyan, Hayk</creator><creator>Eisenreich, Doris</creator><creator>Lindt, Evgenia</creator><creator>Wendlandt, Martin</creator><creator>Scharf, Florentine</creator><creator>Benet-Pages, Anna</creator><creator>Sendelbach, Kai</creator><creator>Neuhann, Teresa</creator><creator>Abicht, Angela</creator><creator>Holinski-Feder, Elke</creator><creator>Koehler, Udo</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5172-2818</orcidid></search><sort><creationdate>20240307</creationdate><title>Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method</title><author>Barseghyan, Hayk ; 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However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM's concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the
gene due to a balanced reciprocal translocation; (2) disruption of the
gene due to an inverted insertion; (3) disruption of the
gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38540401</pmid><doi>10.3390/genes15030342</doi><orcidid>https://orcid.org/0000-0002-5172-2818</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Breakpoints Carrier Proteins Centromere Chromosome Mapping Chromosomes Copy number Diagnostic equipment (Medical) DNA microarrays Gene deletion Gene mapping Genes Genetic disorders Genetic Markers Genomes Genomics Haplotypes Humans Labeling Methods Microarray Analysis Muscular dystrophy Nbea gene Nerve Tissue Proteins Patients Translocation, Genetic - genetics TSC2 gene |
| title | Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method |
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