A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies
Several types of haemoglobinopathies are caused by copy number variants (CNVs). While diagnosis is often based on haematological and biochemical parameters, a definitive diagnosis requires molecular DNA analysis. In some cases, the molecular characterisation of large deletions/duplications is challe...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15920 |
| _version_ | 1797406873113067520 |
|---|---|
| author | Anna Minaidou Stella Tamana Coralea Stephanou Maria Xenophontos Cornelis L. Harteveld Celeste Bento Marina Kleanthous Petros Kountouris |
| author_facet | Anna Minaidou Stella Tamana Coralea Stephanou Maria Xenophontos Cornelis L. Harteveld Celeste Bento Marina Kleanthous Petros Kountouris |
| author_sort | Anna Minaidou |
| collection | DOAJ |
| description | Several types of haemoglobinopathies are caused by copy number variants (CNVs). While diagnosis is often based on haematological and biochemical parameters, a definitive diagnosis requires molecular DNA analysis. In some cases, the molecular characterisation of large deletions/duplications is challenging and inconclusive and often requires the use of specific diagnostic procedures, such as multiplex ligation-dependent probe amplification (MLPA). Herein, we collected and comprehensively analysed all known CNVs associated with haemoglobinopathies. The dataset of 291 CNVs was retrieved from the IthaGenes database and was further manually annotated to specify genomic locations, breakpoints and MLPA probes relevant for each CNV. We developed IthaCNVs, a publicly available and easy-to-use online tool that can facilitate the diagnosis of rare and diagnostically challenging haemoglobinopathy cases attributed to CNVs. Importantly, it facilitates the filtering of available entries based on the type of breakpoint information, on specific chromosomal and locus positions, on MLPA probes, and on affected gene(s). IthaCNVs brings together manually curated information about CNV genomic locations, functional effects, and information that can facilitate CNV characterisation through MLPA. It can help laboratory staff and clinicians confirm suspected diagnosis of CNVs based on molecular DNA screening and analysis. |
| first_indexed | 2024-03-09T03:32:58Z |
| format | Article |
| id | doaj.art-e31a4fdfab6f497b84807391d51b8824 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:32:58Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e31a4fdfab6f497b84807391d51b88242023-12-03T14:53:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241592010.3390/ijms232415920A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with HaemoglobinopathiesAnna Minaidou0Stella Tamana1Coralea Stephanou2Maria Xenophontos3Cornelis L. Harteveld4Celeste Bento5Marina Kleanthous6Petros Kountouris7Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusMolecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusMolecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusMolecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusHuman and Clinical Genetics Department, Leiden University Medical Center, P.O. Box 9600, 2333 ZC Leiden, The NetherlandsDepartment of Haematology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, PortugalMolecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusMolecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, CyprusSeveral types of haemoglobinopathies are caused by copy number variants (CNVs). While diagnosis is often based on haematological and biochemical parameters, a definitive diagnosis requires molecular DNA analysis. In some cases, the molecular characterisation of large deletions/duplications is challenging and inconclusive and often requires the use of specific diagnostic procedures, such as multiplex ligation-dependent probe amplification (MLPA). Herein, we collected and comprehensively analysed all known CNVs associated with haemoglobinopathies. The dataset of 291 CNVs was retrieved from the IthaGenes database and was further manually annotated to specify genomic locations, breakpoints and MLPA probes relevant for each CNV. We developed IthaCNVs, a publicly available and easy-to-use online tool that can facilitate the diagnosis of rare and diagnostically challenging haemoglobinopathy cases attributed to CNVs. Importantly, it facilitates the filtering of available entries based on the type of breakpoint information, on specific chromosomal and locus positions, on MLPA probes, and on affected gene(s). IthaCNVs brings together manually curated information about CNV genomic locations, functional effects, and information that can facilitate CNV characterisation through MLPA. It can help laboratory staff and clinicians confirm suspected diagnosis of CNVs based on molecular DNA screening and analysis.https://www.mdpi.com/1422-0067/23/24/15920haemoglobinopathiescopy number variants (CNVs)MLPA |
| spellingShingle | Anna Minaidou Stella Tamana Coralea Stephanou Maria Xenophontos Cornelis L. Harteveld Celeste Bento Marina Kleanthous Petros Kountouris A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies International Journal of Molecular Sciences haemoglobinopathies copy number variants (CNVs) MLPA |
| title | A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies |
| title_full | A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies |
| title_fullStr | A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies |
| title_full_unstemmed | A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies |
| title_short | A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies |
| title_sort | novel tool for the analysis and detection of copy number variants associated with haemoglobinopathies |
| topic | haemoglobinopathies copy number variants (CNVs) MLPA |
| url | https://www.mdpi.com/1422-0067/23/24/15920 |
| work_keys_str_mv | AT annaminaidou anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT stellatamana anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT coraleastephanou anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT mariaxenophontos anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT cornelislharteveld anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT celestebento anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT marinakleanthous anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT petroskountouris anoveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT annaminaidou noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT stellatamana noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT coraleastephanou noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT mariaxenophontos noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT cornelislharteveld noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT celestebento noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT marinakleanthous noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies AT petroskountouris noveltoolfortheanalysisanddetectionofcopynumbervariantsassociatedwithhaemoglobinopathies |