Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children
The aim of this study was to identify genetic markers in the Cluster; intergenic region; and , , , and genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hemato...
Gespeichert in:
| Veröffentlicht in: | Genes 2024-04, Vol.15 (4), p.469 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 4 |
| container_start_page | 469 |
| container_title | Genes |
| container_volume | 15 |
| creator | Ginete, Catarina Delgadinho, Mariana Santos, Brígida Miranda, Armandina Silva, Carina Guerreiro, Paulo Chimusa, Emile R Brito, Miguel |
| description | The aim of this study was to identify genetic markers in the
Cluster;
intergenic region; and
,
,
, and
genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients' severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the
gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach. |
| doi_str_mv | 10.3390/genes15040469 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_3047951752</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A793549312</galeid><sourcerecordid>A793549312</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-8d150d24d62bd6769030cc0cb62f7db76a1464a5f1e9fae6139855e2ea2b82133</originalsourceid><addsrcrecordid>eNqFkc1rFTEUxYMottQu3UrAjZup-c5k-RhsFSoq6nrIJDfvpc5Lnsm8Rf97M7R-VARvFvcSfvdwkoPQc0ouODfk9RYSVCqJIEKZR-iUEc07IZh8_Md8gs5rvSGtBGGEyKfohPdKC0H4Kfp01SSW6PD77GOIUCrOAX-O7tsMeIB5xpsE-2jxxx2kvNweAMeELR7yLpdlZTdpm2eb8LCLsy-QnqEnwc4Vzu_7Gfp6-ebL8La7_nD1bthcd04IuXS9b749E16xySutDOHEOeImxYL2k1aWCiWsDBRMsKAoN72UwMCyqWeU8zP06k73UPL3I9Rl3MfqmmObIB_ryKnkUhElxf9RIrSRVEvW0Jd_oTf5WFJ7yEqpXhtK1G9qa2cYYwp5KdatouNGGy6F4XTVuvgH1Y5vP-pyghDb_YOF7m7BlVxrgTAeStzbcjtSMq6Bjw8Cb_yLe7PHaQ_-F_0zXv4D-jih0Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3046879106</pqid></control><display><type>article</type><title>Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Ginete, Catarina ; Delgadinho, Mariana ; Santos, Brígida ; Miranda, Armandina ; Silva, Carina ; Guerreiro, Paulo ; Chimusa, Emile R ; Brito, Miguel</creator><creatorcontrib>Ginete, Catarina ; Delgadinho, Mariana ; Santos, Brígida ; Miranda, Armandina ; Silva, Carina ; Guerreiro, Paulo ; Chimusa, Emile R ; Brito, Miguel</creatorcontrib><description>The aim of this study was to identify genetic markers in the
Cluster;
intergenic region; and
,
,
, and
genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients' severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the
gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes15040469</identifier><identifier>PMID: 38674403</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adolescent ; Anemia ; Anemia, Sickle Cell - genetics ; Angola ; Child ; Child, Preschool ; Consortia ; Datasets ; Female ; Fetal Hemoglobin - genetics ; Fetuses ; Genes ; Genes, Modifier ; Genetic aspects ; Genetic diversity ; Genetic markers ; Genetic variability ; Genomes ; Genomics ; Genotype & phenotype ; GTP-Binding Proteins ; Hematology ; Hemoglobin ; Humans ; intergenic DNA ; introns ; Kruppel-Like Transcription Factors - genetics ; Male ; Medical prognosis ; Mutation ; Next-generation sequencing ; Ontology ; Phenotype ; Phenotypes ; phenotypic variation ; Phenotypic variations ; Polymorphism, Single Nucleotide ; Principal components analysis ; Quality control ; Repressor Proteins - genetics ; Sickle cell anemia ; Sickle cell disease ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Software</subject><ispartof>Genes, 2024-04, Vol.15 (4), p.469</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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c445t-8d150d24d62bd6769030cc0cb62f7db76a1464a5f1e9fae6139855e2ea2b82133</cites><orcidid>0000-0003-0586-9154 ; 0000-0001-6394-658X ; 0000-0003-1021-7935 ; 0000-0002-2334-782X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38674403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ginete, Catarina</creatorcontrib><creatorcontrib>Delgadinho, Mariana</creatorcontrib><creatorcontrib>Santos, Brígida</creatorcontrib><creatorcontrib>Miranda, Armandina</creatorcontrib><creatorcontrib>Silva, Carina</creatorcontrib><creatorcontrib>Guerreiro, Paulo</creatorcontrib><creatorcontrib>Chimusa, Emile R</creatorcontrib><creatorcontrib>Brito, Miguel</creatorcontrib><title>Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children</title><title>Genes</title><addtitle>Genes (Basel)</addtitle><description>The aim of this study was to identify genetic markers in the
Cluster;
intergenic region; and
,
,
, and
genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients' severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the
gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.</description><subject>Adolescent</subject><subject>Anemia</subject><subject>Anemia, Sickle Cell - genetics</subject><subject>Angola</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Consortia</subject><subject>Datasets</subject><subject>Female</subject><subject>Fetal Hemoglobin - genetics</subject><subject>Fetuses</subject><subject>Genes</subject><subject>Genes, Modifier</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic markers</subject><subject>Genetic variability</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>GTP-Binding Proteins</subject><subject>Hematology</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>intergenic DNA</subject><subject>introns</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Ontology</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>phenotypic variation</subject><subject>Phenotypic variations</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Principal components analysis</subject><subject>Quality control</subject><subject>Repressor Proteins - genetics</subject><subject>Sickle cell anemia</subject><subject>Sickle cell disease</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Software</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>BENPR</sourceid><recordid>eNqFkc1rFTEUxYMottQu3UrAjZup-c5k-RhsFSoq6nrIJDfvpc5Lnsm8Rf97M7R-VARvFvcSfvdwkoPQc0ouODfk9RYSVCqJIEKZR-iUEc07IZh8_Md8gs5rvSGtBGGEyKfohPdKC0H4Kfp01SSW6PD77GOIUCrOAX-O7tsMeIB5xpsE-2jxxx2kvNweAMeELR7yLpdlZTdpm2eb8LCLsy-QnqEnwc4Vzu_7Gfp6-ebL8La7_nD1bthcd04IuXS9b749E16xySutDOHEOeImxYL2k1aWCiWsDBRMsKAoN72UwMCyqWeU8zP06k73UPL3I9Rl3MfqmmObIB_ryKnkUhElxf9RIrSRVEvW0Jd_oTf5WFJ7yEqpXhtK1G9qa2cYYwp5KdatouNGGy6F4XTVuvgH1Y5vP-pyghDb_YOF7m7BlVxrgTAeStzbcjtSMq6Bjw8Cb_yLe7PHaQ_-F_0zXv4D-jih0Q</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Ginete, Catarina</creator><creator>Delgadinho, Mariana</creator><creator>Santos, Brígida</creator><creator>Miranda, Armandina</creator><creator>Silva, Carina</creator><creator>Guerreiro, Paulo</creator><creator>Chimusa, Emile R</creator><creator>Brito, Miguel</creator><general>MDPI AG</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>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-0586-9154</orcidid><orcidid>https://orcid.org/0000-0001-6394-658X</orcidid><orcidid>https://orcid.org/0000-0003-1021-7935</orcidid><orcidid>https://orcid.org/0000-0002-2334-782X</orcidid></search><sort><creationdate>20240401</creationdate><title>Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children</title><author>Ginete, Catarina ; Delgadinho, Mariana ; Santos, Brígida ; Miranda, Armandina ; Silva, Carina ; Guerreiro, Paulo ; Chimusa, Emile R ; Brito, Miguel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-8d150d24d62bd6769030cc0cb62f7db76a1464a5f1e9fae6139855e2ea2b82133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Anemia</topic><topic>Anemia, Sickle Cell - genetics</topic><topic>Angola</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Consortia</topic><topic>Datasets</topic><topic>Female</topic><topic>Fetal Hemoglobin - genetics</topic><topic>Fetuses</topic><topic>Genes</topic><topic>Genes, Modifier</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic markers</topic><topic>Genetic variability</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype & phenotype</topic><topic>GTP-Binding Proteins</topic><topic>Hematology</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>intergenic DNA</topic><topic>introns</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Mutation</topic><topic>Next-generation sequencing</topic><topic>Ontology</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>phenotypic variation</topic><topic>Phenotypic variations</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Principal components analysis</topic><topic>Quality control</topic><topic>Repressor Proteins - genetics</topic><topic>Sickle cell anemia</topic><topic>Sickle cell disease</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Software</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ginete, Catarina</creatorcontrib><creatorcontrib>Delgadinho, Mariana</creatorcontrib><creatorcontrib>Santos, Brígida</creatorcontrib><creatorcontrib>Miranda, Armandina</creatorcontrib><creatorcontrib>Silva, Carina</creatorcontrib><creatorcontrib>Guerreiro, Paulo</creatorcontrib><creatorcontrib>Chimusa, Emile R</creatorcontrib><creatorcontrib>Brito, Miguel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Genes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ginete, Catarina</au><au>Delgadinho, Mariana</au><au>Santos, Brígida</au><au>Miranda, Armandina</au><au>Silva, Carina</au><au>Guerreiro, Paulo</au><au>Chimusa, Emile R</au><au>Brito, Miguel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children</atitle><jtitle>Genes</jtitle><addtitle>Genes (Basel)</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>15</volume><issue>4</issue><spage>469</spage><pages>469-</pages><issn>2073-4425</issn><eissn>2073-4425</eissn><abstract>The aim of this study was to identify genetic markers in the
Cluster;
intergenic region; and
,
,
, and
genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients' severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the
gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38674403</pmid><doi>10.3390/genes15040469</doi><orcidid>https://orcid.org/0000-0003-0586-9154</orcidid><orcidid>https://orcid.org/0000-0001-6394-658X</orcidid><orcidid>https://orcid.org/0000-0003-1021-7935</orcidid><orcidid>https://orcid.org/0000-0002-2334-782X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2073-4425 |
| ispartof | Genes, 2024-04, Vol.15 (4), p.469 |
| issn | 2073-4425 2073-4425 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3047951752 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Adolescent Anemia Anemia, Sickle Cell - genetics Angola Child Child, Preschool Consortia Datasets Female Fetal Hemoglobin - genetics Fetuses Genes Genes, Modifier Genetic aspects Genetic diversity Genetic markers Genetic variability Genomes Genomics Genotype & phenotype GTP-Binding Proteins Hematology Hemoglobin Humans intergenic DNA introns Kruppel-Like Transcription Factors - genetics Male Medical prognosis Mutation Next-generation sequencing Ontology Phenotype Phenotypes phenotypic variation Phenotypic variations Polymorphism, Single Nucleotide Principal components analysis Quality control Repressor Proteins - genetics Sickle cell anemia Sickle cell disease Single nucleotide polymorphisms Single-nucleotide polymorphism Software |
| title | Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T16%3A44%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Modifiers%20of%20Sickle%20Cell%20Anemia%20Phenotype%20in%20a%20Cohort%20of%20Angolan%20Children&rft.jtitle=Genes&rft.au=Ginete,%20Catarina&rft.date=2024-04-01&rft.volume=15&rft.issue=4&rft.spage=469&rft.pages=469-&rft.issn=2073-4425&rft.eissn=2073-4425&rft_id=info:doi/10.3390/genes15040469&rft_dat=%3Cgale_proqu%3EA793549312%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3046879106&rft_id=info:pmid/38674403&rft_galeid=A793549312&rfr_iscdi=true |