Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene
•There are carriers of complex α-globin gene cluster variants.•Conventional technology cannot identify complex genetic structures.•TGS can identify complex α-thalassemia gene variants.•TGS is effective for thalassemia genotyping. Thalassemia is a monogenic disorder with a high carrier rate in the so...
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| Veröffentlicht in: | Gene 2022-05, Vol.822, p.146332-146332, Article 146332 |
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| creator | Long, Ju Sun, Lei Gong, Feifei Zhang, Chenghong Mao, Aiping Lu, Yulin Li, Jiaqi Liu, Enqi |
| description | •There are carriers of complex α-globin gene cluster variants.•Conventional technology cannot identify complex genetic structures.•TGS can identify complex α-thalassemia gene variants.•TGS is effective for thalassemia genotyping.
Thalassemia is a monogenic disorder with a high carrier rate in the southern region of China. Most laboratories currently follow the protocol of testing hematologic indicators in individuals with positive hematologic indicators and then using the hot-spot mutation test kit. A novel thalassemia gene test is performed if there is a mismatch between the hematology and hot-spot mutation test results. However, due to the large population in southern China, some individuals carry complex α-globin gene cluster (CAGC) variants in NG_000006.1, which are difficult to detect using conventional thalassemia genetic analysis protocols, leading to missed or false genetic test results for individuals carrying these complex α-globin gene cluster variants. When an individual carries a complex α-thalassemia gene variant, and an individual carries a β- thalassemia gene variant, there may be clinical symptoms that might complicate clinical consultation and prenatal diagnosis if not accurately detected. Third-generation sequencing (TGS) enables long-read single-molecule sequencing with high detection accuracy, and long-length DNA chain reads in high-fidelity reads mode. TGS can be used to analyze high homology and rich GC DNA sequences.
Four samples that showed abnormalities in the thalassemia genetic test were studied using TGS, revealing that they carried genotypes with complex α-globin gene cluster variants, one of which was a complex variant αα anti3.7 α anti3.7 α 17.2.
TGS detects complex α-globin gene cluster variants. This study may provide a reference protocol for the use of TGS for the detection of complex α-globin gene cluster variants. TGS can reveal individuals with complex α-thalassemia genotypes in the population and improve the accuracy of genetic counseling and prenatal diagnosis. |
| doi_str_mv | 10.1016/j.gene.2022.146332 |
| format | Article |
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Thalassemia is a monogenic disorder with a high carrier rate in the southern region of China. Most laboratories currently follow the protocol of testing hematologic indicators in individuals with positive hematologic indicators and then using the hot-spot mutation test kit. A novel thalassemia gene test is performed if there is a mismatch between the hematology and hot-spot mutation test results. However, due to the large population in southern China, some individuals carry complex α-globin gene cluster (CAGC) variants in NG_000006.1, which are difficult to detect using conventional thalassemia genetic analysis protocols, leading to missed or false genetic test results for individuals carrying these complex α-globin gene cluster variants. When an individual carries a complex α-thalassemia gene variant, and an individual carries a β- thalassemia gene variant, there may be clinical symptoms that might complicate clinical consultation and prenatal diagnosis if not accurately detected. Third-generation sequencing (TGS) enables long-read single-molecule sequencing with high detection accuracy, and long-length DNA chain reads in high-fidelity reads mode. TGS can be used to analyze high homology and rich GC DNA sequences.
Four samples that showed abnormalities in the thalassemia genetic test were studied using TGS, revealing that they carried genotypes with complex α-globin gene cluster variants, one of which was a complex variant αα anti3.7 α anti3.7 α 17.2.
TGS detects complex α-globin gene cluster variants. This study may provide a reference protocol for the use of TGS for the detection of complex α-globin gene cluster variants. TGS can reveal individuals with complex α-thalassemia genotypes in the population and improve the accuracy of genetic counseling and prenatal diagnosis.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2022.146332</identifier><identifier>PMID: 35181504</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Alpha-globin gene cluster ; alpha-Globins - genetics ; alpha-Thalassemia - diagnosis ; alpha-Thalassemia - genetics ; China ; Complex variants ; Early Diagnosis ; Female ; Genetic Variation ; Genotyping ; High-Throughput Nucleotide Sequencing ; Humans ; Long-read single-molecule sequencing ; Male ; Multigene Family ; Pregnancy ; Prenatal Diagnosis ; Sensitivity and Specificity ; Sequence Analysis, DNA - methods ; Single Molecule Imaging - methods ; Thalassemia ; Third-generation sequencing</subject><ispartof>Gene, 2022-05, Vol.822, p.146332-146332, Article 146332</ispartof><rights>2022 Elsevier B.V.</rights><rights>Copyright © 2022 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-c9058b0694bb11b4cbb73c7989eab3c4e5a00ece59aa15525580d85091d50af23</citedby><cites>FETCH-LOGICAL-c356t-c9058b0694bb11b4cbb73c7989eab3c4e5a00ece59aa15525580d85091d50af23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.gene.2022.146332$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35181504$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Long, Ju</creatorcontrib><creatorcontrib>Sun, Lei</creatorcontrib><creatorcontrib>Gong, Feifei</creatorcontrib><creatorcontrib>Zhang, Chenghong</creatorcontrib><creatorcontrib>Mao, Aiping</creatorcontrib><creatorcontrib>Lu, Yulin</creatorcontrib><creatorcontrib>Li, Jiaqi</creatorcontrib><creatorcontrib>Liu, Enqi</creatorcontrib><title>Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene</title><title>Gene</title><addtitle>Gene</addtitle><description>•There are carriers of complex α-globin gene cluster variants.•Conventional technology cannot identify complex genetic structures.•TGS can identify complex α-thalassemia gene variants.•TGS is effective for thalassemia genotyping.
Thalassemia is a monogenic disorder with a high carrier rate in the southern region of China. Most laboratories currently follow the protocol of testing hematologic indicators in individuals with positive hematologic indicators and then using the hot-spot mutation test kit. A novel thalassemia gene test is performed if there is a mismatch between the hematology and hot-spot mutation test results. However, due to the large population in southern China, some individuals carry complex α-globin gene cluster (CAGC) variants in NG_000006.1, which are difficult to detect using conventional thalassemia genetic analysis protocols, leading to missed or false genetic test results for individuals carrying these complex α-globin gene cluster variants. When an individual carries a complex α-thalassemia gene variant, and an individual carries a β- thalassemia gene variant, there may be clinical symptoms that might complicate clinical consultation and prenatal diagnosis if not accurately detected. Third-generation sequencing (TGS) enables long-read single-molecule sequencing with high detection accuracy, and long-length DNA chain reads in high-fidelity reads mode. TGS can be used to analyze high homology and rich GC DNA sequences.
Four samples that showed abnormalities in the thalassemia genetic test were studied using TGS, revealing that they carried genotypes with complex α-globin gene cluster variants, one of which was a complex variant αα anti3.7 α anti3.7 α 17.2.
TGS detects complex α-globin gene cluster variants. This study may provide a reference protocol for the use of TGS for the detection of complex α-globin gene cluster variants. TGS can reveal individuals with complex α-thalassemia genotypes in the population and improve the accuracy of genetic counseling and prenatal diagnosis.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alpha-globin gene cluster</subject><subject>alpha-Globins - genetics</subject><subject>alpha-Thalassemia - diagnosis</subject><subject>alpha-Thalassemia - genetics</subject><subject>China</subject><subject>Complex variants</subject><subject>Early Diagnosis</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Genotyping</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Long-read single-molecule sequencing</subject><subject>Male</subject><subject>Multigene Family</subject><subject>Pregnancy</subject><subject>Prenatal Diagnosis</subject><subject>Sensitivity and Specificity</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Single Molecule Imaging - methods</subject><subject>Thalassemia</subject><subject>Third-generation sequencing</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1KxDAQx4Moun68gAfJ0UvXSdK0jXgR8QsEL3qUkKazbpa2WZPuoo_li_hMpqx6dC4Dw39-zPwIOWYwZcCKs8X0FXuccuB8yvJCCL5FJqwqVQYgqm0yAVFWGWNM7ZH9GBeQSkq-S_aEZBWTkE_Iy9PchSYbQcEMzvc04tsKe-v613N6SXu_xpYO3re0wQHtEKn13bLFd7o2wZk-DVxPhznSr89smJvWxIidM3REHpKdmWkjHv30A_J8c_10dZc9PN7eX10-ZFbIYsisAlnVUKi8rhmrc1vXpbClqhSaWtgcpQFAi1IZw9IHUlbQVBIUaySYGRcH5HTDXQafro-D7ly02LamR7-KmhcCFC9FyVKUb6I2-BgDzvQyuM6ED81Aj1r1Qo-n61Gr3mhNSyc__FXdYfO38usxBS42AUxfrh0GHa1LFrFxIUnTjXf_8b8BPUOJsA</recordid><startdate>20220515</startdate><enddate>20220515</enddate><creator>Long, Ju</creator><creator>Sun, Lei</creator><creator>Gong, Feifei</creator><creator>Zhang, Chenghong</creator><creator>Mao, Aiping</creator><creator>Lu, Yulin</creator><creator>Li, Jiaqi</creator><creator>Liu, Enqi</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20220515</creationdate><title>Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene</title><author>Long, Ju ; Sun, Lei ; Gong, Feifei ; Zhang, Chenghong ; Mao, Aiping ; Lu, Yulin ; Li, Jiaqi ; Liu, Enqi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-c9058b0694bb11b4cbb73c7989eab3c4e5a00ece59aa15525580d85091d50af23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alpha-globin gene cluster</topic><topic>alpha-Globins - genetics</topic><topic>alpha-Thalassemia - diagnosis</topic><topic>alpha-Thalassemia - genetics</topic><topic>China</topic><topic>Complex variants</topic><topic>Early Diagnosis</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Genotyping</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Long-read single-molecule sequencing</topic><topic>Male</topic><topic>Multigene Family</topic><topic>Pregnancy</topic><topic>Prenatal Diagnosis</topic><topic>Sensitivity and Specificity</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Single Molecule Imaging - methods</topic><topic>Thalassemia</topic><topic>Third-generation sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Long, Ju</creatorcontrib><creatorcontrib>Sun, Lei</creatorcontrib><creatorcontrib>Gong, Feifei</creatorcontrib><creatorcontrib>Zhang, Chenghong</creatorcontrib><creatorcontrib>Mao, Aiping</creatorcontrib><creatorcontrib>Lu, Yulin</creatorcontrib><creatorcontrib>Li, Jiaqi</creatorcontrib><creatorcontrib>Liu, Enqi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Long, Ju</au><au>Sun, Lei</au><au>Gong, Feifei</au><au>Zhang, Chenghong</au><au>Mao, Aiping</au><au>Lu, Yulin</au><au>Li, Jiaqi</au><au>Liu, Enqi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2022-05-15</date><risdate>2022</risdate><volume>822</volume><spage>146332</spage><epage>146332</epage><pages>146332-146332</pages><artnum>146332</artnum><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>•There are carriers of complex α-globin gene cluster variants.•Conventional technology cannot identify complex genetic structures.•TGS can identify complex α-thalassemia gene variants.•TGS is effective for thalassemia genotyping.
Thalassemia is a monogenic disorder with a high carrier rate in the southern region of China. Most laboratories currently follow the protocol of testing hematologic indicators in individuals with positive hematologic indicators and then using the hot-spot mutation test kit. A novel thalassemia gene test is performed if there is a mismatch between the hematology and hot-spot mutation test results. However, due to the large population in southern China, some individuals carry complex α-globin gene cluster (CAGC) variants in NG_000006.1, which are difficult to detect using conventional thalassemia genetic analysis protocols, leading to missed or false genetic test results for individuals carrying these complex α-globin gene cluster variants. When an individual carries a complex α-thalassemia gene variant, and an individual carries a β- thalassemia gene variant, there may be clinical symptoms that might complicate clinical consultation and prenatal diagnosis if not accurately detected. Third-generation sequencing (TGS) enables long-read single-molecule sequencing with high detection accuracy, and long-length DNA chain reads in high-fidelity reads mode. TGS can be used to analyze high homology and rich GC DNA sequences.
Four samples that showed abnormalities in the thalassemia genetic test were studied using TGS, revealing that they carried genotypes with complex α-globin gene cluster variants, one of which was a complex variant αα anti3.7 α anti3.7 α 17.2.
TGS detects complex α-globin gene cluster variants. This study may provide a reference protocol for the use of TGS for the detection of complex α-globin gene cluster variants. TGS can reveal individuals with complex α-thalassemia genotypes in the population and improve the accuracy of genetic counseling and prenatal diagnosis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>35181504</pmid><doi>10.1016/j.gene.2022.146332</doi><tpages>1</tpages></addata></record> |
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| subjects | Adolescent Adult Alpha-globin gene cluster alpha-Globins - genetics alpha-Thalassemia - diagnosis alpha-Thalassemia - genetics China Complex variants Early Diagnosis Female Genetic Variation Genotyping High-Throughput Nucleotide Sequencing Humans Long-read single-molecule sequencing Male Multigene Family Pregnancy Prenatal Diagnosis Sensitivity and Specificity Sequence Analysis, DNA - methods Single Molecule Imaging - methods Thalassemia Third-generation sequencing |
| title | Third-generation sequencing: A novel tool detects complex variants in the α-thalassemia gene |
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