Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies
Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the co...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00847/full |
| _version_ | 1818560343689920512 |
|---|---|
| author | Michael Seleman Rodrigo Hoyos-Bachiloglu Raif S. Geha Janet Chou |
| author_facet | Michael Seleman Rodrigo Hoyos-Bachiloglu Raif S. Geha Janet Chou |
| author_sort | Michael Seleman |
| collection | DOAJ |
| description | Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission, and with variable penetrance. This review examines the uses of next-generation DNA sequencing (NGS) in the diagnosis of PIDs. While whole genome sequencing identifies variants throughout the genome, whole exome sequencing sequences only the protein-coding regions within a genome, and targeted gene panels sequence only a specific cohort of genes. The advantages and limitations of each sequencing approach are compared. The complexities of variant interpretation and variant validation remain the major challenge in wide-spread implementation of these technologies. Lastly, the roles of NGS in newborn screening and precision therapeutics for individuals with PID are also addressed. |
| first_indexed | 2024-12-14T00:37:17Z |
| format | Article |
| id | doaj.art-054dfc6198a04fcdae7a26ad3eef4008 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:37:17Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-054dfc6198a04fcdae7a26ad3eef40082022-12-21T23:24:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-07-01810.3389/fimmu.2017.00847264192Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary ImmunodeficienciesMichael Seleman0Rodrigo Hoyos-Bachiloglu1Raif S. Geha2Janet Chou3Division of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesPrimary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission, and with variable penetrance. This review examines the uses of next-generation DNA sequencing (NGS) in the diagnosis of PIDs. While whole genome sequencing identifies variants throughout the genome, whole exome sequencing sequences only the protein-coding regions within a genome, and targeted gene panels sequence only a specific cohort of genes. The advantages and limitations of each sequencing approach are compared. The complexities of variant interpretation and variant validation remain the major challenge in wide-spread implementation of these technologies. Lastly, the roles of NGS in newborn screening and precision therapeutics for individuals with PID are also addressed.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00847/fullprimary immunodeficiencynext-generation sequencingwhole exome sequencinggene panelsgenomics |
| spellingShingle | Michael Seleman Rodrigo Hoyos-Bachiloglu Raif S. Geha Janet Chou Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies Frontiers in Immunology primary immunodeficiency next-generation sequencing whole exome sequencing gene panels genomics |
| title | Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies |
| title_full | Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies |
| title_fullStr | Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies |
| title_full_unstemmed | Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies |
| title_short | Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies |
| title_sort | uses of next generation sequencing technologies for the diagnosis of primary immunodeficiencies |
| topic | primary immunodeficiency next-generation sequencing whole exome sequencing gene panels genomics |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00847/full |
| work_keys_str_mv | AT michaelseleman usesofnextgenerationsequencingtechnologiesforthediagnosisofprimaryimmunodeficiencies AT rodrigohoyosbachiloglu usesofnextgenerationsequencingtechnologiesforthediagnosisofprimaryimmunodeficiencies AT raifsgeha usesofnextgenerationsequencingtechnologiesforthediagnosisofprimaryimmunodeficiencies AT janetchou usesofnextgenerationsequencingtechnologiesforthediagnosisofprimaryimmunodeficiencies |