Genomic complexity and clinical significance of the RCCX locus
Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2024-11-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/18243.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850199601827545088 |
|---|---|
| author | Vladimir V. Shiryagin Andrey A. Devyatkin Oleg D. Fateev Ekaterina S. Petriaikina Viktor P. Bogdanov Zoia G. Antysheva Pavel Yu Volchkov Sergey M. Yudin Mary Woroncow Veronika I. Skvortsova |
| author_facet | Vladimir V. Shiryagin Andrey A. Devyatkin Oleg D. Fateev Ekaterina S. Petriaikina Viktor P. Bogdanov Zoia G. Antysheva Pavel Yu Volchkov Sergey M. Yudin Mary Woroncow Veronika I. Skvortsova |
| author_sort | Vladimir V. Shiryagin |
| collection | DOAJ |
| description | Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX–CAH due to CYP21A2 deficiency. |
| format | Article |
| id | doaj-art-def71c42885148e0bddfa3b335ec718d |
| institution | OA Journals |
| issn | 2167-8359 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj-art-def71c42885148e0bddfa3b335ec718d2025-08-20T02:12:34ZengPeerJ Inc.PeerJ2167-83592024-11-0112e1824310.7717/peerj.18243Genomic complexity and clinical significance of the RCCX locusVladimir V. Shiryagin0Andrey A. Devyatkin1Oleg D. Fateev2Ekaterina S. Petriaikina3Viktor P. Bogdanov4Zoia G. Antysheva5Pavel Yu Volchkov6Sergey M. Yudin7Mary Woroncow8Veronika I. Skvortsova9Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency (Centre for Strategic Planning of FMBA of Russia), Moscow, RussiaFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency (Centre for Strategic Planning of FMBA of Russia), Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency (Centre for Strategic Planning of FMBA of Russia), Moscow, RussiaFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, RussiaFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, RussiaFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency (Centre for Strategic Planning of FMBA of Russia), Moscow, RussiaDepartment of Fundamental Medicine, Lomonosov Moscow State University, Moscow, RussiaThe Federal Medical Biological Agency (FMBA of Russia), Moscow, RussiaNearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX–CAH due to CYP21A2 deficiency.https://peerj.com/articles/18243.pdfWhole genome sequencingHydroxylase-21CYP21A1PCYP21A2CAHRCCX |
| spellingShingle | Vladimir V. Shiryagin Andrey A. Devyatkin Oleg D. Fateev Ekaterina S. Petriaikina Viktor P. Bogdanov Zoia G. Antysheva Pavel Yu Volchkov Sergey M. Yudin Mary Woroncow Veronika I. Skvortsova Genomic complexity and clinical significance of the RCCX locus PeerJ Whole genome sequencing Hydroxylase-21 CYP21A1P CYP21A2 CAH RCCX |
| title | Genomic complexity and clinical significance of the RCCX locus |
| title_full | Genomic complexity and clinical significance of the RCCX locus |
| title_fullStr | Genomic complexity and clinical significance of the RCCX locus |
| title_full_unstemmed | Genomic complexity and clinical significance of the RCCX locus |
| title_short | Genomic complexity and clinical significance of the RCCX locus |
| title_sort | genomic complexity and clinical significance of the rccx locus |
| topic | Whole genome sequencing Hydroxylase-21 CYP21A1P CYP21A2 CAH RCCX |
| url | https://peerj.com/articles/18243.pdf |
| work_keys_str_mv | AT vladimirvshiryagin genomiccomplexityandclinicalsignificanceoftherccxlocus AT andreyadevyatkin genomiccomplexityandclinicalsignificanceoftherccxlocus AT olegdfateev genomiccomplexityandclinicalsignificanceoftherccxlocus AT ekaterinaspetriaikina genomiccomplexityandclinicalsignificanceoftherccxlocus AT viktorpbogdanov genomiccomplexityandclinicalsignificanceoftherccxlocus AT zoiagantysheva genomiccomplexityandclinicalsignificanceoftherccxlocus AT pavelyuvolchkov genomiccomplexityandclinicalsignificanceoftherccxlocus AT sergeymyudin genomiccomplexityandclinicalsignificanceoftherccxlocus AT maryworoncow genomiccomplexityandclinicalsignificanceoftherccxlocus AT veronikaiskvortsova genomiccomplexityandclinicalsignificanceoftherccxlocus |