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
{"title":"RCCX 基因座的基因组复杂性和临床意义。","authors":"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","doi":"10.7717/peerj.18243","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>CYP21A2</i> deficiency.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"12 ","pages":"e18243"},"PeriodicalIF":2.3000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542561/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genomic complexity and clinical significance of the RCCX locus.\",\"authors\":\"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\",\"doi\":\"10.7717/peerj.18243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>CYP21A2</i> deficiency.</p>\",\"PeriodicalId\":19799,\"journal\":{\"name\":\"PeerJ\",\"volume\":\"12 \",\"pages\":\"e18243\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542561/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PeerJ\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.7717/peerj.18243\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PeerJ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7717/peerj.18243","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
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 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.
期刊介绍:
PeerJ is an open access peer-reviewed scientific journal covering research in the biological and medical sciences. At PeerJ, authors take out a lifetime publication plan (for as little as $99) which allows them to publish articles in the journal for free, forever. PeerJ has 5 Nobel Prize Winners on the Board; they have won several industry and media awards; and they are widely recognized as being one of the most interesting recent developments in academic publishing.