medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.06.5-15medgen-3010Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕORIGINAL ARTICLEАнализ числа копий гена STRC и псевдогена STRCP1 в выборке якутов с нормальным слухомSTRC gene and STRCP1 pseudogene copy number variant analysis in a sample of Yakuts with normal hearingПшенниковаВ. Г.PshennikovaV. G.

Пшенникова Вера Геннадиевна.

677018, Якутск, Россия, ул. Ярославского, д. 6/3

Vera G. Pshennikova.

6/3, Yaroslavsky st., Yakutsk, 677010

psennikovavera@mail.ruЧердоноваА. М.CherdonovaA. M.

677000, Якутск, Россия, ул. Белинского, д. 58

58, Belinsky st., Yakutsk, 677000

БорисоваТ. В.BorisovaT. V.

677000, Якутск, Россия, ул. Белинского, д. 58

58, Belinsky st., Yakutsk, 677000

ТерютинФ. М.TeryutinF. M.

677018, Якутск, Россия, ул. Ярославского, д. 6/3

6/3, Yaroslavsky st., Yakutsk, 677010

БарашковН. А.BarashkovN. A.

677018, Якутск, Россия, ул. Ярославского, д. 6/3

6/3, Yaroslavsky st., Yakutsk, 677010

ФедороваС. А.FedorovaS. A.

677000, Якутск, Россия, ул. Белинского, д. 58

58, Belinsky st., Yakutsk, 677000

ФГБНУ Якутский научный центр комплексных медицинских проблемРоссияYakut Scientific Center for Complex Medical ProblemsRussian FederationФГАОУ ВО Северо-Восточный федеральный университет им. М.К. АммосоваРоссияM.K. Ammosov North-Eastern Federal UniversityRussian Federation202521082025246515Copyright © Пшенникова В.Г., Чердонова А.М., Борисова Т.В., Терютин Ф.М., Барашков Н.А., Федорова С.А., 20252025Пшенникова В.Г., Чердонова А.М., Борисова Т.В., Терютин Ф.М., Барашков Н.А., Федорова С.А.Pshennikova V.G., Cherdonova A.M., Borisova T.V., Teryutin F.M., Barashkov N.A., Fedorova S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3010

Вариации числа копий (CNV) гена STRC являются основной причиной аутосомно-рецессивной формы глухоты 16 типа (DFNB16, ОMIM #603720). Диагностическое тестирование DFNB16 затруднено сложностью организации хромосомного региона 15q15.3, содержащего сегментную дупликацию пяти генов, в том числе гена STRC и его высокогомологичного псевдогена STRCP1. Клинически DFNB16 ассоциирована с легкой и умеренной формой потери слуха, что, по нашему мнению, связано с компенсаторным эффектом псевдогена, как это было показано при спинальной мышечной атрофии. В связи с этим для понимания молекулярных механизмов возникновения и клинических особенностей DFNB16 актуальным является изучение числа копий не только гена STRC, но и его псевдогена STRCP1. В настоящем исследовании методом ПЦР в реальном времени (ПЦР-РВ) был проведен анализ числа копий гена STRC и псевдогена STRCP1 в выборке якутов с нормальным слухом (n=113). Всего изменения числа копий в гене STRC были обнаружены у 7 (6,2%) человек, в псевдогене STRCP1 у 16 (14,1%) человек. Выявлено, что данные изменения числа копий, вероятнее всего, произошли в результате неравного кроссинговера (STRC/STRCP1 – делеция/делеция или норма), случаев, связанных с генной конверсией (STRC/STRCP1 – делеция/дупликация или дупликация/делеция), обнаружено не было. Сравнительный анализ частот измененных копий гена STRC и псевдогена STRCP1 выявил достоверные различия между делециями (1,8%) и дупликациями (11,5%) в области псевдогена STRCP1 (χ2=8,64, р<0,01), в то время как в области гена STRC таких различий не наблюдалось (делеции – 2,6%, дупликации – 3,5%, χ2=0,15, р>0,05). Снижение частоты протяженных делеций в области псевдогена STRCP1 в популяции якутов, вероятно, связано с давлением отбора, что свидетельствует о возможной компенсаторной роли псевдогена при отсутствии рабочей копии гена STRC.

Copy number variations (CNV) in the STRC gene are the main cause of autosomal recessive deafness type 16 (DFNB16, OMIM #603720). Genetic testing of DFNB16 is complicated by the complexity of the chromosomal region (15q15.3) containing a segmental duplication of five genes, including the STRC gene and its highly homologous pseudogene STRCP1. Clinically, DFNB16 is associated with a mild and moderate form of hearing loss, which, in our opinion, is due to the compensatory effect of the pseudogene, as was shown in spinal muscular atrophy. In this regard, to understand the molecular mechanisms of occurrence and clinical features of DFNB16, it is relevant to study the number of copies of not only the STRC gene, but also the STRCP1 pseudogene. In total, copy number changes in the STRC gene were detected in 7 (6.2%) individuals, and in the STRCP1 pseudogene in 16 (14.1%) individuals. It was found that these copy number changes most likely occurred as a result of unequal crossing over (STRC/STRCP1 – deletion/deletion or norm), cases associated with gene conversion (STRC/STRCP1 – deletion/duplication or vice versa duplication/deletion) were not detected. Comparative analysis of the frequency of altered copies of the STRC gene and the STRCP1 pseudogene revealed reliable differences between deletions (1.8%) and duplications (11.5%) in the STRCP1 pseudogene region (χ2=8.64, p<0.01), while in the STRC gene region, such differences were not observed (deletions – 2.6%, duplications – 3.5%, χ2=0.15, p>0.05). A decrease in the frequency of extended deletions in the STRCP1 pseudogene region in the Yakut population is probably associated with selection pressure, which indicates a possible compensatory role of the pseudogene in the absence of a functional copy of STRC.

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The authors declare that there are no conflicts of interest present.