medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-224Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHФрагментный анализ полиморфизма (TG)mTn интрона 8 гена CFTRCFTR fragment analysis of intron 8 (TG)mTn polymorphismМарковаЕ. В.MarkovaE. V.genlab.kcrm@mail.ruТатаруД. А.TataruD. A.noemail@neicon.ruПредаО. Г.PredaO. G.noemail@neicon.ruКрасноярский центр репродуктивной медициныРоссияKrasnoyarsk Center for Reproductive MedicineRussian Federation2017180420171611119Copyright © Маркова Е.В., Татару Д.А., Преда О.Г., 20172017Маркова Е.В., Татару Д.А., Преда О.Г.Markova E.V., Tataru D.A., Preda O.G.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/224

Полиморфный политимидиновый локус ( Tn) , локализованный в области сайта сплайсинга интрона 8 гена трансмембранного регулятора муковисцидоза ( CFTR ) ассоциирован с различной эффективностью сплайсинга экзона 9. Гены, несущие 5T -аллель, имеют наибольший уровень потери экзона 9 в мРНК. TG -повторы - (TG)m , непосредственно предшествующие Tn , также модулируют сплайсинг и могут являться причиной неполной пенетрантности аллеля 5T . Анализ полиморфизма (TG)mTn интрона 8 важен для диагностики врожденной аплазии семявыносящих протоков, а также для изучения полиморфного фона гена CFTR . В нашем исследовании предложен метод двухраундной ПЦР и фрагментного анализа для генотипирования поли-Т-последовательности, TG -тракта и молекулярного гаплотипирования (TG)mTn -локуса. Метод был применен для поли-Т-генотипирования 2261 образца (без частых мутаций гена), и (TG)mTn -гаплотипирования 292 из них. Частоты аллелей 5T , 7T и 9T соответствовали данным для европеоидных популяций. Наиболее распространенным TG -аллелем был 11TG (59,0%), гаплотипом - 7T-11TG (52,3%). Аллель 9T был преимущественно сцеплен с 10TG (71,9%). Среди хромосом, несущих аллель 5T, гаплотип 5T-12TG обнаружен в 18,0%, 5T-13TG - в 1,1%.

A polymorphic polythymidine (Tn) locus located within splice site of IVS8 of the cystic ?brosis transmembrane conductance regulator ( CFTR ) gene is associated with variable efficiency of exon 9 splicing. Genes that carry 5T allele have the highest levels of exon 9 skipping. (TG)m tract located immediately upstream of the Tn can also modulate exon 9 skipping and may account for the partial penetrance of the 5T allele. Analysis of (TG)mTn polymorphism is important for the diagnosis of congenital bilateral absence of the vas deferens (CBAVD) and for investigation of polymorphic backgrounds of the CFTR gene. To detect poly-T-alleles, TG -repeats and molecular haplotyping (TG)mTn we developed nested PCR and fragment analysis. Allele frequencies of the 5T , 7T and 9T (N=2261) were consistent with the distribution for Caucasians. TG -repeats and (TG)mTn haplotypes were analyzed for 292 individuals. The major allele was 11TG (59.0%) аnd the major haplotypes - 7T-11TG (52.3%). 9T allele was mainly linked with 10TG (71.9%). 5T-12TG and 5T-13TG haplotypes were found in 18.0% and 1.1% of 5T chromosomes.

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