Research Article


DOI :10.26650/IUITFD.2021.913346   IUP :10.26650/IUITFD.2021.913346    Full Text (PDF)

COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA

Barış SalmanEmrah YücesanBedia SamancıBaşar BilgiçHaşmet Ayhan Hanağasıİbrahim Hakan GürvitUğur ÖzbekSibel Aylin Uğur İşeri

Objective: To explore the underlying genetic variations and mechanisms in a family affected by isolated dystonia. Material and Method: We employed whole genome Single Nucleotide Polymorphism (SNP) based linkage analysis along with whole exome sequencing (WES) in a consanguineous family presenting with isolated dystonia. An in-house pipeline compiled for WES analysis along with in-depth in silico prediction algorithms were used to assess the associated data produced in this study. Sanger sequencing was used for variant confirmation and segregation. Results: Data analysis included locus oriented WES variant prioritization and cryptic splicing predictions. We detected a homozygous and synonymous variation rs748449895 (NM_015125.4: c.4143C>T; p.(Thr1381=)) in the capicua transcriptional repressor, CIC. This variation disrupts the YB-1 RNA recognition motif and creates an alternative SRp20 RNA recognition motif. Conclusion: The resulting variant might cause the dystonia phenotype by affecting the alternative splicing of CIC transcript and altering the exon inclusion motif which may disrupt the ATXN1– CIC complex.

DOI :10.26650/IUITFD.2021.913346   IUP :10.26650/IUITFD.2021.913346    Full Text (PDF)

BAĞLANTI VE TÜM EKZOM DİZİLEME ANALİZLERİNİN BİRLİKTE DEĞERLENDİRİLMESİYLE CIC GENİNİN İZOLE DİSTONİ ADAYI OLARAK BELİRLENMESİ

Barış SalmanEmrah YücesanBedia SamancıBaşar BilgiçHaşmet Ayhan Hanağasıİbrahim Hakan GürvitUğur ÖzbekSibel Aylin Uğur İşeri

Amaç: İzole distoni hastalığından etkilenmiş bir ailede hastalığa neden olan genetik varyasyonları ve mekanizmaları keşfetmek. Gereç ve Yöntem: İzole distoni hastalığı tanısı konmuş ve akraba evliliği bulunan bir ailede, tüm genom Single Nucleotide Polymorphism (SNP) temelli bağlantı analizi ile beraber tüm ekzom dizileme (TED) gerçekleştirildi. TED analizleri için laboratuvarımızda geliştirilen akış hattı ve in siliko tahmin algoritmaları bu çalışmada üretilen verinin ilişkilendirilmesinde kullanıldı. Sanger dizileme varyantların doğrulanması ve ayrımı için kullanıldı. Bulgular: SNP dizimi ile genotipleme, bağlantı analizi ve ekzom dizileme analizleri sonucu rs748449895 (NM_015125.4: c. 4143C>T;p.(Thr1381=)) homozigot sinonim varyantı tespit edildi. Devamındaki biyoinformatik analizler varyantın YB-1 RNA tanıma motifi olduğunu gösterdi. Bu varyant YB-1 RNA tanıma motifini bozarak, SRp20 RNA tanıma motifi oluşturmaktadır. Sonuç: Bulunan varyant, ekzon katılma motifini değiştirerek CIC transkriptinin alternatif kırpılmasını etkileyip ATXN1-CIC kompleksini bozarak distoni fenotipine yol açabilir. 


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APA

Salman, B., Yücesan, E., Samancı, B., Bilgiç, B., Hanağası, H.A., Gürvit, İ.H., Özbek, U., & Uğur İşeri, S.A. (2021). COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA. Journal of Istanbul Faculty of Medicine, 84(4), 457-463. https://doi.org/10.26650/IUITFD.2021.913346


AMA

Salman B, Yücesan E, Samancı B, Bilgiç B, Hanağası H A, Gürvit İ H, Özbek U, Uğur İşeri S A. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA. Journal of Istanbul Faculty of Medicine. 2021;84(4):457-463. https://doi.org/10.26650/IUITFD.2021.913346


ABNT

Salman, B.; Yücesan, E.; Samancı, B.; Bilgiç, B.; Hanağası, H.A.; Gürvit, İ.H.; Özbek, U.; Uğur İşeri, S.A. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 84, n. 4, p. 457-463, 2021.


Chicago: Author-Date Style

Salman, Barış, and Emrah Yücesan and Bedia Samancı and Başar Bilgiç and Haşmet Ayhan Hanağası and İbrahim Hakan Gürvit and Uğur Özbek and Sibel Aylin Uğur İşeri. 2021. “COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA.” Journal of Istanbul Faculty of Medicine 84, no. 4: 457-463. https://doi.org/10.26650/IUITFD.2021.913346


Chicago: Humanities Style

Salman, Barış, and Emrah Yücesan and Bedia Samancı and Başar Bilgiç and Haşmet Ayhan Hanağası and İbrahim Hakan Gürvit and Uğur Özbek and Sibel Aylin Uğur İşeri. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA.” Journal of Istanbul Faculty of Medicine 84, no. 4 (Oct. 2021): 457-463. https://doi.org/10.26650/IUITFD.2021.913346


Harvard: Australian Style

Salman, B & Yücesan, E & Samancı, B & Bilgiç, B & Hanağası, HA & Gürvit, İH & Özbek, U & Uğur İşeri, SA 2021, 'COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA', Journal of Istanbul Faculty of Medicine, vol. 84, no. 4, pp. 457-463, viewed 20 Oct. 2021, https://doi.org/10.26650/IUITFD.2021.913346


Harvard: Author-Date Style

Salman, B. and Yücesan, E. and Samancı, B. and Bilgiç, B. and Hanağası, H.A. and Gürvit, İ.H. and Özbek, U. and Uğur İşeri, S.A. (2021) ‘COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA’, Journal of Istanbul Faculty of Medicine, 84(4), pp. 457-463. https://doi.org/10.26650/IUITFD.2021.913346 (20 Oct. 2021).


MLA

Salman, Barış, and Emrah Yücesan and Bedia Samancı and Başar Bilgiç and Haşmet Ayhan Hanağası and İbrahim Hakan Gürvit and Uğur Özbek and Sibel Aylin Uğur İşeri. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA.” Journal of Istanbul Faculty of Medicine, vol. 84, no. 4, 2021, pp. 457-463. [Database Container], https://doi.org/10.26650/IUITFD.2021.913346


Vancouver

Salman B, Yücesan E, Samancı B, Bilgiç B, Hanağası HA, Gürvit İH, Özbek U, Uğur İşeri SA. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA. Journal of Istanbul Faculty of Medicine [Internet]. 20 Oct. 2021 [cited 20 Oct. 2021];84(4):457-463. Available from: https://doi.org/10.26650/IUITFD.2021.913346 doi: 10.26650/IUITFD.2021.913346


ISNAD

Salman, Barış - Yücesan, Emrah - Samancı, Bedia - Bilgiç, Başar - Hanağası, HaşmetAyhan - Gürvit, İbrahimHakan - Özbek, Uğur - Uğur İşeri, SibelAylin. COMBINED ANALYSIS OF LINKAGE AND WHOLE EXOME SEQUENCING REVEALS CIC AS A CANDIDATE GENE FOR ISOLATED DYSTONIA”. Journal of Istanbul Faculty of Medicine 84/4 (Oct. 2021): 457-463. https://doi.org/10.26650/IUITFD.2021.913346



TIMELINE


Submitted26.04.2021
Accepted28.05.2021
Published Online31.08.2021

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