Türkiye'deki kistik fibrozisli hastalarda CFTR geni DNA varyantlarının karakterizasyonu ve fenotipik özellikleri ile ilişkisi
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Dosyalar
Tarih
2017
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kistik fibrozis birçok vücut sistemini etkileyen otozomal resesif bir hastalıktır. Kistik fibrozis transmembran regulatör (CFTR) geninde meydana gelen mutasyonlar, bu haslığa neden olur. CFTR geni insanda kromozom 7 üzerinde lokalize olup 250000 nükleotidden meydana gelir. ABCC7 olarakta bilinen CFTR proteini hücrede kanal proteini olarak görev yapar ve klor iyonlarının hücre içine ve dışına geçişini kontrol eder. CFTR genindeki mutasyonlar, CFTR proteininin yapısında değişikliğe neden olabilir. Sağlıklı (control grup) 25 bireylerden ve kistik fibrozis şüphelisi 30 bireylerden genomik DNA örnekleri DNA sekans yöntemi ile karşılaştırılmıştır. Tüm gen analizi ile CFTR genindeki mutasyonlar tespit edilmiştir. Sağlıklı bireylerin hiç birinde hastalık yapıcı mutasyon gözlenmezken, buna karşın hasta grubunda, 26 farklı mutasyon gözlenmiştir. Hasta grubunda en yaygın gözlenen mutasyonlar ve görülme oranları sırasıyla, F508del (%13.3), F1052V (%13.3), I148T (%10), R297Q (%6.6), E92K (%6.6), E632X (%6.6), bunların yanında R74W (%3.3), G126D (%3.3), L183I (%3.3), G178R (%3.3), K174X (%3.3), R347P (%3.3), E379X (%3.3), T388M (%3.3), M472V (%3.3), G542X (%3.3), I807M (%3.3), I982I (%3.3), L1034F (%3.3), Y1092H (%3.3), K1165E (%3.3), T1220I (%3.3), S1235R (%3.3), W1282X (%3.3), S1426F (%3.3) mutasyon oranları saptanmıştır. Çalışmamızda veri tabanında yer almayan altı yeni mutasyon ilk olarak tanımlandı. Bu mutasyonlardan üçü misens (M472V, K1165E, L1034F) biri sinonim (I982I) ve iki taneside stop kodon (K174X, E632X) mutasyonlarıdır.
Cystic fibrosis (CF) is an autosomal recessive disease that affects many body systems. It is caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene is located on chromosome 7 and consisted of 250.000 DNA nucleotids. The CFTR protein also known as ABCC7 acts as a channel protein which control transition of chloride ions to the inside and outside of the cells. The mutations in the CFTR gene can cause changes in the structure of the CFTR protein. In this study, genomic DNA samples taken from healthy (control group=25) individuals were compared with the individuals with CF clinical pre-diagnosis (working group =30) via the using of DNA sequencing method. Mutations in the CFTR gene were detected by whole gene analysis. None of the pathogenic mutations were observed in healthy individuals, however, in the patient group, 26 different mutations have been observed. The most common mutations observed in the patient group and the observation rates were F508del (13.3%), F1052V (13.3%), I148T (10%), R297Q (6.6%), E92K (6.6%) and E632X (6.6%) R74W(3.3%), G126D (3.3%), L183I (3.3%), G178R (3.3%), K174X (3.3%), R347P (3.3%), E379X (3.3% (3.3%), K1165E (3.3%), T1220I (3.3%), S1235R (3.3%), I1270M (3.3%), I807M (3.3%), I982I 3.3%), W1282X (3.3%) and S1426F (3.3%). Also in our study, six novel mutations were first described which are three missense (M472V, K1165E, L1034F), one synonym (I982I) and two stop codons (K174X, E632X) mutations Keywords: Cystic fibrosis, CF, CFTR, Mutation, DNA sequencing.
Cystic fibrosis (CF) is an autosomal recessive disease that affects many body systems. It is caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene is located on chromosome 7 and consisted of 250.000 DNA nucleotids. The CFTR protein also known as ABCC7 acts as a channel protein which control transition of chloride ions to the inside and outside of the cells. The mutations in the CFTR gene can cause changes in the structure of the CFTR protein. In this study, genomic DNA samples taken from healthy (control group=25) individuals were compared with the individuals with CF clinical pre-diagnosis (working group =30) via the using of DNA sequencing method. Mutations in the CFTR gene were detected by whole gene analysis. None of the pathogenic mutations were observed in healthy individuals, however, in the patient group, 26 different mutations have been observed. The most common mutations observed in the patient group and the observation rates were F508del (13.3%), F1052V (13.3%), I148T (10%), R297Q (6.6%), E92K (6.6%) and E632X (6.6%) R74W(3.3%), G126D (3.3%), L183I (3.3%), G178R (3.3%), K174X (3.3%), R347P (3.3%), E379X (3.3% (3.3%), K1165E (3.3%), T1220I (3.3%), S1235R (3.3%), I1270M (3.3%), I807M (3.3%), I982I 3.3%), W1282X (3.3%) and S1426F (3.3%). Also in our study, six novel mutations were first described which are three missense (M472V, K1165E, L1034F), one synonym (I982I) and two stop codons (K174X, E632X) mutations Keywords: Cystic fibrosis, CF, CFTR, Mutation, DNA sequencing.
Açıklama
Anahtar Kelimeler
Kistik Fiborizis, CF, CFTR, Mutasyon, DNA., Cystic Fibrosis, CF, CFTR, Mutation, DNA Sequencing
