PKHD1 Geni Yanlış Anlam Mutasyonları Kedilerde Sebebi Bilinmeyen Böbrek Hastalıkları İçin Önemli Olabilir mi?

Year 2021, , 168 - 171, 12.12.2021

Nüket Bilgen

https://doi.org/10.31196/huvfd.983895

Abstract

Polikistik böbrek hastalığı (PKD), insanlarda otozomal resesif ve otozomal dominant olarak görülen heterojenik arka planı olan genetik bir hastalıktır. Kedilerde otozomal dominant PKD sıklıkla rapor edilirken, otozomal resesif PKD bildirilmemiştir. Tüm genom dizilemesi yapılmış olan siyam ırkı bir erkek kedide biyoinformatik analizler sonucunda PKHD1 geninde çeşitli yanlış anlam mutasyonları tespit edilmiştir. Bu Siyam ırkı kedinin kastrasyon için özel bir veteriner kliniğine getirilmesinin ardından böbrek ve karaciğeri izlemek için geniş kan paneli yapıldı ve yüksek BUN ve kreatinin değerleri gözlendi. Ayrıca GPT değerinin de 2,5 kat olduğu belirlendi. Kedilerde nadiren PKD1 mutasyonundan bağımsız kistik böbrek vakaları bildirilmektedir. Ancak otozomal çekinik polikistik böbrek hastalığına neden olan genler için kedi genomları daha önce incelenmemiştir. Bu çalışmada kedi genom verilerinde (n=100) otozomal resesif PKD’ye neden olan PKHD1 geni incelenmiştir. İnceleme sonucunda SIFT skoru yüksek 4 farklı mutasyon belirlenmiş ve bu mutasyonların PKHD1 geninden üretilen 7 transkriptte dur kodonu oluşumu ve dur kodonu kaybı ile sonuçlandığı ortaya konmuştur. Nadir hastalık olmasını destekler nitelikte, belirlenen mutasyonların frekanslarının 0.003, 0.001, 0.001 ve 0.003 olduğu hesaplanmıştır.

Keywords

Böbrek, Kedi, genom, PKHD1 geni

Thanks

99 Kedi Genom konsorsiyumuna veri paylaşımı için teşekkür ederiz.

Could PKHD1 Gene Missense Mutations Be İmportant for İdiopathic Kidney Disease in Cats?

Abstract

Polycystic kidney disease (PKD) is a genetic disease with a heterogeneous background seen in humans as autosomal recessive and autosomal dominant. While autosomal dominant PKD is frequently reported in cats, autosomal recessive PKD has not been reported. Various missense mutations in the PKHD1 gene were detected as a result of bioinformatic analyzes in a male cat whose whole genome was sequenced. After this Siamese cat was brought to a private veterinary clinic for castration, a broad blood panel was performed to monitor kidney and liver, and elevated BUN and creatinine values were observed. In addition, the GPT value was determined to be 2.5 times higher. Cases of cystic kidney independent of PKD1 mutation have been reported rarely in cats. However, cat genomes have not been previously
examined for genes that cause autosomal recessive polycystic kidney disease. In this study, the PKHD1 gene, which causes autosomal recessive PKD, was examined in cat genome data (n=100). As a result of the examination, four different mutations with high SIFT scores were identified. These mutations resulted in stop codon formation and loss of stop codons in 7 transcripts produced from the PKHD1 gene. The frequencies of the determined mutations were calculated to be 0.003, 0.001, 0.001, and 0.003, which supports the fact that it is a rare disease.

Keywords

Cat, Genome, Kidney, PKHD1 gene

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