PKD1

PKD1 ( polycystic kidney disease for Abbreviation for 1 (autosomal dominant) = " polycystic kidney disease 1 ( autosomal dominant) ") is a gene that is contained both in humans and other mammalian species in the genome.

Function

The PKD1 gene encoding the glycoprotein polycystin -1. Polycystin is a multifunctional protein that plays an important role, among others, in the maturation of epithelial cells and in the maintenance of renal epithelial differentiation, as well as in organizing the structure of the nephrons in the early fetal stage. Mutations in PKD1 can be inherited as an autosomal dominant and then lead to autosomal dominant polycystic kidney disease ( ADPKD ) - the most common life-threatening inherited disease in humans. In cats, this leads to polycystic kidney disease that occurs mainly in Persian cats.

Genetics

The PKD1 gene is located on chromosome 16 in humans locus p13.3. PKD1 is closely coupled to the locus of the alpha - globin, as well as the PGP marker ( Phosphoglycolatphosphatase ). This region, in which PKD1 is comprises 750 kb and is rich in CpG dinucleotides. The PKD1 gene itself covers 52 kb and contains 50 exons. Of different splice variants of the gene are known which encode different isoforms. Six pseudogenes of PKD1 on chromosome 16 have been described, which have a similarity of about 95 to 97% for PKD1. Although these regions in the genome to be transcribed, but not translated by the lack of an appropriate start codon, since the mRNA may not bind to the ribosomal subunits. The high number of pseudogenes suggests a lack of stability of this region points to chromosome 16.

Mutations

In a study published in 2001, the entire coding region of PKD1 was investigated for potential disease-causing mutations. This 69 mutations and 32 polymorphisms were discovered, distributed relatively evenly over the entire gene. The fact that only three of the mutations are also found on the homologous genes is interpreted to the effect that gene conversion can not be the main cause of the high rate of mutation of PKD1. 32% of the mutations found in this study are nonsense mutations, and 29.6%, deletions and insertions. Mutations at splice sites have a share of 6.2%. From the available data, a mutation rate of 1.8 × 10-5 per generation was calculated. This is an unusually high value for a human gene dar.

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