PKD1

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Schematic representation of polycystin-1 and polycystin-2 on a cell

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

function

The PKD1 gene encodes the glycoprotein polycystin-1 . Polycystin is a multifunctional protein that plays an important role in the maturation of epithelial cells and the maintenance of renal epithelial differentiation, as well as in the organization of the structure of the nephrons in the early fetal stage. Mutations in PKD1 can autosomal - dominant inherited 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 , which is particularly common in Persian cats.

genetics

Rendered structural model of polycystin 1, which is encoded by PKD1

The PKD1 gene is located in humans on chromosome 16 gene locus p13.3. PKD1 is closely linked to the locus of the alpha globin and the PGP marker ( phosphoglycolate phosphatase ). This region, in which PKD1 is located, comprises 750 kb and is rich in CpG dinucleotides . The PKD1 gene itself is 52 kb and contains 50 exons . Different splice variants are known of the gene , which encode different isoforms . Six pseudogenes of PKD1 on chromosome 16 have been described so far, which have a similarity of about 95 to 97% to PKD1. These areas in the genome are transcribed , but not translated due to the lack of a suitable start codon , since the mRNA cannot bind to the ribosome subunits. The high number of pseudogenes indicates an insufficient stability of this region on chromosome 16.

Mutations

In a study published in 2001, the entire coding region of PKD1 was examined for potential disease-causing mutations. 69 mutations and 32 polymorphisms were discovered, which are distributed fairly evenly over the entire gene. The fact that only three of the mutations can also be found on the homologous genes is interpreted to mean that gene conversions cannot be the main cause of the high mutation rate in PKD1. 32% of the mutations found in this study are nonsense mutations and 29.6% are deletions and insertions . Mutations at splice points account for 6.2%. A mutation rate of 1.8 × 10 −5 per generation was calculated from the available data . This is an unusually high value for a human gene.

Individual evidence

  1. ↑ C. Stayner and J. Zhou: Polycystin channels and kidney disease. In: Trends in Pharmacological Sciences 22, 2001, pp. 543-546. PMID 11698076 .
  2. ↑ ML Watson et al.: Studies of genetic linkage between adult polycystic kidney disease and three markers on chromosome 16. In: J. Med. Genet. 24, 1987, pp. 457-461. PMID 2821260 .
  3. ↑ GG Germino et al: The gene for autosomal dominant polycystic kidney disease lies in a 750-kb CpG-rich region. In: Genomics 13, 1992, pp. 144-151. PMID 1577479 .
  4. ↑ a b J. Hughes et al: The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. In: Nature Genetics 10, 1995, pp. 151-160. PMID 7663510 .
  5. ↑ BJ Loftus et al .: Genome Duplications and Other Features in 12 Mb of DNA Sequence from Human Chromosome 16p and 16q. In: Genomics 60, 1999, pp. 295-308. PMID 10493829 .
  6. ↑ a b E.C. cap: Molecular biological studies on the PKD1 gene in cats. Dissertation, Justus Liebig University Giessen, 2008.
  7. ^ S. Rossetti et al.: Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications. In: Am. J. Hum. Genet. 68, 2001, pp. 46-63. PMID 11115377 .

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