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Molecular diagnostics for autosomal dominant polycystic kidney disease

Nature Reviews Nephrology volume 6, pages 197–206 (2010)Cite this article

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common nephropathy caused by mutations in either PKD1 or PKD2. Mutations in PKD1 account for ∼85% of cases and cause more severe disease than mutations in PKD2. Diagnosis of ADPKD before the onset of symptoms is usually performed using renal imaging by either ultrasonography, CT or MRI. In general, these modalities are reliable for the diagnosis of ADPKD in older individuals. However, molecular testing can be valuable when a definite diagnosis is required in young individuals, in individuals with a negative family history of ADPKD, and to facilitate preimplantation genetic diagnosis. Although linkage-based diagnostic approaches are feasible in large families, direct mutation screening is generally more applicable. As ADPKD displays a high level of allelic heterogeneity, complete screening of both genes is required. Consequently, such screening approaches are expensive. Screening of individuals with ADPKD detects mutations in up to 91% of cases. However, only ∼65% of patients have definite mutations with ∼26% having nondefinite changes that require further evaluation. Collation of known variants in the ADPKD mutation database and systematic scoring of nondefinite variants is increasing the diagnostic value of molecular screening. Genic information can be of prognostic value and recent investigation of hypomorphic PKD1 alleles suggests that allelic information may also be valuable in some atypical cases. In the future, when effective therapies are developed for ADPKD, molecular testing may become increasingly widespread. Rapid developments in DNA sequencing may also revolutionize testing.

Key Points

  • Molecular diagnostics is available and increasingly informative in autosomal dominant polycystic kidney disease (ADPKD)

  • Determining the disease status of potential living, related donors is where molecular diagnostics is most valuable at present

  • A molecular diagnosis can clarify the disease status in patients with a negative family history and/or unusually mild or severe polycystic kidney disease

  • Determining whether a family carries mutations in PKD1 or PKD2 is of prognostic value

  • Hypomorphic PKD1 alleles can significantly modify the ADPKD phenotype and the identification of specific alleles may be of prognostic value, especially in early-onset ADPKD

  • As therapies for ADPKD are developed, molecular testing will likely become increasingly valuable

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Figure 1: Gene structure of PKD1 and PKD2 and protein structure of polycystin-1 and polycystin-2.
Figure 2: Summary of data from the ADPKD mutation database.

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References

  1. Harris, P. C. & Torres, V. E. in GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washginton, Seattle. 1997–2008 [online], (2008).

    Google Scholar 

  2. Torres, V. E., Harris, P. C. & Pirson, Y. Autosomal dominant polycystic kidney disease. Lancet 369, 1287–1301 (2007).

    Article  PubMed  Google Scholar 

  3. Dalgaard, O. Z. Bilateral polycystic disease of the kidneys: A follow-up of two hundred and eighty-four patients and their families. Acta Med. Scand. Suppl. 328, 1–255 (1957).

    CAS  PubMed  Google Scholar 

  4. Iglesias, C. G. et al. Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota. Am. J. Kidney Dis. 2, 630–639 (1983).

    CAS  PubMed  Google Scholar 

  5. US Renal Data System. (National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2007).

  6. Belz, M. M. et al. Familial clustering of ruptured intracranial aneurysms in autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 38, 770–776 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Rossetti, S. et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet 361, 2196–2201 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Pirson, Y., Chauveau, D. & Torres, V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 13, 269–276 (2002).

    PubMed  Google Scholar 

  9. Grantham, J. J. et al. Volume progression in polycystic kidney disease. N. Engl. J. Med. 354, 2122–2130 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Hateboer, N. et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. Lancet 353, 103–107 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Shamshirsaz, A. et al. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int. 68, 2218–2224 (2005).

    Article  PubMed  Google Scholar 

  12. Zerres, K., Rudnik-Schöneborn, S., Deget, F. & German Working Group on Paediatric Nephrology. Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. J. Med. Genet. 30, 583–588 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. European Polycystic Kidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 77, 881–894 (1994).

  14. Mochizuki, T. et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272, 1339–1342 (1996).

    Article  CAS  PubMed  Google Scholar 

  15. Rossetti, S. et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 18, 2143–2160 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Harris, P. C. et al. Cyst number but not the rate of cystic growth is associated with the mutated gene in ADPKD. J. Am. Soc. Nephrol. 17, 3013–3019 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Torra, R. et al. Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients. Am. J. Kidney Dis. 36, 728–734 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Barua, M. et al. Family history of renal disease severity predicts the mutated gene in ADPKD. J. Am. Soc. Nephrol. 20, 1833–1838 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dicks, E. et al. Incident renal events and risk factors in autosomal dominant polycystic kidney disease: a population and family-based cohort followed for 22 years. Clin. J. Am. Soc. Nephrol. 1, 710–717 (2006).

    Article  PubMed  Google Scholar 

  20. Rossetti, S. et al. An Olmsted County population-based study indicates that PKD2 is more common than previously described [abstract]. J. Am. Soc. Nephrol. 18, 365A (2007).

  21. Geberth, S., Ritz, E., Zeier, M. & Stier, E. Anticipation of age at renal death in autosomal dominant polycystic kidney disease (ADPKD)? Nephrol. Dial. Transplant. 10, 1603–1606 (1995).

    CAS  PubMed  Google Scholar 

  22. Gabow, P. A. Autosomal dominant polycystic kidney disease - more than a renal disease. Am. J. Kidney Dis. 16, 403–413 (1990).

    Article  CAS  PubMed  Google Scholar 

  23. Reed, B. Y. et al. Variation in age at ESRD in autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 51, 173–183 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hughes, J. et al. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat. Genet. 10, 151–160 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. International Polycystic Kidney Disease Consortium. Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. Cell 81, 289–298 (1995).

  26. Loftus, B. J. et al. Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics 60, 295–308 (1999).

    Article  CAS  PubMed  Google Scholar 

  27. Martin, J. et al. The sequence and analysis of duplication-rich human chromosome 16. Nature 432, 988–994 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. Phakdeekitcharoen, B., Watnick, T. J. & Germino, G. G. Mutation analysis of the entire replicated portion of PKD1 using genomic DNA samples. J. Am. Soc. Nephrol. 12, 955–963 (2001).

    CAS  PubMed  Google Scholar 

  29. Rossetti, S. et al. A complete mutation screen of the ADPKD genes by DHPLC. Kidney Int. 61, 1588–1599 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Veldhuisen, B. et al. A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). Am. J. Hum. Genet. 61, 547–555 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sandford, R. et al. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Hum. Mol. Genet. 6, 1483–1489 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Fliegauf, M., Benzing, T. & Omran, H. When cilia go bad: cilia defects and ciliopathies. Nat. Rev. Mol. Cell. Biol. 8, 880–893 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Pazour, G. J., San Agustin, J. T., Follit, J. A., Rosenbaum, J. L. & Witman, G. B. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12, R378–R380 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Yoder, B. K., Hou, X. & Guay-Woodford, L. M. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J. Am. Soc. Nephrol. 13, 2508–2516 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Sharif-Naeini, R. et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139, 587–596 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Battini, L. et al. Loss of polycystin-1 causes centrosome amplification and genomic instability. Hum. Mol. Genet. 17, 2819–2833 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li, X. et al. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat. Cell Biol. 7, 1202–1212 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Happé, H. et al. Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Hum. Mol. Genet. 18, 2532–2542 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Torres, V. E. & Harris, P. C. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 76, 149–168 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Reed, B. et al. Presence of de novo mutations in autosomal dominant polycystic kidney disease patients without family history. Am. J. Kidney Dis. 52, 1042–1050 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rossetti, S. et al. Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications. Am. J. Hum. Genet. 68, 46–63 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Pei, Y. et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J. Am. Soc. Nephrol. 20, 205–212 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ravine, D. et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 343, 824–827 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Nascimento, A. B. et al. Rapid MR imaging detection of renal cysts: age-based standards. Radiology 221, 628–632 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Carrim, Z. I. & Murchison, J. T. The prevalence of simple renal and hepatic cysts detected by spiral computed tomography. Clin. Radiol. 58, 626–629 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Huang, E. et al. DNA testing for live kidney donors at risk for autosomal dominant polycystic kidney disease. Transplantation 87, 133–137 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Blumenfeld, J. D. Pretransplant genetic testing of live kidney donors at risk for autosomal dominant polycystic kidney disease. Transplantation 87, 6–7 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Edghill, E. L., Bingham, C., Ellard, S. & Hattersley, A. T. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J. Med. Genet. 43, 84–90 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Faguer, S. et al. Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1beta (hepatocyte nuclear factor-1beta) heterozygous whole-gene deletion. Am. J. Kidney Dis. 50, 1023–1027 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Heidet, L. et al. Spectrum of HNF1B mutations in a cohort of patients harboring renal diseases [abstract]. J. Am. Soc. Nephrol. 20, 773A (2009).

    Article  CAS  Google Scholar 

  52. Davila, S. et al. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat. Genet. 36, 575–577 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Drenth, J. P., te Morsche, R. H., Smink, R., Bonifacino, J. S. & Jansen, J. B. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat. Genet. 33, 345–347 (2003).

    Article  CAS  PubMed  Google Scholar 

  54. Li, A. et al. Mutations in PRKCSH cause isolated autosomal dominant polycystic liver disease. Am. J. Hum. Genet. 72, 691–703 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Adeva, M. et al. Clinical and molecular characterization defines a broadened spectrum of autosomal recessive polycystic kidney disease (ARPKD). Medicine 85, 1–21 (2006).

    Article  PubMed  Google Scholar 

  56. Peral, B. et al. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease 1 population. Am. J. Hum. Genet. 54, 899–908 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhao, X. et al. Molecular diagnostics in autosomal dominant polycystic kidney disease: utility and limitations. Clin. J. Am. Soc. Nephrol. 8, 146–152 (2008).

    Article  Google Scholar 

  58. De Rycke, M. et al. PGD for autosomal dominant polycystic kidney disease type 1. Mol. Hum. Reprod. 11, 65–71 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Tan, Y. C. et al. Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease. Hum. Mutat. 30, 264–273 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Garcia-Gonzalez, M. A. et al. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol. Genet. Metab. 92, 160–167 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. PKD Foundation Autosomal Dominant Polycystic Kidney Disease: Mutation Database [online], (2010).

  62. Magistroni, R. et al. Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 14, 1164–1174 (2003).

    Article  PubMed  Google Scholar 

  63. Rossetti, S. et al. Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int. 75, 848–855 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Consugar, M. B. et al. Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1/TSC2 contiguous gene syndrome. Kidney Int. 74, 1468–1479 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Brook-Carter, P. T. et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—a contiguous gene syndrome. Nat. Genet. 8, 328–332 (1994).

    Article  CAS  PubMed  Google Scholar 

  66. Sampson, J. R. et al. Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene. Am. J. Hum. Genet. 61, 843–851 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Koulen, P. et al. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4, 191–197 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Qian, F. et al. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc. Natl Acad. Sci. USA 99, 16981–16986 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Forman, J. R., Qamar, S., Paci, E., Sandford, R. N. & Clarke, J. The remarkable mechanical strength of polycystin-1 supports a direct role in mechanotransduction. J. Mol. Biol. 349, 861–871 (2005).

    Article  CAS  PubMed  Google Scholar 

  70. Ma, L., Xu, M., Forman, J. R., Clarke, J. & Oberhauser, A. F. Naturally occurring mutations alter the stability of polycystin-1 PKD domains. J. Biol. Chem. 284, 32942–32949 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Qian, F., Wei, W., Germino, G. & Oberhauser, A. The nanomechanics of polycystin-1 extracellular region. J. Biol. Chem. 280, 40723–40730 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Consugar, M. B. et al. Characteristics of CRISP ADPKD patients with no detected base-pair mutations [abstract]. J. Am. Soc. Nephrol. 19, 125A (2008).

    Article  CAS  Google Scholar 

  73. King, K., Flinter, F. A., Nihalani, V. & Green, P. M. Unusual deep intronic mutations in the COL4A5 gene cause X linked Alport syndrome. Hum. Genet. 111, 548–554 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Gorlov, I. P., Gorlova, O. Y., Frazier, M. L. & Amos, C. I. Missense mutations in hMLH1 and hMSH2 are associated with exonic splicing enhancers. Am. J. Hum. Genet. 73, 1157–1161 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Daoust, M. C., Reynolds, D. M., Bichet, D. G. & Somlo, S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics 25, 733–736 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. de Almeida, S. et al. Autosomal dominant polycystic kidney disease: evidence for the existence of a third locus in a Portuguese family. Hum. Genet. 96, 83–88 (1995).

    Article  CAS  PubMed  Google Scholar 

  77. Consugar, M. et al. PKD3 revisited with improved PKD1 and PKD2 haplotyping and mutation screening [abstract]. J. Am. Soc. Nephrol. 16, 358A (2005).

    Google Scholar 

  78. Connor, A. et al. Mosaicism in autosomal dominant polycystic kidney disease revealed by genetic testing to enable living related renal transplantation. Am. J. Transplant. 8, 232–237 (2008).

    CAS  PubMed  Google Scholar 

  79. Rossetti, S. et al. The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J. Am. Soc. Nephrol. 13, 1230–1237 (2002).

    Article  CAS  PubMed  Google Scholar 

  80. Bergmann, C. et al. Spectrum of mutations in the gene for autosomal recessive polycystic kidney disease (ARPKD/PKHD1). J. Am. Soc. Nephrol. 14, 76–89 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Jiang, S. T. et al. Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am. J. Pathol. 168, 205–220 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kim, I. et al. Polycystin-2 expression is regulated by a PC2-binding domain in the intracellular portion of fibrocystin. J. Biol. Chem. 283, 31559–31566 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lantinga-van Leeuwen, I. S. et al. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum. Mol. Genet. 13, 3069–3077 (2004).

    Article  CAS  PubMed  Google Scholar 

  84. Sandford, R. N. The diversity of PKD1 alleles: implications for disease pathogenesis and genetic counseling. Kidney Int. 75, 765–767 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Fain, P. R. et al. Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int. 67, 1256–1267 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Paterson, A. D. et al. Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 16, 755–762 (2005).

    Article  PubMed  Google Scholar 

  87. Tucker, T., Marra, M. & Friedman, J. M. Massively parallel sequencing: the next big thing in genetic medicine. Am. J. Hum. Genet. 85, 142–154 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mardis, E. R. The impact of next-generation sequencing technology on genetics. Trends Genet. 24, 133–141 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Voelkerding, K. V., Dames, S. A. & Durtschi, J. D. Next-generation sequencing: from basic research to diagnostics. Clin. Chem. 55, 641–658 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Mardis, E. R. Next-generation DNA sequencing methods. Annu. Rev. Genomics Hum. Genet. 9, 387–402 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. Eid, J. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138 (2009).

    Article  CAS  PubMed  Google Scholar 

  92. Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Branton, D. et al. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 26, 1146–1153 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ravine, D., Gibson, R. N., Donlan, J. & Sheffield, L. J. An ultrasound renal cyst prevalence survey: specificity data for inherited renal cystic diseases. Am. J. Kidney Dis. 22, 803–807 (1993).

    Article  CAS  PubMed  Google Scholar 

  95. Grantham, R. Amino acid difference formula to help explain protein evolution. Science 185, 862–864 (1974).

    Article  CAS  PubMed  Google Scholar 

  96. Bork Group and Sunyaev Lab. PolyPhen: prediction of functional effect on human nsSNPs [online], (2009).

  97. J. Craig Venter Institute. SIFT [online], (2009).

  98. International Agency for Research on Cancer. Align GVGD [online], (2009).

  99. Desmet, F. O. et al. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acid Research [online], (2009).

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  1. Division of Nephrology and Hypertension and Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    Peter C. Harris & Sandro Rossetti

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Harris, P., Rossetti, S. Molecular diagnostics for autosomal dominant polycystic kidney disease. Nat Rev Nephrol 6, 197–206 (2010). https://doi.org/10.1038/nrneph.2010.18

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