Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. A gene defect located on the short arm of chromosome 16 is responsible for the disease in roughly 86% of affected European families. Using highly polymorphic microsatellite DNA markers, we have assigned a second gene for ADPKD to chromosome 4. In eight families with clear evidence against linkage to chromosome 16 markers, linkage analysis with the markers D4S231 and D4S423, demonstrated a multipoint lod score of 22.42.
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References
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. 328, 1–255 (1957).
Chapman, A.B. et al. Intracranial aneurysms in autosomal dominant polycystic kidney disease. New Engl. J. Med. 327, 916–920 (1992).
Reeders, S.T. et al. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature 317, 542–544 (1985).
Kimberling, W.J. et al. Linkage heterogeneity of autosomal dominant polycystic kidney disease. New Engl. J. Med. 319, 913–917 (1988).
Romeo, G. et al. A second genetic locus for autosomal dominant polycystic kidney disease. Lancet 2, 8–10 (1988).
Norby, S., Sorensen, A.W.S. & Boesen, P. Non-allelic heterogeneity of autosomal dominant polycystic kidney disease? in Progress in Clinicaland Biological Research. Genetics of Kidney Disorders (ed. Bartsocas, C.S.) 83–88 (Alan R. Liss, New York, 1989).
Brissenden, J.E., Roscoe, J.M., Simpson, N.E. & Silverman, M. Linkage exclusion between the autosomal dominant Polycystic Kidney Disease locus and chromosome 16 markers in a new family. J. Am. Soc. Nephr. 2, 913–919 (1991).
Fossdal, R. et al. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis. Hum. Genet. 91, 609–613 (1993).
Peters, D.J.M. & Sandkuijl, L.A. Genetic heterogeneity of polycystic kidney disease in Europe. in Contributions to Nephrology, Vol. 97: Polycystic Kidney Disease (eds Breuning, M.H., Devoto, M. & Romeo, G.) 128–139 (Basel, Karger, 1992).
Nørby, S. & Schwartz, M. Possible locus for polycystic kidney disease on chromosome 2. Lancet 1, 323–324 (1990).
Ravine, D. et al. Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet 340, 1330–1333 (1992).
Bear, J.C., Parfrey, P.S., Morgan, M., Martin, C.J. & Cramer, B.C. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am. J. med. Genet. 43, 548–553 (1992).
Parfrey, P.S. et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. New Engl. J. Med. 323, 1085–1090 (1990).
Gabow, P.A. et al. Factors affecting the progression of renal disease in autosomal dominant Polycystic Kidney Disease. Kidney International 41, 1311–1319 (1992).
Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).
Mills, K.A. et al. Genetic and pysical maps of human chromosome 4 based on dinucleotide repeats. Genomics 14, 209–219 (1993).
Bear, J.C. et al. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease — data for genetic counseling. Am. J. med. Genet. 18, 45–53 (1984).
Dobin, A. et al. Segregation analysis of Autosomal Dominant Polycystic Kidney Disease. Gen. Epidem. 10, 189–200 (1993).
Somlo, S. et al. Fine genetic localization of the gene for autosomal dominant polycystic kidney disease (PKD1) with respect to physically mapped markers. Genomics 13, 152–158 (1992).
Germino, G.G. et al. The gene for autosomal dominant polycystic kidney disease lies in a 750 kb CpG-rich region. Genomics 13, 144–151 (1992).
Gillespie, G.A.J., Somlo, S., Germino, G.G., Weinstat-Saslow, D. & Reeders, S.T. CpG island in the region of an autosomal dominant polycystic kidney disease locus defines the 5′ end of a gene encoding a putative proton channel. Proc. natn. Acad. Sci. U.S.A. 88, 4289–4293 (1991).
Germino, G.G., Somlo, S., Weinstat-Saslow, D. & Reeders, S.T. Positional cloning approach to the dominant polycystic kidney disease gene, PKD1. Kidney International 43, (suppl.39) 20–25 (1993).
Gusella, F. et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306, 234–238 (1983).
Wijmenga, C. et al. Location of facioscapulohumeral muscular dysthrophy gene on chromosome 4. Lancet 336, 651–653 (1991).
Sleister, H.M. et al. Construction of a human chromosome 4 YAC pool and analysis of artificial chromosome stability. Nucl. Acids Res. 20, 3419–3425 (1992).
van Ommen, G.J.B., Buetow, K.H. & Murray, J.C. Report of the committee on the genetic constitution of chromosome 4. in Chromosome Coordinating meeting (1992), Genome priority reports, (eds Cuticchia, A.J., Pearson, P.L. & Klinger, H.P.) 221–248 Karger, Basel, 1993.
Goold, R.D. et al. The development of sequence-tagged sites for human chromosome 4. Hum. molec. Genet. 2, 1271–1288 (1993).
NIH/CEPH Collaborative Mapping Group. A comprehensive genetic linkage map of the human genome. Science 258, 67–86 (1992).
Weber, J.L. & May, P.E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. hum. Genet. 44, 388–396 (1989).
Lathrop, G.M. & Lalouel, J.M. Easy calculations of lod scores and genetic risks on small computers. Am. J. hum. Genet. 36, 460–465 (1984).
Fenton, I.L.A. Megabase/PKD: a genetic database for polycystic kidney disease. in Contributions to Nephrology 97: Polycystic kidney disease, (eds Breuning, M. H., Devoto, M. & Romeo, G.) 118–127 (Karger, Basel, 1992).
Ott, J. Analysis of human linkage (John Hopkins, Baltimore, 1985).
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Peters, D., Spruit, L., Saris, J. et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet 5, 359–362 (1993). https://doi.org/10.1038/ng1293-359
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DOI: https://doi.org/10.1038/ng1293-359
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