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Am J Hum Genet. May 1991; 48(5): 911–925.
PMCID: PMC1683054

A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates


Utilizing the CEPH reference panel and genotypic data for 53 markers, we have constructed a 20-locus multipoint genetic map of human chromosome 4. New RFLPs are reported for four loci. The map integrates a high-resolution genetic map of 4p16 into a continuous map extending to 4q31 and an unlinked cluster of three loci at 4q35. The 20 linked markers form a continuous linkage group of 152 cM in males and 202 cM in females. Likely genetic locations are provided for 25 polymorphic anonymous sequences and 28 gene-specific RFLPs. The map was constructed employing the LINKAGE and CRIMAP computational methodologies to build the multipoint map via a stepwise algorithm. A detailed 10-point map of the 4p16 region constructed from the CEPH panel provides evidence for heterogeneity in the linkage maps constructed from families segregating for Huntington disease (HD). It additionally provides evidence for position-specific recombination frequencies in the telomeric region of 4p.

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  • Beck JS, Sager R, Murray JC. A ScaI RFLP demonstrated for the GRO gene on chromosome 4. Nucleic Acids Res. 1989 Nov 11;17(21):8895–8895. [PMC free article] [PubMed]
  • Berdahl LD, Murray JC, Besmer P. A HindIII RFLP demonstrated for the kit oncogene on chromosome 4. Nucleic Acids Res. 1988 May 25;16(10):4740–4740. [PMC free article] [PubMed]
  • Berdahl LD, Smith RF, Murray JC, Buetow KH. A TaqI RFLP demonstrated for pIBS17 [D4S123], a single copy sequence on chromosome 4. Nucleic Acids Res. 1988 Mar 25;16(6):2743–2743. [PMC free article] [PubMed]
  • Bootsma D, McAlpine PJ. Report of the committee on the genetic constitution of chromosomes 2, 3, 4, and 5. Cytogenet Cell Genet. 1979;25(1-4):21–31. [PubMed]
  • Bućan M, Zimmer M, Whaley WL, Poustka A, Youngman S, Allitto BA, Ormondroyd E, Smith B, Pohl TM, MacDonald M, et al. Physical maps of 4p16.3, the area expected to contain the Huntington disease mutation. Genomics. 1990 Jan;6(1):1–15. [PubMed]
  • Carlock LR, Vo TD, DeHaven CR, Murray JC. An anonymous genomic clone that detects a frequent RFLP adjacent to the D4S10 (G8) marker and Huntington's disease. Nucleic Acids Res. 1987 Jan 12;15(1):377–377. [PMC free article] [PubMed]
  • Chandley AC, Mitchell AR. Hypervariable minisatellite regions are sites for crossing-over at meiosis in man. Cytogenet Cell Genet. 1988;48(3):152–155. [PubMed]
  • Collick A, Jeffreys AJ. Detection of a novel minisatellite-specific DNA-binding protein. Nucleic Acids Res. 1990 Feb 11;18(3):625–629. [PMC free article] [PubMed]
  • Cox DR, Murray JC, Buetow KH. Report of the committee on the genetic constitution of chromosome 4. Cytogenet Cell Genet. 1989;51(1-4):121–136. [PubMed]
  • Dietz JN, Robbins T, Cannon LA, Schwartz CE, Carey JC, Johnson JP, Kivlin J, Skolnick MH. Linkage analysis of Von Recklinghausen neurofibromatosis: chromosomes 4 and 19. Genet Epidemiol. 1986;3(5):313–321. [PubMed]
  • Doggett NA, Cheng JF, Smith CL, Cantor CR. The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10011–10014. [PMC free article] [PubMed]
  • Donis-Keller H, Green P, Helms C, Cartinhour S, Weiffenbach B, Stephens K, Keith TP, Bowden DW, Smith DR, Lander ES, et al. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. [PubMed]
  • Edwards JH. The interpretation of lods in linkage analysis. Cytogenet Cell Genet. 1976;16(1-5):289–293. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Georgiou C, Shull M, Lane LK, Lingrel JB, Murray JC. RFLPs for ATP1BL1 (beta subunit Na+/K+ ATPase pseudogene) on chromosome 4. Nucleic Acids Res. 1989 Nov 11;17(21):8894–8894. [PMC free article] [PubMed]
  • Gilliam TC, Bucan M, MacDonald ME, Zimmer M, Haines JL, Cheng SV, Pohl TM, Meyers RH, Whaley WL, Allitto BA, et al. A DNA segment encoding two genes very tightly linked to Huntington's disease. Science. 1987 Nov 13;238(4829):950–952. [PubMed]
  • Gilliam TC, Scambler P, Robbins T, Ingle C, Williamson R, Davies KE. The positions of three restriction fragment length polymorphisms on chromosome 4 relative to known genetic markers. Hum Genet. 1984;68(2):154–158. [PubMed]
  • Gilliam TC, Tanzi RE, Haines JL, Bonner TI, Faryniarz AG, Hobbs WJ, MacDonald ME, Cheng SV, Folstein SE, Conneally PM, et al. Localization of the Huntington's disease gene to a small segment of chromosome 4 flanked by D4S10 and the telomere. Cell. 1987 Aug 14;50(4):565–571. [PubMed]
  • Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature. 1983 Nov 17;306(5940):234–238. [PubMed]
  • Guzzo C, Weiner M, Rappaport E, LaRocco P, Surrey S, Poncz M, Schwartz E. An Eco R1 polymorphism of a human platelet factor 4 (PF4) gene. Nucleic Acids Res. 1987 Jan 12;15(1):380–380. [PMC free article] [PubMed]
  • Hayden MR, Hewitt J, Wasmuth JJ, Kastelein JJ, Langlois S, Conneally M, Haines J, Smith B, Hilbert C, Allard D. A polymorphic DNA marker that represents a conserved expressed sequence in the region of the Huntington disease gene. Am J Hum Genet. 1988 Jan;42(1):125–131. [PMC free article] [PubMed]
  • Hultén M. Chiasma distribution at diakinesis in the normal human male. Hereditas. 1974;76(1):55–78. [PubMed]
  • Humphries SE, Imam AM, Robbins TP, Cook M, Carritt B, Ingle C, Williamson R. The identification of a DNA polymorphism of the alpha fibrinogen gene, and the regional assignment of the human fibrinogen genes to 4q26-qter. Hum Genet. 1984;68(2):148–153. [PubMed]
  • Kato A, Asakai R, Davie EW, Aoki N. Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4. Cytogenet Cell Genet. 1989;52(1-2):77–78. [PubMed]
  • Lathrop M, Nakamura Y, Cartwright P, O'Connell P, Leppert M, Jones C, Tateishi H, Bragg T, Lalouel JM, White R. A primary genetic map of markers of human chromosome 10. Genomics. 1988 Feb;2(2):157–164. [PubMed]
  • Leysens NJ, Newkirk NG, Murray JC. SacI and XbaI polymorphisms detected by lipocortin 2A (LPC2A). Nucleic Acids Res. 1989 Jul 11;17(13):5417–5417. [PMC free article] [PubMed]
  • MacDonald ME, Haines JL, Zimmer M, Cheng SV, Youngman S, Whaley WL, Wexler N, Bucan M, Allitto BA, Smith B, et al. Recombination events suggest potential sites for the Huntington's disease gene. Neuron. 1989 Aug;3(2):183–190. [PubMed]
  • Mikkelsen M, Jacobsen P, Henningsen K. Possible localization of Gc-System on chromosome 4. Loss of long arm 4 material associated with father-child incompatibility within the Gc-System. Hum Hered. 1977;27(2):105–107. [PubMed]
  • Milner EC, Lotshaw CL, Willems van Dijk K, Charmley P, Concannon P, Schroeder HW., Jr Isolation and mapping of a polymorphic DNA sequence pH30 on chromosome 4[HGM provisional no. D4S139]. Nucleic Acids Res. 1989 May 25;17(10):4002–4002. [PMC free article] [PubMed]
  • Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ. Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. Hum Genet. 1990 Jan;84(2):185–187. [PubMed]
  • MORTON NE. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed]
  • Murray JC, Buetow KH, Smith M, Carlock L, Chakravarti A, Ferrell RF, Gedamu L, Gilliam C, Shiang R, DeHaven CR. Pairwise linkage analysis of 11 loci on human chromosome 4. Am J Hum Genet. 1988 Mar;42(3):490–497. [PMC free article] [PubMed]
  • Murray JC, Demopulos CM, Lawn RM, Motulsky AG. Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5951–5955. [PMC free article] [PubMed]
  • Murray JC, Shiang R, Carlock LR, Smith M, Buetow KH. Rapid RFLP screening procedure identifies new polymorphisms at albumin and alcohol dehydrogenase loci. Hum Genet. 1987 Jul;76(3):274–277. [PubMed]
  • Nakamura Y, Carlson M, Ballard L, O'Connell P, Leppert M, Lathrop GM, Lalouel JM, White R. Isolation and mapping of a polymorphic DNA sequence (pMCOC14) on chromosome 4p [D4S124]. Nucleic Acids Res. 1988 Jul 11;16(13):6254–6254. [PMC free article] [PubMed]
  • Nakamura Y, Culver M, O'Connell P, Leppert M, Lathrop GM, Lalouel JM, White R. Isolation and mapping of a polymorphic DNA sequence (pYNZ32) on chromosome 4p [D4S125]. Nucleic Acids Res. 1988 May 11;16(9):4186–4186. [PMC free article] [PubMed]
  • Pasquinelli C, Garreau F, Bougueleret L, Cariani E, Grzeschik KH, Thiers V, Croissant O, Hadchouel M, Tiollais P, Bréchot C. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors. J Virol. 1988 Feb;62(2):629–632. [PMC free article] [PubMed]
  • Pohl TM, Zimmer M, MacDonald ME, Smith B, Bucan M, Poustka A, Volinia S, Searle S, Zehetner G, Wasmuth JJ, et al. Construction of a NotI linking library and isolation of new markers close to the Huntington's disease gene. Nucleic Acids Res. 1988 Oct 11;16(19):9185–9198. [PMC free article] [PubMed]
  • Pritchard CA, Casher D, Uglum E, Cox DR, Myers RM. Isolation and field-inversion gel electrophoresis analysis of DNA markers located close to the Huntington disease gene. Genomics. 1989 Apr;4(3):408–418. [PubMed]
  • Richards JE, Gilliam TC, Cole JL, Drumm ML, Wasmuth JJ, Gusella JF, Collins FS. Chromosome jumping from D4S10 (G8) toward the Huntington disease gene. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6437–6441. [PMC free article] [PubMed]
  • Ritty TM, Murray JC. A new HincII RFLP for epidermal growth factor (EGF) on chromosome 4. Nucleic Acids Res. 1989 Jul 25;17(14):5870–5870. [PMC free article] [PubMed]
  • Royle NJ, Clarkson RE, Wong Z, Jeffreys AJ. Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. Genomics. 1988 Nov;3(4):352–360. [PubMed]
  • Scambler PJ, Lord R, Bates G, Williamson R. RFLP for D4S12, an anonymous single copy genomic clone at 4pter-4q26 [HGM8 provisional no. D4S12]. Nucleic Acids Res. 1985 Apr 25;13(8):3016–3016. [PMC free article] [PubMed]
  • Rouleau GA, Haines JL, Bazanowski A, Colella-Crowley A, Trofatter JA, Wexler NS, Conneally PM, Gusella JF. A genetic linkage map of the long arm of human chromosome 22. Genomics. 1989 Jan;4(1):1–6. [PubMed]
  • Smith B, Skarecky D, Bengtsson U, Magenis RE, Carpenter N, Wasmuth JJ. Isolation of DNA markers in the direction of the Huntington disease gene from the G8 locus. Am J Hum Genet. 1988 Feb;42(2):335–344. [PMC free article] [PubMed]
  • Snell RG, Lazarou LP, Youngman S, Quarrell OW, Wasmuth JJ, Shaw DJ, Harper PS. Linkage disequilibrium in Huntington's disease: an improved localisation for the gene. J Med Genet. 1989 Nov;26(11):673–675. [PMC free article] [PubMed]
  • Szauter P. An analysis of regional constraints on exchange in Drosophila melanogaster using recombination-defective meiotic mutants. Genetics. 1984 Jan;106(1):45–71. [PMC free article] [PubMed]
  • Theilmann J, Kanani S, Shiang R, Robbins C, Quarrell O, Huggins M, Hedrick A, Weber B, Collins C, Wasmuth JJ, et al. Non-random association between alleles detected at D4S95 and D4S98 and the Huntington's disease gene. J Med Genet. 1989 Nov;26(11):676–681. [PMC free article] [PubMed]
  • Whaley WL, Michiels F, MacDonald ME, Romano D, Zimmer M, Smith B, Leavitt J, Bucan M, Haines JL, Gilliam TC, et al. Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4. Nucleic Acids Res. 1988 Dec 23;16(24):11769–11780. [PMC free article] [PubMed]
  • Wood S, Starr TV, Shukin RJ. Isolation and characterization of DNA probes from a flow-sorted human chromosome 8 library that detect restriction fragment length polymorphism (RFLP). Am J Hum Genet. 1986 Dec;39(6):744–750. [PMC free article] [PubMed]
  • Youngman S, Shaw DJ, Gusella JF, MacDonald M, Stanbridge EJ, Wasmuth J, Harper PS. A DNA probe, D5 [D4S90] mapping to human chromosome 4p16.3. Nucleic Acids Res. 1988 Feb 25;16(4):1648–1648. [PMC free article] [PubMed]

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