Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 May;64(5):1427–1439. doi: 10.1086/302358

Evidence for effective suppression of recombination in the chromosome 17q21 segment spanning RNU2-BRCA1.

X Liu 1, D F Barker 1
PMCID: PMC1377881  PMID: 10205276

Abstract

Characterization of associations between polymorphic sites located throughout the approximately 200-400-kb variable-length region spanning RNU2-BRCA1 reveals nearly complete linkage disequilibrium. This segment spans the RNU2 array, which includes 6-30 tandem copies of the U2 snRNA gene, and an adjacent region containing NBR1, the LBRCA1 pseudogene, NBR2, and BRCA1 in a tandemly duplicated structure. A series of biallelic polymorphisms define two common haplotypes that do not vary significantly, in structure or frequency, between populations of primarily European (n=275) or Asian (n=34) ancestry. Lower-frequency variants occurring at distantly located sites within this region also show very strong associations. The rarer haplotype classes appear to be distinguished by mutational alteration and are not recombination products of the two major classes. The two major haplotypes also exhibit significantly different allele-length distributions for local simple tandem-repeat markers. The conservation of extensive distinct chromosomal haplotypes during a long period of human population expansion and divergence indicates that selective forces or specific chromosomal mechanisms result in effective recombination suppression. The extreme degree of long-range linkage disequilibrium at this locus may be exceeded only by that reported for the human MHC locus, where allele-specific functional interactions are believed to be significant. These findings have implications for the estimation of the time of origin of BRCA1 mutations having a founder effect, the interpretation of the significance of rare allelic variants, and the study of the origins of modern populations.

Full Text

The Full Text of this article is available as a PDF (380.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abeliovich D., Kaduri L., Lerer I., Weinberg N., Amir G., Sagi M., Zlotogora J., Heching N., Peretz T. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet. 1997 Mar;60(3):505–514. [PMC free article] [PubMed] [Google Scholar]
  2. Albertsen H. M., Smith S. A., Mazoyer S., Fujimoto E., Stevens J., Williams B., Rodriguez P., Cropp C. S., Slijepcevic P., Carlson M. A physical map and candidate genes in the BRCA1 region on chromosome 17q12-21. Nat Genet. 1994 Aug;7(4):472–479. doi: 10.1038/ng0894-472. [DOI] [PubMed] [Google Scholar]
  3. Armour J. A., Anttinen T., May C. A., Vega E. E., Sajantila A., Kidd J. R., Kidd K. K., Bertranpetit J., Päbo S., Jeffreys A. J. Minisatellite diversity supports a recent African origin for modern humans. Nat Genet. 1996 Jun;13(2):154–160. doi: 10.1038/ng0696-154. [DOI] [PubMed] [Google Scholar]
  4. Balnaves M. E., Nasioulas S., Dahl H. H., Forrest S. Direct PCR from CVS and blood lysates for detection of cystic fibrosis and Duchenne muscular dystrophy deletions. Nucleic Acids Res. 1991 Mar 11;19(5):1155–1155. doi: 10.1093/nar/19.5.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bar-Sade R. B., Kruglikova A., Modan B., Gak E., Hirsh-Yechezkel G., Theodor L., Novikov I., Gershoni-Baruch R., Risel S., Papa M. Z. The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim. Hum Mol Genet. 1998 May;7(5):801–805. doi: 10.1093/hmg/7.5.801. [DOI] [PubMed] [Google Scholar]
  6. Barker D. F., Almeida E. R., Casey G., Fain P. R., Liao S. Y., Masunaka I., Noble B., Kurosaki T., Anton-Culver H. BRCA1 R841W: a strong candidate for a common mutation with moderate phenotype. Genet Epidemiol. 1996;13(6):595–604. doi: 10.1002/(SICI)1098-2272(1996)13:6<595::AID-GEPI5>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  7. Barker D. F., Fain P. R. Definition and mapping of STSs at STR and RFLP loci in Xp11-Xq22. Genomics. 1993 Dec;18(3):712–716. doi: 10.1016/s0888-7543(05)80381-7. [DOI] [PubMed] [Google Scholar]
  8. Barker D. F., Liu X., Almeida E. R. The BRCA1 and 1A1.3B promoters are parallel elements of a genomic duplication at 17q21. Genomics. 1996 Dec 1;38(2):215–222. doi: 10.1006/geno.1996.0618. [DOI] [PubMed] [Google Scholar]
  9. Barker D., Holm T., White R. A locus on chromosome 11p with multiple restriction site polymorphisms. Am J Hum Genet. 1984 Nov;36(6):1159–1171. [PMC free article] [PubMed] [Google Scholar]
  10. Begovich A. B., McClure G. R., Suraj V. C., Helmuth R. C., Fildes N., Bugawan T. L., Erlich H. A., Klitz W. Polymorphism, recombination, and linkage disequilibrium within the HLA class II region. J Immunol. 1992 Jan 1;148(1):249–258. [PubMed] [Google Scholar]
  11. Bennett-Baker P. E., Kiousis S., Chandrasekharappa S. C., King S. E., Abel K. J., Collins F. S., Weber B. L., Chamberlain J. S. Isolation of tetranucleotide repeat polymorphisms flanking the BRCA1 gene. Genomics. 1996 Feb 15;32(1):163–167. doi: 10.1006/geno.1996.0097. [DOI] [PubMed] [Google Scholar]
  12. Blackshear P. E., Goldsworthy S. M., Foley J. F., McAllister K. A., Bennett L. M., Collins N. K., Bunch D. O., Brown P., Wiseman R. W., Davis B. J. Brca1 and Brca2 expression patterns in mitotic and meiotic cells of mice. Oncogene. 1998 Jan 8;16(1):61–68. doi: 10.1038/sj.onc.1201506. [DOI] [PubMed] [Google Scholar]
  13. Blouin J. L., Christie D. H., Gos A., Lynn A., Morris M. A., Ledbetter D. H., Chakravarti A., Antonarakis S. E. A new dinucleotide repeat polymorphism at the telomere of chromosome 21q reveals a significant difference between male and female rates of recombination. Am J Hum Genet. 1995 Aug;57(2):388–394. [PMC free article] [PubMed] [Google Scholar]
  14. Brinkmann B., Klintschar M., Neuhuber F., Hühne J., Rolf B. Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet. 1998 Jun;62(6):1408–1415. doi: 10.1086/301869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Brown M. A., Xu C. F., Nicolai H., Griffiths B., Chambers J. A., Black D., Solomon E. The 5' end of the BRCA1 gene lies within a duplicated region of human chromosome 17q21. Oncogene. 1996 Jun 20;12(12):2507–2513. [PubMed] [Google Scholar]
  16. Buetow K. H., Shiang R., Yang P., Nakamura Y., Lathrop G. M., White R., Wasmuth J. J., Wood S., Berdahl L. D., Leysens N. J. A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates. Am J Hum Genet. 1991 May;48(5):911–925. [PMC free article] [PubMed] [Google Scholar]
  17. Callebaut I., Mornon J. P. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett. 1997 Jan 2;400(1):25–30. doi: 10.1016/s0014-5793(96)01312-9. [DOI] [PubMed] [Google Scholar]
  18. Campbell I. G., Nicolai H. M., Foulkes W. D., Senger G., Stamp G. W., Allan G., Boyer C., Jones K., Bast R. C., Jr, Solomon E. A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. Hum Mol Genet. 1994 Apr;3(4):589–594. doi: 10.1093/hmg/3.4.589. [DOI] [PubMed] [Google Scholar]
  19. Cann R. L. Phylogenetic estimation in humans and neck riddles. Am J Hum Genet. 1997 Apr;60(4):755–757. [PMC free article] [PubMed] [Google Scholar]
  20. Castiglione C. M., Deinard A. S., Speed W. C., Sirugo G., Rosenbaum H. C., Zhang Y., Grandy D. K., Grigorenko E. L., Bonne-Tamir B., Pakstis A. J. Evolution of haplotypes at the DRD2 locus. Am J Hum Genet. 1995 Dec;57(6):1445–1456. [PMC free article] [PubMed] [Google Scholar]
  21. Castilla L. H., Couch F. J., Erdos M. R., Hoskins K. F., Calzone K., Garber J. E., Boyd J., Lubin M. B., Deshano M. L., Brody L. C. Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer. Nat Genet. 1994 Dec;8(4):387–391. doi: 10.1038/ng1294-387. [DOI] [PubMed] [Google Scholar]
  22. Chakravarti A., Buetow K. H., Antonarakis S. E., Waber P. G., Boehm C. D., Kazazian H. H. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet. 1984 Nov;36(6):1239–1258. [PMC free article] [PubMed] [Google Scholar]
  23. Charmley P., Concannon P., Hood L., Rowen L. Frequency and polymorphism of simple sequence repeats in a contiguous 685-kb DNA sequence containing the human T-cell receptor beta-chain gene complex. Genomics. 1995 Oct 10;29(3):760–765. doi: 10.1006/geno.1995.9940. [DOI] [PubMed] [Google Scholar]
  24. Couch F. J., Castilla L. H., Xu J., Abel K. J., Welcsh P., King S. E., Wong L., Ho P. P., Merajver S., Brody L. C. A YAC-, P1-, and cosmid-based physical map of the BRCA1 region on chromosome 17q21. Genomics. 1995 Jan 1;25(1):264–273. doi: 10.1016/0888-7543(95)80134-8. [DOI] [PubMed] [Google Scholar]
  25. Couch F. J., Kiousis S., Castilla L. H., Xu J., Chandrasekharappa S. C., Chamberlain J. S., Collins F. S., Weber B. L. Characterization of 10 new polymorphic dinucleotide repeats and generation of a high-density microsatellite-based physical map of the BRCA1 region of chromosome 17q21. Genomics. 1994 Dec;24(3):419–424. doi: 10.1006/geno.1994.1647. [DOI] [PubMed] [Google Scholar]
  26. Cullen M., Noble J., Erlich H., Thorpe K., Beck S., Klitz W., Trowsdale J., Carrington M. Characterization of recombination in the HLA class II region. Am J Hum Genet. 1997 Feb;60(2):397–407. [PMC free article] [PubMed] [Google Scholar]
  27. Doherty D. G., Vaughan R. W., Donaldson P. T., Mowat A. P. HLA DQA, DQB, and DRB genotyping by oligonucleotide analysis: distribution of alleles and haplotypes in British caucasoids. Hum Immunol. 1992 May;34(1):53–63. doi: 10.1016/0198-8859(92)90085-2. [DOI] [PubMed] [Google Scholar]
  28. Dunning A. M., Chiano M., Smith N. R., Dearden J., Gore M., Oakes S., Wilson C., Stratton M., Peto J., Easton D. Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum Mol Genet. 1997 Feb;6(2):285–289. doi: 10.1093/hmg/6.2.285. [DOI] [PubMed] [Google Scholar]
  29. Durocher F., Shattuck-Eidens D., McClure M., Labrie F., Skolnick M. H., Goldgar D. E., Simard J. Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Mol Genet. 1996 Jun;5(6):835–842. doi: 10.1093/hmg/5.6.835. [DOI] [PubMed] [Google Scholar]
  30. Fain P. R., Goldgar D. E., Wallace M. R., Collins F. S., Wright E., Nguyen K., Barker D. F. Refined physical and genetic mapping of the NF1 region on chromosome 17. Am J Hum Genet. 1989 Nov;45(5):721–728. [PMC free article] [PubMed] [Google Scholar]
  31. Friedman L. S., Ostermeyer E. A., Szabo C. I., Dowd P., Lynch E. D., Rowell S. E., King M. C. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet. 1994 Dec;8(4):399–404. doi: 10.1038/ng1294-399. [DOI] [PubMed] [Google Scholar]
  32. Gao X. J., Sun Y. P., An J. B., Fernandez-Viña M., Qou J. N., Lin L., Stastny P. DNA typing for HLA-DR, and -DP alleles in a Chinese population using the polymerase chain reaction (PCR) and oligonucleotide probes. Tissue Antigens. 1991 Jul;38(1):24–30. doi: 10.1111/j.1399-0039.1991.tb02031.x. [DOI] [PubMed] [Google Scholar]
  33. Gyllensten U. B., Erlich H. A. MHC class II haplotypes and linkage disequilibrium in primates. Hum Immunol. 1993 Jan;36(1):1–10. doi: 10.1016/0198-8859(93)90002-i. [DOI] [PubMed] [Google Scholar]
  34. Harding R. M., Fullerton S. M., Griffiths R. C., Bond J., Cox M. J., Schneider J. A., Moulin D. S., Clegg J. B. Archaic African and Asian lineages in the genetic ancestry of modern humans. Am J Hum Genet. 1997 Apr;60(4):772–789. [PMC free article] [PubMed] [Google Scholar]
  35. Hauge X. Y., Litt M. A study of the origin of 'shadow bands' seen when typing dinucleotide repeat polymorphisms by the PCR. Hum Mol Genet. 1993 Apr;2(4):411–415. doi: 10.1093/hmg/2.4.411. [DOI] [PubMed] [Google Scholar]
  36. Hill W. G., Weir B. S. Variances and covariances of squared linkage disequilibria in finite populations. Theor Popul Biol. 1988 Feb;33(1):54–78. doi: 10.1016/0040-5809(88)90004-4. [DOI] [PubMed] [Google Scholar]
  37. Humphrey J. S., Salim A., Erdos M. R., Collins F. S., Brody L. C., Klausner R. D. Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5820–5825. doi: 10.1073/pnas.94.11.5820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Inoue R., Fukutomi T., Ushijima T., Matsumoto Y., Sugimura T., Nagao M. Germline mutation of BRCA1 in Japanese breast cancer families. Cancer Res. 1995 Aug 15;55(16):3521–3524. [PubMed] [Google Scholar]
  39. Jones K. A., Black D. M., Brown M. A., Griffiths B. L., Nicolai H. M., Chambers J. A., Bonjardim M., Xu C. F., Boyd M., McFarlane R. The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase. Hum Mol Genet. 1994 Nov;3(11):1927–1934. [PubMed] [Google Scholar]
  40. Jorde L. B., Watkins W. S., Carlson M., Groden J., Albertsen H., Thliveris A., Leppert M. Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Am J Hum Genet. 1994 May;54(5):884–898. [PMC free article] [PubMed] [Google Scholar]
  41. Jorde L. B., Watkins W. S., Viskochil D., O'Connell P., Ward K. Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping. Am J Hum Genet. 1993 Nov;53(5):1038–1050. [PMC free article] [PubMed] [Google Scholar]
  42. Klitz W., Stephens J. C., Grote M., Carrington M. Discordant patterns of linkage disequilibrium of the peptide-transporter loci within the HLA class II region. Am J Hum Genet. 1995 Dec;57(6):1436–1444. [PMC free article] [PubMed] [Google Scholar]
  43. Krawczak M., Ball E. V., Cooper D. N. Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am J Hum Genet. 1998 Aug;63(2):474–488. doi: 10.1086/301965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Krawczak M., Cooper D. N. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet. 1991 Mar;86(5):425–441. doi: 10.1007/BF00194629. [DOI] [PubMed] [Google Scholar]
  45. Levy-Lahad E., Catane R., Eisenberg S., Kaufman B., Hornreich G., Lishinsky E., Shohat M., Weber B. L., Beller U., Lahad A. Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet. 1997 May;60(5):1059–1067. [PMC free article] [PubMed] [Google Scholar]
  46. Liao D., Pavelitz T., Kidd J. R., Kidd K. K., Weiner A. M. Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion. EMBO J. 1997 Feb 3;16(3):588–598. doi: 10.1093/emboj/16.3.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Liao D., Weiner A. M. Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT)n.(GA)n microsatellite embedded within the U2 repeat unit. Genomics. 1995 Dec 10;30(3):583–593. doi: 10.1006/geno.1995.1280. [DOI] [PubMed] [Google Scholar]
  48. Lichten M., Goldman A. S. Meiotic recombination hotspots. Annu Rev Genet. 1995;29:423–444. doi: 10.1146/annurev.ge.29.120195.002231. [DOI] [PubMed] [Google Scholar]
  49. Lifton R. P., Sardet C., Pouyssegur J., Lalouel J. M. Cloning of the human genomic amiloride-sensitive Na+/H+ antiporter gene, identification of genetic polymorphisms, and localization on the genetic map of chromosome 1p. Genomics. 1990 May;7(1):131–135. doi: 10.1016/0888-7543(90)90530-8. [DOI] [PubMed] [Google Scholar]
  50. Malfroy L., Roth M. P., Carrington M., Borot N., Volz A., Ziegler A., Coppin H. Heterogeneity in rates of recombination in the 6-Mb region telomeric to the human major histocompatibility complex. Genomics. 1997 Jul 15;43(2):226–231. doi: 10.1006/geno.1997.4800. [DOI] [PubMed] [Google Scholar]
  51. Martin M., Mann D., Carrington M. Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes. Hum Mol Genet. 1995 Mar;4(3):423–428. doi: 10.1093/hmg/4.3.423. [DOI] [PubMed] [Google Scholar]
  52. McGinnis R. E., Spielman R. S. Linkage disequilibrium in the insulin gene region: size variation at the 5' flanking polymorphism and bimodality among "class I" alleles. Am J Hum Genet. 1994 Sep;55(3):526–532. [PMC free article] [PubMed] [Google Scholar]
  53. Miki Y., Swensen J., Shattuck-Eidens D., Futreal P. A., Harshman K., Tavtigian S., Liu Q., Cochran C., Bennett L. M., Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct 7;266(5182):66–71. doi: 10.1126/science.7545954. [DOI] [PubMed] [Google Scholar]
  54. Mountain J. L., Cavalli-Sforza L. L. Multilocus genotypes, a tree of individuals, and human evolutionary history. Am J Hum Genet. 1997 Sep;61(3):705–718. doi: 10.1086/515510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Nagaraja R., MacMillan S., Kere J., Jones C., Griffin S., Schmatz M., Terrell J., Shomaker M., Jermak C., Hott C. X chromosome map at 75-kb STS resolution, revealing extremes of recombination and GC content. Genome Res. 1997 Mar;7(3):210–222. doi: 10.1101/gr.7.3.210. [DOI] [PubMed] [Google Scholar]
  56. Neuhausen S. L., Mazoyer S., Friedman L., Stratton M., Offit K., Caligo A., Tomlinson G., Cannon-Albright L., Bishop T., Kelsell D. Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet. 1996 Feb;58(2):271–280. [PMC free article] [PubMed] [Google Scholar]
  57. Neuhausen S. L., Swensen J., Miki Y., Liu Q., Tavtigian S., Shattuck-Eidens D., Kamb A., Hobbs M. R., Gingrich J., Shizuya H. A P1-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1. Hum Mol Genet. 1994 Nov;3(11):1919–1926. doi: 10.1093/hmg/3.11.1919. [DOI] [PubMed] [Google Scholar]
  58. Newman B., Mu H., Butler L. M., Millikan R. C., Moorman P. G., King M. C. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA. 1998 Mar 25;279(12):915–921. doi: 10.1001/jama.279.12.915. [DOI] [PubMed] [Google Scholar]
  59. Normand T., Narod S., Labrie F., Simard J. Detection of polymorphisms in the estradiol 17 beta-hydroxysteroid dehydrogenase II gene at the EDH17B2 locus on 17q11-q21. Hum Mol Genet. 1993 Apr;2(4):479–483. doi: 10.1093/hmg/2.4.479. [DOI] [PubMed] [Google Scholar]
  60. Pavelitz T., Rusché L., Matera A. G., Scharf J. M., Weiner A. M. Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. EMBO J. 1995 Jan 3;14(1):169–177. doi: 10.1002/j.1460-2075.1995.tb06987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Rodenhiser D., Chakraborty P., Andrews J., Ainsworth P., Mancini D., Lopes E., Singh S. Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs. Oncogene. 1996 Jun 20;12(12):2623–2629. [PubMed] [Google Scholar]
  62. Scully R., Chen J., Plug A., Xiao Y., Weaver D., Feunteun J., Ashley T., Livingston D. M. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell. 1997 Jan 24;88(2):265–275. doi: 10.1016/s0092-8674(00)81847-4. [DOI] [PubMed] [Google Scholar]
  63. Sherrington R., Melmer G., Dixon M., Curtis D., Mankoo B., Kalsi G., Gurling H. Linkage disequilibrium between two highly polymorphic microsatellites. Am J Hum Genet. 1991 Nov;49(5):966–971. [PMC free article] [PubMed] [Google Scholar]
  64. Smith T. M., Lee M. K., Szabo C. I., Jerome N., McEuen M., Taylor M., Hood L., King M. C. Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. Genome Res. 1996 Nov;6(11):1029–1049. doi: 10.1101/gr.6.11.1029. [DOI] [PubMed] [Google Scholar]
  65. Tonin P., Serova O., Simard J., Lenoir G., Feunteun J., Morgan K., Lynch H., Narod S. The gene for hereditary breast-ovarian cancer, BRCA1, maps distal to EDH17B2 in chromosome region 17q12-q21. Hum Mol Genet. 1994 Sep;3(9):1679–1682. doi: 10.1093/hmg/3.9.1679. [DOI] [PubMed] [Google Scholar]
  66. Valero M. C., Velasco E., Valero A., Moreno F., Hernández-Chico C. Linkage disequilibrium between four intragenic polymorphic microsatellites of the NF1 gene and its implications for genetic counselling. J Med Genet. 1996 Jul;33(7):590–593. doi: 10.1136/jmg.33.7.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Watkins W. S., Zenger R., O'Brien E., Nyman D., Eriksson A. W., Renlund M., Jorde L. B. Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region. Am J Hum Genet. 1994 Aug;55(2):348–355. [PMC free article] [PubMed] [Google Scholar]
  68. Weber J. L. Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms. Genomics. 1990 Aug;7(4):524–530. doi: 10.1016/0888-7543(90)90195-z. [DOI] [PubMed] [Google Scholar]
  69. Weber J. L., Wong C. Mutation of human short tandem repeats. Hum Mol Genet. 1993 Aug;2(8):1123–1128. doi: 10.1093/hmg/2.8.1123. [DOI] [PubMed] [Google Scholar]
  70. Westin G., Zabielski J., Hammarström K., Monstein H. J., Bark C., Pettersson U. Clustered genes for human U2 RNA. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3811–3815. doi: 10.1073/pnas.81.12.3811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Xu C. F., Brown M. A., Nicolai H., Chambers J. A., Griffiths B. L., Solomon E. Isolation and characterisation of the NBR2 gene which lies head to head with the human BRCA1 gene. Hum Mol Genet. 1997 Jul;6(7):1057–1062. doi: 10.1093/hmg/6.7.1057. [DOI] [PubMed] [Google Scholar]
  72. Xu C. F., Chambers J. A., Solomon E. Complex regulation of the BRCA1 gene. J Biol Chem. 1997 Aug 22;272(34):20994–20997. doi: 10.1074/jbc.272.34.20994. [DOI] [PubMed] [Google Scholar]
  73. Zabludoff S. D., Wright W. W., Harshman K., Wold B. J. BRCA1 mRNA is expressed highly during meiosis and spermiogenesis but not during mitosis of male germ cells. Oncogene. 1996 Aug 1;13(3):649–653. [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES