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. 1991 Mar;48(3):613–620.

Km typing with PCR: application to population screening.

J H Kurth 1, A M Bowcock 1, H A Erlich 1, S Nevo 1, L L Cavalli-Sforza 1
PMCID: PMC1682986  PMID: 1900145

Abstract

The immunoglobulin kappa light chain (IgK) locus may play a significant role in the pathology of both infectious and autoimmune diseases. Most of the work on IgK genetics has been conducted using immunological techniques for allelic typing and sequence analysis. This is restricted by availability of reagents and can be both expensive and time-consuming. PCR primers were designed to amplify the kappa constant gene (Ck), and four allele-specific oligonucleotides (ASOs) were used to distinguish the alleles in the amplified PCR products. Direct sequencing of PCR products was performed to confirm that the primers specifically amplified the Ck region and the ASOs differentiated the Km alleles. Sequencing of an average of 209 nucleotides of DNA from 50 individuals revealed no variation except at codon 191, which is known to be involved in a frequent polymorphism. An analysis of 347 different individual DNAs from 10 human populations was conducted to determine Km allelic frequencies within these populations and to apply this type of data collection to population studies.

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Selected References

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

  1. Bentley D. L., Rabbitts T. H. Human V kappa immunoglobulin gene number: implications for the origin of antibody diversity. Cell. 1981 Jun;24(3):613–623. doi: 10.1016/0092-8674(81)90088-x. [DOI] [PubMed] [Google Scholar]
  2. Berr C., Dugoujon J. M., Clanet M., Cambon-Thomsen A., Alperovitch A. A possible new genetic marker associated with a severe course of multiple sclerosis, located on chromosome 2: Km. N Engl J Med. 1989 Feb 16;320(7):467–467. doi: 10.1056/NEJM198902163200715. [DOI] [PubMed] [Google Scholar]
  3. Bowcock A. M., Bucci C., Hebert J. M., Kidd J. R., Kidd K. K., Friedlaender J. S., Cavalli-Sforza L. L. Study of 47 DNA markers in five populations from four continents. Gene Geogr. 1987 Apr;1(1):47–64. [PubMed] [Google Scholar]
  4. Brachtel R., Walter H., Beck W., Hilling M. Associations between atopic diseases and the polymorphic systems ABO, Kidd, Inv and red cell acid phosphatase. Hum Genet. 1979 Jul 18;49(3):337–348. doi: 10.1007/BF00569354. [DOI] [PubMed] [Google Scholar]
  5. Cavalli-Sforza L. L., Kidd J. R., Kidd K. K., Bucci C., Bowcock A. M., Hewlett B. S., Freidlaender J. S. DNA markers and genetic variation in the human species. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):411–417. doi: 10.1101/sqb.1986.051.01.049. [DOI] [PubMed] [Google Scholar]
  6. Emanuel B. S., Selden J. R., Chaganti R. S., Jhanwar S., Nowell P. C., Croce C. M. The 2p breakpoint of a 2;8 translocation in Burkitt lymphoma interrupts the V kappa locus. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2444–2446. doi: 10.1073/pnas.81.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hartl P., Lipp M. Generation of a variant t(2;8) translocation of Burkitt's lymphoma by site-specific recombination via the kappa light-chain joining signals. Mol Cell Biol. 1987 Jun;7(6):2037–2045. doi: 10.1128/mcb.7.6.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hieter P. A., Max E. E., Seidman J. G., Maizel J. V., Jr, Leder P. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments. Cell. 1980 Nov;22(1 Pt 1):197–207. doi: 10.1016/0092-8674(80)90168-3. [DOI] [PubMed] [Google Scholar]
  9. Kijner C. H., Yousem S. A. Systemic light chain deposition disease presenting as multiple pulmonary nodules. A case report and review of the literature. Am J Surg Pathol. 1988 May;12(5):405–413. doi: 10.1097/00000478-198805000-00009. [DOI] [PubMed] [Google Scholar]
  10. Klobeck H. G., Solomon A., Zachau H. G. Contribution of human V kappa II germ-line genes to light-chain diversity. Nature. 1984 May 3;309(5963):73–76. doi: 10.1038/309073a0. [DOI] [PubMed] [Google Scholar]
  11. Le Petit J. C., Van Loghem E., De Lange G., Berthoux F. C., Chapuis-Cellier C., Serre J. L. GM, AM, PI and KM markers in mesangial IGA glomerulonephritis. J Immunogenet. 1981 Oct;8(5):415–418. [PubMed] [Google Scholar]
  12. Lenoir A. A., Pandey J. P., Granoff D. M. Antibody responses of black children to Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer-membrane protein conjugate vaccine in relation to the Km(1) allotype. J Infect Dis. 1988 Jun;157(6):1242–1245. doi: 10.1093/infdis/157.6.1242. [DOI] [PubMed] [Google Scholar]
  13. Magrath I., Erikson J., Whang-Peng J., Sieverts H., Armstrong G., Benjamin D., Triche T., Alabaster O., Croce C. M. Synthesis of kappa light chains by cell lines containing an 8;22 chromosomal translocation derived from a male homosexual with Burkitt's lymphoma. Science. 1983 Dec 9;222(4628):1094–1098. doi: 10.1126/science.6316501. [DOI] [PubMed] [Google Scholar]
  14. Milstein C. P., Steinberg A. G., McLaughlin C. L., Solomon A. Amino acid sequence change associated with genetic marker Inv(2) of human immunoglobulin. Nature. 1974 Mar 8;248(5444):160–161. doi: 10.1038/248160a0. [DOI] [PubMed] [Google Scholar]
  15. Reynolds J., Weir B. S., Cockerham C. C. Estimation of the coancestry coefficient: basis for a short-term genetic distance. Genetics. 1983 Nov;105(3):767–779. doi: 10.1093/genetics/105.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Saiki R. K., Chang C. A., Levenson C. H., Warren T. C., Boehm C. D., Kazazian H. H., Jr, Erlich H. A. Diagnosis of sickle cell anemia and beta-thalassemia with enzymatically amplified DNA and nonradioactive allele-specific oligonucleotide probes. N Engl J Med. 1988 Sep 1;319(9):537–541. doi: 10.1056/NEJM198809013190903. [DOI] [PubMed] [Google Scholar]
  17. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  18. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stevenson J. C., Schanfield M. S., Sandler S. G. Immunoglobulin allotypes in Jewish populations living in Israel and the United States. Am J Phys Anthropol. 1985 Jul;67(3):195–207. doi: 10.1002/ajpa.1330670305. [DOI] [PubMed] [Google Scholar]
  20. Taussig M. J. Molecular genetics of immunoglobulins. Immunol Suppl. 1988;1:7–15. [PubMed] [Google Scholar]
  21. Terry W. D., Fahley J. L., Steinberg A. G. GM and INV factors in subclasses of human IgG. J Exp Med. 1965 Dec 1;122(6):1087–1102. doi: 10.1084/jem.122.6.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vogel F., Kruger J., Chakravartti M. R., Ritter H., Flatz G. ABO blood groups , Inv serum groups, and serum proteins in leprosy patients from West Bengal (India). Humangenetik. 1971;12(4):284–301. doi: 10.1007/BF00278049. [DOI] [PubMed] [Google Scholar]
  23. Whittingham S., Propert D. N., Mackay I. R. A strong association between the antinuclear antibody anti-La (SS-B) and the kappa chain allotype Km(1). Immunogenetics. 1984;19(4):295–299. doi: 10.1007/BF00345402. [DOI] [PubMed] [Google Scholar]
  24. Zimmer F. J., Hameister H., Schek H., Zachau H. G. Transposition of human immunoglobulin V kappa genes within the same chromosome and the mechanism of their amplification. EMBO J. 1990 May;9(5):1535–1542. doi: 10.1002/j.1460-2075.1990.tb08272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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