Abstract
Genetic analyses of multiple restriction fragment length polymorphisms, revealed by a single DNA probe containing the switch region of the immunoglobulin constant heavy-chain (IgCH) mu gene, are presented here in detail. Five of the polymorphic loci segregate in complete linkage with IgCH allotypic markers, while one appears to be located at more than 10 centimorgans from the IgCH region. A study of over 100 random haplotypes typed at eight linked loci, including the Ig switch polymorphisms and the classical Gm-Am allotypes, allowed us to construct an evolutionary tree by which each haplotypic variant can be derived one from the other either by single-step mutation or by recombination. A few of the recombinant haplotypes appeared to carry large DNA duplications that could be explained by unequal crossing over; others might postulate gene-conversion events. Linkage disequilibria observed between the IgCH-linked loci were compared with expected ones. A heterogeneous distribution of recombination rates is clearly documented, a "hot" region of recombination being present between the gamma 2 and switch alpha 2 loci.
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- Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
- Bech-Hansen N. T., Linsley P. S., Cox D. W. Restriction fragment length polymorphisms associated with immunoglobulin C gamma genes reveal linkage disequilibrium and genomic organization. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6952–6956. doi: 10.1073/pnas.80.22.6952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carroll M. C., Campbell R. D., Bentley D. R., Porter R. R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984 Jan 19;307(5948):237–241. doi: 10.1038/307237a0. [DOI] [PubMed] [Google Scholar]
- Donald J. A., Ball S. P. Approximate linkage equilibrium between two polymorphic sites within the gene for human complement component 3. Ann Hum Genet. 1984 Jul;48(Pt 3):269–273. doi: 10.1111/j.1469-1809.1984.tb01024.x. [DOI] [PubMed] [Google Scholar]
- Egel R. Intergenic conversion and reiterated genes. Nature. 1981 Mar 19;290(5803):191–192. doi: 10.1038/290191a0. [DOI] [PubMed] [Google Scholar]
- Flanagan J. G., Rabbitts T. H. Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes. Nature. 1982 Dec 23;300(5894):709–713. doi: 10.1038/300709a0. [DOI] [PubMed] [Google Scholar]
- Karlin S., Piazza A. Statistical methods for assessing linkage disequilibrium at the HLA-A, B, C loci. Ann Hum Genet. 1981 Feb;45(Pt 1):79–94. doi: 10.1111/j.1469-1809.1981.tb00308.x. [DOI] [PubMed] [Google Scholar]
- Kirsch I. R., Morton C. C., Nakahara K., Leder P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982 Apr 16;216(4543):301–303. doi: 10.1126/science.6801764. [DOI] [PubMed] [Google Scholar]
- Lefranc M. P., Lefranc G., Rabbitts T. H. Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature. 1982 Dec 23;300(5894):760–762. doi: 10.1038/300760a0. [DOI] [PubMed] [Google Scholar]
- Lefranc M. P., Lefranc G., de Lange G., Out T. A., van den Broek P. J., van Nieuwkoop J., Radl J., Helal A. N., Chaabani H., van Loghem E. Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions. Mol Biol Med. 1983 Sep;1(2):207–217. [PubMed] [Google Scholar]
- Migone N., Feder J., Cann H., van West B., Hwang J., Takahashi N., Honjo T., Piazza A., Cavalli-Sforza L. L. Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man. Proc Natl Acad Sci U S A. 1983 Jan;80(2):467–471. doi: 10.1073/pnas.80.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Migone N., Oliviero S., de Lange G., Delacroix D. L., Boschis D., Altruda F., Silengo L., DeMarchi M., Carbonara A. O. Multiple gene deletions within the human immunoglobulin heavy-chain cluster. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5811–5815. doi: 10.1073/pnas.81.18.5811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morton N. E., Simpson S. P. Kinship mapping of multilocus systems. Hum Genet. 1983;64(2):103–104. doi: 10.1007/BF00327102. [DOI] [PubMed] [Google Scholar]
- Natvig J. B., Kunkel H. G. Human immunoglobulins: classes, subclasses, genetic variants, and idiotypes. Adv Immunol. 1973;16:1–59. doi: 10.1016/s0065-2776(08)60295-3. [DOI] [PubMed] [Google Scholar]
- Renwick J. H. Progress in mapping human autosomes. Br Med Bull. 1969 Jan;25(1):65–73. doi: 10.1093/oxfordjournals.bmb.a070673. [DOI] [PubMed] [Google Scholar]
- Shimizu A., Takahashi N., Yaoita Y., Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell. 1982 Mar;28(3):499–506. doi: 10.1016/0092-8674(82)90204-5. [DOI] [PubMed] [Google Scholar]
- Steinmetz M., Minard K., Horvath S., McNicholas J., Srelinger J., Wake C., Long E., Mach B., Hood L. A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature. 1982 Nov 4;300(5887):35–42. doi: 10.1038/300035a0. [DOI] [PubMed] [Google Scholar]
- Sved J. A., Feldman M. W. Correlation and probability methods for one and two loci. Theor Popul Biol. 1973 Mar;4(1):129–132. doi: 10.1016/0040-5809(73)90008-7. [DOI] [PubMed] [Google Scholar]
- Sved J. A. Linkage disequilibrium and homozygosity of chromosome segments in finite populations. Theor Popul Biol. 1971 Jun;2(2):125–141. doi: 10.1016/0040-5809(71)90011-6. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Nakai S., Honjo T. Cloning of human immunoglobulin mu gene and comparison with mouse mu gene. Nucleic Acids Res. 1980 Dec 20;8(24):5983–5991. doi: 10.1093/nar/8.24.5983. [DOI] [PMC free article] [PubMed] [Google Scholar]