Home LiteratureArticle Details
PMID: 12628931 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

High-resolution sperm typing of meiotic recombination in the mouse MHC Ebeta gene.

The EMBO journal ·Vol. 22 ·No. 6 ·2003-03-17 ·Pages 1389-97

Yauk CL, Bois PR, Jeffreys AJ

Abstract

Meiotic crossovers detected by pedigree analysis in the mouse MHC cluster into hotspots. To explore the properties of hotspots, we subjected the class II E(beta) gene to high-resolution sperm crossover analysis. We confirm the presence of a highly localized hotspot 1.0-1.6 kb wide in the second intron of E(beta) and show that it is flanked by DNA which is almost completely recombinationally inert. Mice heterozygous for haplotype s and another MHC haplotype show major haplotype-dependant variation in crossover rate but always the same hotspot, even in crosses including the highly diverged p haplotype. Crossovers in reciprocal orientations occur at similar rates but show different distributions across the hotspot, with the position of centre points in the two orientations shifted on average by 400 bp. This asymmetry results in crossover products showing biased gene conversion in favour of hotspot markers from the non-initiating haplotype, and supports the double-strand break repair model of recombination, with haplotype s as the most efficient crossover initiator. The detailed behaviour of the E(beta) hotspot, including evidence for highly localized recombination initiation, is strikingly similar to human hotspots.

MeSH Terms
Alleles Animals Base Sequence Crossing Over, Genetic Genes, MHC Class II Genetic Markers Genetic Variation Haplotypes Introns Major Histocompatibility Complex Male Meiosis/genetics Mice Mice, Inbred C57BL Mice, Inbred Strains Polymorphism, Single Nucleotide Recombination, Genetic Spermatozoa/metabolism
Chemicals
Genetic Markers
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yauk C L
Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK. [email protected]
Bois P R J
Jeffreys A J
References (33)
33 references, click to expand
  1. Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex.
    Science. 1986 Oct 10;234(4773):173-9 PMID: 3018929
  2. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  3. Molecular characterization of meiotic recombination within the major histocompatibility complex of the mouse: mapping of crossover sites within the I region.
    Biochem Genet. 1987 Aug;25(7-8):513-26 PMID: 2895998
  4. Restriction fragment analysis of H-2 recombinant mouse strains with crossovers between E alpha and C4 genes.
    Immunogenetics. 1989;30(5):387-9 PMID: 2572548
  5. Structural and genetic properties of the Eb recombinational hotspot in the mouse.
    Immunogenetics. 1991;33(2):132-40 PMID: 1847899
  6. Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse.
    EMBO J. 1991 Mar;10(3):681-6 PMID: 2001681
  7. Molecular mapping of murine I region recombinants. III. Crossing over at two discrete sites within the beta 1-beta 2 intron of the E beta gene.
    J Immunol. 1991 Oct 15;147(8):2764-70 PMID: 1918991
  8. Multiple sites of crossing over within the Eb recombinational hotspot in the mouse.
    Mamm Genome. 1992;2(2):123-9 PMID: 1347471
  9. Evidence that nucleotide sequence identity is a requirement for meiotic crossing over within the mouse Eb recombinational hot spot.
    Genomics. 1992 Aug;13(4):1334-6 PMID: 1505968
  10. Hotspots of meiotic recombination in the mouse major histocompatibility complex.
    Genetica. 1993;88(2-3):187-96 PMID: 8224858
  11. Complex gene conversion events in germline mutation at human minisatellites.
    Nat Genet. 1994 Feb;6(2):136-45 PMID: 8162067
  12. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae.
    Genetics. 1994 May;137(1):19-39 PMID: 8056309
  13. Analysis of recombinational hot spots associated with the p haplotype of the mouse MHC.
    Genomics. 1994 Sep 1;23(1):168-77 PMID: 7829068
  14. Hotspots of homologous recombination in mouse meiosis.
    Adv Biophys. 1995;31:119-32 PMID: 7625269
  15. Allele-dependent recombination frequency: homology requirement in meiotic recombination at the hot spot in the mouse major histocompatibility complex.
    Genomics. 1995 May 20;27(2):298-305 PMID: 7557996
  16. Ea recombinational hot spot in the mouse major histocompatibility complex maps to the fourth intron of the Ea gene.
    Genome Res. 1996 Mar;6(3):195-201 PMID: 8963896
  17. The hotspot conversion paradox and the evolution of meiotic recombination.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8058-63 PMID: 9223314
  18. Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9757-62 PMID: 9275197
  19. High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot.
    Hum Mol Genet. 2000 Mar 22;9(5):725-33 PMID: 10749979
  20. Comparison of human genetic and sequence-based physical maps.
    Nature. 2001 Feb 15;409(6822):951-3 PMID: 11237020
  21. Meiotic recombination hot spots and cold spots.
    Nat Rev Genet. 2001 May;2(5):360-9 PMID: 11331902
  22. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex.
    Nat Genet. 2001 Oct;29(2):217-22 PMID: 11586303
  23. Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot.
    Nat Genet. 2002 Jul;31(3):267-71 PMID: 12089523
  24. An initiation site for meiotic crossing-over and gene conversion in the mouse.
    Nat Genet. 2002 Oct;32(2):296-9 PMID: 12244318
  25. A molecular map of the immune response region from the major histocompatibility complex of the mouse.
    Nature. 1982 Nov 4;300(5887):35-42 PMID: 6290895
  26. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520-4 PMID: 6310581
  27. The nucleotide sequence of the murine I-E beta b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex.
    EMBO J. 1984 Jun;3(6):1221-5 PMID: 6086309
  28. The double-strand-break repair model for recombination.
    Cell. 1983 May;33(1):25-35 PMID: 6380756
  29. Hypervariable 'minisatellite' regions in human DNA.
    Nature. 1985 Mar 7-13;314(6006):67-73 PMID: 3856104
  30. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585-8 PMID: 3856838
  31. Recombination in the mammalian germ line.
    Curr Top Dev Biol. 1998;37:1-35 PMID: 9352182
  32. High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot.
    Mol Cell. 1998 Aug;2(2):267-73 PMID: 9734365
  33. Recombination hot spots within the I region of the mouse H-2 complex map to the E beta and E alpha genes.
    Immunogenetics. 1986;24(6):352-60 PMID: 3025083
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2003-03-17
Pages
1389-97
Language
English
Region
England
NLM ID
8208664
PMCID
PMC151079
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]