Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-10

AUTHORS

Alec J. Jeffreys, Liisa Kauppi, Rita Neumann

ABSTRACT

There is considerable interest in understanding patterns of linkage disequilibrium (LD) in the human genome, to aid investigations of human evolution and facilitate association studies in complex disease. The relative influences of meiotic crossover distribution and population history on LD remain unclear, however. In particular, it is uncertain to what extent crossovers are clustered into 'hot spots, that might influence LD patterns. As a first step to investigating the relationship between LD and recombination, we have analyzed a 216-kb segment of the class II region of the major histocompatibility complex (MHC) already characterized for familial crossovers. High-resolution LD analysis shows the existence of extended domains of strong association interrupted by patchwork areas of LD breakdown. Sperm typing shows that these areas correspond precisely to meiotic crossover hot spots. All six hot spots defined share a remarkably similar symmetrical morphology but vary considerably in intensity, and are not obviously associated with any primary DNA sequence determinants of hot-spot activity. These hot spots occur in clusters and together account for almost all crossovers in this region of the MHC. These data show that, within the MHC at least, crossovers are far from randomly distributed at the molecular level and that recombination hot spots can profoundly affect LD patterns. More... »

PAGES

217-222

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1001-217

DOI

http://dx.doi.org/10.1038/ng1001-217

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028187903

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11586303


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49 schema:description There is considerable interest in understanding patterns of linkage disequilibrium (LD) in the human genome, to aid investigations of human evolution and facilitate association studies in complex disease. The relative influences of meiotic crossover distribution and population history on LD remain unclear, however. In particular, it is uncertain to what extent crossovers are clustered into 'hot spots, that might influence LD patterns. As a first step to investigating the relationship between LD and recombination, we have analyzed a 216-kb segment of the class II region of the major histocompatibility complex (MHC) already characterized for familial crossovers. High-resolution LD analysis shows the existence of extended domains of strong association interrupted by patchwork areas of LD breakdown. Sperm typing shows that these areas correspond precisely to meiotic crossover hot spots. All six hot spots defined share a remarkably similar symmetrical morphology but vary considerably in intensity, and are not obviously associated with any primary DNA sequence determinants of hot-spot activity. These hot spots occur in clusters and together account for almost all crossovers in this region of the MHC. These data show that, within the MHC at least, crossovers are far from randomly distributed at the molecular level and that recombination hot spots can profoundly affect LD patterns.
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