title: Localized breakdown in linkage disequilibrium does not always predict sperm crossover hot spots in the human MHC class II region.
abstract: To investigate the relationship between meiotic crossover hot spots and block-like linkage disequilibrium (LD), we have extended our high-resolution studies of the human MHC class II region to a 90-kb segment upstream of the HLA-DOA gene. LD blocks in this region are not as well defined as in the neighboring 210-kb DNA segment but do show two regions of LD breakdown in which coalescent analysis indicates substantial historical recombination. Sperm crossover analysis of one region revealed a novel localized hot spot similar in intensity and morphology to most other MHC hot spots. Crossovers at this hot spot are not obviously affected by a large insertion/deletion polymorphism near the hot spot. The second region of LD breakdown, within the DPB1 gene, shows an extremely low level of sperm crossover activity and does not contain a sperm crossover hot spot. These results highlight the complexity of LD patterns and the importance of experimentally verifying crossover hot spots.
authors.affiliation: Department of Genetics, University of Leicester, Leicester LE1 7RH, UK. kauppiL@mskcc.org
authors.forename: Liisa
authors.initials: L
authors.lastname: Kauppi
authors.forename: Michael P H
authors.initials: MP
authors.lastname: Stumpf
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Jeffreys
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002874:Chromosome Mapping; D024161:Collagen Type XI / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016254:Mutagenesis, Insertional; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D000949:Histocompatibility Antigens Class II; C071692:TAP2 protein, human