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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Carrington, M. Beck, S. Thorpe, K. Erlich, H. Cullen, M. Noble, J. Klitz, W. Trowsdale, J. |
| Description | Country affiliation: United States Author Affiliation: Cullen M ( Intramural Research Support Program, SAIC Frederick, National Cancer Institute--Frederick Cancer Research and Development Center, MD 21702, USA.) |
| Abstract | Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 (approximately 15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA)12 tandem repeat within the TAP2 gene. |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| Journal | The American Journal of Human Genetics |
| Issue Number | 2 |
| Volume Number | 60 |
| Language | English |
| Publisher | Cell Press (on behalf of American Society of Human Genetics) |
| Publisher Date | 1997-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genes, Mhc Class Ii Hla-d Antigens Genetics Histocompatibility Antigens Class Ii Recombination, Genetic Atp-binding Cassette Transporters Crossing Over, Genetic Genetic Markers Hla-dq Antigens Hla-dq Beta-chains Hla-dr Antigens Hla-drb1 Chains Haplotypes Linkage Disequilibrium Microsatellite Repeats Polymorphism, Single-stranded Conformational Protein-serine-threonine Kinases Research Support, U.s. Gov't, P.h.s. Discipline Human Genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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