Polymorphism, recombination, and linkage disequilibrium within the HLA class II region

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Journal of Immunology; (United States)

OSTI ID:7160666

Begovich, A B; McClure, G R; Suraj, V C; Helmuth, R C; Fildes, N; Bugawan, T L; Erlich, H A ^[1]; Klitz, W ^[2]

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1. Cetus Corp., Emeryville, CA (United States)
2. Univ. of California, Berkeley, CA (United States)

Thirty-nine CEPH families, comprised of 502 individuals, have been typed for the HLA class II genes DRB1, DQA1, DQB1, and DPB1 using nonradioactive sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA. This population, which consists of 266 independent chromosomes, contains 27 DRB1, 7 DQA1, 12 DQB1, and 17 DPB1 alleles. Analysis of the distribution of allele frequencies using the homozygosity statistic, which gives an indication of past selection pressures, suggests that balancing selection has acted on the DRB1, DQA1, and DQB1 loci. The distribution of DPB1 alleles, however, suggests a different evolutionary past. Family data permits the estimation of recombination rates and the unambiguous assignment of haplotypes. No recombinants were found between DRB1, DQA1, and DQB1; however, recombinants were detected between DQB1 and DPB1, resulting in an estimated recombination fraction of [ge]0.008 [+-] 0.004. Only 33 distinct DRB1-DQA1-DQB1 haplotypes were found in this population which illustrates the extreme nonrandom haplotypic association of alleles at these loci. A few of these haplotypes are unusual (previously unreported) for a Caucasian population and most likely result from past recombination events between the DR and DQ subregions. Examination of disequilibrium across the HLA region using these data and the available serologic HLA-A and HLA-B types of these samples shows that global disequilibrium between these loci declines with the recombination fraction, approaching statistic nonsignificance at the most distant interval, HLA-A and HLA-DP. DR-DQ haplotypes in linkage disequilibrium with DPB1 and B are noted and, finally, the evolutionary origin of certain class II haplotypes is addressed. 63 refs., 3 figs., 8 tabs.

• OSTI ID: 7160666
• Journal Information: Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 148:1; ISSN JOIMA3; ISSN 0022-1767
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANTIGENS
BIOLOGICAL EVOLUTION
BIOLOGICAL VARIABILITY
GENETIC MAPPING
GENETIC VARIABILITY
HISTOCOMPATIBILITY COMPLEX
MAPPING
RFLPS