Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.

We have updated the catalogue of common and well-documented (CWD) HLA alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and –DPB1 loci in IMGT/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and –DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being “common” (having known frequencies) and 707 as being “well-documented” on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program’s bioinformatics web pages.

The use of polymerase chain reaction (PCR) and oligonucleotide hybridization offers a new approach for the definition of HLA class II alleles. It has been possible to determine 43 alleles of DRB1, four of DRB3, two of DRB4, four of DRB5, eight of DQA1, and 14 of DQB1. These alleles are inherited together in members of families and form closely associated groups which are found repeatedly and in characteristic patterns in different populations. We have determined the HLA class II alleles and analyzed their association in 431 healthy unrelated subjects including 161 North American Caucasians, 53 Latin Americans, 61 Blacks, 88 Chinese, and 68 Israeli Jews. For-locus haplotypes (DRB1; DRB3/4/5; DQA1; DQB1) were derived from 79 B cell lines and the analysis of segregation in 34 nuclear families. The B-cell lines yielded 37 and the families showed the same, and 20 other, haplotypic combinations. In addition to these 57 haplotypes, associated alleles were assigned in the unrelated panels following certain rules. The resulting haplotypes were assigned to groups known to share associated alleles. The groups were: 1) DR1, DR2, and DRw10 (13 haplotypes); 2) DR3 and DRw6 (26 haplotypes); 3) DR5 and DRw8 (24 haplotypes); 4) DR4, DR7, and DR9 (24 haplotypes). Their distribution in populations with different ethnic backgrounds was analyzed. The expressed DRB4 allele and its null mutant were determined by PCR and oligonucleotide hybridization. The different DR7 haplotypes resulting from these determinations were analyzed in a panel of 130 North American Caucasoids. This comprehensive analysis of class II HLA haplotypes in human populations should be useful in understanding the role of these genes and in various applications including anthropology, disease susceptibility, and transplantation of allogeneic organs and tissues.