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ProjectsReport of the Anthropology / Human Genetic Diversity Component
The Anthropology / Human Genetic Diversity/Anthropology project of the 14th Workshop is building on the work completed as part of the 13th Workshop Anthropology project. Our goal is to extend the determination of HLA class I and class II allele and haplotype frequencies in a broad sample of human populations by typing 13th Workshop populations at additional class I and class II loci, and by incorporating new population samples into the study. Such studies of allele and haplotype diversity in different populations can shed light on the evolution of HLA polymorphism as well as on the evolution and migration of human populations. In a clinical context, knowledge of the allele frequency distributions in various populations is critical to the strategy of establishing and searching bone marrow donor registries as well as in studies of HLA-associated disease susceptibility. The genotype data generated in this project are being deposited in the IHWG online database, where they will be subjected to centralized analyses. Participating investigators are welcome to carry out their own analyses of the genotype data generated by their laboratories. The PyPop program (http//:allele5.biol.berkeley.edu/pypop/) is available for such analyses, and the Biostatistics component is available for consultation on any analyses and results. These analyses will be presented for discussion at the 14th Workshop. While data generation and analysis will continue after the Workshop, these data and analyses will be made available to the scientific community through online databases such as the NIH's MHC database (http://www.ncbi.nlm.nih.gov/mhc/) after participants have had time to publish their findings. GenotypingInvestigators are welcome to use the genotyping systems of their choice, as long as high-resolution data are generated, and as long as the genotyping laboratory meets minimum quality control standards for the submission of data to the IHWG database. In order to facilitate the analysis of data generated with a variety of genotyping methods, investigators should be able to list of all the alleles that can be detected by their typing system, even if those alleles are never detected in any samples. In addition, high-resolution reverse format class I and II line strip typing reagents (RLS reagents) for the HLA-A, B, C, DQA1, DQB1, DPA1, and DPB1 loci will be made available for the use of Anthropology project investigators until July 31, 2005. The RLS reagents for the DQ locus and DP locus are immobilized on single strips (i.e., a DQ strip and a separate DP strip), and these reagents are described as DQA1/B1 and DPA1/B1 "co-amplification" (co-amp) reagents. The use of these co-amp reagents permits eight HLA loci to be genotyped in six PCR reactions. PopulationsNew investigators have been and are being approached for recruitment to the project, with a focus on recruitment in areas of the world that were poorly represented in the 13th Workshop (e.g., Australia, South America, Africa, and East Asia). By recruiting participants in these regions, we hope to increase the number of population samples from these regions of the world available for genotyping. Ideally, the size of the populations sampled should be sufficient to provide reliable estimates of allele frequencies. Population samples for which the number of sampled individuals is less than 50 will not be very informative. If at all possible, it is desirable for the population to be sufficiently large to be able to estimate two- and three-locus haplotype frequencies. Thus, population samples with more than 100 individuals are recommended. Information about inbreeding, pedigrees, admixture, socio-cultural and linguistic traits and population structure is also valuable, where possible. All samples included in this project must have been collected in accordance with local standards for ethical use of human subjects. Knowledge of and respect for informed consent and human subjects regulations in the country/region where populations were sampled are absolute requisites for participation in this project. To date, new populations have been enrolled and new data generation begun for populations from the following regions: Bangladesh, Bulgaria (Roma/Gypsies), China ( Zhejiang Han), Colombia (Spanish), Easter Island, India (Jat Sikhs, Kashmiri Brahmins, and Jarawas), Martinique, Mexico (Tarahumaras, Mixtecos, Lacandones, and Seris), Singapore, South Africa (Xhosa and Cape Admixed), Taiwan (Han and Aboriginal), United States (African American), Uzbekistan (Uzbek), Venezuela, Vietnam (Kinh and Muong). In addition, genotype data for approximately 10 Indian populations that were not analyzed as part of the 13 th Workshop will be included in these 14 th Workshop analyses. Class I and class II genotypes for the 52 populations represented by the CEPH-Human Genome Diversity Project cell panel will be included as well. AnalysesOverall, the preliminary conclusions drawn in the 13th Workshop will be further investigated, and new hypotheses will be tested. Allele and haplotype frequencies will be estimated along with linkage disequilibrium (LD) values. Population samples will be evaluated for deviations from Hardy-Weinberg equilibrium proportions. The influence of selective forces will be investigated using Ewens-Watterson homozygosity tests and LD analyses. The apportionment of diversity between populations and within and among subsets of populations will be explored through a variety of population genetics analyses. Population relationships will be examined to make inferences about population migrations and history. ParticipationInvestigators wishing to participate in the Anthropology project should visit the Anthropology / Human Genetic Diversity component pages of the IHWG web site at http://www.ihwg.org/components/diversr.html. We are looking forward to working with you on the 14th Workshop Anthropology Project. 14th Workshop Anthropology / Human Genetic Diversity Component team Henry A. Erlich, Steve Mack, Alicia Sanchez-Mazas and Jason Hill |
