Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
BACKGROUND-The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.METHODS-We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios.
The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis.
Although it is thought that infection with human T‐lymphotropic virus type I (HTLV‐I) is immunosuppressive, this has not been clearly demonstrated among healthy carriers, and there are no data concerning delayed‐type hypersensitivity (DTH). To evaluate this hypothesis, DTH to purified protein derivative (PPD) of tuberculin was measured in 126 healthy adults from an endemic area for HTLV‐I infection in southern Japan. Among the 39 HTLV‐I carriers, only 15% had detectable induration following PPD exposure, compared to 46% of the 87 non‐carriers. In addition, the size of erythema among those carriers with a positive reaction was about 70% of that among non‐carriers. Overall, there was a significantly inverse association between the degree of DTH response and prevalence of antibody. In relation to subjects with strong to moderate reaction, those with negative or indefinite reaction were 6 times more likely to be a carrier. This association was much stronger among subjects aged 60 years or older than among younger persons. These findings indicate that there is subclinical immunosuppression among HTLV‐I carriers, which increases with age.
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