No abstract

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.

No abstract

Endemic infection with the human T cell leukemia/lymphoma viruses I and II (HTLV-I/II) is now recognized to be worldwide, and is becoming epidemic among intravenous drug abusers (IVDAs) in the United States and Europe. The number of people around the world infected with HTLV-I can be estimated as between 10 and 20 million (Table 1). HTLV-I causes a rapidly progressing adult T cell leukemia/lymphoma (ATLL), and an incurable progressive neuromyelopathy named tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), as well as a number of less well-studied syndromes. There is evidence that coinfection with HTLV-I or -II accelerates progression to AIDS. The cumulative lifetime risk of developing ATLL or TSP/HAM is around 5%, which, in terms of the induction of serious diseases, places HTLV-I in the same category of viruses for which efficient vaccines are made and used. Furthermore, there are factors favoring the feasibility of a vaccine against HTLV-I, in that the virus displays relatively low antigenic variability, natural immunity occurs in humans, and experimental vaccination with the envelope (Env) antigen is successful in animal models. A vaccine against HTLV-I would be of significant public health value in the fields of oncology, neurology, and AIDS, and it would serve as a pathfinder for a vaccine against HIV.

While in the United States and northern Europe, human herpesvirus 8 (HHV-8) appears to be mainly sexually transmitted with primary infection occurring in adulthood, the modes of transmission remain unknown in East and Central Africa, where Kaposi's sarcoma (KS) is a long-standing endemic disease, occurring not only in adults but also in children. The aim of our present study was to determine the prevalence of HHV-8 infection in children from Yaoundé , Cameroon, Central Africa. Specific antibodies directed against both latent and lytic HHV-8 antigens were detected and titrated, with an immunofluorescence assay using the KS-1 cell line, in the plasma of 258 children and adolescents, of 32 mother and child pairs and of 189 pregnant women. Two different HHV-8 DNA-specific sequences were searched in the buffy coat by PCR assays. The overall HHV-8 seroprevalence was 27.5% among these children and adolescents. In newborns, seroprevalence reached 46%, reflecting passive transmission of maternal IgG. This was followed by a marked drop. Then, beginning around 4 years of age, a regular increase of HHV-8 antibodies took place, reaching 39% in the 12-to 14-year age group and 48% above 15 years, a rate similar ( Kaposi's sarcoma-associated herpesvirus (KSHV), now named human herpesvirus 8 (HHV-8), was uncovered in 1994 in Kaposi's sarcoma (KS) skin lesions as foreign DNA sequences absent from healthy skin tissue (Chang et al., 1994). Very rapidly, the complete sequence of this new human gamma herpesvirus was obtained and indicated the presence of sequence homologies with 2 known herpesviruses, namely, Epstein-Barr Virus (EBV) and herpesvirus saimiri (HVS), both oncogenic, but also with human genes involved in the control of cell mitosis. HHV-8, which has been detected in every studied case of KS whether of the classic, endemic, epidemic, post-transplant or pediatric form (Buonaguro et al., 1996;Chang et al., 1994;Moore et al., 1996;Kasalo et al., 1997), is now considered the etiological agent of this tumor. This virus has further been associated with primary effusion lymphomas (Gessain et al., 1997) and a subset of multicentric Castleman's disease (Gessain et al., 1996). The availability of specific and sensitive serological assays, developed from different sources, allows epidemiological surveys.Based on the few available studies (Simpson et al., 1996;Gao et al., 1996;Kedes et al., 1996;Lennette et al., 1996;Martin et al., 1998;Melbye et al., 1998;Calabro et al., 1997; Withby et al., 1998), it appears that HHV-8 is not a worldwide, ubiquitous virus and that its level of endemicity correlates with the prevalence rates of KS in a given population or geographical area. Thus, while in the United States and the United Kingdom HHV-8 infection seems quite rare in the general population (1% to 5% of HHV-8-seropositive blood donors) and KS occurrence is very low, the situation is different in southern Italy and Greece, where HHV-8 exhibits higher prevalence together with the classic form of KS

( Table 1). This series include 126 leukemias and 124 lym-

A prospective epidemiological study was carried out in the West Nile District of Uganda from 1972 to 1979 in order to investigate the aetiological role of the Epstein-Barr virus (EBV) in Burkitt's lymphoma (BL). By 1976, fourteen BL cases had been detected among the 42,000 children originally bled in the study area. Testing of sera from BL candidates and neighbourhood controls showed that children who develop BL later have EBV/VCA titres several dilutions higher than their age- and sex-matched neighbours. This appearance of a strong EBV activity long before BL development was taken as evidence of a causal role of EBV in BL. In order to add to the unique material of pre-bled BL cases, BL detection was continued up to March 1979 when field work became impossible in Uganda. Two additional pre-bled BL cases were found during this extension of the study. The serological and virological evaluation of these additional cases showed that the EBV/VCA titres, but not the EA and EBNA titres, were about two dilutions higher in the BL candidates than in the controls. Hybridization assays showed that both lymphomas contained EBV/DNA in the tumour cells. These additional results thus confirm the findings in the first 14 cases and strengthen the epidemiological evidence for a causal role of the EBV in endemic BL.

The aim of this study was to investigate the distribution of human T-cell leukemia virus type 1 (HTLV-1) in various organs of serially sacrificed squirrel monkeys (Saimiri sciureus) in order to localize the reservoir of the virus and to evaluate the relationship between viral expression and the humoral or cellular immune response during infection. Six squirrel monkeys infected with HTLV-1 were sacrificed 6, 12, and 35 days and 3, 6, and 26 months after inoculation, and 20 organs and tissues were collected from each animal. PCR and reverse transcription-PCR (RT-PCR) were performed with gag and tax primers. Proviral DNA was detected by PCR in peripheral blood mononuclear cells (PBMCs) of monkeys sacrificed 6 days after inoculation and in PBMCs, spleens, and lymph nodes of monkeys sacrificed 12 and 35 days and 3, 6, and 26 months after inoculation. Furthermore, tax/rex mRNA was detected by RT-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12. In this animal, scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in situ hybridization in frozen sections of the spleen, around the germinal centers and close to the arterial capillaries. Anti-HTLV-1 cell-mediated immunity was evaluated at various times after inoculation. Anti-p40Tax and anti-Env cytolytic T-cell responses were detected 2 months after infection and remained detectable thereafter. When Tax peptides were used, this response appeared to be directed against various Tax epitopes. Our results indicate that squirrel monkeys represent a promising animal model for studying the early events of HTLV-1 infection and for evaluating candidate vaccines against HTLV-1.