[show abstract][hide abstract] ABSTRACT: To characterize linkage disequilibrium (LD) levels in human populations, we have analyzed 10 independent noncoding segments in three population samples from the major ethnic groups--that is, Africans, Asians, and Europeans. Descriptive statistics show that LD decays much faster in the African samples than in the non-African ones. With the assumption of an equilibrium model, we estimated the population crossing-over parameter (4N(e)r(bp), where N(e) is the effective population size and r(bp) is the crossing-over rate per generation between adjacent base pairs) in the presence of gene conversion. In the African sample, LD and polymorphism levels lead to similar estimates of effective population size, as expected under an equilibrium model. Conversely, in both non-African samples, LD levels suggest a smaller effective population size than that implied by polymorphism levels. This observation is paralleled by significant departures from an equilibrium model in the spectrum of allele frequencies of the non-African samples. Besides ruling out the possibility that non-African populations are at equilibrium, these results suggest different demographic history (temporal and spatial) of these groups. Interestingly, the African sample fits the expectations of an equilibrium model based on polymorphism and divergence levels and on frequency spectrum. For this sample, the estimated ratio of gene conversion to crossing-over rates is 7.3 for a mean tract length of 500 bp, suggesting that gene conversion may be more frequent than previously thought. These findings imply that disease-association studies will require a much denser map of polymorphic sites in African than in non-African populations.
The American Journal of Human Genetics 11/2001; 69(4):831-43. · 11.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sensitization to cockroach allergens is an important epidemiologic risk factor for asthma, particularly among African Americans living in urban environments. A recent genome screen in the Hutterites, a white founder population, identified a linkage between an HLA-linked marker and sensitization to cockroach allergens.
Our purpose was to determine whether alleles at one or more HLA loci are associated with sensitization to cockroach allergens in ethnically diverse populations.
Alleles at 14 HLA region loci were studied in the Hutterites. On the basis of these results, selected loci were examined in 54 African Americans with cockroach sensitization (cases) and 65 African Americans without cockroach sensitization (controls). Sensitivity to cockroach allergens was assessed in both samples by skin prick test to purified cockroach allergens (Periplaneta americana and Blatella germanica).
Significant associations between cockroach allergies and DRB1*0101 (P(corrected) =.0066), DQA1*0101 (P(corrected) =.0012), and DQB1*0501 (P(corrected) =.00096) were detected in the Hutterites. In the African American sample, the most significant association was with the DRB1*0102 allele (P(corrected) =.0088, odds ratio 16.4, 95% confidence interval 2.0, 131). The DRB1*0101 allele was infrequent in the African American sample (frequency 0.06) and the DRB1*0102 allele was absent in the Hutterites. DRB1*0101 and DRB1*0102 are closely related alleles that differ from nearly all other DRB1 alleles at 3 amino acids in the 1 peptide binding domain of the HLA-DR molecule.
The DRB1*0101 allele in the Hutterites and the DRB1*0102 allele in African Americans confer risk for cockroach sensitization. Elucidating this interaction at the molecular level may allow for more targeted treatment and prevention of atopic asthma in inner-city populations.
Journal of Allergy and Clinical Immunology 06/2000; 105(5):960-6. · 12.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: Onchocerciasis, also known as "river blindness", presents a plenum of clinical manifestations which vary from one individual to another, and from one area to another. This large spectrum of clinical manifestations of the disease is an indication of the complexity of the pathogenesis of onchocerciasis and suggests that many interacting factors might influence the clinical features of the disease. The present study has focused on the heterogenicity of the host immune response as a plausible explanation for differences in clinical manifestations of the infection. Host genetic factors, namely HLA genes, might play an important role in determining the nature of the immune response mounted against the parasite Onchocerca volvulus, and thus the development of different manifestations of the infection. Genetic diversity of onchocerciasis was assessed in different endemic foci in Cameroon. In order to investigate the possibility that the Major Histocompatibility Complex (MHC) genes might be associated with the different clinical types of onchocerciasis, 146 subjects living in three endemic areas of Cameroon were studied. They were classified in four groups: A (asymptomatic subjects), P (putatively immune subjects) L (patients with localised disease) and G (patients with generalised disease). The four groups differed in the distribution of HLA class II alleles as determined by Direct Heteroduplex Analysis. On the one hand, allele HLA-DQA1*0501 appeared to be associated with protection against severe onchocerciasis; on the other, allele HLA-DQB1*0201 might play an important role in the severe form of the disease.
Bulletin de la Société de pathologie exotique 06/1999; 92(2):85-90.
[show abstract][hide abstract] ABSTRACT: Studying proteolytic activity of Onchocerca volvulus (nematode causing "river blindness") shows that it is able to digest a variety of substrates such as: azoalbumine, azocoll and elastin-orcein with specific activity of 0.28, 0.57 and 1.48 mg/hour/mg of extract respectively. These enzymes are active at various pH such as pH 5.0, 8.0 and 10.0 with highest activity at pH 8.0. The effect of specific inhibitors and activators indicates that the extract might contain serine, metallo and thyoproteases. The electrophoresis of the extract on a polyacrylamide gel copolymerized with gelatin shows many proteins with enzymatic activities with molecular weight of 16.6, 43.6, 45.7, 56.2, 60.2, 61.6 and 63.1 KD respectively. The Onchocerca volvulus worm contains proteases of various enzymatic activities: a non specific activity on protein such as on azoalbumin and specific activities on collagen and elastin. These enzymes could play an important role in the survival of parasites in human hosts.
Bulletin de la Société de pathologie exotique 03/1999; 92(1):9-12.
[show abstract][hide abstract] ABSTRACT: Sensitive, specific and low-cost diagnostic tests for onchocerciasis are indispensable for monitoring the efficacy of control programs, as well as for preventing blindness (when the tests are combined with efficacious chemotherapy. Three new tests to detect Onchocerca-specific antigens in tears, dermal fluid and urine employ antibodies to O. volvulus-specific recombinant proteins, Oncho-C27 and OvD3B, encoded by genes within the immunodominant Onchocerca OV 33-3 gene family, and expressed in yeast and in E. coli, respectively. In these assays, Onchocerca-specific antigens in test samples are bound onto a solid surface and revealed using appropriate enzyme-labelled antibodies. Proteins in the samples are first transferred to Hybond-N + membrane disks or nitrocellulose paper using either a transblot or a dotblot machine, and then reacted with specific O. volvulus antibodies. Bound antibodies are revealed with species-specific peroxidase-labelled antibodies and peroxidase substrate. Positive tests give a brown colour. In one of the two assays developed to detect Onchocerca antigens in tears, the sensitivity was enhanced by first adsorbing the specific antibodies onto the membrane surface in order to immobilize and concentrate the Onchocerca-specific antigen molecules on the membrane. The specificity of the recombinant proteins for Onchocerca volvulus had been verified by ELISA, classical Western blot and modified DSIA. The tests are a dipstick immunobinding assay for ocular microfilariae (DSIA), a transblot immunobinding assay for the detection of skin microfilariae (TADA) and a dot-blot immunobinding assay for detecting urinary microfilariae and their antigens (DIA). Their specificity and sensitivity were evaluated in the field on 110 subjects with proven ocular microfilariae, 130 subjects with clinical and parasitological evidence of onchocerciasis, 25 subjects infected with other helminths and 120 normal controls. The minimal detection limits of Oncho-C27 protein by DSIA, TADA and DIA were 500 ng/ml, 154 ng/ml and 508 ng/ml, respectively By contrast, their sensitivities were: 100% for DSIA and 82.5% for TADA employed on samples of tears; 97% for TADA skin test and 96% for DIA used on urine samples.
Tropical Medicine & International Health 06/1998; 3(5):339-48. · 2.94 Impact Factor