Biochemistry and Molecular Biology

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Browsing Biochemistry and Molecular Biology by Subject "Africa"

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    Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans
    (2024-05-03) Nyambo, Thomas B.
    Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.
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    Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.
    (Pharmacogenomics, 2011-11-01) Nyambo, Thomas B.
    Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution. Aims: We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations. Materials & methods: We have resequenced approximately 2800 bp for each of the NAT1 and NAT2 gene regions, as well as the pseudogene NATP1, in 197 African and 132 nonAfrican individuals. Results & conclusion: We observe a signature of balancing selection maintaining variation in the 3’-UTR of NAT1, suggesting that these variants may play a functional role that is currently undefined. In addition, we observed high levels of nonsynonymous functional variation at the NAT2 locus that differs amongst ethnically diverse populations.
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    Convergent adaptation of human lactase persistence in Africa and Europe.
    (Nature genetics, 2007-12-10) Nyambo, Thomas B.
    A SNP in the gene encoding lactase (LCT) (C/T-13910) is associated with the ability to digest milk as adults (lactase persistence) in Europeans, but the genetic basis of lactase persistence in Africans was previously unknown. We conducted a genotype-phenotype association study in 470 Tanzanians, Kenyans and Sudanese and identified three SNPs (G/C-14010, T/G-13915 and C/G-13907) that are associated with lactase persistence and that have derived alleles that significantly enhance transcription from the LCT promoter in vitro. These SNPs originated on different haplotype backgrounds from the European C/T-13910 SNP and from each other. Genotyping across a 3-Mb region demonstrated haplotype homozygosity extending >2.0 Mb on chromosomes carrying C-14010, consistent with a selective sweep over the past ∼7,000 years. These data provide a marked example of convergent evolution due to strong selective pressure resulting from shared cultural traits—animal domestication and adult milk consumption.
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    Shorter telomere length in Europeans than in Africans due to polygenetic adaptation.
    (Human molecular genetic, 2016) Nyambo, Thomas B.
    Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethnic differences in risks for human diseases that have been linked to LTL.