20 research outputs found
Group-based pharmacogenetic prediction: is it feasible and do current NHS England ethnic classifications provide appropriate data?
Inter-individual variation of drug metabolising enzymes (DMEs) leads to variable efficacy of many drugs and even adverse drug responses. Consequently, it would be desirable to test variants of many DMEs before drug treatment. Inter-ethnic differences in frequency mean that the choice of SNPs to test may vary across population groups. Here we examine the utility of testing representative groups as a way of assessing what variants might be tested. We show that publicly available population information is potentially useful for determining loci for pre-treatment genetic testing, and for determining the most prevalent risk haplotypes in defined groups. However, we also show that the NHS England classifications have limitations for grouping for these purposes, in particular for people of African descent. We conclude: (1) genotyping of hospital patients and people from the hospital catchment area confers no advantage over using samples from appropriate existing ethnic group collections or publicly available data, (2) given the current NHS England Black African grouping, a decision as to whether to test, would have to apply to all patients of recent Black African ancestry to cover reported risk alleles and (3) the current scarcity of available genome and drug effect data from Africans is a problem for both testing and treatment decisions
Frequency of LCT -13910C>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups
<p>Abstract</p> <p>Background</p> <p>Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups.</p> <p>Methods</p> <p>We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 ± 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism.</p> <p>Results</p> <p>Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (~57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (<it>P </it>< 0.01).</p> <p>Conclusion</p> <p>The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied.</p
The Microcephalin Ancestral Allele in a Neanderthal Individual
Background: The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans.1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. Methodology/Principal Findings: Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH
Ancient proteins provide evidence of dairy consumption in eastern Africa
Consuming the milk of other species is a unique adaptation of Homo sapiens, with implications for health, birth spacing and evolution. Key questions nonetheless remain regarding the origins of dairying and its relationship to the genetically-determined ability to drink milk into adulthood through lactase persistence (LP). As a major centre of LP diversity, Africa is of significant interest to the evolution of dairying. Here we report proteomic evidence for milk consumption in ancient Africa. Using liquid chromatography tandem mass spectrometry (LC-MS/MS) we identify dairy proteins in human dental calculus from northeastern Africa, directly demonstrating milk consumption at least six millennia ago. Our findings indicate that pastoralist groups were drinking milk as soon as herding spread into eastern Africa, at a time when the genetic adaptation for milk digestion was absent or rare. Our study links LP status in specific ancient individuals with direct evidence for their consumption of dairy products
It's Getting Better All the Time: Comparative Perspectives from Oceania and West Africa on Genetic Analysis and Archaeology
Technological advances are making genetic data collection and analysis
feasible on a scale unimaginable only a few years ago. Early genetic research using
mitochondrial DNA and the Y chromosome provided important insights for macroscale
modeling of regional and continent-wide population movements, but the capacity to
study the entire genome now opens an era of finer-grained,mesoscale studies of regional
and local population histories that are more compatible with the scale of archaeological
analysis. The utility of integrating both types of data is illustrated by a case study from
Oceania, where genetic studies were used to evaluate two models for the geographic
origins of the populations that colonized Polynesia beginning ca. 3000 BP, bringing with
them the distinctive Lapita cultural assemblage. A second case study considers the
application of genetic studies to an understanding of Fulbe history, especially that of
the pastoral Fulbe. Both archaeological and genetic data are underdeveloped for the
key Fulbe homeland regions of Mauritania and Senegal, but recent research in the
Middle Senegal Valley permits some conjectures on the history of Fulbe nomadic
pastoralism. The article concludes with suggestions for a multidisciplinary research
agenda to expand and upgrade the quality of relevant archaeological data, incorporate
biodistance studies of human skeletal material, and improve and expand genetic
sampling using more historically sensitive collection protocols