Caucasian Genes in American Negroes

Reed, T. Edward

doi:10.1126/science.165.3895.762

Cited by 288 publications

(122 citation statements)

References 16 publications

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“…Unauthorized reproduction of this article is prohibited. African-Americans [3,13]. Accordingly, the similar frequencies of TPMT Ã 3A and TPMT Ã 3C observed in our study can be attributed to the extensive interethnic crossings, with a high level of genetic admixture, that is characteristic of the Brazilian population [14].…”

supporting

confidence: 50%

“…This contrasts with the wide differences in the frequencies of these alleles in other ethnic groups ( Table 2, other studies). Thus, among Caucasians, TPMT Ã 3A is three-to five-fold more frequent than TPMT Ã 3C [3,9,11] whereas, in Africans, TPMT Ã 3A is not detected and TPMT Ã 3C frequency is 5-7% [12,13]. In African-Americans, these two alleles coexist, but TPMT Ã 3C is three-fold more frequent than TPMT Ã 3A [3].…”

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confidence: 99%

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Thiopurine methyltransferase phenotypes and genotypes in Brazilians

2003

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The polymorphism of thiopurine methyltransferase (TPMT) was studied in 306 healthy Brazilians who were classed, on the basis of self-declared colour and ancestry, as Euroderived (n 81), Afro-derived (n 18) or having interethnic admixture (n 204). TPMT activity (range 0.17-25.93 U) displayed a trimodal distribution of high (> 11.3 U; 9% of individuals), intermediate (5-11.3 U; 9.8%) and low (0.17 U; 0.3%) phenotypes. The occurrence of the TPMT mutations 238G>C, 460G>A and 719A>G was investigated in all individuals with low or intermediate phenotype, and in 43 with high-activity phenotype. None and two mutant alleles were associated with high-or low-activity phenotypes, respectively, whereas one mutant allele was detected in 26 of the 30 intermediate phenotype individuals. The allele frequencies of TPMT Ã 2, TPMT Ã 3A and TPMT Ã 3C did not differ between individuals classed as Euro-derived (0.76%, 2.03% and 2.54%, respectively) or having interethnic admixture (0.60%, 1.81% and 1.81%, respectively). Furthermore, within each of these groups, the frequencies of TPMT Ã 3A and TPMT Ã 3C were not significantly different. Brazil has one of the most heterogeneous populations in the world. Extensive interethnic crosses over the last 500 years, between autochthonous Amerindians, European colonizers and Africans contributed to the gene pool of the present-day approximately 175 million Brazilians. The heterogeneity of the Brazilian population has important implications for pharmacogenetics because extrapolation of data derived from well-defined ethnic groups is clearly not applicable to the majority of Brazilians. Recognition of this fact has stimulated pharmacogenetic studies in the Brazilian population, and we report the first systematic investigation of genetic polymorphism of thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) in Brazilians. A seminal study on a Caucasian-American population revealed that the TPMT activity displays a trimodal distribution, with 89% of individuals exhibiting high activity, 11% exhibiting intermediate activity and approximately one in 300 having deficient activity [1]. The genetic basis and the molecular mechanisms underlying TPMT polymorphism have been intensively investigated and, to our knowledge, nine nonfunctional mutant alleles have been described to date [2]. Four of these alleles, namely TPMT Ã 2 (238G.C), TPMT Ã 3A (460G.A and 719A.G), TPMT Ã 3B (460G.A) and TPMT Ã 3C (719A.G) account for 78-95% of the lower-activity genotypes in different populations [3,4]. In the present study, phenotyping and genotyping procedures were combined to evaluate the polymorphism of TPMT in 306 healthy Brazilian subjects. Preliminary results have been presented previously in abstract form [5].The study protocol was approved by the Ethics Committee of the Brazilian National Cancer Institute (INCA), and written informed consent was obtained from all volunteers, who were recruited at the INCA blood bank. Previously described polymerase chain reaction-based methods [4] and radiochemical assay [6,7] were emp...

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Thiopurine methyltransferase phenotypes and genotypes in Brazilians

2003

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“…2E). An interesting question one can address with these kinds of data is whether regions of the genome show substantially high European or West African ancestry across all individuals in the sample [e.g., as may be the case if a particular allele from one of the ancestral populations was under strong selection (36)(37)(38)(39)]. For our analysis, we considered genomic regions as potential candidates for increased European or West African ancestry if the mean ancestry for the region across the 365 African-American individuals was 3 SDs above or below the genome-wide average of West African ancestry (78.1%).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide patterns of population structure and admixture in West Africans and African Americans

Bryc

Auton

Nelson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

433

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Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans ( n = 365) and individuals with ancestry from West Africa ( n = 203 from 12 populations) and Europe ( n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th–75th percentiles: 11.6–27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.

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“…This difference is probably due to differences in racial admixture which is known to vary among African Americans residing within different geographic regions of the US. [35][36][37] Our study is the first to examine the frequencies of the CYP2C9*6 and CYP2C9*11 alleles in a large African American population. CYP2C9*6 (818delA, frameshift) contains a premature stop codon, resulting in a null allele that dramatically decreases the metabolism of phenytoin and warfarin.…”

Section: Discussionmentioning

confidence: 99%

Influence of CYP2C9 Genotype on Warfarin Dose Among African–Americans and European–Americans

Limdi

Goldstein

Blaisdell

et al. 2007

Personalized Medicine

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Background-Cytochrome P4502C9 (CYP2C9) plays a vital role in drug metabolism. There has been an increased effort to identify polymorphisms within the gene and determine their clinical consequences. However, most of these efforts have focused on populations of European descent. Herein we report the influence of CYP2C9 genotype on warfarin dose among European American and African American patients. We also identify two new mutations; one in the coding region and one in the non-coding region of the CYP2C9 gene.

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Caucasian Genes in American Negroes

Cited by 288 publications

References 16 publications

Thiopurine methyltransferase phenotypes and genotypes in Brazilians

Thiopurine methyltransferase phenotypes and genotypes in Brazilians

Genome-wide patterns of population structure and admixture in West Africans and African Americans

Influence of CYP2C9 Genotype on Warfarin Dose Among African–Americans and European–Americans

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