Afro-Derived Amazonian Populations: Inferring Continental Ancestry and Population Substructure

A panel of Ancestry Informative Markers (AIMs) was used to identify population substructure and estimate individual and overall interethnic admixture in 294 individuals from seven African-derived communities of the Brazilian Amazon. A panel of 48 biallelic markers, representing the insertion (IN) or the deletion (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic admixture estimates showed high miscegenation with other ethnic groups in all populations (between 46% and 64%). The proportion of ancestral genes varied significantly among individuals of the sample: the contribution of African genes varied between 12% and 75%; of European genes between 10% and 73%; and of Amerindians genes between 8% and 66%. The obtained data reveal a high contribution of Amerindian genes in these communities, unlike in other African-derived communities of the Northeast and the South of Brazil. In addition, the majority of the Amerindian contribution may result from the preferential inclusion of indigenous women in the African descent groups. High heterogeneity of the proportion of interethnic admixture among analyzed individuals was found when the proportion of ancestral genes of each individual of the sample was estimated. This heterogeneity is reflected in the fact that four populations can be considered as substructured and that the global African descent sample is possibly formed by two subpopulations

Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

<div><p>Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (<em>LCT</em>) in the <em>MCM6</em> gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the <em>MCM6</em> region associated with the lactase persistence phenotype and to determine the distribution of <em>LCT</em> gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the <em>MCM6</em> gene region that acts as an enhancer for the <em>LCT</em> gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. <em>LCT</em> haplotypes were derived from the 10 <em>LCT</em> SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of <em>LCT</em> haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification.</p> </div

Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará

Abstract Background Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. Methods All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non‐PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. Results Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10‐11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. Conclusion In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula

<i>LCT</i> haplotypes frequencies ± standard error in the Brazilian population.

<p>If only one chromosome was identified, the standard error was not estimated.</p>a<p>Nomenclature according to Hollox et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046520#pone.0046520-Hollox1" target="_blank">[14]</a>.</p>b<p>n = number of individuals.</p

Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para

Laboratory of Inborn Errors of Metabolism of the Federal University of Pará in the performance of laboratory testsFederal University of Pará. Institute of Biological Sciences. Laboratory of Inborn Errors of Metabolism. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará.Institute of Health Sciences. Faculty of Nutrition. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Human and Medical Genetics. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Inborn Errors of Metabolism. Belém, PA, Brazil.Background: Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. Methods: All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non-PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. Results: Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10-11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. Conclusion: In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula

Number of −13779*C, −13937*A, −14010*C, and −14011*T alleles according to the population.

a<p>Heterozygous A and U <i>LCT</i> haplotypes.</p>b<p>Heterozygous A and P <i>LCT</i> haplotypes.</p>c<p>Homozygous A <i>LCT</i> haplotype.</p>d<p>Heterozygous C and U <i>LCT</i> haplotypes; heterozygous C and B <i>LCT</i> haplotypes.</p>e<p>Heterozygous A and g <i>LCT</i> haplotypes.</p>f<p>Homozygous A <i>LCT</i> haplotype; heterozygous A and E <i>LCT</i> haplotypes; heterozygous A and S <i>LCT</i> haplotypes.</p

MDS of several populations <i>LCT</i> haplotypes.

<p>Nonmetric Multidimensional Scaling analysis of <i>LCT</i> haplotypes based on D_A distance showing the relationships among the four Brazilian populations with their parental groups: Brazilian Amerindians <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046520#pone.0046520-Friedrich1" target="_blank">[26]</a>; Southern Europeans, Northern Europeans, and Bantu-speaking South Africans <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046520#pone.0046520-Hollox1" target="_blank">[14]</a>. NorEur  =  Northern European, SouEur  =  Southern European, Euro  =  Porto Alegre Euro-descendant, Afro  =  Porto Alegre Afro-descendant.</p

Geographic location of the 3 Brazilian cities where the samples were collected.

<p>Geographic location of the 3 Brazilian cities where the samples were collected.</p

Frequencies of the combinations found between the −13910 C>T and −22018 G>A alleles in the Brazilian population.

<p>Frequencies of the combinations found between the −13910 C>T and −22018 G>A alleles in the Brazilian population.</p

F_ST values of haplotype frequencies among Brazilians and with the parental populations (Amerindians, Bantu-speaking population from Africa, Southern and Northern Europeans).

<p>F_ST values in bold are statistically significant (p<0.0001).</p>a<p>Haplotype frequencies from Friedrich et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046520#pone.0046520-Friedrich1" target="_blank">[26]</a>.</p>b<p>Haplotype frequencies from Hollox et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046520#pone.0046520-Hollox1" target="_blank">[14]</a>.</p