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Currently, the vast majority of genomic research cohorts are made up of participants with European ancestry. Genomic medicine will only reach its full potential when genomic studies become more broadly representative of global populations. We are working to support the establishment of genomic medicine in developing countries in Latin America via studies of ethnically and ancestrally diverse Colombian populations. The goal of this study was to analyze the effect of ethnicity and genetic ancestry on observed disease prevalence and predicted disease risk in Colombia. Population distributions of Colombia's three major ethnic groups - Mestizo, Afro-Colombian, and Indigenous - were compared to disease prevalence and socioeconomic indicators. Indigenous and Mestizo ethnicity show the highest correlations with disease prevalence, whereas the effect of Afro-Colombian ethnicity is substantially lower. Mestizo ethnicity is mostly negatively correlated with six high-impact health conditions and positively correlated with seven of eight common cancers; Indigenous ethnicity shows the opposite effect. Malaria prevalence in particular is strongly correlated with ethnicity. Disease prevalence co-varies across geographic regions, consistent with the regional distribution of ethnic groups. Ethnicity is also correlated with regional variation in human development, partially explaining the observed differences in disease prevalence. Patterns of genetic ancestry and admixture for a cohort of 624 individuals from Medellín were compared to disease risk inferred via polygenic risk scores (PRS). African genetic ancestry is most strongly correlated with predicted disease risk, whereas European and Native American ancestry show weaker effects. African ancestry is mostly positively correlated with disease risk, and European ancestry is mostly negatively correlated. The relationships between ethnicity and disease prevalence do not show an overall correspondence with the relationships between ancestry and disease risk. We discuss possible reasons for the divergent health effects of ethnicity and ancestry as well as the implication of our results for the development of precision medicine in Colombia.
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Previous studies have shown the sugarcane microbiome harbors diverse plant growth promoting microorganisms, including nitrogen-fixing bacteria (diazotrophs), which can serve as biofertilizers. The genomes of 22 diazotrophs from Colombian sugarcane fields were sequenced to investigate potential biofertilizers. A genome-enabled computational phenotyping approach was developed to prioritize sugarcane associated diazotrophs according to their potential as biofertilizers. This method selects isolates that have potential for nitrogen fixation and other plant growth promoting (PGP) phenotypes while showing low risk for virulence and antibiotic resistance. Intact nitrogenase (nif) genes and operons were found in 18 of the isolates. Isolates also encode phosphate solubilization and siderophore production operons, and other PGP genes. The majority of sugarcane isolates showed uniformly low predicted virulence and antibiotic resistance compared to clinical isolates. Six strains with the highest overall genotype scores were experimentally evaluated for nitrogen fixation, phosphate solubilization, and the production of siderophores, gibberellic acid, and indole acetic acid. Results from the biochemical assays were consistent and validated computational phenotype predictions. A genotypic and phenotypic threshold was observed that separated strains by their potential for PGP versus predicted pathogenicity. Our results indicate that computational phenotyping is a promising tool for the assessment of bacteria detected in agricultural ecosystems.
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Proteínas de Bactérias/genética , Genoma Bacteriano , Bactérias Fixadoras de Nitrogênio/fisiologia , Saccharum/microbiologia , Agricultura , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Genômica/métodos , Klebsiella/genética , Klebsiella/isolamento & purificação , Bactérias Fixadoras de Nitrogênio/efeitos dos fármacos , Bactérias Fixadoras de Nitrogênio/genética , Bactérias Fixadoras de Nitrogênio/isolamento & purificação , Oxirredutases/genética , Rizosfera , Microbiologia do Solo , Fatores de Virulência/genéticaRESUMO
In this study, IL-6 levels were assessed as inflammatory biomarker of bacterial sepsis in patients hospitalized at the ICU of the hospital of Colombia. Materials and methods: Prospective study on 62 patients diagnosed with sepsis and septic shock. An ELISA assay was used to test serum levels of IL-6 at admission and 48 h after admission. Variables were analyzed by χ2 test (alfa <0.05). Multivariable Cox regression was used to determine the survival with the statistical program SPSS v23.00. Results: Patient's median age was 53 years old and 59.7% were male. Lung was the most common primary site of infection (43.5%), and hypertension comorbidity with higher prevalence (40%). Infection by Gram negative bacteria were significantly more frequent among patients than Gram positive (P = 0.037). Overall, survival analysis showed that 10 (16.1%) patients died with a survival median of 7.00 +4.874 (2-3) days. In patients with sepsis we detected a significant decline in the average of IL-6 serum levels after 48 h of admission [7.50 (SD: 7.00-68.00) pg/mL vs. 68.00 [SD: 7.00-300.00] pg/mL (P = 0.000). Only 25% of patients with septic shock who presented high levels of IL-6 at the time of admission and at 48 h had a survival up to 15 days (P = 0.005). Conclusion: We found significant differences between the plasma levels of IL-6 during the first 48 h after admission to the ICU among patients with sepsis and septic shock. Patients with sepsis had a significant decline in IL-6 levels, whereas in patients who developed septic shock, levels of this cytokine remained high and have a lower survival compared to those who maintained low levels of IL-6.
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Genome-wide association studies have uncovered thousands of genetic variants that are associated with a wide variety of human traits. Knowledge of how trait-associated variants are distributed within and between populations can provide insight into the genetic basis of group-specific phenotypic differences, particularly for health-related traits. We analyzed the genetic divergence levels for 1) individual trait-associated variants and 2) collections of variants that function together to encode polygenic traits, between two neighboring populations in Colombia that have distinct demographic profiles: Antioquia (Mestizo) and Chocó (Afro-Colombian). Genetic ancestry analysis showed 62% European, 32% Native American, and 6% African ancestry for Antioquia compared with 76% African, 10% European, and 14% Native American ancestry for Chocó, consistent with demography and previous results. Ancestry differences can confound cross-population comparison of polygenic risk scores (PRS); however, we did not find any systematic bias in PRS distributions for the two populations studied here, and population-specific differences in PRS were, for the most part, small and symmetrically distributed around zero. Both genetic differentiation at individual trait-associated single nucleotide polymorphisms and population-specific PRS differences between Antioquia and Chocó largely reflected anthropometric phenotypic differences that can be readily observed between the populations along with reported disease prevalence differences. Cases where population-specific differences in genetic risk did not align with observed trait (disease) prevalence point to the importance of environmental contributions to phenotypic variance, for both infectious and complex, common disease. The results reported here are distributed via a web-based platform for searching trait-associated variants and PRS divergence levels at http://map.chocogen.com (last accessed August 12, 2020).
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Predisposição Genética para Doença , Genoma Humano , Herança Multifatorial , Fenótipo , Grupos Raciais/genética , Colômbia , HumanosRESUMO
BACKGROUND: Hispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations. METHODS: Whole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here. RESULTS: T2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences. CONCLUSIONS: T2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.
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Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Hispânico ou Latino/genética , População Branca/genética , Colômbia , Diabetes Mellitus Tipo 2/epidemiologia , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Fatores de Risco , Estados UnidosRESUMO
INTRODUCTION: Relapses in tuberculosis occur due to endogenous reactivations or exogenous reinfections and represent up to 27% of tuberculosis cases. Its importance lies in the risk of the appearance of multidrug-resistant Mycobacterium tuberculosis strains. According to the reports published in 2011 by the Colombian Instituto Nacional de Salud, there were 572 relapse cases reported in the country, i.e., a rate of 4.9%. Data of the tuberculosis control program from the Secretaría de Salud Municipal in Cali reported a relapse rate of 6%, higher than the national one, during 2013 and 2014. OBJECTIVE: To determine the risk factors associated with relapse in patients with pulmonary tuberculosis in Cali. MATERIALS AND METHODS: We conducted an observational, analytical, and case-control study (1:1), which comprised 81 cases of pulmonary tuberculosis relapses detected in 2013 and 2014. Additionally, we collected data on socio-demographic and clinical variables, as well as lifestyle and health services, to identify the potential risk factors associated with tuberculosis relapses. We used logistic regression to identify the risk factors. RESULTS: After adjustments for some variables, our multivariate logistic regression analysis showed that the body mass index (BMI) (OR=0.90, 95%CI: 0.81-0.99) and population density (OR=0.99, 95%CI: 0.98-1.00) were inversely associated with tuberculosis relapses. Alcohol consumption increased the likelihood of tuberculosis relapse (OR=5.56, 95%CI: 1.18-26.26). CONCLUSIONS: Body mass index and population density were inversely associated with pulmonary tuberculosis relapses in Cali. On the contrary, alcohol consumption increased the likelihood of tuberculosis relapses.
Introducción. Las recaídas en la tuberculosis se deben a reactivaciones endógenas o reinfecciones exógenas y alcanzan hasta el 27 % de los casos. Su importancia radica en el riesgo de aparición de cepas de Mycobacterium tuberculosis resistentes a múltiples fármacos. Según informes del Instituto Nacional de Salud de Colombia, en el 2011 se reportaron 572 recaídas, lo que representa un porcentaje del 4,9 %. Datos del programa de tuberculosis de la Secretaría de Salud Municipal de Cali registraron una tasa de recaídas del 6 % durante el 2013 y el 2014, lo que supera la tasa nacional. Objetivo. Determinar los factores asociados con la recaída en pacientes con tuberculosis pulmonar. Materiales y métodos. Se hizo un estudio observacional, analítico y de casos y controles en pacientes diagnosticados con tuberculosis pulmonar detectados entre el 2013 y el 2014. Se estudiaron las variables sociodemográficas, clínicas, de estilo de vida y las relacionadas con el programa y los factores de riesgo; se determinaron utilizando regresión logística. Resultados. Después de ajustar por otras variables, la regresión logística evidenció dos factores inversamente asociados con las recaídas: el índice de masa corporal (OR=0,90; IC95%: 0,810,99) y la densidad poblacional en las comunas (OR=0,99; IC95%:0,991,00. El consumo de alcohol aumentó la probabilidad de recaída (OR=5,56; IC95%: 1,18 26,26). Conclusiones. El índice de masa corporal y la densidad poblacional se asociaron inversamente con las recaídas por tuberculosis pulmonar en Cali. El consumo de alcohol estuvo directamente relacionado.
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Tuberculose Pulmonar/epidemiologia , Estudos de Casos e Controles , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de RiscoRESUMO
Introduction: Relapses in tuberculosis occur due to endogenous reactivations or exogenous reinfections and represent up to 27% of tuberculosis cases. Its importance lies in the risk of the appearance of multidrug-resistant Mycobacterium tuberculosis strains. According to the reports published in 2011 by the Colombian Instituto Nacional de Salud, there were 572 relapse cases reported in the country, i.e., a rate of 4.9%. Data of the tuberculosis control program from the Secretaría de Salud Municipal in Cali reported a relapse rate of 6%, higher than the national one, during 2013 and 2014. Objective: To determine the risk factors associated with relapse in patients with pulmonary tuberculosis in Cali. Materials and methods: We conducted an observational, analytical, and case-control study (1:1), which comprised 81 cases of pulmonary tuberculosis relapses detected in 2013 and 2014. Additionally, we collected data on socio-demographic and clinical variables, as well as lifestyle and health services, to identify the potential risk factors associated with tuberculosis relapses. We used logistic regression to identify the risk factors. Results: After adjustments for some variables, our multivariate logistic regression analysis showed that the body mass index (BMI) (OR=0.90, 95%CI: 0.81-0.99) and population density (OR=0.99, 95%CI: 0.98-1.00) were inversely associated with tuberculosis relapses. Alcohol consumption increased the likelihood of tuberculosis relapse (OR=5.56, 95%CI: 1.18-26.26). Conclusions: Body mass index and population density were inversely associated with pulmonary tuberculosis relapses in Cali. On the contrary, alcohol consumption increased the likelihood of tuberculosis relapses.
Introducción. Las recaídas en la tuberculosis se deben a reactivaciones endógenas o reinfecciones exógenas y alcanzan hasta el 27 % de los casos. Su importancia radica en el riesgo de aparición de cepas de Mycobacterium tuberculosis resistentes a múltiples fármacos. Según informes del Instituto Nacional de Salud de Colombia, en el 2011 se reportaron 572 recaídas, lo que representa un porcentaje del 4,9 %. Datos del programa de tuberculosis de la Secretaría de Salud Municipal de Cali registraron una tasa de recaídas del 6 % durante el 2013 y el 2014, lo que supera la tasa nacional. Objetivo. Determinar los factores asociados con la recaída en pacientes con tuberculosis pulmonar. Materiales y métodos. Se hizo un estudio observacional, analítico y de casos y controles en pacientes diagnosticados con tuberculosis pulmonar detectados entre el 2013 y el 2014. Se estudiaron las variables sociodemográficas, clínicas, de estilo de vida y las relacionadas con el programa y los factores de riesgo; se determinaron utilizando regresión logística. Resultados. Después de ajustar por otras variables, la regresión logística evidenció dos factores inversamente asociados con las recaídas: el índice de masa corporal (OR=0,90; IC95%: 0,81-0,99) y la densidad poblacional en las comunas (OR=0,99; IC95%:0,99-1,00. El consumo de alcohol aumentó la probabilidad de recaída (OR=5,56; IC95%: 1,18 - 26,26). Conclusiones. El índice de masa corporal y la densidad poblacional se asociaron inversamente con las recaídas por tuberculosis pulmonar en Cali. El consumo de alcohol estuvo directamente relacionado.
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Tuberculose Pulmonar , Recidiva , Índice de Massa Corporal , ColômbiaRESUMO
BACKGROUND: Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico. RESULTS: Our screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employ a combined evidence approach to evaluate levels of ancestry enrichment at single loci across multiple populations and multiple loci that function together to encode polygenic traits. We find cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus, such as HLA-A, HLA-DRB51, and HLA-DRB5, show independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system show evidence of admixture-enabled polygenic selection in Latin American populations. CONCLUSIONS: The results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.
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Evolução Molecular , Genoma Humano , Seleção Genética , Adaptação Fisiológica , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Herança Multifatorial , Polimorfismo Genético , América do SulRESUMO
While genomic approaches to precision medicine hold great promise, they remain prohibitively expensive for developing countries. The precision public health paradigm, whereby healthcare decisions are made at the level of populations as opposed to individuals, provides one way for the genomics revolution to directly impact health outcomes in the developing world. Genomic approaches to precision public health require a deep understanding of local population genomics, which is still missing for many developing countries. We are investigating the population genomics of genetic variants that mediate drug response in an effort to inform healthcare decisions in Colombia. Our work focuses on two neighboring populations with distinct ancestry profiles: Antioquia and Chocó. Antioquia has primarily European genetic ancestry followed by Native American and African components, whereas Chocó shows mainly African ancestry with lower levels of Native American and European admixture. We performed a survey of the global distribution of pharmacogenomic variants followed by a more focused study of pharmacogenomic allele frequency differences between the two Colombian populations. Worldwide, we found pharmacogenomic variants to have both unusually high minor allele frequencies and high levels of population differentiation. A number of these pharmacogenomic variants also show anomalous effect allele frequencies within and between the two Colombian populations, and these differences were found to be associated with their distinct genetic ancestry profiles. For example, the C allele of the single nucleotide polymorphism (SNP) rs4149056 [Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1)∗5], which is associated with an increased risk of toxicity to a commonly prescribed statin, is found at relatively high frequency in Antioquia and is associated with European ancestry. In addition to pharmacogenomic alleles related to increased toxicity risk, we also have evidence that alleles related to dosage and metabolism have large frequency differences between the two populations, which are associated with their specific ancestries. Using these findings, we have developed and validated an inexpensive allele-specific PCR assay to test for the presence of such population-enriched pharmacogenomic SNPs in Colombia. These results serve as an example of how population-centered approaches to pharmacogenomics can help to realize the promise of precision medicine in resource-limited settings.
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Members of the Klebsiella genus promote plant growth. We report here draft whole-genome sequences for 15 Klebsiella sp. isolates from sugarcane fields in the Cauca Valley of Colombia. The genomes of these isolates were characterized as part of a broader effort to evaluate their utility as endemic plant growth-promoting biofertilizers.
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Differences in genetic ancestry and socioeconomic status (SES) among Latin American populations have been linked to health disparities for a number of complex diseases, such as diabetes. We used a population genomic approach to investigate the role that genetic ancestry and socioeconomic status (SES) play in the epidemiology of type 2 diabetes (T2D) for two Colombian populations: Chocó (Afro-Latino) and Antioquia (Mestizo). Chocó has significantly higher predicted genetic risk for T2D compared to Antioquia, and the elevated predicted risk for T2D in Chocó is correlated with higher African ancestry. Despite its elevated predicted genetic risk, the population of Chocó has a three-times lower observed T2D prevalence than Antioquia, indicating that environmental factors better explain differences in T2D outcomes for Colombia. Chocó has substantially lower SES than Antioquia, suggesting that low SES in Chocó serves as a protective factor against T2D. The combination of lower prevalence of T2D and lower SES in Chocó may seem surprising given the protective nature of elevated SES in many populations in developed countries. However, low SES has also been documented to be a protective factor in rural populations in less developed countries, and this appears to be the case when comparing Chocó to Antioquia.
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Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Colômbia , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Linhagem , Prevalência , Fatores SocioeconômicosRESUMO
At least 20% of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia's Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared with 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to overestimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population, and Medellín having relatively more shared ancestry with West African populations in Sierra Leone and Gambia. Both populations show very similar Spanish ancestry within Europe and virtually identical patterns of Native American ancestry, with main contributions from the Embera and Waunana tribes. When the three subcontinental ancestry components are considered jointly, the populations of Chocó and Medellín are shown to be most closely related, to the exclusion of the other admixed American populations that we analyzed. We consider the implications of the existence of shared subcontinental ancestries for Colombian populations that appear, at first glance, to be clearly distinct with respect to competing notions of national identity that emphasize ethnic mixing (mestizaje) vs. group-specific identities (multiculturalism).
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População Negra/genética , População Branca/genética , Colômbia , Etnicidade/genética , Genética Populacional , Genoma Humano , HumanosRESUMO
OBJECTIVE: Chocó is a state located on the Pacific coast of Colombia that has a majority Afro-Colombian population. The objective of this study was to characterize the genetic ancestry, admixture and diversity of the population of Chocó, Colombia. METHODOLOGY: Genetic variation was characterized for a sample of 101 donors (61 female and 40 male) from the state of Chocó. Genotypes were determined for each individual via the characterization of 610,545 single nucleotide polymorphisms genome-wide. Haplotypes for the uniparental mitochondrial DNA (female) and Y-DNA (male) chromosomes were also determined. These data were used for comparative analyses with a number of worldwide populations, including putative ancestral populations from Africa, the Americas and Europe, along with several admixed American populations. RESULTS: The population of Chocó has predominantly African genetic ancestry (75.8%) with approximately equal parts European (13.4%) and Native American (11.1%) ancestry. Chocó shows relatively high levels of three-way genetic admixture, and far higher levels of Native American ancestry, compared to other New World African populations from the Caribbean and the United States. There is a striking pattern of sex-specific ancestry in Chocó, with Native American admixture along the female lineage and European admixture along the male lineage. The population of Chocó is also characterized by relatively high levels of overall genetic diversity compared to both putative ancestral populations and other admixed American populations. CONCLUSION: These results suggest a unique genetic heritage for the population of Chocó and underscore the profound human genetic diversity that can be found in the region.
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The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%-96.7%), followed by Native American (average = 18.1%, range = 2.1%-33.3%) and African (average = 7.3%, range = 0.2%-38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment.
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Etnicidade/genética , Genoma Humano/genética , África , Alelos , População Negra/genética , Europa (Continente) , Genética Populacional/métodos , Genômica , Haplótipos/genética , Humanos , População Branca/genéticaRESUMO
Introducción: la preeclampsia constituye una causa importante de morbimortalidad materna y perinatal en el mundo. Su etiopatogenia es aún un enigma; sin embargo, los avances en genómica y proteómica prometen la identificación temprana de la enfermedad o del riesgo de padecerla. Objetivo: hacer una reflexión sobre los avances más promisorios de la genómica y proteómica, en el tamizaje y/o predicción de la preeclampsia. Conclusiones: dos polimorfismos funcionales, uno en el gen ACE (I/D) y otro en el gen COMT (Val158Met), poseen los resultados más promisorios para cumplir con el objetivo de identificar genéticamente a las mujeres con mayor riesgo de desarrollar preeclampsia durante un embarazo. Por su parte, la proteómica ha identificado a la SERPINA-1 como un biomarcador útil para detectar en la orina de las embarazadas que estén desarrollando la preeclampsia, con al menos 10 semanas de antelación a las manifestaciones clínicas de la misma y la necesidad de finalizar el embarazo. En conjunto, estos avances llevados a la práctica clínica podrían reducir el impacto de esta patología en la salud materna.
Introduction: preeclampsia is an important cause of maternal and perinatal morbi-mortality throughout the world. Its etiopathogeny still remains an enigma; however, the advances made in genomics and proteomics promise early identification of the disease or the risk of suffering from it. Objective: thoughts on the most promising advances in genomics and proteomics regarding the pressing goal of early detection and/or prediction of preeclampsia risk. Conclusions: two functional polymorphisms, one on the ACE gene (I/D) and another one in the COMT gene (Val158Met) are the most promising results of genomics for identifying women at genetically higher risk of developing preeclampsia during pregnancy. Proteomics has identified SERPINA-1 as a useful biomarker for detecting preeclampsia in the urine of pregnant women at least 10 weeks before clinical manifestations as well as the need for early termination of pregnancy. Such recent progress in genomics and proteomics adapted to clinical practice might reduce the impact of this disease on maternal health.
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Humanos , Feminino , Adulto , Genômica , Bem-Estar Materno , Pré-Eclâmpsia , Gravidez , ProteômicaRESUMO
Merozoite surface protein 1 (MSP-1) is a polymorphic malaria protein with functional domains involved in parasite erythrocyte interaction. Plasmodium vivax MSP-1 has a fragment (Pv200L) that has been identified as a potential subunit vaccine because it is highly immunogenic and induces partial protection against infectious parasite challenge in vaccinated monkeys. To determine the extent of genetic polymorphism and its effect on the translated protein, we sequenced the Pv200L coding region from isolates of 26 P. vivax-infected patients in a malaria-endemic area of Colombia. The extent of nucleotide diversity (π) in these isolates (0.061 ± 0.004) was significantly lower (P ≤ 0.001) than that observed in Thai and Brazilian isolates; 0.083 ± 0.006 and 0.090 ± 0.006, respectively. We found two new alleles and several previously unidentified dimorphic substitutions and significant size polymorphism. The presence of highly conserved blocks in this fragment has important implications for the development of Pv200L as a subunit vaccine candidate.
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Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Malária Vivax/epidemiologia , Proteína 1 de Superfície de Merozoito/genética , Plasmodium vivax/genética , Polimorfismo Genético , Animais , Sequência de Bases , Colômbia/epidemiologia , Sistema do Grupo Sanguíneo Duffy , Humanos , Malária Vivax/imunologia , Malária Vivax/parasitologia , Filogenia , Mutação PuntualRESUMO
The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] = 39.8-64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI = 61.8-82.1) of P. vivax-infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 10(6)) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Vacinas Antimaláricas/imunologia , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Proteína 1 de Superfície de Merozoito/química , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Antígenos de Superfície/química , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Cebidae , Colômbia/epidemiologia , Estudos Transversais , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Imunização , Imunoglobulina G/sangue , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/genética , Malária Vivax/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Plasmodium vivax/imunologia , Plasmodium vivax/patogenicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Estudos SoroepidemiológicosRESUMO
The Duffy antigen (Fy) is necessary for Plasmodium vivax invasion of human erythrocytes. Some populations have a highly prevalent Fy-negative phenotype; such persons are naturally protected from P. vivax blood infection but are expected to completely support the P. vivax pre-erythrocytic cycle, representing a valuable model for studying the immune response during these parasitic stages. We typed 214 individuals, mostly Afro-Colombians, from a P. vivax-endemic area for Fy expression and determined the antibody response to P. vivax pre-erythrocytic (sporozoites and CS) and blood-stage antigens (blood forms, P. vivax merozoite surface protein 1, and P. vivax Duffy binding protein [PvDBP]). Antibody titers to P. vivax circumsporozoite protein, P11, and N-terminal peptides and the number of responders were similar in Fy-negative and Fy-positive individuals. The number of responders to sporozoites, blood forms, and PvDBP were different between these groups. Thus, Fy-negative individuals from malaria-endemic areas can be used to study the immune response to the P. vivax liver phase without interference of the erythrocytic cycle.