Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these ...variants has been poorly studied.
To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection.
Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant.
Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006).
Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.
Host genetics is recognized as an influential factor for the development of dengue disease.
This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 ...for TLR3, and rs7248637 for DC-SIGN.
Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry.
For Afro-Colombians, the allele rs8192284 C offered protection against dengue OR=0.425,(0.204-0.887), p=0.020. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians OR=2.389, (1.170-4.879), p=0.015 and Mestizos OR=2.329, (1.283-4.226), p=0.005. The reproducibility for rs8192284 C/C OR=2.45, (1.05-5.76), p=0.013 remained after adjustment by Amerindian ancestry OR=2.52, (1.04-6.09), p=0.013. The reproducibility for rs3775290 A/A OR=2.48, (1.09-5.65), p=0.033 remained after adjustment by European OR=2.34, (1.02-5.35), p=0.048, Amerindian OR=2.49, (1.09-5.66), p=0.035, and African ancestry OR=2.37, (1.04-5.41), p=0.046. Finally, the association of dengue fever with the allelic combination CAG OR=2.07, (1.06-4.05), p=0.033 remained after adjustment by Amerindian ancestry OR=2.16, (1.09-4.28), p=0.028.
Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population.
Historical and genetic evidences suggest that the recently founded population of Antioquia (Colombia) is potentially useful for the genetic mapping of complex traits. This population was established ...in the 16th–17th centuries through the admixture of Amerinds, Europeans, and Africans and grew in relative isolation until the late 19th century. To examine the origin of the founders of Antioquia, we typed 11 markers on the nonrecombining portion of the Y chromosome and four markers on mtDNA in a sample of individuals with confirmed Antioquian ancestry. The polymorphisms on the Y chromosome (five biallelic markers and six microsatellites) allow an approximation to the origin of founder men, and those on mtDNA identify the four major founder Native American lineages. These data indicate that ∼94% of the Y chromosomes are European, 5% are African, and 1% are Amerind. Y-chromosome data are consistent with an origin of founders predominantly in southern Spain but also suggest that a fraction came from northern Iberia and that some possibly had a Sephardic origin. In stark contrast with the Y-chromosome, ∼90% of the mtDNA gene pool of Antioquia is Amerind, with the frequency of the four Amerind founder lineages being closest to Native Americans currently living in the area. These results indicate a highly asymmetric pattern of mating in early Antioquia, involving mostly immigrant men and local native women. The discordance of our data with blood-group estimates of admixture suggests that the number of founder men was larger than that of women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mitochondrial DNA has proven its utility for the study of insect evolution. Genes such as cytochrome b (Cytb) and the transfer gene for serine (SertRNA) can be used to compare closely related ...organisms.
The phylogenetic utility of Cytb-SertRNA-IG1-ND1 was tested for polymorphisms, and secondary structure modeling in SertRNA was done to detect possible cryptic species in Anopheles neivai.
Specimens from Colombia, Guatemala, and the type locality in Panamá were collected and sequenced for specimen comparison based on DNA polymorphisms, and secondary structure modeling for the SertRNA gene.
Thirty-six sequences for A. neivai and A. pholidotus were obtained.
Polymorphic variants were detected in A. neivai for Cytb-SertRNA-IG1- ND1. Despite this variation in A. neivai, cryptic species could not be detected.
Background
Intellectual disability (ID) is the limitation of intellectual functioning and adaptive behavior before 18 years of age. In a consanguineous family of 149 members, this disease is ...expressed in 9 individuals. Here, we report one branch of a family tree with three siblings, presenting severe ID, delayed speech development, cataracts, strabismus, gait disturbance, cerebellar syndrome, seizures in one of them, and eyelid ptosis in two. Brain magnetic resonance imaging (MRI) with hippocampal malrotation, brain atrophy and white matter hyperintensities in all cases. Thinning of the corpus callosum in two of them.
Method
We conducted whole exome sequencing analysis in nine subjects from one multigenerational family of Colombian origin. The study was carried out at the University of Antioquia,Colombia with the approval of the ethics committee. A medical, neurological, neuropsychological examination and brain MRI were performed in all cases.
Result
We identified a single nucleotide deletion in the SPAG9 gene, which codes for the JIP4 protein. The frameshift generates a premature stop codon (p.Tyr914Ter). The deletion is classified as pathogenic, according to the ACMG / AMP guidelines. The variant co‐segregated in the respective family as an autosomal recessive trait.
Conclusion
JIP 4 has two functions: As scaffold protein that potentiates the p38 MAPK signaling cascade under stress conditions and as dynein‐dynactin motor adapter for lysosomal retrograde flow, regulating the constitutive transport of lysosomes. Both functions could be associated in the disease mechanism. The absence of JIP 4 may be responsible for the disease in the family, altering neuronal homeostasis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
We report an integrated analysis of nuclear (autosomal, X‐ and Y‐chromosome) short tandem repeat (STR) data and mtDNA D‐loop sequences obtained in the same set of 22 Native populations from ...across the Americas. A north to south gradient of decreasing population diversity was observed, in agreement with a settlement of the Americas from the extreme northwest of the continent. This correlation is stronger with “least cost distances,” which consider the coasts as facilitators of migration. Continent‐wide estimates of population structure are highest for the Y‐chromosome and lowest for the autosomes, consistent with the effective size of the different marker systems examined. Population differentiation is highest in East South America and lowest in Meso America and the Andean region. Regional analyses suggest a deviation from mutation–drift equilibrium consistent with population expansion in Meso America and the Andes and population contraction in Northwest and East South America. These data hint at an early divergence of Andean and non‐Andean South Americans and at a contrasting demographic history for populations from these regions.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Introducción. Las poblaciones de Aedes aegypti pueden experimentar cambios en cuanto a su abundancia y diversidad genética y, con ello, su potencial evolutivo para responder al control vectorial. El ...conocimiento de los cambios en la variación genética a escala espacio-temporal, permite entender mejor la epidemiología del dengue y contribuye al diseño adecuado y oportuno de estrategias antivectoriales. Objetivo. Evaluar los cambios genéticos, la diversidad y el flujo génico en seis poblaciones microgeográficas de Ae. aegypti en Medellín en diferentes períodos epidemiológicos del dengue. Materiales y métodos. En 255 especímenes provenientes de seis barrios de Medellín, se evaluó la variación en la composición de los haplotipos mtDNA CO1 , así como la diversidad y la diferenciación genética en un período epidémico (2010) y en otro endémico (2012). Resultados. Se detectaron dos grupos de haplotipos muy diferenciados entre sí en ambos períodos, al igual que un haplotipo de alta frecuencia presente en todos los barrios. La mayor diversidad de haplotipos se registró en el 2012, pero la mayor diversidad de nucleótidos se presentó en el 2010. No se observó correlación significativa entre las distancias genéticas y geográficas. Conclusión. La composición genética de Ae. aegypti varía temporalmente sin un patrón predecible. La presencia de un haplotipo de gran frecuencia en ambos períodos podría ser indicio de una variación persistente adaptada al control vectorial. Sin embargo, la circulación simultánea de haplotipos CO1 muy diferenciados y compatibles con múltiples introducciones, sugiere que diversos acervos genéticos serían aptos para la transmisión. Estos resultados son compatibles con la dispersión del mosquito por efecto de actividades antrópicas, lo cual posibilitaría la diseminación rápida del virus durante epidemias en Medellín.
Introducción. La hipertensión arterial es una enfermedad multifactorial influenciada por componentes genéticos y ambientales, cuya prevalencia varía entre grupos étnicos. Se han llevado a cabo ...numerosos estudios en genes de sistemas reguladores de la presión arterial, como el sistema renina-angiotensinaaldosterona, el sistema nervioso simpático, los factores endoteliales, y el balance de sodio, mostrando resultados incongruentes entre poblaciones. Objetivos. Evaluar el efecto de variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 y del componente ancestral individual, sobre la hipertensión arterial y las cifras de presión arterial en una muestra de población antioqueña. Materiales y métodos. Se genotipificaron 107 casos y 253 controles para 12 variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 , y para 20 marcadores informativos de ascendencia. Se evaluó la asociación de los polimorfismos y sus interacciones, y de la composición genética ancestral con hipertensión y cifras de presión arterial. Resultados. Los genes ADD2 , rs4852706 (OR=3,0; p=0,023); DRD1 , rs686 (OR=0,38; p=0,012) y ADRB2 , rs1042718 (OR=10,0; p=0,008); y combinaciones genotípicas de DRD1 con AGTR1 ; de AGT con ADD1 ; y de ADD1 con ATP2B1 y PTGS2 , se asociaron con hipertensión arterial. El componente ancestral amerindio se asoció con disminución en la presión arterial diastólica. Conclusiones. Variantes en los genes ADD2 , DRD1 , ADRB2 , AGTR1 , AGT , ADD1 , ATP2B1 y PTGS2 , individualmente o en su interacción, se encuentran asociadas con hipertensión. El componente ancestral amerindio tiene un efecto sobre las cifras de presión arterial.
Insulin resistance and defects in other related glycemic traits are common findings in the context of Metabolic Syndrome. Although genetic factors are clearly implied in susceptibility, and some gene ...variants have been identified mainly in populations of European ancestry, little is known about this aspect in admixed populations. The association of insulin resistance, β-cell function, fasting insulin and glucose levels with 48 gene variants, previously related to metabolic syndrome components, and with the ancestral genetic composition, estimated on 50 ancestry informative markers, was evaluated in 417 individuals from the Colombian admixed population. The Native American genetic ancestry was associated with a low β-cell function (odds ratio (OR) of 1.73 and 95% confidence interval (95% CI) of 1.07–2.81, p = 0.026). Significant genotypic associations were obtained (q-value < 0.05) for gene variants in ACE (rs4340; OR (95% CI): 2.79 (1.58–4.91), insulin resistance; mean difference (95% CI): 0.273 (0.141; 0.406), fasting insulin), ADIPOR2 (rs11061971; OR (95% CI): 0.14 (0.04–0.48), low β-cell function), MTNR1B (rs10830963; mean difference (95% CI): 0.032 (0.013; 0.051), fasting glucose) and GCK (rs4607517; mean difference (95% CI): 0.038 (0.020;0.056) and rs1799884; mean difference (95% CI): 0.027 (0.013–0.041), fasting glucose). Also the well-known gene variants rs7903146 in TCF7L2, and rs17817449 in FTO, were nominally associated with hyperglycemia (rs7903146), as well as with higher fasting insulin levels (rs17817449). Our findings indicate that gene variants in ACE, ADIPOR2, MTNR1B, GCK, TCF7L2 and FTO, are associated with glycemic traits in the admixed Colombian population, while a higher Native American genetic component is related to lower β-cell function.
•Native American ancestry is a risk factor for low β-cell function.•Gene variant rs11061971 is associated with better β-cell function.•Gene variants in or near GCK, MTNR1B and TCF7L2 are associated with hyperglycemia.•Gene variant rs4340 of ACE is associated with Insulin resistance and higher insulin levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
El objetivo del estudio fue describir la calidad de vida relacionada con la salud (CVRS) y su asociación con aspectos sociodemográficos, el exceso de peso u obesidad y la actividad física (AF) en un ...grupo de adolescentes de la ciudad de Medellín (Colombia). Para evaluar dichas variables se aplicaron diferentes instrumentos a 399 participantes. Las dimensiones de la CVRS con mayores puntuaciones fueron Apoyo Social y Amigos y Estado de Ánimo y Sentimientos. Ser hombre, tener una menor edad, cursar primaria, tener padres con educación superior, pertenecer a estrato socioeconómico alto, no tener obesidad por porcentaje de grasa o perímetro abdominal y presentar un nivel alto de AF se relacionaron con una mejor CVRS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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