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Introduction: Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported., Methods: This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population., Results: When the analyses were adjusted for known risk factors such as age, sex, presence of APOE[Latin Small Letter Open E]4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOE[Latin Small Letter Open E]4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers., Conclusions: Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOE[Latin Small Letter Open E]4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.

Objective: The association of variants in CLU, CR1, PICALM, BIN1, ABCA7, and CD33 genes with late-onset Alzheimer's disease (LOAD) was evaluated and confirmed through genome-wide association study. However, it is unknown whether these associations can be replicated in admixed populations., Methods: The association of 14 single-nucleotide polymorphisms in those genes was evaluated in 280 LOAD cases and 357 controls from the Colombian population., Results: In a multivariate analysis using age, gender, APOE∊4 status, and admixture covariates, significant associations were obtained ( P < .05) for variants in BIN1 (rs744373, odds ratio [OR]: 1.42), CLU (rs11136000, OR: 0.66), PICALM (rs541458, OR: 0.69), ABCA7 (rs3764650, OR: 1.7), and CD33 (rs3865444, OR: 1.12). Likewise, a significant interaction effect was observed between CLU and CR1 variants with APOE., Conclusion: This study replicated the associations previously reported in populations of European ancestry and shows that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene-gene interactions in the etiology of neurodegenerative diseases.

The aim of this study was to explore the association between some SNPs of the TNF, LTA, IL1B and IL10 genes with cytokine concentrations and clinical course in Colombian septic patients. We conducted a cross-sectional study to genotype 415 septic patients and 205 patients without sepsis for the SNPs -308(G/A) rs1800629 of TNF; +252 (G/A) rs909253 of LTA; -511(A/G) rs16944 and +3953(C/T) rs1143634 of IL1B; and -1082(A/G) rs1800896, -819(C/T) rs1800871 and -592(C/A) rs1800872 of IL10. The association of theses SNPs with the following parameters was evaluated: (1) the presence of sepsis; (2) severity and clinical outcomes; (3) APACHE II and SOFA scores; and (4) procalcitonin, C-reactive protein, tumor necrosis factor, lymphotoxin alpha, interleukin 1 beta and interleukin 10 plasma concentrations. We found an association between the SNP LTA +252 with the development of sepsis [OR 1.29 (1.00-1.68)]; the SNP IL10 -1082 with sepsis severity [OR 0.53 (0.29-0.97)]; the TNF -308 with mortality [OR 0.33 (0.12-0.95)]; and the IL10 -592 and IL10 -1082 with admission to the intensive care unit (ICU) [OR 3.36 (1.57-7.18)] and [OR 0.18 (0.04-0.86)], respectively. None of the SNPs were associated with cytokine levels, procalcitonin and C-reactive protein serum concentrations, nor with APACHE II and SOFA scores. Our results suggest that these genetic variants play an important role in the development of sepsis and its clinical course.

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

Introduction: Aedes aegypti populations may experience changes in abundance and genetic diversity in addition to changes in their evolutionary capability to respond to vector control. The knowledge on the changes in genetic variation on a spatio-temporal scale improves the epidemiological understanding of dengue and supports the appropriate and timely design of vector control strategies., Objective: To assess the genetic changes, diversity and gene flow in six microgeographical populations of Ae. aegypti in Medellín for different epidemiological periods of dengue., Materials and Methods: A total of 255 specimens from six different neighborhoods in Medellín were used to assess variations in the CO1 mtDNA haplotype composition, diversity and genetic differentiation for an epidemic period (2010) and an endemic period (2012)., Results: Two groups of highly differentiated haplotypes were present in both periods, and a high-frequency haplotype was assessed for all neighborhoods. The highest haplotype diversity was recorded in 2012, but the maximum nucleotide diversity was recorded in 2010. No significant correlation between genetic and geographic distances was observed., Conclusions: The genetic composition of Ae. aegypti varies over time without a predictable pattern. In addition, the presence of a high-frequency haplotype in both periods could indicate a persistent variation adapted to vector control. However, the simultaneous movement of highly differentiated CO1 haplotypes compatible with multiple introductions suggests that different gene pools would be suitable for transmission. These results are consistent with mosquito dispersion due to human activities, which would enable the rapid spread of the virus during epidemics in Medellin.

Background: A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics., Methods: We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation., Results: All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype., Conclusions: The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: The geographical distribution of genes plays a key role in genetic epidemiology. The Chilean population has three major stem groups (Native American, European and African)., Aim: To estimate the regional rate of American, European and African admixture of the Chilean population., Subjects and Methods: Forty single nucleotide polymorphisms (SNP´s) which exhibit substantially different frequencies between Amerindian populations (ancestry-informative markers or AIM´s), were genotyped in a sample of 923 Chilean participants to estimate individual genetic ancestry., Results: The American, European and African individual average admixture estimates for the 15 Chilean Regions were relatively homogeneous and not statistically different. However, higher American components were found in northern and southern Chile and higher European components were found in central Chile. A negative correlation between African admixture and latitude was observed. On the average, American and European genetic contributions were similar and significantly higher than the African contribution. Weighted mean American, European and African genetic contributions of 44.34% ± 3 9%, 51.85% ± 5.44% and 3.81% ± 0.45%, were estimated. Fifty two percent of subjects harbor African genes. Individuals with Aymara and Mapuche surnames have an American admixture of 58.64% and 68.33%, respectively., Conclusions: Half of the Chilean population harbors African genes. Participants with Aymara and Mapuche surnames had a higher American genetic contribution than the general Chilean population. These results confirm the usefulness of surnames as a first approximation to determine genetic ancestry.

Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations., Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia., Methods and Materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined., Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure., Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (θ) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus.

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

Introduction: Autism spectrum disorders are severe neurodevelopmental disorders with a strong genetic component. The potential role of the serotoninergic system in the development of autistic disorder has been based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Multiple molecules involved in serotonin metabolism and neurotransmission have been studied; however, replication studies have been inconsistent. This may be partially related to the marked genetic heterogeneity of autism in different populations., Objectives: The relationship between autism and single nucleotide polymorphisms of SLC6A4, HTR2A and ITGB3 genes was evaluated in an urban population of northwestern Colombia., Materials and Methods: In Antioquia, Colombia, 42 families with history of autism were screened for 10 SNPs in SLC6A4, HTR2A and ITGB3 genes and evaluated for associations with the transmission disequilibrium test. The interactions among these genes and autism was assessed with multidimensional reduction methods., Results: A significant main effect was seen among the SLC6A4 gene variants rs4583306 (OR=2.6, p=0.004) and rs2066713 (OR=2.2, p=0.03). No main effect of the ITGB3 or HTR2A variants was found, however, in the interaction effects, the SLC6A4 and HTR2A genes demonstrated significant evidence of association with autism (p<0.001)., Conclusion: Significant association of markers were discovered within the SLC6A4 gene and the combination of SLC6A4 and HTR2A (S-A) genes to autism. These results were consistent with previous studies conducted in other populations and provide further evidence for the implication of the serotoninergic system in the etiology of autistic disorders.

Introduction: The negative homozygous condition for the Duffy blood group (Fy-/Fy-) confers natural resistance to Plasmodium vivax infection. Studies carried out in pursuing this direction in Colombia are scarce., Objective: To describe the relationship between Duffy genotypes in three ethnic communities of La Italia (Chocó) and malarial infection., Methods: This is a descriptive, cross-sectional study in symptomatic and asymptomatic subjects with malaria., Sample Size: Afro-Colombians 73; Amerindian (Emberá) 74, and Mestizo, 171. The presence of Plasmodium infection was assessed by thick smear and the status of the Duffy gene was studied by PCR and RFLP to help identify changes to T-46C and A131G which originate the genotypes T/T, T/C , C/C and G/G, G/A, A/A., Results: Infection by Plasmodium was detected in 17% of cases with 62% due to P. falciparum and 27% due to P. vivax. Duffy genotypes were significantly associated with ethnicity (p= 0.003). Individuals with the C/C, A/A diplotypes were exclusively infected by P. falciparum, whereas the other diplotypes were infected with either of the species. In the Amerindian and Mestizo populations, the frequency of the T-46 allele was 0.90-1.00, among Afro-Colombians this was 0.50, the same as with the C allele and with an absence of heterozygous. At locus 131, the maximum frequency of the G allele was 0.30 in Amerindians and the maximum of the A allele was 0.69 in Afro-Colombians., Conclusions: In the Amerindian and mestizo populations studied, there was a predominance of the allele T-46 (FY+) but this was not observed with the P. vivax infection. P. vivax was ruled out in all FY- individuals.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Introduction: The environmental risk factors such as food intake and physival activity, are determinants in the etiology of metabolic syndrome in overweight adolescents., Objective: To explore the association between environmental risk factors and components presence of metabolic syndrome in overweight youngsters in Medellín., Materials and Methods: Adolescents between the ages of 10 and 18 were selected for a cross sectional study. Body composition by anthropometry, blood pressure, lipid profile, glucose, insulin, food intake and physical activity level were assessed in the study population., Results: The prevalence for metabolic syndrome components of hypertriglyceridemia was 40.9%; hypertension, 20.9%; low HDLc, 15.6%; high waist circumference, 4.0%, and hyperglycemia, 0.9%; the overall prevalence of metabolic syndrome was 3.1%. There was a statistical difference (p<0.005) between the consumption of calories, simple and total carbohydrates and the presence of the components; no association was found between the level of physical activity and the presence of components (p>0.05). The logistic regression model showed a higher probability of having at least one component if the youngster was male (p=0.022), with a higher BMI (Body Mass Index)(p=0.019) and was located in the fourth simple carbohydrates consumption quartile (p=0.036)., Conclusions: Environmental risk factors associated with components of metabolic syndrome were the increased consumption of calories, simple and complex carbohydrates, all directly related to the BMI. In contrast, the level of physical activity, family history and personal risk factors showed no association. The metabolic syndrome only occurred in youngsters with obesity.

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., (© 2010 The Authors Annals of Human Genetics © 2010 Blackwell Publishing Ltd/University College London.)

Comparative studies of linkage disequilibrium (LD) can provide insights into human demographic history. Here, we characterize LD in six Native American populations using seven microsatellite markers in Xq13, a region of the genome extensively studied in populations around the world. Native Americans show relatively low diversity and high LD, in agreement with recent genome-wide survey and a scenario of sequential founder effects accompanying human population dispersal around the globe. LD in Native Americans is similar to that observed in some recently described small population isolates and higher than in large European isolates (e.g., Finns), which have been extensively analyzed in medical genetics studies. Haplotype analyses are consistent with a colonization of the New World by a differentiated East Asian population, followed by extensive genetic drift in the Americas., ((c) 2009 Wiley-Liss, Inc.)

Introduction: The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance., Objective: The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus., Materials and Methods: In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry., Results: Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p = 0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found. These associations remained after adjustment using individual genetic admixture estimates., Conclusion: Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.

The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The E280A mutation of the presenilin 1 gene has been found to be the most common associate in Alzheimers patients with a family history of this disease. Presenilin 1 is a critical component of the g-secretase complex and plays an essential role in the production of amyloid-beta peptide. This peptide has been strongly associated with the physiopathology of the disease., Objective: The E280A mutation in the presenilin 1 was investigated for increased production of amyloid-beta , as a response to gain in gamma-secretase function., Materials and Methods: Levels of systemic amyloid-beta were measured with congo red staining and immuno-histochemistry of the tissues of affected cadavers, compared with non-affected cadavers. The 40 and 42 amino acid amyloid-beta levels were quantified by ELISA assay in CHO cell cultures. The amyloid precursor protein expressed by the cultures was detected by transfection with the cDNAs of presenilin 1 carrying the M146L, E280A, DE9 y L392V mutations., Results: Protein deposits were found in all tissues investigatged, but only a few with beta -amyloid deposition. No differences were observed in the amount or location of amyloid-beta between affected and unaffected cadavers. Not increase was noted in the production of amyloid-beta from the CHO cells transfected with cDNA from any of the mutations of presenilin 1., Conclusions: The E280A mutation in the presenilin 1 gene was not associated with the increased production of amyloid-beta in non-neuronal peripheral tissues, or in the in vitro model. This is in contrast to the expectation in a gamma-secretase gain of function.

Introduction: Genetic studies of Trypanosoma cruzi have tried to establish relations between genetic variants and their biological characteristics, such as clinical manifestations, host or geographic origin. However, much controversy exists on the associations between the commonly used DNA markers with group, clinical characteristics and disease epidemiology., Objective: In this study determined the variability of the genes that code for the proteins trypanothione reductase and cruzipain, both involved in the infection and survival of the parasite in the mammalian host, was studied and the association between genetic polymorphism and biological and geographic sources in Colombian T. cruzi strains was examined., Materials and Methods: The genotypes for each of six SNPs (single nucleotide polymorphisms) for trypanothione reductase and eight SNPs for cruzipain genes were identified by polymerase chain reaction-restriction fragment length polymorphism in 36 T. cruzi Colombian stocks from several regions and biological origins., Results: Three genotypes were identified for trypanothione reductase with Acy I and Hae III enzymes and six genotypes for cruzipain with the Rsa I, Ban I and Bsu 361 enzymes., Conclusions: For trypanothione reductase, an association was not established with biological or geographical origin; however, alleles at positions 102 and 210 allowed discrimination with groups I and II. For cruzipain, specific genotypes were associated with group, biological and geographic origin. The usefulness of molecular markers on these genes was demonstrated for the determination and differentiation of genetic varieties in T. cruzi.

Introduction: Surname frequency (isonymy) is used as a marker of paternal lineage and is used to characterize human population structure. Principles of isonymy were used to determine the genetic structure, migration rates, ancestry relations and origins of populations. This analysis was applied to two historically related local populations which currently are considered to be genetically isolated., Objective: The genetic relationships and influence zones of the Aranzazu and Marinilla populations were assessed by means of surname frequency analysis., Materials and Methods: Data originated from database with the title "System of Identification of Beneficiaries of the Social Programs" database or Sisben. Population parameters such as a priori kinship (phi(ii)), population homogeneity with B and C estimators, and Cavalli-Sforza's genetic distance were calculated for (a) three towns of Marinilla and its influence zone and (b) Aranzazu. The Rionegro population served as an external, comparison population., Results: The Aranzazu and Marinilla populations showed the higher homogeneity (B value between 0.25 and 0.5) in contrast with Rionegro (B = 0.159), as well as greater a priori kinship values (4), between 0.003 and 0.010). The lowest distances were found between Marinilla and Aranzazu., Conclusions: Aranzazu is a population with characteristics similar to those of Marinilla and its influence zone. The close similarity of genetic characteristics for these populations is due probably to a founder effect. Furthermore, the genetic similarity predicts that genetic diseases will have the same etiology in both populations and provides optimum conditions for gene mapping studies.

We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.

Background: In patients with colorectal carcinoma, insertions or deletions of short sequences of DNA, a phenomenon called microsatellite instability, are observed., Aim: To look for microsatellite instability and mutations of MLH1 and MSH2 gene mutations in patients with colorectal carcinoma., Material and Methods: Ten patients with sporadic colorectal carcinoma and 31 patients fulfilling criteria for hereditary nonpolyposis colon cancer (HNPCC), aged 9 to 70 years, were studied. Microsatellite instability was studied in samples of tumor and peripheral blood mononuclear cell DNA. Six markers were amplified by polymerase chain reaction and capillary electrophoresis. In samples with microsatellite instability, mutations of MLH1 and MSH2 genes were studied by direct sequencing., Results: Thirty four percent of patients had microsatellite instability and among these, 76% had a high degree of instability. BAT40 marker had the higher frequency of instability. No mutations for MLH1 and MSH2 genes were observed. However a new polymorphism, C399T, was identified in exon 3 of MSH2 gene. This polymorphism was observed both in patients with sporadic colorectal carcinoma and patients with HNPCC., Conclusions: There is a high frequency of microsatellite instability among patients with colorectal cancer. A new polymorphism, not previously reported, was identified in MSH2 gene.