Juan J. Yunis

Phylogenetics of worldwide human populations as determined by polymorphic Alu insertions

Alu elements, the largest family of interspersed repeats, mobilize throughout the genomes of primates by retroposition. Alu are present in humans in an excess of 500 000 copies per haploid genome. Since some of the insertion alleles have not reached fixation, they remain polymorphic and can be used as biallelic DNA marker systems in investigations of human evolution. In this study, six polymorphic Alu insertional (PAI) loci were used as genetic markers. These markers are thought to be selectively neutral. The presence of these six PAIs was determined by a polymerase chain reaction (PCR)‐based assay in 1646 individuals from 47 populations from around the world. Examination of the populations by plotting the first and second principal components, shows the expected segregation of populations according to geographical vicinity and established ethnic affinities. Centroid analysis demonstrated that sub‐Sahara populations have experienced higher than average gene flow and/or represent larger populations as compared to groups in other parts of the globe and especially to known inbreed populations. This is consistent with greater heterogeneity and diversity expected of source groups. In addition, maximum likelihood (ML) analyses were performed with these 47 populations and a hypothetical ancestral group lacking the insertion in all six loci. Analysis of our data supports the Out of Africa hypothesis. African populations and admixed groups of African descent formed a single monophyletic group with a basal placement on the tree, which grouped closest to the hypothetical ancestor.

Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population

Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies.

Results of the 1999-2000 collaborative exercise and proficiency testing program on mitochondrial DNA of the GEP-ISFG: an inter-laboratory study of the observed variability in the heteroplasmy level of hair from the same donor.

The Spanish and Portuguese working group (GEP) of international society for forensic genetics (ISFG) 1999-2000 collaborative exercise on mitochondrial DNA (mtDNA) included the analysis of four bloodstain samples and one hair shaft sample by 19 participating laboratories from Spain, Portugal and several Latin-American countries. A wide range of sequence results at position 16,093 of the HV1 (from T or C homoplasmy to different levels of heteroplasmy) were submitted by the different participating laboratories from the hair shaft sample during the first phase of this exercise. During the discussion of these results in the Annual GEP-ISFG 2000 Conference a second phase of this exercise was established with two main objectives: (i) to evaluate the incidence of the HV1 sequence heteroplasmy detected in Phase I across different sample types from the same donor including blood, saliva, and hair shafts, (ii) to perform a technical review of the electropherograms to evaluate the relative levels of heteroplasmies obtained by the different laboratories and also to examine the source of possible errors detected in Phase I. Anonymous review of the raw sequence data permitted the detection of three transcription errors and three errors due to methodological problems. Highly variable levels of heteroplasmy were found in the hair shaft and more stability in blood and saliva. Three laboratories found variable levels of heteroplasmy at position 16,093 across adjacent fragments from the same hair shaft. Two laboratories also described more than one heteroplasmic position from a single hair. The relevance of these findings for the interpretation of mtDNA data in the forensic context is also discussed.

Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia.

In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimers disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brain-derived neurotrophic factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia. There was not association between UCHL1 polymorphism and AD in our sample. We have found an initial association with BDNF polymorphism in familial cases and with COMT polymorphism in male and sporadic patients. These initial associations were lost after Bonferroni correction for multiple testing. Unadjusted results may be compatible with the expected functional effect of variations in these genes on pathological memory and cognitive dysfunction, as has been implicated in animal and cell models and also from neuropsychological analysis of normal subjects carriers of the AD associated genotypes. An exploration of functional variants in these and in other synaptic plasticity-related genes (a synaptogenomics approach) in independent larger samples will be important to discover new genes associated with AD.

The 2000–2001 GEP–ISFG Collaborative Exercise on mtDNA: assessing the cause of unsuccessful mtDNA PCR amplification of hair shaft samples

We report the results of Spanish and Portuguese working group (GEP) of International Society of Forensic Genetics (ISFG) Collaborative Exercise 2001-2002 on mitochondrial DNA (mtDNA) analysis. 64 laboratories from Spain, Portugal and several Latin-American countries participated in this quality control exercise. Five samples were sent to the participating laboratories, four blood stains (M1-M4) and a sample (M5) consisting of two hair shaft fragments. M4 was non-human (Felis catus) in origin; therefore, the capacity of the labs to identify the biological source of this sample was an integral part of the exercise. Some labs detected the non-human origin of M4 by carrying out immuno-diffussion techniques using antihuman serum, whereas others identified the specific animal origin by testing the sample against a set of animal antibodies or by means of the analysis of mtDNA regions (Cyt-b, 12S, and 16S genes). The results of the other three human blood stains (M1-M3) improved in relation to the last Collaborative Exercises but those related to hairs yielded a low rate of success which clearly contrasts with previous results. As a consequence of this, some labs performed additional analysis showing that the origin of this low efficiency was not the presence of inhibitors, but the low quantity of DNA present in these specific hair samples and the degradation. As a general conclusion the results emphasize the need of external proficiency testing as part of the accreditation procedure for the labs performing mtDNA analysis in forensic casework.

Exploration of genetic susceptibility factors for Parkinson’s disease in a South American sample

1Neurosciences Research Group, School of Medicine and Institute of Genetics, Universidad Nacional de Colombia, Bogota, Colombia 2Department of Internal Medicine, 3Department of Pediatrics, 4Department of Pathology, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia 5MSc Program in Neurosciences, Universidad Nacional de Colombia, Bogota, Colombia 6Present address: Biomedical Science Research Group, School of Medicine, Universidad Antonio Narino, Bogota, Colombia

Apolipoprotein E genotyping in a sample of Colombian patients with Alzheimer's disease

Abstract Apolipoprotein E e4 (APOEe4) allele has been associated with an increased risk for Alzheimers disease (AD) in diverse populations. Few studies have been carried out in Hispano-Americans and results are inconclusive due to ethnic diversity. This study determined the frequency of APOE alleles in a group of 61 Caucasian-Mestizos patients with probable AD, and 61 age- and sex-matched controls. APOEe4 frequency was 36.8% for patients, and 8.2% for controls (P

Population data on 6 short tandem repeat loci in a sample of Caucasian-Mestizos from Colombia.

Abstract Blood samples from 409–452 unrelated Colombian Caucasian-Mestizo individuals were amplified and typed for six short tandem repeat (STR) markers (HUMF13A01, HUMFES/FPS, HUMVWA, HUMCSF1PO, HUMTPOX, HUMTH01). The allele frequencies, genotype frequencies, heterozygocity, mean paternity exclusion chance, polymorphism information content, discrimination power, assumption of independence within and between loci and Hardy Weinberg equilibrium were determined. The results demonstrate that all markers conform to Hardy-Weinberg equilibrium expectations. In addition, the results demonstrate the assumption of independence within and between the loci analysed. The mean exclusion chance (MEC) was 0.9851 for all six STR loci analysed and the discrimination power (DP) was 0.9999973. Therefore, this Colombian population database can be used in identity testing to estimate the frequency of a multiple PCR-based locus DNA profile in forensic cases as well as in paternity testing.

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.

Population frequency for the short tandem repeat loci D18S849, D3S1744, and D12S1090 in Caucasian-Mestizo and African descent populations of Colombia.

Blood samples from 489 unrelated Caucasian Mestizo and 252 individuals of African descent in Colombia were amplified and typed for three short tandem repeat (STR) markers (D12S1090, D3S1744, and D18S849). All markers conformed to Hardy-Weinberg equilibrium expectations in both populations studied. In addition, heterozygosity, mean exclusion chance, polymorphism information content, discrimination power, and the assumption of independence within and between loci were determined. The mean exclusion chance for all three STR markers is 0.9750 in the Caucasian Mestizo population and 0.9731 in the African Colombian Population. The discrimination power is 0.999925 and 0.999911 in the Caucasian Mestizo and African Colombian respectively.