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The profile of mutations in the CFTR gene, which reflects the heterogeneity of its inhabitants, shows the complexity of the molecular diagnosis of CF mutations in most of the Latin American countries.

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We report the first specific human immunoglobulin subclass probe which was obtained by subcloning the gamma 3 hinge region. This specific y3 probe allowed us to identify with certainty the Cy3 gene on Southern genomic blots, to describe the first Cy3 restriction fragment length polymorphism (EZZ y3 RF) and to show that an IgG3 selective deficiency, previously described serologically, was not due to a deletion of the Cy3 gene. Such a probe should be particularly useful for screening libraries from individuals with IgG3 immunodeficiencies or presenting unusual Cy3 genes and, consequently, for studying the Cy gene evolution.

Cystic Fibrosis is a worldwide distributed hereditary disease. The incidence of the main (p.F508del) and other frequent mutations has been determined in a great number of countries and ethnic groups, but its incidence in most Latin American countries has remained unknown until recently. It is now beginning to be recognized as a frequent cause of infant mortality, and some countries report the incidence of their mutations. Colombia started several years ago a concerted program of molecular study of patients which were clinically diagnosed as probable cystic fibrosis. We screened the whole CFTR (ABCC7) coding sequence in 92 patients from 6 different geographic regions, using conventional PAGE analyses and DGGE followed by sequencing. Additionally, we established the frequency of the p.F508del mutation in 130 unrelated healthy controls. The results of this pilot study in Colombian patients from various ethnic admixture show six main mutations: p.F508del (41.8%), c.1811+1.6kbA>G (6.5%), p.G542X (3.8%), p.S549R (2.2%), p.W1282X (1.1%) and p.R1162X (1.1%). Thirteen other rare mutations, including three novel, were detected, accounting for a total of 63.6% known mutations. There is a great variability between the geographic regions, both in the frequency of the p.F508del mutation and non-p.F508del CF chromosomes. Our results point to a varied origin of the disease genes. These results also show that careful scrutiny of the mutations is needed in each part of Latin America in order to establish priority-screening protocols adapted to each country and region.

A population genetic study was carried out with the APOE, APOB and ACE loci in 17 Colombian human populations. Ten of them were Amerindian communities coming from the northeastern part of Colombia, Pacific region, Eastern Plains and Amazonia. Six were black populations from Providence Island, Caribbean and Pacific coasts. Finally, the Mestizo population of Bogota was studied as well. The APOE and ACE loci were in Hardy-Weinberg equilibrium, whereas the APOB locus was not studied in all populations. The genetic heterogeneity was substantially greater among the Amerindian populations (G_ST = 0.059) than in the Afrocolombian populations (G_ST = 0.009). Also the gene flow population pair estimates were so much higher among the Afrocolombian populations (Nm = 49.08 ± 43.07) than among Amerindian populations (Nm = 9.66 ± 18.04). Different phylogenetic and multivariant analyses showed that the Amerindian populations analyzed were clustered in three different arrays: one constituted by the Colombian northeastern and Pacific populations, the second one by the two Amazon populations (Coreguaje and Nukak) and the last one by the Yuco (the unique Caribbe-speaking population among those studied). The latter population was highly divergent from a genetic point of view from the remainder Amerindian populations studied. By using the Mantel test, the existence of a positive and significant correlation between the genetic and geographical distances found among Amerindian populations was demonstrated. This fact was not observed among the Afrocolombian populations. Nevertheless, an isolation-by-distance Slatkin analysis test did not show a significant clear structure of this special pattern among the Indian tribes studied.

PCR/SSOP typing methods were used to analyze the HLA Class II DRB1, DQA1, DQB1 and DPB1 loci of samples from three African American populations of Colombia. Forty samples from the Cauca (Pacific), and twenty samples each from the Choco (North Pacific Coast) and the Providencia (Caribbean island) populations, were collected and the Class II loci analyzed under the auspices of the Expedicion Humana. Despite the limited number of samples analyzed, the African Colombian populations exhibit a very high degree of class II polymorphism. A great diversity of DRB1 alleles was found, with representatives from all serological classes, including 19 DRB1 alleles in the Providencia, 16 in the Cauca and 14 in the Choco groups. In addition, a novel DQB1*02 allele (*0203) was found in two individuals from the Cauca population of the Pacific Coast. The sequence of the DQB1*0203 allele, associated with DR3, differs from DQB1*0201 by only one nucleotide substitution (C-->A) in the second position of codon 57, resulting in an Ala to Asp change. The addition of DQB1*0203 brings the total number of DQB1 alleles identified to date to 26. HLA class II diversity is much greater in these African Colombian populations than that seen in nearby Amerindian populations. Analysis of regional Colombian African American HLA population genetics is discussed with respect to the Colombian Amerindian HLA genetics described in an accompanying paper.