mtDNA variation in the chibcha ameridian huetar from Costa Rica

Artículo científico -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1994The genetic variation in a Chibcha-speaking Amerindian tribe from lower Central America, the Huetar, was analyzed using nucleotide sequences of the hypervariable segments of the mitochondria! DNA (mtDNA) control region, the frequencies of 10 Amerindian-specific mtDNA haplotypes, and the regional distribution of private protein polymorphisms. The sequencing of 713 base pairs (bp) in the control regions of 27 individuals revealed 11 distinct lineages. These were defined by 24 variable sites and a 6-bp deletion between nucleotide pairs (np) 106 and 111. The 6-bp deletion is a new mtDNA marker that will be valuable for Amerindian taxonomic research. Control region sequences and mtDNA haplotype analyses reveal that Huetar nitDNAs are distributed in 'Amerindian clusters" A, B, and D. A maximum-hlrellhood phylogenetic tree suggests a single origin for the 6-bp Huetar deletion in the sample. mtDNA haplotype analysis and the presence of previously characterized private protein variants (PEPA*F, TF*DCHI, and the absence of DI*A) show that the Huetar harbor polymorphisms of considerable antiquity, suggesting an early divergence from the regional founder gene pool for this population. The data also reflect a drastic constriction in population size. an evolutionary event with a proposed central effect on Huetar genetic structure.Universidad de Costa Rica, Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

A multistep docking and scoring protocol for congeneric series: Implementation on kinase DFG-out type II inhibitors

AIM:Rescoring of docking-binding poses can significantly improve molecular docking results. Our aim was to evaluate postprocessing docking protocols in order to determine the most suitable methodology for the study of the binding of congeneric compounds to protein kinases. MATERIALS & METHODS:Diverse ligand-receptor poses generated after docking were submitted to different relaxation protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area approach was applied for the evaluation of the binding affinity of complexes obtained. The performance of various Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methodologies was compared. RESULTS:The inclusion of a postprocessing protocol after docking enhances the quality of the results, although the best methodology is system dependent. CONCLUSION:An examination of the interactions established has allowed us to suggest useful modifications for the design of new type II inhibitors.Postprint (author's final draft

Direct screening of a mitochindrial DNA deletion valuable for Ameridian evolutionary research [resumen]

Artículo científico -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1994. Debido a las políticas de la revista en la que el artículo fue publicado, este no es posible distribuir la versión del editor/PDF; no obstante, se adjunta el URL de publicación original.A rapid, simple restriction isotyping method is described for the direct screening of a previously characterized Amerindian mitochondrial DNA (mtDNA) marker ;onsisting of a 6-bp "Huetar" deletion. In a sample of 31 maternally non-related Chibchan Amerindian Bribri from Costa Rica, this deletion was present in 74%, arguing for the usefulness of this private polymorphism for Amerindian taxonomic research.Universidad de Costa Rica, Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

D-Loop mtDNA deletion as a Unique marker of chibchan Ameridians [resumen]

Cartas al editor-- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1994Carta al editor. Torroni et al. (1993) presented an extensive restriction-site analysis of Native American mtDNAs from 17 widely dis- tributed Na-Dene and Amerindian tribes. For sometime we have been analyzing mtDNA control region sequences of several Chibcha-speaking Amerindian tribes from Costa Rica and Panama. Some Huetar individuals from central Costa Rica (not included in Torroni et al.'s tribes) present a 6-bp deletion encompassing nucleotides 106-111 (not reported before), subsequently denominated "Huetar deletion" (Santos 1992, Santos et al., in press). This marker has been found in different frequencies in several Chibchan groups (Bribri, Cabecar, Guaymi, and Kuna), but not in another located in the northern region of lower Central America (Miskito). According to our sequence data, the Huetar deletion carriers have lost restriction site MspI 104, as well as BsiHKAI (BioLabs) or its isoschizomers (Santos and Barrantes 1994). Therefore the -104i mutation in haplotypes 51-53 from Chibchan groups (Torroni et al. 1993) corresponds exactly to the Huetar deletion.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

A multistep docking and scoring protocol for congeneric series: Implementation on kinase DFG-out type II inhibitors

AIM:Rescoring of docking-binding poses can significantly improve molecular docking results. Our aim was to evaluate postprocessing docking protocols in order to determine the most suitable methodology for the study of the binding of congeneric compounds to protein kinases. MATERIALS & METHODS:Diverse ligand-receptor poses generated after docking were submitted to different relaxation protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area approach was applied for the evaluation of the binding affinity of complexes obtained. The performance of various Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methodologies was compared. RESULTS:The inclusion of a postprocessing protocol after docking enhances the quality of the results, although the best methodology is system dependent. CONCLUSION:An examination of the interactions established has allowed us to suggest useful modifications for the design of new type II inhibitors

Phenylketonuria in Costa Rica: preliminary spectrum of PAH mutations and their associations with highly polymorphic haplotypes

Artículo científico -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1996. Este artículo es privado debido a limitaciones de derechos de autor.A preliminary evaluation of the molecular basis of phenylketonuria (PKU) in Costa Rica was made by performing mutational analyses in the six PKU families identified to date. These studies revealed the presence of the previously reported European mutations IVS ntS, L48S, E221G and IVS12M1 as well as the novel mutation IVS7nt3. The combined use of the STR, VNTR and Xmol polymorphic systems for the PAH gene resulted in a discriminant distribution of haplotypes among normal and mutant chromosomes and suggests its potential usefulness for future diagnostic applications in Costa Rican PKU kindreds. This is the first report of a genetic analysis in a Central American PKU population.Baylor College of Medicine, HoustonInstitute of Human and Molecular GeneticsUniversidad de Costa Rica, Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA