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A Ruiz-Linares

Publications and source records attributed to A Ruiz-Linares.

15 recordsLinked to original sources
PubMed2002

Mutations in FOXL2 underlying BPES (types 1 and 2) in Colombian families.

We report the genetic characterization of one family with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type 1 and two families with BPES type 2 from a historically isolated population in northwest Colombia. Linkage and haplotype analyses indicate that BPES in these families is linked to 3q23. Mutation screening of FOXL2 in the family with BPES type 1 revealed a novel 394C --> T nonsense mutation which deletes the forkhead DNA binding domain. The two families with BPES type 2 both carry an in-frame 30 bp duplication that leads to the elongation of a polyalanine tract. This duplication has been previously reported in Europe, where recurrent mutation has been demonstrated in unrelated familial and sporadic BPES cases. The recurrent nature of this duplication seems to relate to the secondary structure of this DNA region. The genotype-phenotype correlation seen in the Colombian families is consistent with the recent proposal that BPES type 1 is caused by truncating mutations leading to haploinsufficiency, while BPES type 2 is due to mutations generating elongated protein products.

Blepharophimosis↗
PubMed2002

Y-chromosome biallelic polymorphisms and Native American population structure.

It has been proposed that women had a higher migration rate than men throughout human evolutionary history. However, in a recent study of South American natives using mtDNA restriction fragment polymorphisms and Y-chromosome microsatellites we failed to detect a significant difference in estimates of migration rates between the sexes. As the high mutation rate of microsatellites might affect estimates of population structure, we now examine biallelic polymorphisms in both mtDNA and the Y-chromosome. Analyses of these markers in Amerinds from North, Central and South America agree with our previous findings in not supporting a higher migration rate for women in these populations. Furthermore, they underline the importance of genetic drift in the evolution of Amerinds and suggest the existence of a North to South gradient of increasing drift in the Americas.

Chromosomes, Human, Y↗
PubMed2001

A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile Parkinsonism in a population from North West Colombia.

We report the molecular characterization of three multiplex families and a sporadic case of juvenile Parkinsonism identified in the province of Antioquia (Colombia). Linkage and haplotype analysis using markers in 6q25.2-27 indicated that Parkinsonism in the pedigrees is linked to the parkin gene (maximum LOD-score of 3.85) but that they carry two different mutant haplotypes. Sequence analysis revealed a novel G to A transition in exon 6 at position 736 (G736A) of parkin. This change results in a non-conservative cysteine for tyrosine substitution. All affected individuals from two families were homozygous for this mutation, which was not detected in 100 normal controls. Patients from the family carrying the second haplotype and the sporadic case were homozygous for a GT insertion in exon 3. This mutation has been previously identified in French families with juvenile Parkinsonism. The concomitant presence of founder effects and allelic heterogeneity in Antioquia might relate to the founding admixture at the origin of this population.

Adolescent↗
PubMed2000

Autosomal, mtDNA, and Y-chromosome diversity in Amerinds: pre- and post-Columbian patterns of gene flow in South America.

To evaluate sex-specific differences in gene flow between Native American populations from South America and between those populations and recent immigrants to the New World, we examined the genetic diversity at uni- and biparental genetic markers of five Native American populations from Colombia and in published surveys from native South Americans. The Colombian populations were typed for five polymorphisms in mtDNA, five restriction sites in the beta-globin gene cluster, the DQA1 gene, and nine autosomal microsatellites. Elsewhere, we published results for seven Y-chromosome microsatellites in the same populations. Autosomal polymorphisms showed a mean G(ST) of 6.8%, in agreement with extensive classical marker studies of South American populations. MtDNA and Y-chromosome markers resulted in G(ST) values of 0.18 and 0.165, respectively. When only Y chromosomes of confirmed Amerind origin were used in the calculations (as defined by the presence of allele T at locus DYS199), G(ST) increased to 0.22. G(ST) values calculated from published data for other South American natives were 0.3 and 0.29 for mtDNA and Amerind Y chromosomes, respectively. The concordance of these estimates does not support an important difference in migration rates between the sexes throughout the history of South Amerinds. Admixture analysis of the Colombian populations suggests an asymmetric pattern of mating involving mostly immigrant men and native women.

Africa↗
PubMed2000

Strong Amerind/white sex bias and a possible Sephardic contribution among the founders of a population in northwest Colombia.

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 approximately 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, approximately 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.

Africa, Northern↗
PubMed2000

An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia.

The short variant of a functional length polymorphism in the promoter region of the serotonin transporter has been associated with several behavioural and psychiatric traits, including bipolar mood disorder. The same short allele has also been implicated as a modifier of the bipolar phenotype. Here we evaluate the etiologic/modifier role of this polymorphism in a case (N=103) / control (N=112) sample for bipolar mood disorder (type I) collected from an isolated South American population. We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample. However, an excess of the short allele was seen in younger cases and in cases with psychotic symptoms. When combined with data from the literature, the increased frequency of the short allele in patients with psychotic symptoms was statistically significant.

Age of Onset↗
PubMed2000

Sickle cell anemia and beta-globin gene cluster haplotypes in Colombia.

We studied 46 unrelated sickle cell anemia patients from the western region of Colombia which has the largest Black population of the country. Twenty-three children and 23 adults were studied. The distribution of haplotypes in the children was 58% Bantu, 38% Benin, and 4% Senegal, and in the adults it was 59.4% Bantu, 35.1% Benin, and 5.5% Senegal (p = 0.920). All 92 chromosomes had typical African haplotypes, Bantu 55.5%, Benin 34.8%, Senegal, 4.3%, and Cameroon, 5.4%. Our results suggest a lack of differential survival among patients with sickle cell anemia and typical beta-globin gene cluster haplotypes. They also agree closely with historical data that indicate that most African slaves brought to Colombia originated from Angola (Bantu population) and the Sao Thomó Island in the Bight of Benin (Central West Africa).

Adolescent↗
PubMed1999

Microsatellites provide evidence for Y chromosome diversity among the founders of the New World.

Recently, Y chromosome markers have begun to be used to study Native American origins. Available data have been interpreted as indicating that the colonizers of the New World carried a single founder haplotype. However, these early studies have been based on a few, mostly complex polymorphisms of insufficient resolution to determine whether observed diversity stems from admixture or diversity among the colonizers. Because the interpretation of Y chromosomal variation in the New World depends on founding diversity, it is important to develop marker systems with finer resolution. Here we evaluate the hypothesis of a single-founder Y haplotype for Amerinds by using 11 Y-specific markers in five Colombian Amerind populations. Two of these markers (DYS271, DYS287) are reliable indicators of admixture and detected three non-Amerind chromosomes in our sample. Two other markers (DYS199, M19) are single-nucleotide polymorphisms mostly restricted to Native Americans. The relatedness of chromosomes defined by these two markers was evaluated by constructing haplotypes with seven microsatellite loci (DYS388 to 394). The microsatellite backgrounds found on the two haplogroups defined by marker DYS199 demonstrate the existence of at least two Amerind founder haplotypes, one of them (carrying allele DYS199 T) largely restricted to Native Americans. The estimated age and distribution of these haplogroups places them among the founders of the New World.

Colombia↗
PubMed1998

[Antiochian genealogies in which idiopathic epilepsy presents familial conglomeration. Simulations of power for the detection of genetic linkage].

OBJECTIVE AND METHODS: We have analyzed a set of multigenerational extended pedigrees ascertained from affected cases of idiopathic epilepsy in the Antioquian Neurologic Institute. All pedigrees show familial aggregation of several forms of non myoclonic idiopathic epilepsy. In a recent paper, we have demonstrated that generalized idiopathic epilepsy of the awakening type is better explained by the existence of a major gene. In this paper, we have explored by simulation techniques the usefulness of the bigger pedigrees for linkage analysis. By using simlink and taking into account the parameters of the major gene, we have estimated that total power of three families is approximately 100 million times favoring the linkage detection. RESULTS AND CONCLUSIONS: These analyses suggest that the major gene accounting by the susceptibility to develop generalized idiopathic epilepsy of the awakening type could be localized by typifying affected families belonging to the Paisa community from Antioquia, Colombia (Acta Neurol Colomb 1997; 13: 69-75).

Adolescent↗
PubMed1997

Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation.

OBJECTIVES: To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene. DESIGN: Clinical histories were obtained by patient and family interviews and through medical or civil records. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 have definitive (autopsy-proven) early-onset AD, 93 have probable early-onset AD, and 29 have possible early-onset AD. SETTING: Community based in Antioquia, Colombia. PATIENTS: A population-based sample in which all members of 5 extended families (nearly 3000 individuals) were surveyed. Criteria for inclusion required obtaining sufficient information to categorize the individual as affected. MAIN OUTCOME MEASURES: Age at onset, neuropsychological profile, neurologic history, and examination. RESULTS: The patients had a mean age at onset of 46.8 years (range, 34-62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentation was memory loss followed by behavior and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. CONCLUSIONS: Other than the early onset, this clinical phenotype is indistinguishable from sporadic AD except that affected individuals frequently complained of headache preceding and during the disease. Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.

Adult↗
PubMed1994

High resolution of human evolutionary trees with polymorphic microsatellites.

Genetic variation at hypervariable loci is being used extensively for linkage analysis and individual identification, and may be useful for inter-population studies. Here we show that polymorphic microsatellites (primarily CA repeats) allow trees of human individuals to be constructed that reflect their geographic origin with remarkable accuracy. This is achieved by the analysis of a large number of loci for each individual, in spite of the small variations in allele frequencies existing between populations. Reliable evolutionary relationships could also be established in comparisons among human populations but not among great ape species, probably because of constraints on allele length variation. Among human populations, diversity of microsatellites is highest in Africa, which is in contrast to other nuclear markers and supports the hypothesis of an African origin for humans.

Africa↗
PubMed1989

Modulations of the in vitro translational efficiencies of Yellow Fever virus mRNAs: interactions between coding and noncoding regions.

As an approach to define the structural features within the 5' noncoding region of Yellow Fever virus (YFV) that modulate mRNA translational efficiency, we have studied how minor changes in this region affect the translational capacity in vitro of the corresponding mRNAs. A cDNA sequence coding for part of the YFV structural proteins was inserted into the vector pGEM3 containing the bacteriophage T7 promoter. This vector was engineered by site-directed mutagenesis to permit in vitro synthesis of transcripts containing only 5 vector nucleotides at their 5' end. The sequence of the YFV 5' untranslated region was further modified in order to alter the secondary structure of resulting T7 transcripts. The efficiency of these messengers in programming cell-free translation systems varied from 1- to 15-fold, correlating inversely with the potential of the 5' untranslated sequences to form stable secondary structures. A chimaeric messenger containing the YFV 5' noncoding (5' NC) region linked to a heterologous mRNA derived from Germiston virus, was tested for its in vitro translatability. We found a translational efficiency about 2-fold higher than that obtained with homologous transcripts, suggesting that YFV 5' NC region can function as a potential enhancer for gene expression. Data obtained with a series of plasmids constructed by linking the native YFV 5'NC region to various coding regions of the YFV genome indicated that interactions between the untranslated sequence and protein coding regions influence mRNAs translational efficiency.

Base Sequence↗
PubMed1989

Processing of yellow fever virus polyprotein: role of cellular proteases in maturation of the structural proteins.

The yellow fever virus (YFV) cDNA segment coding for the part of the precursor polyprotein generating the structural proteins C (capsid), prM (precursor to the membrane protein M), and E (envelope) was expressed in vitro by using the T7 promoter-polymerase transcription system coupled to translation in rabbit reticulocyte lysates. A polypeptide of the expected molecular weight was observed to accumulate in the assay and was processed into proteins C, prM, and E only when dog pancreas microsomal membranes were added to the translation system. Proteins prM and E were translocated inside the endoplasmic reticulum, where prM underwent glycosylation. Regions essential for translocation of these proteins were localized to the 18- and 15-amino-acid C-terminal hydrophobic regions of proteins C and prM, respectively. Translocation of protein prM appeared to be less efficient than that of protein E. Maturation of these proteins followed different kinetics, indicating that the prM signal is probably cleaved off more slowly. A polypeptide composed of proteins C and prM, similar to the NVx polypeptide described in yellow fever virus-infected cells, was also produced in the in vitro system in the presence of membranes. No mature protein M was detected, suggesting that the cleavage of prM to M is a late processing event mediated by a protease different from endoplasmic reticulum signalases.

Biological Transport↗
PubMedDate not supplied

[Genetic linkage analysis of Gilles de la Tourette Syndrome in a Colombian family].

INTRODUCTION: Gilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder characterized by phonic and motor tics. Although its physiopathologic bases are unknown, the cortical-striatal-thalamic-cortical circuit has been studied. The association of GTS with attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), motors tics (MT) or phonics tics (PT), the high family aggregation, and the concordance studies in twins, support the genetics bases of this disorder. Currently, GTS is accepted as a complex disorder and the associated disorders could be alternative expressions of the same syndrome. AIM: To evaluate genetic linkage to 2p11, 6p24, 11q23, 20q13 and 21q22 regions in an Antioquian family with enough power to detect linkage. PATIENTS AND METHODS: With the Linkage program and using autosomic dominant, recessive and additive inheritance models, the genetic linkage was calculated; two phenotypic spectra was considered: one broad spectrum including affected individuals with GTS, ADHD, OCD, MT, and PT, and a narrow spectrum with only GTS. RESULTS: The most probable inheritance pattern for a susceptibility locus in GTS and its associated disorders in this family is autosomic additive. The presence of a locus involved in GTS in the 2p11 region has been rejected. CONCLUSION: The linkage values for D20S1085 and D6S477 markers are suggestive and therefore it is not possible reject that these markers will be in linkage disequilibrium with genes involved in the GTS, ADHD, OCD, MT, and PT etiology.

Adolescent↗