Genomic medicine in cardiology

Q4Editoriale3-e

El análisis genético de paleo-colombianos de Nemocón, Cundinamarca proporciona revelaciones sobre el poblamiento temprano del Noroeste de Suramérica

23 páginasThe Checua site within Nemocón in the eastern Andean Region of Colombia has produced evidence of hunter-gatherer activities from 9500-8700 cal yr BP. The aim of this work was to analyze genetically the Checua group according to mitochondrial DNA HVR-I sequence data. Following strict criteria of authenticity for studies of ancient DNA, extracted DNA was amplified and sequenced for each of the human remains. Twelve of the 22 human remains from Checua were successfully assessed (54.54%) in this study. Paleo-Colombian Checua revealed the Native American haplogroups A2, B2 and C1, plus the rare haplogroup D4h3a, reported for the first time in ancient Colombia. Comparison between Paleo-American and modern Colombian genetic data demonstrates the continuity of A2, B2, and C1, and a probable discontinuity of D4h3a since prehistoric times in Colombia, if not a shortage of D4h3a records in the literature and/or databases, while D1 is present in modern Colombia. The presence of D4h3a, A2, B2, and C1 haplogroups from Colombian early Holocene burials supports genetic evidence for Paleo-American dispersals downward by the Pacific coast. Our Paleo-Colombian DNA data, along with other genetic, archaeological, and paleoenvironmental published data, allow us to bring forward an Integrated Migration Model for the early peopling of northwestern South America, which involved different movements: (1) North-to-South along the coast; (2) West-to-East across the Andean mountain ranges; (3) Riverine discovery and riverside colonization

Genetic analysis of pre-Columbian human remains from Lower Magdalena suggests a migratory route and matrilineal genetic continuity in Northern South America

El análisis del ADN en restos de poblaciones prehispánicas ha permitido aproximarse al origen genético de una proporción importante de los habitantes de la actual Colombia. Los resultados arqueológicos de la tradición de Malambo, cuyo origen se remonta a 3.000 años A.P. en el bajo Magdalena, se complementaron con estudios genéticos de cuatro individuos asociados con esta población. Para ello se extrajo ADN de muestras de dientes y huesos. El ADN extraído se purificó y se amplificó por PCR para su posterior secuenciación y análisis filogenético. El haplogroupo B2j se identificó y se caracterizó mediante la mutación G16361A, así como la deleción de 9pb y las mutaciones diagnósticas del haplogrupo B. Este mismo haplogrupo fue descrito recientemente en un individuo en Venezuela, lo que sugiere la filiación genética matrilineal y su continuidad en el norte de SuraméricaDNA analysis in pre-Hispanic populations remains has allowed approaching the genetic origins of inhabitants in present-day Colombia. In this work, we complemented the archaeological results on the Malambo tradition, originated 3000 years B.P. in Lower Magdalena, with genetic studies of bone remains of four individuals associated with this population. We extracted DNA from bone samples and purified and amplified them by PCR for further sequencing and phylogenetic analysis. We identified the B2j haplogroup in all individuals as characterized by a G16361A mutation, as well as a 9-pb deletion and diagnostic mutations of haplogroup B. This same haplogroup was recently described in an individual in Venezuela suggesting genetic maternal filiation and continuity in northern South AmericaN/

De curandis hominum morbis : an 18th century prescription for stroke management by volatile alkali in the new Kingdom of Granada

boticarios, barberos, médicos y protomédicos, es consecuencia de la experiencia de individuos anónimos de las poblaciones locales, que fueron capaces de percibir directamente en la naturaleza elementos útiles a la terapia, así como de la existencia de principios activos no validados, o bien de efectos placebo. Objetivo: Presentar y analizar desde la perspectiva de la medicina moderna, una receta médica del siglo XVIII en el Nuevo Reino de Granada, en la cual se prescribe el álkali volátil para disminuir síntomas generados por afecciones del sistema musculoesquelético. Desarrollo: En el periodo Colonial, pese a la carencia de estudios o evidencia que respaldara, se utilizaban términos como fármacos, con una dosificación establecida e indicaciones. Se presenta y analiza a la luz de la medicina moderna una receta mÈdica del siglo XVIII para el tratamiento de la apoplexia con efectos benéficos al aumentar el flujo sanguÌneo al cerebro y la disponibilidad de oxÌgeno asÌ mismo aumentando el metabolismo neuronal. El amoníaco puede inducir hiperexcitabilidad neuronal, bloqueo de la actividad de la glutaminasa, reducir la descomposición de glutamina en glutamato y amonÌaco en las terminaciones nerviosas, sin embargo, dosis elevadas podrÌan llegar a producir muerte celular o fallo respiratorio. Conclusiones: El advenimiento de nuevas tecnologías ha permitido avances en el diagnóstico, prevención y tratamiento de múltiples enfermedades. En este contexto, los tratamientos del pasado se han visto relegados a curiosidades históricas. El legado terapéutico colonial conservado en los archivos locales permite viajar al pasado para intentar comprender racionalmente los medicamentos de nuestros predecesores. Existe evidencia cientÌfica que respalda la efectividad del alkali volátil para diversas enfermedades, entre estas la apoplejía. No obstante, una descripción vaga o ausente de la posología, signos, síntomas y comorbilidades, dificulta analizar la eficacia de este tratamiento histórico.The use of medicinal plants and mineral resources in the New Kingdom of Granada in colonial times by apothecaries, barbers, doctors and protomedics, is a consequence of the experience of anonymous individuals from the local populations, who were able to perceive directly in nature elements useful to the therapy, as well as the existence of non-validated active principles, or even placebo effects. Objective: To present and analyze from the perspective of modern medicine, a medical prescription from the 18th century in the New Kingdom of Granada. In which volatile alkali is prescribed to reduce symptoms generated by conditions of the musculoskeletal system. AIM: In the Colonial period, despite the lack of studies or evidence to support, terms were used as drugs, with an established dosage and indications. An 18th century medical prescription for the treatment of stroke is presented and analyzed in the light of modern medicine beneficial effects by increasing blood flow to the brain and the availability of oxygen also increasing neuronal metabolism. Ammonia can induce neuronal hyperexcitability, block glutaminase activity, reduce glutamine breakdown in glutamate and ammonia in nerve endings, however, high doses could lead to cell death or respiratory failure. Conclusions: The advent of new technologies has enabled advances in the diagnosis, prevention and treatment of multiple diseases. In this context, past treatments have been relegated to historical curiosities. The colonial therapeutic legacy preserved in the local archives allows us to travel to the past and try to rationally understand the medicines of our predecessors. There is scientific evidence supporting the effectiveness of volatile alkali for various diseases, including stroke. However, a vague or even absent description of dosage, signs, symptoms and comorbidities, makes it difficult to analyze the effectiveness of this historical treatment.N/

“Asthma”: Prescription for treatment in the Viceroyalty of New Granada in the 18th century

OBJETIVO: presentar una receta médica del siglo XVIII en el Virreinato de la Nueva Granada, que describe el tratamiento de asma. MATERIALES Y MÉTODOS: búsqueda en el archivo histórico de la Biblioteca Octavio Arizmendi Posada en la Universidad de La Sabana (Chía, Colombia), donde se conserva una colección de un centenar de recetas médicas coloniales del siglo XVIII; se realiza una transcripción de una de ellas, titulada “Asthma”, con una ulterior revisión de la literatura científica pertinente. CONCLUSIONES: esta receta médica colonial muestra su utilidad para calmar los síntomas por asma y constituye un claro ejemplo de terapias comparadas a través del tiempo. Además, esta prescripción constituye un ejemplo documental de la evolución histórica de la medicina, desde los tiempos coloniales de los entonces territorios de ultramar de la Corona Española.OBJECTIVE: To present a medical prescription of the eighteenth century in the Vicero-yalty of New Granada, which describes the treatment of asthma. MATERIALS AND METHODS: A documentary search in the historical archive of the Octavio Arizmendi Posada Library at the University of La Sabana (Chía, Colombia) was performed, where a collection of a hundred colonial medical recipes of the 18th century is preserved; we present a transcription of one of them, entitled “Asthma”, with a subsequent revision of the pertinent scientific literature. CONCLUSIONS: This colonial prescription shows its usefulness for treating symptoms induced by asthma and constitutes a clear example of compared therapeutics through the ages. In addition, this prescription should also be recognized as a documentary example of the historical evolution of medicine, since the colonial times of the overseas territories of the Spanish Crown.https://orcid.org/0000-0002-5592-3844https://orcid.org/0000-0002-8080-0723https://orcid.org/0000-0001-7300-6401Revista Nacional - IndexadaN

Opilation and menstrual suppression : An 18th century medical prescription in the New Kingdom of Granada

Objetivo: presentar y definir el contexto de una receta médica que data del siglo XVIII en el Nuevo Reino de Granada, utilizada para la supresión de la menstruación, y analizar, a la luz de los conocimientos actuales, si sus ingredientes en conjunto podrían o no lograr la inhibición del sangrado menstrual. Materiales y métodos: búsqueda documental en el Archivo Histórico de la Biblioteca Octavio Arizmendi Posada en la Universidad de La Sabana, donde se identifica la receta "Opilación y supresión de menstruos", y, posteriormente, se realizó una revisión de la literatura disponible en las bases de datos SciELO/proQuest en el periodo 1993-2015. Conclusiones: en la receta manuscrita hallada se describen múltiples ingredientes que, analizados a la luz de los conocimientos actuales, y en su conjunto, no tienen validez para lograr el pretendido efecto supresor. Sin embargo, se reconocen las propiedades antianémicas del "vitriolo líquido de Marte", y el posible efecto que ejercería el ejercicio excesivo formulado en medio del ciclo menstrual, aunque en la receta no se describe con exactitud la frecuencia ni la intensidad con la que este debería ser realizado para lograr una supresión del menstruo.Q365-70Objective: To present and define the context of a medical prescription dating from the eighteenth century in the New Kingdom of Granada, used for the suppression of menstruation, and to analyze it in the light of current knowledge as to whether its ingredients as a whole, may or may not achieve inhibition of menstrual bleeding. Materials and methods: documentary search in the Historical Archives of the Octavio Arizmendi Posada Library at Universidad de La Sabana where the prescription “Opilation and menstrual suppression” was found. A review of the literature available in SciELO/proQuest databases was subsequently conducted for the period 1993–2015. Conclusions: The manuscript found describe multiple ingredients that, as a whole, and analyzed in light of current knowledge, are not valid to achieve the alleged suppressive effect. However, the components of the “liquid vitriol of Mars” could be recognized as having antianemic properties, and the potential suppressive effect of prescribing vigorous exercise in the middle of the menstrual cycle, although the recipe does not accurately describe the frequency or intensity of exercising to achieve the desired effect

Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients

9 páginasPathogenic BRCA1/2 germline mutations confer high risks of breast and ovarian cancer to women of European ancestry. Characterization of BRCA1/2 mutations in other ethnic groups is also medically important. We comprehensively screened 68 Colombian breast/ovarian cancer families for small-range mutations, 221 families for large-genomic rearrangements, and 1,022 unselected breast cancer cases for Colombian founder mutations in BRCA1/2. The risk of cancer among relatives of mutation carriers and the mutation penetrance were estimated by survival analysis. Identified BRCA2 mutations included 6310delGA and the recurrent 1991del4 mutations. A novel large BRCA2 deletion was found in 0.9% of the screened families. Among unselected breast cancer cases, 3.3% tested positive for BRCA1/3450del4, 2.2% for BRCA1/A1708E, 1.1% for BRCA2/3034del4, and 0.4% for BRCA2/1991del4. Female relatives of carriers of BRCA1/2 founder mutations showed a 5.90 times higher risk of breast cancer, when the woman herself carried a BRCA1 mutation compared to a non-carrier (95% CI 2.01–17.3). The estimated cumulative risk of breast cancer by age 70 years for BRCA1 mutations carriers was 14% (95% CI 5–38) compared to 3% for the general Colombian population (relative risk of breast cancer 4.05). Together with known founder mutations, reported novel variants may ease a cost-effective BRCA1/2 screening in women with Colombian ancestry

Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes

8 páginasNonsyndromic Cleft Lip and/or Palate (NSCLP) is regarded as a multifactorial condition in which clefting is an isolated phenotype, distinguished from the largely monogenic, syndromic forms which include clefts among a spectrum of phenotypes. Nonsyndromic clefting has been shown to arise through complex interactions between genetic and environmental factors. However, there is increasing evidence that the broad NSCLP classification may include a proportion of cases showing familial patterns of inheritance and contain highly penetrant deleterious variation in specific genes. Through exome sequencing of multi-case families ascertained in Bogota, Colombia, we identify 28 non-synonymous single nucleotide variants that are considered damaging by at least one predictive score. We discuss the functional impact of candidate variants identified. In one family we find a coding variant in the MSX1 gene which is predicted damaging by multiple scores. This variant is in exon 2, a highly conserved region of the gene. Previous sequencing has suggested that mutations in MSX1 may account for ~2% of NSCLP. Our analysis further supports evidence that a proportion of NSCLP cases arise through monogenic coding mutations, though further work is required to unravel the complex interplay of genetics and environment involved in facial clefting

High genetic diversity on a sample of pre‐Columbian bone remains from Guane territories in northwestern Colombia

Q1Q1Artículo de investigación637-649Ancient DNA was recovered from 17individuals found in a rock shelter in the district of ‘‘LaPurnia’’ (Santander, Colombia). This region is the home-land of pre-Columbian Guane, whom spread over the‘‘Rı ́o Suarez’’ to the ‘‘Rı ́o de Oro’’, and were surroundedto the west by the Central Andes, south and east by foot-hills of Eastern Andes, and north by the ‘‘Chicamocha’’river canyon. Guanes established in a region that strad-dles the Andes and the northern Amazon basin, possiblymaking it an unavoidable conduit for people moving toand from South America. We amplified mtDNA hyper-variable region I (HVI) segments from ancient boneremains, and the resulting sequences were comparedwith both ancient and modern mitochondrial hap-logroups from American and non-American populations. Samples showed a distribution of 35% for haplogroup A,41% for haplogroup B and 24% for haplogroup D. Ninehaplotypes were found in 17 samples, indicating anunusually high genetic diversity on a single site ancientpopulation. Among them, three haplotypes have notbeen previously found in America, two are shared inAsia, and one is a private haplotype. Despite geographi-cal barriers that eventually isolated them, an importantinfluence of gene flow from neighboring pre-Columbiancommunities, mainly Muiscas, could explain the highgenetic polymorphism of this community before theSpanish conquest, and argues against Guanes as being agenetic isolate