Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components

BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

Muir-Torre Syndrome: case report and molecular characterization / Sindrome de Muir-Torre: relato de caso e caracterizacao molecular

CONTEXT: Muir-Torre syndrome is a rare autosomal dominant genodermatosis caused by mutations in the mismatch repair genes. It is characterized by the presence of sebaceous skin tumors and internal malignancies, affecting mainly the colon, rectum and urogenital tract. Awareness of this syndrome among physicians can lead to early diagnosis of these malignancies and a better prognosis. CASE REPORT: We report the case of a Chilean patient who, over the course of several years, had multiple skin lesions, endometrial cancer and colon cancer. The syndrome was diagnosed using molecular techniques such as microsatellite instability analysis, immunohistochemistry and DNA sequencing, which allowed us to find the causative mutation. CONCLUSION: Molecular diagnostics is a highly useful tool, since it allows clinicians to confirm the presence of mutations causing Muir-Torre syndrome. It is complementary to the analysis of the clinical data, such as dermatological presentation, presence of visceral malignancies and family history of colorectal tumors, and it provides important knowledge to help physicians and patients choose between treatment options. .

CONTEXTO: A síndrome de Muir-Torre é uma genodermatose autossômica dominante rara causada por mutações nos genes de reparo de incorreções. Caracteriza-se pela presença de tumores sebáceos da pele e doenças malignas internas, afetando principalmente cólon, reto e trato urogenital. A consciência desta síndrome pelos médicos pode levar ao diagnóstico precoce dessas doenças malignas e a um melhor prognóstico. RELATO DE CASO: Relatamos o caso de uma paciente chilena que, ao longo de vários anos, teve lesões cutâneas múltiplas, câncer de endométrio e câncer de cólon. A síndrome foi diagnosticada com técnicas moleculares, como a análise de instabilidade de microssatélites, imunoistoquímica e sequenciamento de DNA, o que nos permitiu encontrar a mutação causadora. CONCLUSÃO: Diagnóstico molecular é uma ferramenta muito útil, uma vez que permite que os clínicos confirmem a presença de mutações causadoras de síndrome de Muir-Torre. É complementar para a análise dos dados clínicos, tais como a apresentação dermatológica, a presença de doenças malignas viscerais e história familiar de tumores colorrectais, e fornece conhecimentos importantes para ajudar os médicos e os pacientes a escolher entre opções de tratamento. .

Prevalence of the 35delG mutation in the GJB2 gene in two samples of non-syndromic deaf subjects from Chile

Hearing loss is the most common inherited sensorial deficiency in humans; about 1 in 1000 children suffer from severe or profound hearing loss at birth. Mutations in the GJB2 gene are the most common cause of prelingual, non-syndromic autosomal recessive deafness in many populations; the c.35delG mutation is the most common in Caucasian populations. The frequency of the c.35delG mutation was estimated in two samples of deaf patients from Santiago, Chile. Unrelated non-syndromic sensorioneural deaf patients were examined: Group 1 consisted of 47 unrelated individuals with neurosensory deafness referred to the Chilean Cochlear Implant Program; Group 2 included 66 school children with prelingual deafness attending special education institutions for deaf people. Individuals with profound to moderate isolated neurosensory hearing loss with unknown etiology were included. The presence of the c.35delG mutation was evaluated by the allele-specific polymerase chain reaction method (PCR), and in some cases it was confirmed by direct DNA sequencing of the coding region of the GJB2 gene. Deaf relatives were present in 20.3% of the cases. We found 19.5% (22/113) patients with the c.35delG mutation, 6 of them homozygous; these rates are similar to frequencies found in other Latin American countries.

Larval interactions between a colonizing population of Drosophila subobscura and three established species of Drosophila in Chile

A viabilidade ovo-adulto e o tempo de desenvolvimento em Drosophila subobscura é bastante modificada pela acumulaçäo de resíduos bióticos de larvas de D. pavani, D. immigrans e D. melanogaster. Este efeito poderia ser um fator regulador importante para estas espécies na natureza

Sib-Sib segregation distortions for the ABO system: the influence of maternal phenotype

Uma amostra de 2227 pares consecutivos de irmäos, classificados de acordo com o fenótipo materno, foi examinada quanto aos desvios da segregaçäo para o sistema sangüíneo ABO. As sub-amostras de pares nascidos de mäes A, B e O, bem como a amostra total, desviam significativamente das proporçöes esperadas de segregaçäo. Houve um excesso significativo de pares que näo tinham o mesmo fenótipo em comum, mas isso näo ocorreu em irmäos nascidos de mäes B. Houve um número maior do esperado de pares A-O e A-B na matriz total de pares, um número maior de pares A-B e O-B na matriz de mäes A, um número maior de pares A-O e O-A na matriz de mäes B e um número maior de pares O-B e B-O na matriz de mäes O. As mäes BO heterozigotas segregaram preferencialmente os alelos O, uma condiçäo que näo foi significativa nas mäes AO heterozigotas. Estes resultados contradizem os mecanismos aceitos de incompatibilidade. Um sistema hipotético de tolerância materna induzido no início da gravidez por óvulos que possuem um gene que está faltando na mäe poderia explicar tais fatos

Distorsiones ABO y Rh, en hermanos recién nacidos / ABO and Rh distortions, in newuborn brothers

Se realiza un estudio de distribución de grupos sanguíneos ABO y Rh en 2734 parejas de hermanos consecutivos nacidos en el Hospital Clínico de la Universidad de Chile y en Clínica Alemana, de Santiago. Las proporciones esperadas de las distintas parejas hermano-hermano para el grupo ABO se calcularon según el método de matrices ITO para hermanos. La distribución de las distintas parejas de hermanos se alejó significativamente de lo esperado: 1§) hubo mayor cantidad de segundos hermanos grupo B que primeros; 2§) hubo exceso de individuos en los casilleros A-B (primer hermano A - segundo hermano B) y A-O en la muestra del Hospital Clínico de la Universidad de Chile; 3§) hubo ausencia de elementos en el casillero B-A de la muestra de Clínica Alemana. Estas distorsiones fueron evidentes sólo cuando ambos hermanos eran Rh(+)