Genetic linkage analysis in the age of whole-genome sequencing

For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Prevalência da anemia em crianças avaliada pela palidez palmar e exame laboratorial: implicações para enfermagem Sentimientos de mujeres-madres delante de la cirugía neonatal en las malformaciones congénitas Prevalence of anemia in children assessed by clinical method known as "palmar pallor" and the laboratory exam: implications for nursing

Buscou-se analisar a prevalência de anemia ferropriva em crianças e comparar os dados obtidos pelo método clínico "palidez palmar" e exame laboratorial em uma Estratégia de Saúde da Família no município de Panambi/RS. Pesquisa exploratória/descritiva, quantitativa, realizada de março a junho de 2009. Foram sujeitos 41 crianças de 2 meses a 5 anos. Os dados foram analisados pela estatística descritiva. Das crianças, 51,2% eram do sexo masculino; 41,46% estavam na faixa etária de 0 a 12 meses; 53,6% das famílias situavam-se no nível social D e 43,9% dos chefes de família tinham o Ensino Fundamental completo ou o Ensino Médio incompleto. Pela palidez palmar, a prevalência de anemia foi de 51,2% e pelo exame laboratorial, de 58,53%. O estudo mostra que a palidez palmar e o exame laboratorial, quando usados juntos, fornecem um diagnóstico mais preciso da anemia ferropriva, podendo ser inseridos na prática assistencial da enfermagem na ESF.<br>Se intenta analizar la prevalencia de anemia por deficiencia de fierro en niños y comparar el método clínico "palidez palmar" y el examen de laboratorio en una Estrategia de Salud de la Familia en la municipalidad de Panambi-RS. La pesquisa exploratoria, descriptiva y cuantitativa fue realizada de marzo hasta junio de 2009. Los sujetos fueron 41 niños de 2 meses a 5 años de edad. Los datos fueron analizados por la estadística descriptiva. Del total de niños, 51,2% eran del sexo masculino; 41,46% estaban en la franja etaria de 0 a 12 meses; 53,6% de las familias se sitúan en el nivel social D y 43,9% de los jefes de familia tienen la Enseñanza Fundamental Completa o la Enseñanza Media Incompleta. Por la palidez palmar, la prevalencia de anemia fue de 51,2% y por el examen de laboratorio, de 58,53%. El estudio muestra que la palidez palmar y el examen de laboratorio, cuando usados juntos, proveen un diagnóstico más preciso de la anemia por deficiencia de fierro, pudiendo ser inserido en la práctica asistencial de enfermería en la ESF.<br>We sought to examine the prevalence of iron deficiency anemia in children and compare the data obtained by the clinical method known as "palmar pallor" and the laboratory exam on the Family Health Strategy services in the municipality of Panambi-RS. The exploratory, descriptive and quantitative research was carried out from March to June 2009. The subjects were 41 children from the age of 2 months up to 5 years old. The data were analyzed by descriptive statistics. Out of the total number of children, 51,2% of them were male; 41,46% of them fit in the age frame from 0 to 12 months old; 53,6% belonged to families of D social level while 43,9% of the family chiefs have complete Elementary Education or incomplete Junior High School. Considering the palmar pallor, the prevalence of anemia was 51,2% and as per the lab exam, by 58,53%. The study shows that the palmar pallor and the laboratory exam when used together provide a more accurate diagnosis of iron deficiency anemia, can be inserted in the professional nursing practice in the ESF