Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential

Impairment of bone mass development in children with chronic cholestatic liver disease

Objective To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF-1 levels in children with chronic cholestatic disease (CCLD).Patients and measurements A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7.2 +/- 4.8 years) and 22 control subjects (mean age 7.6 +/- 4.5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25-hydroxyvitamin D, PTH and IGF-1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient.Results Z-score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0.107 +/- 0.02 vs. CCLD = 0.092 +/- 0.02 g/cm(3), P < 0.05) and after conversion for bone age. All participants showed normal 25-hydroxyvitamin D levels, with no significant differences in serum levels of 25-hydroxyvitamin D and PTH between groups. IGF-1 levels were significantly lower in the CCLD group (control = 19.6 +/- 16.8 vs. CCLD = 6.4 +/- 7.6 nmol/l, P < 0.05) and a positive correlation was observed between whole body BMD and IGF-1 in this group.Conclusions These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF-1 production might be responsible, at least in part, for the low bone mass of these patients.Univ São Paulo, Sch Med Ribeirao Preto, Dept Internal Med, Div Endocrinol & Metab, BR-14049900 São Paulo, BrazilUniv São Paulo, Sch Med Ribeirao Preto, Dept Pediat, Div Gastroenterol & Hepatol, São Paulo, BrazilWeb of Scienc

Fast psychomotor functioning in anorexia nervosa: Effect of weight restoration

Item does not contain fulltextIn a previous study young seriously underweight anorexia nervosa (AN) patients in the early phase of treatment were found to react faster in psychomotor tasks. To further understand this finding we studied the impact of weight restoration on the performance of AN patients in drawing and copying tasks. A group of 17 female AN patients, aged 14 to 25, was compared with 17 healthy controls, matched for sex, age and educational level. Patients were tested when severely underweight and after weight restoration. Control subjects were also tested twice. Using computerized recording and analysis of writing and drawing behavior, reaction times and drawing times were derived, while cognitive and motor demands were manipulated. Overall, AN patients showed shorter reaction times in copying tasks and shorter drawing time in the drawing task than normal controls, and this pattern persisted after weight restoration. No significant group (AN vs. controls) by session (test vs. retest) effect emerged. The finding of a consistent pattern of shorter reaction and drawing times in AN patients before and after weight restoration is compatible with a personality characteristic of perfectionism and overachievement in AN patients