Wellcome Trust Centre for Human Genetics

About: Wellcome Trust Centre for Human Genetics is a facility organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 2122 authors who have published 4269 publications receiving 433899 citations.

Glucose-6-phosphate dehydrogenase deficiency and malaria

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme that is essential for a cell's capacity to withstand oxidant stress. G6PD deficiency is the commonest enzymopathy of humans, affecting over 400 million persons worldwide. The geographical correlation of its distribution with the historical endemicity of malaria suggests that 66PD deficiency has risen in frequency through natural selection by malaria. This is supported by data from in vitro studies that demonstrate impaired growth of P. falciparum parasites in G6PD-deficient erythrocytes. Attempts to confirm that G6PD deficiency is protective in field studies of malaria have yielded conflicting results, but recent results from large case control studies conducted in East and West Africa provide strong evidence that the most common African G6PD deficiency variant, G6PD A-, is associated with a significant reduction in the risk of severe malaria for both G6PD female heterozygotes and male hemizygotes. The effect of female homozygotes on severe malaria remains unclear but can probably be assumed to be similar to that of comparably deficient male hemizygotes.

A genotype calling algorithm for the Illumina BeadArray platform

Abstract: Motivation: Large-scale genotyping relies on the use of unsupervised automated calling algorithms to assign genotypes to hybridization data. A number of such calling algorithms have been recently established for the Affymetrix GeneChip genotyping technology. Here, we present a fast and accurate genotype calling algorithm for the Illumina BeadArray genotyping platforms. As the technology moves towards assaying millions of genetic polymorphisms simultaneously, there is a need for an integrated and easy-to-use software for calling genotypes. Results: We have introduced a model-based genotype calling algorithm which does not rely on having prior training data or require computationally intensive procedures. The algorithm can assign genotypes to hybridization data from thousands of individuals simultaneously and pools information across multiple individuals to improve the calling. The method can accommodate variations in hybridization intensities which result in dramatic shifts of the position of the genotype clouds by identifying the optimal coordinates to initialize the algorithm. By incorporating the process of perturbation analysis, we can obtain a quality metric measuring the stability of the assigned genotype calls. We show that this quality metric can be used to identify SNPs with low call rates and accuracy. Availability: The C++ executable for the algorithm described here is available by request from the authors. Contact:teo@well.ox.ac.uk or tgc@well.ox.ac.uk

Gene expression changes with age in skin, adipose tissue, blood and brain.

Abstract: Background: Previous studies have demonstrated that gene expression levels change with age These changes are hypothesized to influence the aging rate of an individual We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age Results: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue Only two genes expressed in lymphoblastoid cell lines showed significant changes with age Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years We identified only one age-related gene common to the three tissues There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues Conclusions: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases

Quantitative-Trait Locus for Specific Language and Reading Deficits on Chromosome 6p

Abstract: Reading disability (RD), or dyslexia, is a complex cognitive disorder manifested by difficulties in learning to read, in otherwise normal individuals. Individuals with RD manifest deficits in several reading and language skills. Previous research has suggested the existence of a quantitative-trait locus (QTL) for RD on the short arm of chromosome 6. In the present study, RD subjects' performance in several measures of word recognition and component skills of orthographic coding, phonological decoding, and phoneme awareness were individually subjected to QTL analysis, with a new sample of 126 sib pairs, by means of a multipoint mapping method and eight informative DNA markers on chromosome 6 (D6S461, D6S276, D6S105, D6S306, D6S258, D6S439, D6S291, and D6S1019). The results indicate significant linkage across a distance of at least 5 cM for deficits in orthographic (LOD = 3.10) and phonological (LOD = 2.42) skills, confirming previous findings.