1,721,020 research outputs found
Linkage disequilibrium patterns for the identification of functional regions of the non-coding genome
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Linkage disequilibrium maps highlight differential selection pressures between three breeds of <i>Gallus gallus</i>
No full textAnalysis of loss of heterozygosity by whole-exome sequencing yields insights into pseudomyxoma peritonei
No full textGenomic data analysis: populations, patients and pipelines
No full textMethods for the ascertainment of genotype data have become more cost efficient by orders of magnitude with the use of high-density genotyping arrays and the advent of next generation sequencing (NGS). The resulting deluge of data has required ever advancing analytical approaches in order for the maximal information to be gleaned from these extensive data.In this work, many application of NGS to clinical research are discussed. This includes the application of targeted gene sequencing to a cohort of 83 patients with chronic kidney disease, whole-exome investigations of eight families with cleft lip/palate phenotypes, as well as five cases where analytical lessons can be learned from exome sequenced cases harbouring pathogenic variants refractory to identification. Additionally, a novel QC tool for the unambiguous tracking of samples undergoing exome sequencing is presented.Furthermore, work is presented investigating the linkage disequilibrium (LD) patterns in populations applying the Malecot-Morton model. We demonstrate that array genotyping is insufficient for the accurate determination of ne LD patterns in the human genome, with whole-genome sequencing providing more representative LD maps. Finally, we apply similar methods to Gallus gallus, generating the highest resolution maps of LD presented to date, showing that the patterns are highly discordant between commercial lines, and define features associated with recombination.Overall, we highlight the diversity of ways in which genetic data can be utilised effectively in the age of genomic `big data', and present tools which may be of benefit to other researchers utilising these technologies<br/
Rapid identification of Saccharomyces eubayanus and its hybrids
No full textThe Saccharomyces species Saccharomyces eubayanus was recently discovered in Patagonia. Genomic, genetic and phylogenetic data all suggest that it is one of the two parents of the hybrid yeast S. pastorianus (S. cerevisiae being the other). Saccharomyces eubayanus genomes can also be found in strains of the hybrid species S. bayanus. Here, we describe a novel pair of PCR primers targeted against the S. eubayanus FSY1 gene that will specifically detect S. eubayanus and hybrids containing this allele of the gene. The primer pair can be used to identify the species using a rapid, inexpensive colony PCR method suitable for a preliminary identification of wild isolates.Keyword
Linkage disequilibrium maps to guide contig ordering for genome assembly
No full textMotivation: Efforts to establish reference genome sequences by \textit{de novo} sequence assembly have to address the difficulty of linking relatively short sequence contigs to form much larger chromosome assemblies. Efficient strategies are required to span gaps and establish contig order and relative orientation. We consider here the use of linkage disequilibrium (LD) maps of sequenced contigs and the utility of LD for ordering, orienting and positioning linked sequences. LD maps are readily constructed from population data and have at least an order of magnitude higher resolution than linkage maps providing the potential to resolve difficult areas in assemblies. We empirically evaluate a linkage disequilibrium map-based method using single nucleotide polymorphism genotype data in a ~216 kilobase region of human 6p21.3 from which three shorter contigs are formed.Results: LD map length is most informative about the correct order and orientation and is suggested by the shortest LD map where the residual error variance is close to one. For regions in strong LD this method may be less informative for correcting inverted contigs than for identifying correct contig orders. For positioning two contigs in linkage disequilibrium with each other the inter-contig distances may be roughly estimated by this method. Availability: The LDMAP program is written in C for a linux platform and is available at https://www.soton.ac.uk/genomicinformatics/research/ld.page<br/
Exome sequencing explained: a practical guide to its clinical application
No full textNext-generation sequencing has catapulted healthcare into a revolutionary genomics era. One such technology, whole-exome sequencing, which targets the protein-coding regions of the genome, has proven success in identifying new causal mutations for diseases of previously unknown etiology. With a successful diagnostic rate approaching 25% for rare disease in recent studies, its clinical utility is becoming increasingly popular. However, the interpretation of whole-exome sequencing data requires expertise in genomic informatics and clinical medicine to ensure the accurate and safe reporting of findings back to the bedside. This is challenged by vast amounts of sequencing data harbouring approximately 25?000 variants per sequenced individual. Computational strategies and fastidious filtering frameworks are thus required to extricate candidate variants in a sea of common polymorphisms. Once prioritized, identified variants require intensive scrutiny at a biological level, and require judicious assessment alongside the clinical phenotype. In the final step, all evidence is collated and documented alongside pathogenicity guidelines to produce an exome report that returns to the clinic. This review provides a practical guide for clinicians and genomic informaticians on the clinical application of whole-exome sequencing. We address sequencing capture and methodology, quality control parameters at different stages of sequencing analysis and propose an exome data filtering strategy that includes primary filtering (for the removal of probable benign variants) and secondary filtering for the prioritization of remaining candidates
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