Daily Archives: November 15, 2014

Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus) and to annotate protein-coding genes and other important genome-encoded features.[1] The genome sequence of an organism includes the collective DNA sequences of each chromosome in the organism. For a bacterium containing a single chromosome, a genome project will aim to map the sequence of that chromosome. For the human species, whose genome includes 22 pairs of autosomes and 2 sex chromosomes, a complete genome sequence will involve 46 separate chromosome sequences.

The Human Genome Project was a landmark genome project that is already having a major impact on research across the life sciences, with potential for spurring numerous medical and commercial developments.[2]

Genome assembly refers to the process of taking a large number of short DNA sequences and putting them back together to create a representation of the original chromosomes from which the DNA originated. In a shotgun sequencing project, all the DNA from a source (usually a single organism, anything from a bacterium to a mammal) is first fractured into millions of small pieces. These pieces are then "read" by automated sequencing machines, which can read up to 1000 nucleotides or bases at a time. (The four bases are adenine, guanine, cytosine, and thymine, represented as AGCT.) A genome assembly algorithm works by taking all the pieces and aligning them to one another, and detecting all places where two of the short sequences, or reads, overlap. These overlapping reads can be merged, and the process continues.

Genome assembly is a very difficult computational problem, made more difficult because many genomes contain large numbers of identical sequences, known as repeats. These repeats can be thousands of nucleotides long, and some occur in thousands of different locations, especially in the large genomes of plants and animals.

The resulting (draft) genome sequence is produced by combining the information sequenced contigs and then employing linking information to create scaffolds. Scaffolds are positioned along the physical map of the chromosomes creating a "golden path".

Originally, most large-scale DNA sequencing centers developed their own software for assembling the sequences that they produced. However, this has changed as the software has grown more complex and as the number of sequencing centers has increased. An example of such assembler Short Oligonucleotide Analysis Package developed by BGI for de novo assembly of human-sized genomes, alignment, SNP detection, resequencing, indel finding, and structural variation analysis.[3][4][5]

Genome annotation is the process of attaching biological information to sequences.[6] It consists of three main steps:

Automatic annotation tools try to perform all this by computer analysis, as opposed to manual annotation (a.k.a. curation) which involves human expertise. Ideally, these approaches co-exist and complement each other in the same annotation pipeline.

The basic level of annotation is using BLAST for finding similarities, and then annotating genomes based on that.[1] However, nowadays more and more additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. Some databases use genome context information, similarity scores, experimental data, and integrations of other resources to provide genome annotations through their Subsystems approach. Other databases (e.g. Ensembl) rely on both curated data sources as well as a range of different software tools in their automated genome annotation pipeline.[7]

Structural annotation consists of the identification of genomic elements.

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Genome project - Wikipedia, the free encyclopedia

Scientists from the University of Liverpool have sequenced the mitochondrial genome in glaucoma patients to help further understanding into the genetic basis for the disease.

Glaucoma is a major cause of irreversible blindness, affecting more than 60 million people worldwide, increasing to an estimated 79.6 million people by 2020. It is thought that the condition has genetic origins and many experiments have shown that new sequencing approaches could help understand how the condition develops.

Studies on primary open-angle glaucoma -- the most common form of glaucoma -- have shown that mutations in mitochondria, the energy generating structures in all cells, could give valuable insight into how to prevent the disease.

Using new gene sequencing techniques, called massively parallel sequencing, the Liverpool team have produced data on the mitochondrial genome taken from glaucoma patients from around the world.

The impact that mitochondrial gene change has on disease progression has been difficult to fully determine as cells in the human body can contain mixtures of healthy and mutated mitochondrial genes. Using this new technology, however, the researchers aim to support the delivery of personalised medicines to identify drugs that will target mutated mitochondria.

Professor Colin Willoughby, from the University's Institute of Ageing and Chronic Disease, explains: "Understanding the genetic basis of glaucoma can direct care by helping to determine the patient's clinical risk of disease progression and visual loss.

"Increasing evidence suggests that mitochondrial dysfunction results in glaucoma and drugs that target mitochondria may emerge as future therapeutic interventions.

"Further studies on larger glaucoma numbers of patients are required to firmly establish the link between genetic defects in the mitochondrial genome and glaucoma development.

"Our research, however, has demonstrated that massively parallel sequencing is a cost-effective approach to detect a wide spectrum of mitochondrial mutations and will improve our ability to understand glaucoma, identify patients at risk of the disease or visual loss and support the development of new treatments."

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DNA sequencing helps identify genetic defects in glaucoma