Higher Biology - 1.8 - Genomics

╔═══°∴,*⋅✲══〖✰〗══✲⋅*,∴°═══╗

Welcome to the final Unit 1 post!

In this key area, there are 4 sections, as follows.

1. Genomic sequencing

2. Phylogenetics

3. Comparative genomics

4. Personal genomics

As always, questions at the end of the post.

Link to Masterpost

════°∴,*⋅✲══〖✰〗══✲⋅*,∴°════

Genomic Sequencing

DNA sequencing is the process of determining the order of nucleotides in a section of DNA. It is now possible to determine the sequence of nucleotides in relatively small sections, i.e. a gene, or very large sections, i.e. a complete genome.

The process by which sequencing can be achieved involves several techniques, and it is only relatively recently that two fields, in particular, have become sufficiently advanced to be incorporated together. PCR and related techniques now produce nucleic acids in sufficient quantity and purity, a computer science and statistical analysis can now cope with the quantity of evidence to rationalise the data into a comprehensible form. The use of computers and statistical analysis is known as bioinformatics.

Sequencing techniques

The development of sequencing techniques began sometime after the development and refinement of the Crick and Watson model of DNA.

By the early 1970s, recombinant DNA technology was becoming established. From this, defined fragments of DNA could be generated, as opposed to samples from bacteriophage or viruses. By 1977, the first complete DNA genome had been established. At the time, two teams were establishing techniques of sequencing.

Early attempts at sequencing were developed by Sanger and Coulson in 1975, called the plus-minus method. This was overtaken by Maxam and Gilbert in 1977, by a method based on chemical modification of DNA followed by cleavage at specific bases and, while accurate, it proved difficult to scale up and involved extensive use of toxic chemicals.

At about the same time, Sanger and his team developed the so-called "Chain Termination" method; this, and its subsequent developments, has become the technique favoured by many. Originally, radioactive materials were used which posed as a hazard, but they were replaced first with UV detection and then fluorescent dyes.

════°∴,*⋅✲══〖✰〗══✲⋅*,∴°════

Phylogenetics

Phylogenetics has been described as the field of biology that deals with identifying and understanding the relationship between the different kinds if life on earth, others use the term 'evolutionary relatedness'. It has become an essential tool in tracing the evolutionary tree of life as first proposed by Darwin.

Originally, the relationship between organisms was traced by comparison of physical characteristics, embryology, and examination of fossil records. Some of this is still in use but, more recently, advances in DNA sequencing have both used to determine the main sequence of events in the evolution of life. Based on this relatively modern approach, life is now classified based on the three domains using a system first proposed by Carl Woese in 1977

It has been over 150 years since Darwin first put forward his idea that all life is related, and it now widely accepted that all life originated in the sea some 3000 million years ago. The first cells developed and replicated themselves in two ways. Some formed into chains, which created algae and plant life, while others developed into hollow balls, which became sponges and the origins of animal life.

These groups grew and differentiated until about 450 million years ago with the development of land animals. As time progressed, greater divergence arose. Several mass extinction events eliminated many types of organism, but also gave those surviving the opportunity to flourish.

Over long periods of time (millions of years), mutations built up at a steady rate in any section of DNA. If the rae could be shown to be reliable, it could be used as a mechanism to estimate the time between mutations, i.e. a clock. This, in turn, can be used to estimate both when and where the organisms diverged from eachother.

The hypothesis states that DNA and protein sequences evolve at a rate that is relatively constant. Where this can be matched with fossil evidence, it is possible to trace evolutionary events and timescales.

However rates of molecular evolution can vary between organisms and so molecular clocks have to be calibrated. To do this, it is necessary to know the absolute age of some evolutionary divergence which can usually be determined from the fossil record.

════°∴,*⋅✲══〖✰〗══✲⋅*,∴°════

Comparitive Genomics

The Genome is the sum total of all the hereditary material within an organism. Genomics is the science of interpreting genes: the study of an organism's genome using information systems, databases and computerised research tools.

Many genomes have been sequenced, particularly those of disease-causing organisms, pest species and species that are important model organisms for research. The following table shows the size of some organisms genomes.

Comparative genomics is the process where the genomes of different species are compared. When comparing genomes from different species, scientists noted that many parts of the genome are highly conserved. This means that some sections of the DNA are identical or almost identical between different species. These conserved regions of DNA are useful in determining evolutionary relationships.

One of the earlier organisms to be sequenced was the puffer fish. The attractions of the puffer fish are that is has one of the most compact genomes of all vertebrates. It roughly contains a similar number of Gene's to humans, but they are contained in only 400 mega bases instead of 3.1 gigabases in humans.

By comparing the puffer fish genome to the human genome, it is possible to establish common functional elements of genes and regulatory sequences. By contrast, the non-functioning genes showed where evolutionary divergence has occurred from a common ancestor, approximately 450 million years ago.

════°∴,*⋅✲══〖✰〗══✲⋅*,∴°════

Personal Genomics

One of the aims of genomics is to explain why some individuals are susceptible to disease while others seem unaffected. By understanding the interaction between genes and the environment, it may even be possible to prevent the onset of some of these complex diseases in individuals.

Personal genomics is the sequencing and analysis of an individuals genome. Once an individual genotype (or part of it) is known, it is compared to references in published literature. From this, any mutations or sequences likely to give rise to disease can be identified. This is now referred to as predictive medicine, which in turn can lead to the appropriate drug treatment if required, a process known as pharmacogenetics.

Key to personal genomics has been cost, which has been decreasing fast. When the first genome was sequenced, it cost roughly three billion american dollars. This genome was a composite of several individuals, as of July 2012, people can have their own genome (or a part of it) sequenced for about £700 and completed within days or hours. However, after sequencing there must be an analysis which may mean further costs and time.

As a result if advances in this field, a question if ethics has also arisen. Insurance companies, bank and others may decline services or increase prices as a result of finding less desirable traits for example higher chances if alzheimer's or other degenerative diseases. This has been termed genetic discrimination. As of 2012 (when my sources were posted), regulations in this and associated fields aren't clear.

Personal genomics could bring about greater understanding of the varying effects of drugs between different individuals. One example is the group of genes responsible of drug metabolism - cytochrome P450 (CYP) genes. Depending on which alleles have been inherited, an individual may be described as an extensive metaboliser and can successfully metabolize certain compounds. Others, however, may be found to be intermediate or poor. As a consequence, patients may find that the drug of choice may be ineffective or cause severe adverse reactions. Clearly, it would be of significant advantage to have this information prior to treatment. It could save the patient from potential danger, and save the often considerable cost of medication.

════°∴,*⋅✲══〖✰〗══✲⋅*,∴°════

Questions (dm for answers)

1.Determining the order of nucleotide bases is known as....

2. What 2 techniques are combined to perform bioinformatics?

3. As a result if sequencing, phylogenetic trees can be formed. What is their purpose?

4. The ...... is the sum total of an organisms DNA. (Fill in the blank)

5. What advantages might be gained from knowing an individuals genome?

╚═══°∴,*⋅✲══〖✰〗══✲⋅*,∴°═══╝

feel free to comment or dm me with any questions!

Just like that, Unit 1 is finished, onto Unit 2 next!