Genome Sequencing Technologies - Part 1
Every individual has a unique DNA sequence, and any changes in DNA can lead to a disease condition. A lot of research has been done so far in the direction of linking the genetic variations with health and disease outcomes. As we know, Human Genome Project (HGP) was one of the largest international collaborative biological projects, whose primary goal was to determine the sequence of human DNA. This project helped in advancement of medical science in many respects like in identification of cancer related genes and mutations, in designing of medicines and prediction of their effects, also, helping in understanding the genetic variation between individuals and designing personalized medications and treatment plans.
Sequencing cost has dropped tremendously since 2002, from hundreds of millions of dollars to just a few thousand dollars. Multiple repositories and consortiums have been established since the first genome sequence, building a rich catalog of genomes from people around the world. Also, these have been used to study genomic level changes in different diseases. Not only human genomes are major focus of the community, but also they are focusing in making inventories of the genomes of microbes, plants, and animals. There is a phenomenal increase in the number of sequenced genomes since 1995, from 85 genomes to ~4500 genomes till 2012. With this large amount of data, the analysis and identification of disease specific genomic factors has also become more and more challenging.
In general there are three major sequencing approaches which are widely being used whole genome, exome, and transcriptome sequencing. Based on scientific question and availability of samples one of these approaches are selected which in turn helps in selecting the right sequencing platform.
Whole genome sequencing is the most expensive method which involves sequencing of entire genome. This technology is still an expensive and difficult method of sequencing. There is a widely used whole genome sequencing technique which is widely used as it produces long and better quality sequencing reads. But there is an important limitation, in order to provide better power to genomic data analysis, a large sample size is required and this being the most expensive technology, is not yet been feasible to be used for population based studies.
Another type of sequencing where the final nucleotide product of our transcription machinery, exons are used. These exons are involved in formation of various proteins in our body. This method is used to identify mutations which help in understanding genetic diseases. This type of sequencing is very useful for identification of genetic abnormalities in congenital defects, in rare genetic disorders. This approach has been favored as it requires only about 5% sequencing of whole genome, which makes it quite cheaper to use. Since there are about 180,000 exons found in the human genome which form all proteins in human body, and the around 85% mutations in these regions have been found to contribute to most of the genetic disorders.
The third and very recent sequencing technology is transcriptomic sequencing. The transcriptome represents a very small percentage of human genome. It has been seen that the transcriptome of a cell is dynamic, as it continuously changes in comparison to human DNA sequence. Due to advancement in next generation sequencing technology, it is now possible to sequence different RNA transcripts in a cell. These transcripts help in understanding, how a single gene codes for multiple proteins, how a hybrid gene is formed by fusion of two genes and how expression of genes alter in a disease condition.
In recent years we have seen a rapid growth and advancement in genomic sequencing technologies. These approaches have been seen highly applicable for both genetic and complex diseases, helping us moving faster towards the goal of personalized medicine. All in all, the future of genomic technologies looks promising.