Next Generation Sequencing Of Human Diseases

Scientist is studying the human genome to determine its sequence. Understanding the genomic sequence can prevent any form of disease, however, each person does not contain the same genomes which means it is hard to understand each genomes sequences. The advantage of understanding the genomics, is to understand how human genomic mutations can lead to life-threating conditions such as cancer and prevent them from happening again. The disadvantage for researching genomics cost a lot of money, the research nearly cost thirteen-billion

Aziz, N., Qin, Z., Bry, L., Driscoll, D. K., Funke, B., Gibson, J. S., & ... Voelkerding, K. V. (2015). College of American Pathologists' Laboratory Standards for Next-Generation Sequencing Clinical Tests. Archives Of Pathology & Laboratory Medicine, 139(4), 481-493 13p.

This manual provides a means to communicate accounting policies and procedures currently in use at Open Genomes Foundation, Inc., a not-for-profit foundation incorporated as a 501(c)(3) organization. Open Genomes Foundation is registered with the Secretary of State of the Commonwealth of Massachusetts.

The work was also supported from Michael Stratton, the Welcome Trust Sanger Institute (WTSI) sequencing and informatics teams, and the WTSI Cancer Genome Project.

The Human Genome Project also referred to as HGP, has really captivated the world at the birth of the 21st Century and it has surely revolutionized the biology field. The project itself commenced officially in 1990 and scheduled for 15 years duration. HGP is so vast and complicated in nature that the most essential goals of the project had to be narrowed down to six; Identify approximately 30,000 genes in human DNA, determine 3 billion sequences of chemical base pairs which compose human DNA, Storage of developed information in databases, improve data analysis tools, transfer related technologies to the private sector and address the (ELSI) – Ethical, Legal, and Social Issues related to HGP. The total US HGP came with a huge price tag of around 3 billion US dollars.

Firstly, shot-gun sequencing requires a large portion of template DNA for each read, and subsequently, numerous strands of template DNA are required for each read since a strand that terminates on each base is required for the construction of a complete sequence. However, a sequence can be achieved through a single strand using next-generation sequencing. Also, next-generation sequencing is a faster process than shot-gun sequencing since the chemical reactions taking place in next-generation sequencing can be merged with signal detection, which cannot be done with shot-gun sequencing, and next-generation sequencing allows more DNA to be read on a single run than compared to shot-gun sequencing. Additionally, next-generation sequencing results in reduced costs since not as much human labor and reagents are required as those needed for shot-gun sequencing. Furthermore, next-generation sequencing is more accurate than shot-gun sequencing as next-generation sequencing involves numerous repeats due to the need for each read to be amplified before sequencing and its dependence on numerous short overlapping reads, in order for multiple sequences of DNA and RNA to be achieved. Also, due to its cheap costs, it would be more economical to perform multiple repeats rather than shot-gun sequencing, whose costs are exceedingly greater. Therefore, due to

If the lifetime of the polymerase is long enough, both strands can be sequenced multiple times (called ‘‘passes”) in a single polymerase read. Moreover, the polymerase read could be split to multiple reads (called subreads) by recognizing and cutting out the adaptor sequences. The consensus sequence of multiple subreads in a single ZMW yields a circular consensus sequence (CCS) read with higher accuracy. If a target DNA is too long to be sequenced only one time in a polymerase read a CCS read cannot be generated, and only a single subread is output instead. Whereas, the CCS sequences are usually generated by transcript sequencing due to its relatively short length. According, Pacific Biosciences developed an independently protocol, Iso-Seq, for long-read transcriptome sequencing, including library construction, size selection, sequencing data collection, and data processing. Iso-Seq allows direct sequencing of transcripts up to 10 kb without use of a reference

Genome-wide association studies (GWAS) are often correlated with personalized medicine. GWAS studies often involve sequencing the entire genome of patients suffering from a specific disease, to look for shared mutations within their genomes (Bush et al., 2012, p.1). These shared mutations are then investigated to assure their direct correlation with the disease, in which this mutation can be used to diagnose future patients by identifying the same mutation in their genome sequence (Bush et al, 2012, p. 3). Occasionally, it is identified that multiple mutations within the genome lead to the same disease (Bush et al., 2012, p.1). In cases where groups of individuals suffer from specific mutations in disease,

The human genome project is an incredible feat. The significance and contributions of the project to the science world has and will have a significant impact of the way we treat, diagnosis, and prepare for diseases if an individual knows they have a predisposition to it. There are two significant contributions that I believe has been very beneficial to the health field. The first is recording and storing all the new found information on genomics into one database. More importantly though is having this enormous information in a database that is easy to navigate and that is useful to multiple different professional fields of study. With this database health personal can see the genomes of different species and over time can be able to the evolutionary changes of genetics of different species. Health professionals can also take the genome of a patient and compare it to the human genome in the database to see if they have a genetic predisposition to a disease or an abnormal genome to diagnose a disease. “Such detailed, fundamental understanding about our bodies will have profound effects on the ways diseases are diagnosed, on the prevention of disease, and on treatments.” (Collins, McKusick, Jegalian, 2012) With the identification/belief that there are “approximately 20,000-25,000 genes in human DNA,” (U.S. Department of Energy Human Genome Project, 2014) we have now begun to identify which genes contribute to diseases. The identification of these mutate genes can be recorded

to find the cause to the disease but they have for 20 genes that may increase and decrease

The field of genomics is quickly and steadily gaining momentum in the field of systematics. Based on an organism’s genetics, it applies novel methods of DNA sequencing and bioinformatics to sequence, construct, and analyze the structure, and consequently, the function, of entire genomes, using the resulting genetic information from different specimens in fine-scale genetic mapping. Advancements in other fields such as human biomedicine may also be dependent on progress made in genomics, especially unresolved problems focused on changes in genes triggered or disrupted in development, susceptibility to infectious disease, mechanisms of DNA recombination and genome plasticity which cannot be adequately interpreted without a precise evolutionary context or hierarchy.

Sanger Sequencing was introduced in 1977 by Frederick Sanger and has been extensively used for at least 35 years (10,11). Even now, it is still frequently used for small scale sequencing work. No breakthrough of whole genome sequencing techniques was made until the launches of Roche 454 GS20 (12) and ABI SOLID (13) in the mid 2000. Soon after that, Ion Torrent (14), PacBio (15) and Illumina (16) platforms have been introduced and quickly occupied the market of genomic sequencing. Not until recently, the third generation sequencing, such as the nanopore (17), has been commercialized and initially tested. A timeline of the development of DNA sequencing platforms was described in Figure 1.

There are more than 10,000 recorded genetic diseases that are passed on through generations affecting millions of people, often with fatal or severely debilitating illness. Scientist worldwide are working to crack the genetic codes to identify genes linked to disease, diagnose abnormalities, and discover new treatment. “The Genetic Disease Foundation is a non-profit 501c (3) organization that established since 1997 by patients and families affected by genetic disorder” (GDF, 2010). The Foundation furnish education programs for everyone and physicians to enhance the knowledge about genetic diseases and the necessity for and availability of testing for many disorders. In addition, the research designed to enhance genetic testing and to find out ways to treat, cure and ultimately avoid genetic disorders. GDF mission is to help prevent and treat genetic disease by supporting research, education and counseling.

The HGP employed a two-phase approach to uncover the human genome sequence. The first phase used DNA shotgun

Science has led to the discovery of DNA and then identification of specific genes in organisms that control heredity and determine a cell 's function. With the advancement of research we are now able to explore the different roles of genes and understand how they might be correlated with diseases.