Whole genome sequencing

[3][4][5] In the future of personalized medicine, whole genome sequence data may be an important tool to guide therapeutic intervention.

[6] The tool of gene sequencing at SNP level is also used to pinpoint functional variants from association studies and improve the knowledge available to researchers interested in evolutionary biology, and hence may lay the foundation for predicting disease susceptibility and drug response.

[12] In contrast, eukaryotes, both unicellular and multicellular such as Amoeba dubia and humans (Homo sapiens) respectively, have much larger genomes (see C-value paradox).

[19] By the year 2000, the second animal and second invertebrate (yet first insect) genome was sequenced – that of the fruit fly Drosophila melanogaster – a popular choice of model organism in experimental research.

This has important advantages in environmental microbiology in cases where a single cell of a particular microorganism species can be isolated from a mixed population by microscopy on the basis of its morphological or other distinguishing characteristics.

The first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991.

[30] In 1995, the innovation of using fragments of varying sizes was introduced,[31] and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets.

[34] All of these technologies continue to employ the basic shotgun strategy, namely, parallelization and template generation via genome fragmentation.

Because sequencing generates a lot of data (for example, there are approximately six billion base pairs in each human diploid genome), its output is stored electronically and requires a large amount of computing power and storage capacity.

[37] A number of public and private companies are competing to develop a full genome sequencing platform that is commercially robust for both research and clinical use,[38] including Illumina,[39] Knome,[40] Sequenom,[41] 454 Life Sciences,[42] Pacific Biosciences,[43] Complete Genomics,[44] Helicos Biosciences,[45] GE Global Research (General Electric), Affymetrix, IBM, Intelligent Bio-Systems,[46] Life Technologies, Oxford Nanopore Technologies,[47] and the Beijing Genomics Institute.

[81][82] An even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical twins) 100-year-old centenarians.

[92] In 2009, Illumina released its first whole genome sequencers that were approved for clinical as opposed to research-only use and doctors at academic medical centers began quietly using them to try to diagnose what was wrong with people whom standard approaches had failed to help.

[93] In 2009, a team from Stanford led by Euan Ashley performed clinical interpretation of a full human genome, that of bioengineer Stephen Quake.

[93] For example, one child had needed around 100 surgeries by the time he was three years old, and his doctor turned to whole genome sequencing to determine the problem; it took a team of around 30 people that included 12 bioinformatics experts, three sequencing technicians, five physicians, two genetic counsellors and two ethicists to identify a rare mutation in the XIAP that was causing widespread problems.

In 2013, the 3Gb-TEST consortium obtained funding from the European Union to prepare the health care system for these innovations in DNA diagnostics.

[citation needed] Genomes2People (G2P), an initiative of Brigham and Women's Hospital and Harvard Medical School was created in 2011 to examine the integration of genomic sequencing into clinical care of adults and children.

[103][104] In 2018, researchers at Rady Children's Hospital Institute for Genomic Medicine in San Diego determined that rapid whole-genome sequencing (rWGS) could diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants.

In a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017, forty-two families received rWGS for etiologic diagnosis of genetic disorders.

The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P = .0015).

Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care.

The findings replicated a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrated improved outcomes, net healthcare savings and consideration as a first tier test in this setting.

[109][110] Meta-analysis of whole genome sequencing studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes.

Some methods have been developed to enable functionally informed rare variant association analysis in biobank-scale cohorts using efficient approaches for summary statistic storage.

[111] In this field, whole genome sequencing represents a great set of improvements and challenges to be faced by the scientific community, as it makes it possible to analyze, quantify and characterize circulating tumor DNA (ctDNA) in the bloodstream.

[112] In 2013, Green and a team of researchers launched the BabySeq Project to study the ethical and medical consequences of sequencing a newborn's DNA.

[116] In 2021, the NIH funded BabySeq2, an implementation study that expanded the BabySeq project, enrolling 500 infants from diverse families and track the effects of their genomic sequencing on their pediatric care.

[117] In 2023, the Lancet opined that in the UK "focusing on improving screening by upgrading targeted gene panels might be more sensible in the short term.

[121] Illumina's CEO, Jay Flatley, wrongly claimed in February 2009 that "by 2019 it will have become routine to map infants' genes when they are born".

[128] The first nearly complete human genomes sequenced were two Americans of predominantly Northwestern European ancestry in 2007 (J. Craig Venter at 7.5-fold coverage,[129][130][131] and James Watson at 7.4-fold).

The work was led by Manuel Corpas and the data obtained by direct-to-consumer genetic testing with 23andMe and the Beijing Genomics Institute.

Electropherograms are commonly used to sequence portions of genomes. [ 1 ]
Schematic karyogram of a human, showing an overview of the human genome , with 22 homologous chromosomes , both the female (XX) and male (XY) versions of the sex chromosome (bottom right), as well as the mitochondrial genome (to scale at bottom left)
The first bacterial whole genome to be sequenced was of the bacterium Haemophilus influenzae .
The worm Caenorhabditis elegans was the first animal to have its whole genome sequenced.
Drosophila melanogaster 's whole genome was sequenced in 2000.
Arabidopsis thaliana was the first plant genome sequenced.
The genome of the lab mouse Mus musculus was published in 2002.
It took 10 years and 50 scientists spanning the globe to sequence the genome of Elaeis guineensis ( oil palm ). This genome was particularly difficult to sequence because it had many repeated sequences which are difficult to organise. [ 8 ]
An ABI PRISM 3100 genetic analyzer. Such capillary sequencers automated the early efforts of sequencing genomes.
Total cost of sequencing a whole human genome as calculated by the NHGRI