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{{short description|Sequences remaining within RNA after RNA splicing}}
{{Distinguish|exosome (disambiguation){{!}}exosome}}

The '''exome''' is composed of all of the [[Exon|exons]] within the [[genome]], the sequences which, when transcribed, remain within the mature [[RNA]] after [[introns]] are removed by [[RNA splicing]]. This includes [[untranslated region]]s of [[messenger RNA]] (mRNA), and [[coding region]]s. [[Exome sequencing]] has proven to be an efficient method of determining the genetic basis of more than two dozen [[Mendelian]] or [[single gene disorders]].<ref name="pmid21946919">{{cite journal | vauthors = Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J | title = Exome sequencing as a tool for Mendelian disease gene discovery | journal = Nature Reviews Genetics | volume = 12 | issue = 11 | pages = 745–55 | date = September 2011 | pmid = 21946919 | doi = 10.1038/nrg3031 | s2cid = 15615317 }}</ref>

== Statistics ==
[[File:Details.png|thumb|360x360px|'''Distinction between [[genome]], exome, and [[transcriptome]].''' The exome consists of all of the exons within the genome. In contrast, the trascriptome varies between cell types (e.g. neurons vs cardiac cells), only involving a portion of the exons that are actually transcribed into mRNA.]]
The human exome consists of roughly 233,785 [[Exon|exons]], about 80% of which are less than 200 [[Base pair|base pairs]] in length, constituting a total of about 1.1% of the total [[genome]], or about 30 megabases of [[DNA]].<ref>{{cite journal | vauthors = Sakharkar MK, Chow VT, Kangueane P | title = Distributions of exons and introns in the human genome | journal = In Silico Biology | volume = 4 | issue = 4 | pages = 387–93 | date = 2004 | pmid = 15217358 }}</ref><ref>{{cite journal | vauthors = Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, etal | title = The sequence of the human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1304–51 | date = February 2001 | pmid = 11181995 | doi = 10.1126/science.1058040 | bibcode = 2001Sci...291.1304V | doi-access = }}</ref><ref name="pmid19684571">{{cite journal | vauthors = Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J | display-authors = 6 | title = Targeted capture and massively parallel sequencing of 12 human exomes | journal = Nature | volume = 461 | issue = 7261 | pages = 272–6 | date = September 2009 | pmid = 19684571 | pmc = 2844771 | doi = 10.1038/nature08250 | bibcode = 2009Natur.461..272N }}</ref> Though composing a very small fraction of the [[genome]], [[Mutation|mutations]] in the exome are thought to harbor 85% of [[Mutation|mutations]] that have a large effect on disease.<ref name="Choi_2009">{{cite journal | vauthors = Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloğlu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP | display-authors = 6 | title = Genetic diagnosis by whole exome capture and massively parallel DNA sequencing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 45 | pages = 19096–101 | date = November 2009 | pmid = 19861545 | pmc = 2768590 | doi = 10.1073/pnas.0910672106 | bibcode = 2009PNAS..10619096C | doi-access = free }}</ref>

== Definition ==
{{See also|List of human protein-coding genes 1|List of human protein-coding genes 2|List of human protein-coding genes 3|List of human protein-coding genes 4}}
It is important to note that the exome is distinct from the [[transcriptome]], which is all of the transcribed RNA within a cell type. While the exome is constant from cell-type to cell-type, the [[transcriptome]] changes based on the structure and function of the cells. As a result, the entirety of the exome is not [[Translation (biology)|translated]] into protein in every cell. Different cell types only [[Transcription (biology)|transcribe]] portions of the exome, and only the [[Coding region|coding regions]] of the exons are eventually translated into proteins.

== Next-generation sequencing ==
[[Next-generation sequencing]] (NGS) allows for the rapid sequencing of large amounts of DNA, significantly advancing the study of genetics, and replacing older methods such as [[Sanger sequencing]]. This technology is starting to become more common in healthcare and research not only because it is a reliable method of determining genetic variations, but also because it is cost effective and allows researchers to sequence entire genomes in anywhere between days to weeks. This compares to former methods which may have taken months. Next-gen sequencing includes both [[Whole exome sequencing|whole-exome sequencing]] and [[Whole genome sequencing|whole-genome sequencing]].<ref>{{Cite web|url=https://medlineplus.gov/genetics/understanding/testing/sequencing|title=What are whole exome sequencing and whole genome sequencing? | work = Genetics Home Reference| publisher = National Library of Medicine, National Institutes of Health, U.S. Department of Health & Human Services |access-date=2019-11-07}}</ref>

=== Whole-exome sequencing ===
Sequencing an individual's exome instead of their entire genome has been proposed to be a more cost-effective and efficient way to diagnose rare [[Genetic disorder|genetic disorders.]]<ref name="Erjavec">{{cite journal | vauthors = Erjavec SO, Gelfman S, Abdelaziz AR, Lee EY, Monga I, Alkelai A, Ionita-Laza I, Petukhova L, Christiano AM| title = Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82| journal = Nat Commun | volume = 13 | issue = 1| page = 800 | date = Feb 2022 | pmid = 35145093 | doi = 10.1038/s41467-022-28343-3| pmc = 8831607 | bibcode = 2022NatCo..13..800E}}</ref><ref>{{cite journal | vauthors = Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM | display-authors = 6 | title = Clinical whole-exome sequencing for the diagnosis of mendelian disorders | journal = The New England Journal of Medicine | volume = 369 | issue = 16 | pages = 1502–11 | date = October 2013 | pmid = 24088041 | pmc = 4211433 | doi = 10.1056/NEJMoa1306555 }}</ref> It has also been found to be more effective than other methods such as [[karyotyping]] and [[microarrays]].<ref>{{cite book |last1=Edelson|first1=P. Kaitlyn |last2=Dugoff |first2=Lorraine |last3=Bromley |first3=Bryann | name-list-style = vanc |chapter = Chapter 11 – Genetic Evaluation of Fetal Sonographic Abnormalities|date=2019-01-01 |title =Perinatal Genetics|pages=105–124|editor-last=Norton|editor-first=Mary E. |editor2-last=Kuller |editor2-first=Jeffrey A. |editor3-last=Dugoff |editor3-first=Lorraine |publisher=Content Repository Only!|isbn=978-0-323-53094-1 }}</ref> This distinction is largely due to the fact that phenotypes of genetic disorders are a result of mutated exons. In addition, since the exome only comprises 1.5% of the total genome, this process is more cost efficient and fast as it involves sequencing around 40 million bases rather than the 3 billion base pairs that make up the genome.<ref>{{cite journal | vauthors = Nagele P | title = Exome sequencing: one small step for malignant hyperthermia, one giant step for our specialty—why exome sequencing matters to all of us, not just the experts | journal = Anesthesiology | volume = 119 | issue = 5 | pages = 1006–8 | date = November 2013 | pmid = 24195944 | pmc = 3980570 | doi = 10.1097/ALN.0b013e3182a8a90c }}</ref>

=== Whole-genome sequencing ===
On the other hand, [[whole genome sequencing]] has been found to capture a more comprehensive view of variants in the DNA compared to [[Exome sequencing|whole-exome sequencing]]. Especially for [[single nucleotide variants]], whole genome sequencing is more powerful and more sensitive than whole-exome sequencing in detecting potentially disease-causing mutations within the exome.<ref>{{cite journal | vauthors = Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB, Antipenko A, Shang L, Boisson B, Casanova JL, Abel L | display-authors = 6 | title = Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 17 | pages = 5473–8 | date = April 2015 | pmid = 25827230 | pmc = 4418901 | doi = 10.1073/pnas.1418631112 | bibcode = 2015PNAS..112.5473B | doi-access = free }}</ref> One must also keep in mind that [[Non-coding region|non-coding regions]] can be involved in the regulation of the exons that make up the exome, and so whole-exome sequencing may not be complete in showing all the sequences at play in forming the exome.

=== Ethical considerations ===
With either form of [[sequencing]], whole-exome sequencing or whole genome sequencing, some have argued that such practices should be done under the consideration of medical ethics. While physicians strive to preserve patient autonomy, sequencing deliberately asks laboratories to look at [[Structural variation|genetic variants]] that may be completely unrelated to the patient's condition at hand and have the potential of revealing findings that were not intentionally sought. In addition, such testing have been suggested to have imply forms of discrimination against particular groups for having certain genes, creating the potential for stigmas or negative attitudes towards that group as a result.<ref>{{cite book| vauthors = Gaff CL, Macciocca I |chapter = Chapter 15 – Genomic Perspective of Genetic Counseling|date=2016-01-01 | title = Medical and Health Genomics|pages=201–212| veditors = Kumar D, Antonarakis S |publisher=Academic Press|doi=10.1016/b978-0-12-420196-5.00015-0|isbn=978-0-12-420196-5 }}</ref>

== Diseases and diagnoses ==
Rare mutations that affect the function of essential proteins constitute the majority of [[Mendelian disease|Mendelian diseases]]. In addition, the overwhelming majority of disease-causing mutations in [[Mendelian inheritance|Mendelian loci]] can be found within the coding region.<ref name="Choi_2009">{{cite journal | vauthors = Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloğlu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP | display-authors = 6 | title = Genetic diagnosis by whole exome capture and massively parallel DNA sequencing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 45 | pages = 19096–101 | date = November 2009 | pmid = 19861545 | pmc = 2768590 | doi = 10.1073/pnas.0910672106 | bibcode = 2009PNAS..10619096C | doi-access = free }}</ref> With the goal of finding methods to best detect harmful mutations and successfully diagnose patients, researchers are looking to the exome for clues to aid in this process.

[[Whole exome sequencing|Whole-exome sequencing]] is a recent technology that has led to the discovery of various genetic disorders and increased the rate of diagnoses of patients with rare genetic disorders. Overall, whole-exome sequencing has allowed healthcare providers to diagnose 30–50% of patients who were thought to have rare Mendelian disorders.{{cn|date=November 2019}} It has been suggested that whole-exome sequencing in clinical settings has many unexplored advantages. Not only can the exome increase our understanding of genetic patterns, but under clinical settings, it has the potential to the change in management of patients with rare and previously unknown disorders, allowing physicians to develop more targeted and personalized interventions.<ref name="pmid25590979">{{cite journal | vauthors = Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF, McSweeney KM, Ben-Zeev B, Nissenkorn A, Anikster Y, Oz-Levi D, Dhindsa RS, Hitomi Y, Schoch K, Spillmann RC, Heimer G, Marek-Yagel D, Tzadok M, Han Y, Worley G, Goldstein J, Jiang YH, Lancet D, Pras E, Shashi V, McHale D, Need AC, Goldstein DB | display-authors = 6 | title = Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios | journal = Genetics in Medicine | volume = 17 | issue = 10 | pages = 774–81 | date = October 2015 | pmid = 25590979 | pmc = 4791490 | doi = 10.1038/gim.2014.191 }}</ref>

For example, [[Bartter syndrome|Bartter Syndrome]], also known as salt-wasting nephropathy, is a hereditary disease of the kidney characterized by [[hypotension]] (low blood pressure), [[hypokalemia]] (low potassium), and [[alkalosis]] (high blood pH) leading to muscle fatigue and varying levels of fatality.<ref>{{Cite web|url=https://medlineplus.gov/genetics/condition/bartter-syndrome/|title=Bartter syndrome | work = Genetics Home Reference| publisher = National Library of Medicine, National Institutes of Health, U.S. Department of Health & Human Services |access-date=2019-11-19}}</ref> It is an example of a rare disease, affecting fewer than one per million people, whose patients have been positively impacted by whole-exome sequencing. Thanks to this method, patients who formerly did not exhibit the classical mutations associated with Bartter Syndrome were formally diagnosed with it after the discovery that the disease has mutations outside of the loci of interest.<ref name="Choi_2009" /> They were thus able to gain more targeted and productive treatment for the disease.

Much of the focus of exome sequencing in the context of disease diagnosis has been on protein coding "loss of function" alleles. Research has shown, however, that future advances that allow the study of non-coding regions, within and without the exome, may lead to additional abilities in the diagnoses of rare Mendelian disorders.<ref name="Frésard_2018">{{cite journal | vauthors = Frésard L, Montgomery SB | title = Diagnosing rare diseases after the exome | journal = Cold Spring Harbor Molecular Case Studies | volume = 4 | issue = 6 | article-number = a003392| date = December 2018 | pmid = 30559314 | pmc = 6318767 | doi = 10.1101/mcs.a003392 }}</ref> The '''exome''' is the part of the [[genome]] composed of [[exon]]s, the sequences which, when transcribed, remain within the mature [[RNA]] after [[introns]] are removed by [[RNA splicing]] and contribute to the final protein product encoded by that gene. It consists of all DNA that is transcribed into mature RNA in cells of any type, as distinct from the [[transcriptome]], which is the RNA that has been transcribed only in a specific cell population. The exome of the [[human genome]] consists of roughly 180,000 [[exon]]s constituting about 1% of the total [[genome]], or about 30 megabases of [[DNA]].<ref>{{cite journal | vauthors = Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J | display-authors = 6 | title = Targeted capture and massively parallel sequencing of 12 human exomes | journal = Nature | volume = 461 | issue = 7261 | pages = 272–6 | date = September 2009 | pmid = 19684571 | pmc = 2844771 | doi = 10.1038/nature08250 | bibcode = 2009Natur.461..272N }}</ref> Though composing a very small fraction of the [[genome]], [[mutation]]s in the exome are thought to harbor 85% of [[mutation]]s that have a large effect on disease.<ref>{{cite journal | vauthors = Suleiman SH, Koko ME, Nasir WH, Elfateh O, Elgizouli UK, Abdallah MO, Alfarouk KO, Hussain A, Faisal S, Ibrahim FM, Romano M, Sultan A, Banks L, Newport M, Baralle F, Elhassan AM, Mohamed HS, Ibrahim ME | display-authors = 6 | title = Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways | journal = Frontiers in Genetics | volume = 6 | page = 288 | date = 2015 | pmid = 26442106 | pmc = 4584935 | doi = 10.3389/fgene.2015.00288 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloğlu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP | display-authors = 6 | title = Genetic diagnosis by whole exome capture and massively parallel DNA sequencing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 45 | pages = 19096–101 | date = November 2009 | pmid = 19861545 | pmc = 2768590 | doi = 10.1073/pnas.0910672106 | bibcode = 2009PNAS..10619096C | doi-access = free }}</ref> [[Exome sequencing]] has proved to be an efficient strategy to determine the genetic basis of more than two dozen [[Mendelian]] or [[single gene disorder]]s.<ref>{{cite journal | vauthors = Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J | title = Exome sequencing as a tool for Mendelian disease gene discovery | journal = Nature Reviews Genetics | volume = 12 | issue = 11 | pages = 745–55 | date = September 2011 | pmid = 21946919 | doi = 10.1038/nrg3031 | s2cid = 15615317 }}</ref>

== See also ==
* [[Coding strand]]
* [[Exome sequencing]]
* [[Gene structure]]
* [[Non-coding DNA]]
* [[Non-coding RNA]]
* [[Transcriptome]]
* [[Transcriptomics]]

== References ==
{{reflist}}

[[Category:Human genetics]]
[[Category:Genetics]]

Exome - История изменений

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