Editing Genotype

{{Short description|Part of the genetic makeup of a cell which determines one of its characteristics}}
{{For|a non-technical introduction to the topic|Introduction to genetics}}
{{TopicTOC-Biology}}
{{TOC right}}
The '''genotype''' of an organism is its complete set of genetic material.<ref>{{Cite web|title=What is genotype? What is phenotype? – pgEd|url=https://pged.org/what-is-genotype-what-is-phenotype/|access-date=2020-06-22|website=pged.org}}</ref> Genotype can also be used to refer to the [[allele]]s or variants an individual carries in a particular gene or genetic location.<ref>{{Cite web|title=Genotype|url=https://www.genome.gov/genetics-glossary/genotype|access-date=2021-11-09|website=Genome.gov|language=en}}</ref> The number of alleles an individual can have in a specific gene depends on the number of copies of each [[chromosome]] found in that species, also referred to as [[ploidy]]. In diploid species like humans, two full sets of chromosomes are present, meaning each individual has two alleles for any given gene. If both alleles are the same, the genotype is referred to as [[Zygosity|homozygous]]. If the alleles are different, the genotype is referred to as heterozygous.

Genotype contributes to [[phenotype]], the observable traits and characteristics in an individual or organism.<ref>{{Cite book|last=Pierce|first=Benjamin|title=Genetics A Conceptual Approach|publisher=Macmillian|year=2020|isbn=978-1-319-29714-5|location=NY, New York}}</ref> The degree to which genotype affects phenotype depends on the trait. For example, the [[petal color]] in a [[pea plant]] is exclusively determined by genotype. The petals can be purple or white depending on the alleles present in the pea plant.<ref>{{cite book |last1= Alberts |first1=Bruce |last2=Bray |first2=Dennis |last3=Hopkin |first3=Karen |last4=Johnson |first4=Alexander |last5=Lewis |first5=Julian |last6=Raff |first6=Martin |last7=Roberts |first7=Keith |last8=Walter |first8=Peter | name-list-style = vanc |title=Essential Cell Biology|date=2014|publisher=Garland Science|location=New York, NY|isbn=978-0-8153-4454-4|pages=659|edition=4th}}</ref> However, other traits are only partially influenced by genotype. These traits are often called [[complex traits]] because they are influenced by additional factors, such as environmental and [[epigenetic]] factors. Not all individuals with the same genotype look or act the same way because appearance and behavior are modified by environmental and growing conditions. Likewise, not all organisms that look alike necessarily have the same genotype.

The term ''genotype'' was coined by the [[Denmark|Danish]] [[botanist]] [[Wilhelm Johannsen]] in 1903.<ref>{{cite journal | vauthors = Johannsen W | date = 1903 | title = Om arvelighed i samfund og i rene linier | language = da | journal = Oversigt Birdy over Det Kongelige Danske Videnskabernes Selskabs Forhandlingerm | volume = 3 | pages = 247–70 }} German ed. {{cite web | title = Erblichkeit in Populationen und in reinen Linien | language = de | location = Jena | publisher = Gustav Fischer | date = 1903 | url = http://caliban.mpiz-koeln.mpg.de/~stueber/johannsen/erblichkeit/index.html | access-date = 2017-07-19 | archive-date = 2009-05-30 | archive-url = https://web.archive.org/web/20090530140510/http://caliban.mpiz-koeln.mpg.de/~stueber/johannsen/erblichkeit/index.html | url-status = dead }}. Also see his monograph {{cite book | vauthors = Johannsen W | title = Arvelighedslærens elementer horse | language = da | trans-title = The Elements of Heredity | location = Copenhagen | date = 1905 }} which was rewritten, enlarged and translated into French as {{cite book | vauthors = Johannsen W | title = Elemente der exakten Erblichkeitslehre | language = de | location = Jena | publisher = Gustav Fischer | date = 1905 | url = http://caliban.mpiz-koeln.mpg.de/~stueber/johannsen/elemente/index.html | access-date = 2017-07-19 | archive-date = 2009-05-30 | archive-url = https://web.archive.org/web/20090530140505/http://caliban.mpiz-koeln.mpg.de/~stueber/johannsen/elemente/index.html | url-status = dead }}</ref>

== Phenotype ==
{{Main|Phenotype}}

Any given gene will usually cause an observable change in an organism, known as the phenotype.  The terms [[genotype–phenotype distinction|genotype and phenotype]] are distinct for at least two reasons:
* To distinguish the source of an observer's knowledge (one can know about genotype by observing DNA; one can know about phenotype by observing outward appearance of an organism).
* Genotype and phenotype are not always directly correlated.  Some genes only express a given phenotype in certain environmental conditions.  Conversely, some phenotypes could be the result of multiple genotypes. The genotype is commonly mixed up with the phenotype which describes the result of both the genetic and the environmental factors giving the observed expression (e.g. blue eyes, hair color, or various hereditary diseases).

A simple example to illustrate genotype as distinct from phenotype is the flower colour in pea plants (see [[Gregor Mendel]]). There are three available genotypes, PP ([[homozygous dominant]]), Pp (heterozygous), and pp (homozygous recessive). All three have different genotypes but the first two have the same phenotype (purple) as distinct from the third (white).

A more technical example to illustrate genotype is the [[single-nucleotide polymorphism]] or SNP.  A SNP occurs when corresponding sequences of [[DNA]] from different individuals differ at one DNA base, for example where the sequence AAGCCTA changes to AAGCTTA.<ref>Vallente, R. U., PhD. (2020). Single Nucleotide Polymorphism. ''Salem Press Encyclopedia of Science''.</ref> This contains two alleles : C and T. SNPs typically have three genotypes, denoted generically AA Aa and aa. In the example above, the three genotypes would be CC, CT and TT. Other types of [[genetic marker]], such as [[microsatellite]]s, can have more than two alleles, and thus many different genotypes.

Penetrance is the proportion of individuals showing a specified genotype in their phenotype under a given set of environmental conditions.<ref>{{cite dictionary |title=A dictionary of zoology |date=2009 |publisher=Oxford University Press |editor=Allaby, Michael |isbn=9780199233410 |edition=3rd |location=Oxford |oclc=260204631}}</ref>

== Mendelian inheritance ==
{{Main|Mendelian inheritance}}[[Image:Punnett square mendel flowers.svg|thumb|right|Here the relation between genotype and phenotype is illustrated, using a [[Punnett square]], for the character of petal colour in a [[pea plant]]. The letters B and b represent alleles for colour and the pictures show the resultant flowers. The diagram shows the cross between two heterozygous parents where B represents the dominant allele (purple) and b represents the recessive allele (white).]]Traits that are determined exclusively by genotype are typically inherited in a [[Mendelian inheritance|Mendelian]] pattern. These laws of inheritance were described extensively by [[Gregor Mendel]], who performed experiments with pea plants to determine how traits were passed on from generation to generation.<ref name=":0">{{Cite web|title=Gregor Mendel and the Principles of Inheritance {{!}} Learn Science at Scitable|url=http://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593|access-date=2021-11-15|website=www.nature.com|language=en}}</ref> He studied phenotypes that were easily observed, such as plant height, petal color, or seed shape.<ref name=":0" /> He was able to observe that if he crossed two true-breeding plants with distinct phenotypes, all the offspring would have the same phenotype. For example, when he crossed a tall plant with a short plant, all the resulting plants would be tall. However, when he self-fertilized the plants that resulted, about 1/4 of the second generation would be short. He concluded that some traits were [[Dominance (genetics)|dominant]], such as tall height, and others were recessive, like short height. Though Mendel was not aware at the time, each phenotype he studied was controlled by a single gene with two alleles. In the case of plant height, one allele caused the plants to be tall, and the other caused plants to be short. When the tall allele was present, the plant would be tall, even if the plant was heterozygous. In order for the plant to be short, it had to be homozygous for the recessive allele.<ref name=":0" /><ref>{{Cite web|title=12.1 Mendel's Experiments and the Laws of Probability – Biology {{!}} OpenStax|url=https://openstax.org/books/biology/pages/12-1-mendels-experiments-and-the-laws-of-probability|access-date=2021-11-15|website=openstax.org|language=en}}</ref>

One way this can be illustrated is using a [[Punnett square]]. In a Punnett square, the genotypes of the parents are placed on the outside. An uppercase letter is typically used to represent the dominant allele, and a lowercase letter is used to represent the recessive allele. The possible genotypes of the offspring can then be determined by combining the parent genotypes.<ref>{{Cite web|date=2016-09-21|title=3.6: Punnett Squares|url=https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Introductory_Biology_(CK-12)/03%3A_Genetics/3.06%3A_Punnett_Squares|access-date=2021-11-15|website=Biology LibreTexts|language=en}}</ref> In the example on the right, both parents are heterozygous, with a genotype of Bb. The offspring can inherit a dominant allele from each parent, making them homozygous with a genotype of BB. The offspring can inherit a dominant allele from one parent and a recessive allele from the other parent, making them heterozygous with a genotype of Bb. Finally, the offspring could inherit a recessive allele from each parent, making them homozygous with a genotype of bb. Plants with the BB and Bb genotypes will look the same, since the B allele is dominant. The plant with the bb genotype will have the recessive trait.

These inheritance patterns can also be applied to [[Genetic disorder|hereditary diseases]] or conditions in humans or animals.<ref name=":12">{{Cite book|last1=Alliance|first1=Genetic|url=https://www.ncbi.nlm.nih.gov/books/NBK132145/|title=Classic Mendelian Genetics (Patterns of Inheritance)|last2=Health|first2=District of Columbia Department of|date=2010-02-17|publisher=Genetic Alliance|language=en}}</ref><ref name=":2">{{Cite web|title=Mendelian Inheritance|url=https://www.genome.gov/genetics-glossary/Mendelian-Inheritance|access-date=2021-11-15|website=Genome.gov|language=en}}</ref><ref name=":3">{{Cite book|last=Strachan|first=T.|url=https://www.worldcat.org/oclc/1083018958|title=Human molecular genetics|publisher=[[Garland Science]]|others=Andrew P. Read|year=2018|isbn=978-0-429-82747-1|edition=5th|location=New York|oclc=1083018958}}</ref> Some conditions are inherited in an [[Autosome|autosomal]] dominant pattern, meaning individuals with the condition typically have an affected parent as well. A classic pedigree for an autosomal dominant condition shows affected individuals in every generation.<ref name=":12"/><ref name=":2" /><ref name=":3" /> [[File:Example autosomal dominant pedigree 01.png|thumb|An example of a pedigree for an autosomal dominant condition]] Other conditions are inherited in an autosomal recessive pattern, where affected individuals do not typically have an affected parent. Since each parent must have a copy of the recessive allele in order to have an affected offspring, the parents are referred to as carriers of the condition.<ref name=":12"/><ref name=":2" /><ref name=":3" />

In autosomal conditions, the sex of the offspring does not play a role in their risk of being affected. In sex-linked conditions, the sex of the offspring affects their chances of having the condition. In humans, females inherit two [[X chromosome]]s, one from each parent, while males inherit an X chromosome from their mother and a Y chromosome from their father. X-linked dominant conditions can be distinguished from autosomal dominant conditions in pedigrees by the lack of transmission from fathers to sons, since affected fathers only pass their X chromosome to their daughters.<ref name=":3" /><ref name=":12"/><ref name=":4">{{Cite web|date=2020-06-24|title=4.4.1: Inheritance patterns for X-linked and Y-linked genes|url=https://bio.libretexts.org/Courses/University_of_Arkansas_Little_Rock/Genetics_BIOL3300_(Fall_2021)/Genetics_Textbook/04%3A_Inheritance/4.04%3A_Exceptions_to_autosomal_inheritance/4.4.01%3A_Inheritance_patterns_for_X-linked_and_Y-linked_genes|access-date=2021-11-15|website=Biology LibreTexts|language=en}}</ref> In X-linked recessive conditions, males are typically affected more commonly because they are hemizygous, with only one X chromosome. In females, the presence of a second X chromosome will prevent the condition from appearing. Females are therefore carriers of the condition and can pass the trait on to their sons.<ref name=":3" /><ref name=":12" /><ref name=":4" />[[File:Example autosomal recessive pedigree.png|thumb|An example of a pedigree for an autosomal recessive condition]]

Mendelian patterns of inheritance can be complicated by additional factors. Some diseases show incomplete [[penetrance]], meaning not all individuals with the disease-causing allele develop signs or symptoms of the disease.<ref name=":3" /><ref name=":8">{{Cite web|date=2021-01-13|title=14.2: Penetrance and Expressivity|url=https://bio.libretexts.org/Courses/Lumen_Learning/Book-_Biology_for_Majors_I_(Lumen)/14%3A_Module_12-_Trait_Inheritance/14.02%3A_Penetrance_and_Expressivity|access-date=2021-11-19|website=Biology LibreTexts|language=en}}</ref><ref name=":9">{{Cite web|title=Phenotype Variability: Penetrance and Expressivity {{!}} Learn Science at Scitable|url=http://www.nature.com/scitable/topicpage/phenotype-variability-penetrance-and-expressivity-573|access-date=2021-11-19|website=www.nature.com|language=en}}</ref> Penetrance can also be age-dependent, meaning signs or symptoms of disease are not visible until later in life. For example, [[Huntington's disease|Huntington disease]] is an autosomal dominant condition, but up to 25% of individuals with the affected genotype will not develop symptoms until after age 50.<ref>{{Citation|last1=Caron|first1=Nicholas S.|title=Huntington Disease|date=1993|url=http://www.ncbi.nlm.nih.gov/books/NBK1305/|work=GeneReviews®|editor-last=Adam|editor-first=Margaret P.|place=Seattle (WA)|publisher=University of Washington, Seattle|pmid=20301482|access-date=2021-11-19|last2=Wright|first2=Galen EB|last3=Hayden|first3=Michael R.|editor2-last=Ardinger|editor2-first=Holly H.|editor3-last=Pagon|editor3-first=Roberta A.|editor4-last=Wallace|editor4-first=Stephanie E.}}</ref> Another factor that can complicate Mendelian inheritance patterns is variable [[Expressivity (genetics)|expressivity]], in which individuals with the same genotype show different signs or symptoms of disease.<ref name=":3" /><ref name=":8" /><ref name=":9" /> For example, individuals with [[polydactyly]] can have a variable number of extra digits.<ref name=":8" /><ref name=":9" />

== Non-Mendelian inheritance ==
{{Main|Non-Mendelian inheritance}}

Many traits are not inherited in a Mendelian fashion, but have more complex patterns of inheritance.

=== Incomplete dominance ===
For some traits, neither allele is completely dominant. Heterozygotes often have an appearance somewhere in between those of homozygotes.<ref name=":52">{{Cite web|title=Genetic Dominance: Genotype-Phenotype Relationships {{!}} Learn Science at Scitable|url=http://www.nature.com/scitable/topicpage/genetic-dominance-genotype-phenotype-relationships-489|access-date=2021-11-15|website=www.nature.com|language=en}}</ref><ref name=":6">{{Citation|last=Frizzell|first=M.A.|title=Incomplete Dominance|date=2013|url=https://linkinghub.elsevier.com/retrieve/pii/B9780123749840007841|encyclopedia=Brenner's Encyclopedia of Genetics|pages=58–60|publisher=Elsevier|language=en|doi=10.1016/b978-0-12-374984-0.00784-1|isbn=978-0-08-096156-9|access-date=2021-11-15|url-access=subscription}}</ref> For example, a cross between true-breeding red and white ''[[Mirabilis jalapa]]'' results in pink flowers.<ref name=":6" />

=== Codominance ===
Codominance refers to traits in which both alleles are expressed in the offspring in approximately equal amounts.<ref name=":7">{{Citation|last=Xia|first=X.|title=Codominance|date=2013|url=https://linkinghub.elsevier.com/retrieve/pii/B9780123749840002783|encyclopedia=Brenner's Encyclopedia of Genetics|pages=63–64|publisher=Elsevier|language=en|doi=10.1016/b978-0-12-374984-0.00278-3|isbn=978-0-08-096156-9|access-date=2021-11-15|url-access=subscription}}</ref> A classic example is the [[ABO blood group system]] in humans, where both the A and B alleles are expressed when they are present. Individuals with the AB genotype have both A and B proteins expressed on their red blood cells.<ref name=":7" /><ref name=":52"/>

=== Epistasis ===
{{Main|Epistasis}}

Epistasis is when the phenotype of one gene is affected by one or more other genes.<ref>{{Cite journal|last1=Gros|first1=Pierre-Alexis|last2=Nagard|first2=Hervé Le|last3=Tenaillon|first3=Olivier|date=2009-05-01|title=The Evolution of Epistasis and Its Links With Genetic Robustness, Complexity and Drift in a Phenotypic Model of Adaptation|url=https://www.genetics.org/content/182/1/277|journal=Genetics|language=en|volume=182|issue=1|pages=277–293|doi=10.1534/genetics.108.099127|issn=0016-6731|pmc=2674823|pmid=19279327}}</ref> This is often through some sort of masking effect of one gene on the other.<ref>{{Cite book|last=Rieger, Rigomar.|url=https://www.worldcat.org/oclc/2202589|title=Glossary of genetics and cytogenetics : classical and molecular|date=1976|publisher=Springer-Verlag|others=Michaelis, Arnd,, Green, Melvin M.|isbn=0-387-07668-9|edition=4th completely rev. |location=Berlin|oclc=2202589}}</ref> For example, the "A" gene codes for hair color, a dominant "A" allele codes for brown hair, and a recessive "a" allele codes for blonde hair, but a separate "B" gene controls hair growth, and a recessive "b" allele causes baldness. If the individual has the BB or Bb genotype, then they produce hair and the hair color phenotype can be observed, but if the individual has a bb genotype, then the person is bald which masks the A gene entirely.

=== Polygenic traits ===
{{Main|Polygene}}

A polygenic trait is one whose phenotype is dependent on the additive effects of multiple genes. The contributions of each of these genes are typically small and add up to a final phenotype with a large amount of variation. A well studied example of this is the number of sensory bristles on a fly.<ref>{{Cite journal|last=Mackay|first=T. F.|date=December 1995|title=The genetic basis of quantitative variation: numbers of sensory bristles of Drosophila melanogaster as a model system|url=https://www.ncbi.nlm.nih.gov/pubmed/8533161|journal=Trends in Genetics|volume=11|issue=12|pages=464–470|doi=10.1016/s0168-9525(00)89154-4|issn=0168-9525|pmid=8533161}}</ref> These types of additive effects is also the explanation for the amount of variation in human eye color.

== Genotyping ==
{{Main|Genotyping}}
Genotyping refers to the method used to determine an individual's genotype. There are a variety of techniques that can be used to assess genotype. The genotyping method typically depends on what information is being sought. Many techniques initially require amplification of the DNA sample, which is commonly done using [[Polymerase chain reaction|PCR]].

Some techniques are designed to investigate specific SNPs or alleles in a particular gene or set of genes, such as whether an individual is a carrier for a particular condition. This can be done via a variety of techniques, including [[allele specific oligonucleotide]] (ASO) probes or [[DNA sequencing]].<ref name=":10">{{Citation|last=Jain|first=Kewal K.|title=Molecular Diagnostics in Personalized Medicine|date=2015|url=https://doi.org/10.1007/978-1-4939-2553-7_2|work=Textbook of Personalized Medicine|pages=35–89|editor-last=Jain|editor-first=Kewal K.|place=New York, NY|publisher=Springer|language=en|doi=10.1007/978-1-4939-2553-7_2|isbn=978-1-4939-2553-7|access-date=2021-11-19|url-access=subscription}}</ref><ref name=":11">{{Cite book|last1=Wallace|first1=Stephanie E.|url=https://www.ncbi.nlm.nih.gov/books/NBK279899/|title=Educational Materials – Genetic Testing: Current Approaches|last2=Bean|first2=Lora JH|date=2020-06-18|publisher=University of Washington, Seattle|language=en}}</ref> Tools such as [[multiplex ligation-dependent probe amplification]] can also be used to look for duplications or deletions of genes or gene sections.<ref name=":11" /> Other techniques are meant to assess a large number of SNPs across the genome, such as [[SNP array]]s.<ref name=":10" /><ref name=":11" /> This type of technology is commonly used for [[Genome-wide association study|genome-wide association studies]].

Large-scale techniques to assess the entire genome are also available. This includes [[Karyotype|karyotyping]] to determine the number of chromosomes an individual has and [[Comparative genomic hybridization|chromosomal microarrays]] to assess for large duplications or deletions in the chromosome.<ref name=":10" /><ref name=":11" /> More detailed information can be determined using [[exome sequencing]], which provides the specific sequence of all DNA in the coding region of the genome, or [[whole genome sequencing]], which sequences the entire genome including non-coding regions.<ref name=":10" /><ref name=":11" />

== Genotype encoding ==
In linear models, the genotypes can be encoded in different manners. Let us consider a biallelic locus with two possible alleles, encoded by <math display="inline">A</math> and <math>a</math>. We consider '''<math>A</math>''' to correspond to the dominant allele to the reference allele <math display="inline">a</math>. The following table details the different encoding.<ref>{{Cite book |title=Encyclopedia of Bioinformatics and Computational Biology |publisher=Elsevier Science |year=2018 |isbn=9780128114322 |editor-last=Schönbach |editor-first=Christian |pages=174 |language=en |editor-last2=Ranganathan |editor-first2=Shoba |editor-last3=Nakai |editor-first3=Kenta}}</ref>
{| class="wikitable"
|+
!Genotype
!<math display="inline">AA</math>
!<math display="inline">Aa</math>
!<math display="inline">aa</math>
|-
|Additive encoding
|0
|1
|2
|-
|Dominant encoding
|1
|1
|0
|-
|Recessive encoding
|0
|0
|1
|-
|Codominant encoding
|0,0
|0,1
|1,0
|}

== See also ==
* [[Endophenotype]]
* [[Nucleic acid sequence]]
* [[Sequence (biology)]]

== References ==
{{reflist|30em}}

== External links ==
{{Wiktionary|genotype}}
{{wiktionary|genotype|phenotype|inheritance|genome}}
{{commons category|Genotypes}}
* [http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/mutations/nomenclature-v3.pdf Genetic nomenclature]

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[[Category:Genetics]]
[[Category:Polymorphism (biology)]]
[[Category:DNA sequencing]]