Editing Non-Mendelian inheritance

{{short description|Type of pattern of inheritance}}
{{More citations needed|date=April 2025}}
[[Image:Gul-Abas-4-O'clock plant.JPG|thumb|''[[Mirabilis jalapa]]'']]
[[Image:Carl Correns.jpg|thumb|[[Carl Correns]]]]
'''Non-Mendelian inheritance''' is any pattern  in which traits do not segregate in accordance with [[Mendelian inheritance#Mendel's laws|Mendel's laws]]. These laws describe the inheritance of traits linked to single [[gene]]s on [[chromosome]]s in the nucleus. In [[Mendelian inheritance]], each parent contributes one of two possible [[allele]]s for a trait. If the [[genotype]]s of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of [[phenotype]]s expected for the population of offspring.  There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.

Certain inherited diseases and their presentation display non-Mendelian patterns, complicating making predictions from family history.<ref name="pmid15358729">{{cite journal |vauthors=Van Heyningen V, Yeyati PL |title=Mechanisms of non-Mendelian inheritance in genetic disease |journal=Hum. Mol. Genet. |volume=13 Spec No 2 |pages=R225–33 |year=2004 |pmid=15358729 |doi=10.1093/hmg/ddh254 |doi-access=free }}</ref>

==Types==
Incomplete dominance, codominance, multiple alleles, and polygenic traits follow Mendel's laws, display Mendelian inheritance, and are explained as extensions of Mendel's laws.<ref>Hartwell, L. (2000). *Genetics: From Genes to Genomes*. United Kingdom: McGraw-Hill. Page 39.</ref>

===Incomplete dominance===
[[File:Incomplete dominance - Antirrhinum majus.png|thumb| ]]
In cases of intermediate inheritance due to [[Dominance (genetics)#Incomplete dominance|incomplete dominance]], the principle of dominance discovered by Mendel does not apply. Nevertheless, the principle of uniformity works, as all offspring in the F<sub>1</sub>-generation have the same genotype and same phenotype. Mendel's principle of segregation of genes applies too, as in the F<sub>2</sub>-generation homozygous individuals with the phenotypes of the P-generation{{clarify|date=July 2024}} appear. Intermediate inheritance was first examined by [[Carl Correns]] in flower colour of ''[[Mirabilis jalapa]]''.<ref>Biology University of Hamburg: ''[http://www1.biologie.uni-hamburg.de/b-online/e08/08a.htm Mendelian Genetics]''</ref> ''[[Antirrhinum majus]]'' also shows intermediate inheritance of the pigmentation of the blossoms.<ref>[[Neil A. Campbell]], [[Jane B. Reece]]: Biologie. Spektrum-Verlag Heidelberg-Berlin 2003, {{ISBN|3-8274-1352-4}}, page 302.</ref>

===Co-dominance===
[[File:Pavlovian black-white chicken rooster 1.jpg|thumb|Co-dominant expression of genes for plumage colours.]]
In cases of [[Dominance (genetics)#Types of Dominance|co-dominance]], the genetic traits of both different alleles of the same gene-locus are clearly [[gene expression|expressed]] in the phenotype. For example, in certain varieties of chicken, the allele for black feathers is co-dominant with the allele for white feathers. Heterozygous chickens have a colour described as "erminette", speckled with black and white feathers appearing separately. Many human genes, including one for a protein that controls cholesterol levels in the blood, show co-dominance too. People with the heterozygous form of this gene produce two different forms of the protein, each with a different effect on cholesterol levels.{{citation needed|date=April 2023}}

===Genetic linkage===
When genes are located on the same chromosome and no [[Chromosomal crossover|crossing over]] took place before the segregation of the chromosomes into the [[gamete]]s, the [[genetic trait]]s will be inherited in connection, because of the [[genetic linkage]]. These cases constitute an exception to the Mendelian rule of independent assortment.{{citation needed|date=April 2023}}

===Multiple alleles===
In Mendelian inheritance, genes have only two alleles, such as ''a'' and ''A''. Mendel consciously chose pairs of genetic traits, represented by two alleles for his inheritance experiments. In nature, such genes often exist in several different forms and are therefore said to have [[multiple alleles]]. An individual usually has only two copies of each gene, but many different alleles are often found within a population. A rabbit's coat color is determined by a single gene that has at least four different alleles. They display a pattern of a dominance-hierarchy that can produce four coat colors. In the genes for the [[Dog coat genetics|dog coat colours]] there are four alleles on the Agouti-locus. The allele "aw" is dominant over the alleles "at" and "a" but recessive under "Ay".{{citation needed|date=April 2023}}

Many other genes have multiple alleles, including the human genes for [[ABO blood type]].<ref>{{Cite journal |last=Crow |first=J. F. |date=January 1993 |title=Felix Bernstein and the first human marker locus |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC1205297/ |journal=Genetics |volume=133 |issue=1 |pages=4–7 |doi=10.1093/genetics/133.1.4 |issn=0016-6731 |pmc=1205297 |pmid=8417988}}</ref>

===Epistasis===
[[File:Cat (30072497623).jpg|thumb|left|In the genepool of cats (''[[Felis catus]]'') there is a recessive allele for orange coat on the X-Chromosome. In a male the Y-Chromosome cannot compensate this, so a tomcat with that allele is born orange. This allele is [[Epistasis|epistatic]] over some other coat color genes.<ref>Schmidt-Küntzel, Nelson G. David et al.: ''[https://www.ncbi.nlm.nih.gov/pubmed/19189955?dopt=Abstract A domestic cat X chromosome linkage map and the sex-linked orange locus: mapping of orange, multiple origins and epistasis over nonagouti.]''</ref><ref>''[https://web.archive.org/web/20090210034018/http://norvegienambre.e-monsite.com/rubrique,orange,222815.html Le gène Orange chez le chat : génotype et phénotype]''</ref>]]
[[File:Charline the cat and her kittens.jpg|thumb|A heterozygous cat with kittens from an orange tomcat: 50 % are orange, 50 % can produce [[eumelanin]]. Here the segregation of her two alleles, one dominant for the ability to produce eumelanin, one recessive for orange, was crucial for the colour of the kittens. With the young males it is decisive which of the two X-Chromosomes they received from the mother, because the Y-Chromosome does not contain a corresponding allele from the father. In the young females it is also decisive which X-Chromosome they got from the mother, because they each have an allele for orange from the father and only homozygotes become orange.]]
If one or more genes cannot be expressed because of another genetic factor hindering their expression, this [[epistasis]] can make it impossible even for dominant alleles on certain other gene-loci to have an effect on the phenotype. An example in [[dog coat genetics]] is the homozygosity with the allele "e e" on the Extension-locus making it impossible to produce any other pigment than pheomelanin. Although the allele "e" is a recessive allele on the extension-locus itself, the presence of two copies leverages the dominance of other coat colour genes. Domestic cats have a gene with a similar effect on the X-chromosome.{{citation needed|date=April 2023}}

===Sex-linked inheritance===
Genetic traits located on [[gonosome]]s sometimes show specific non-Mendelian inheritance patterns. Individuals can develop a recessive trait in the phenotype dependent on their sex—for example, [[Color blindness|colour blindness]] and [[haemophilia]] (see [[Genetic carrier#Carriers in gonosomal inheritances|gonosomal inheritances]]).<ref>Joseph Schacherer: ''[https://www.sciencedirect.com/science/article/pii/S1631069116300294 Beyond the simplicity of Mendelian inheritance]'' Science Direct 2016</ref><ref>Khan Academy: [https://www.khanacademy.org/science/biology/classical-genetics/variations-on-mendelian-genetics/a/variations-on-mendels-laws-overview Variations on Mendel's laws (overview)]</ref> As many of the alleles are dominant or recessive, a true understanding of the principles of [[Mendelian inheritance]] is an important requirement to also understand the more complicated inheritance patterns of sex-linked inheritances.{{citation needed|date=March 2024}}

=== Extranuclear inheritance ===
[[File:Maternal Inheritance - mitochondrial DNA.png|thumb|Example of a pedigree for a genetic trait inherited by mitochondrial DNA in animals and humans. Offspring of the males with the trait don't inherit the trait. Offspring of the females with the trait always inherit the trait (independently from their own sex).]]
[[Extranuclear inheritance]] (also known as cytoplasmic inheritance) is a form of non-Mendelian inheritance also first discovered by Carl Correns in 1908.<ref>{{cite book |last=Klug |first=William S. |author2=Michael R. Cummings |author3=Charlotte A. Spencer  |title=Concepts of Genetics |url=https://archive.org/details/conceptsgenetics00klug_804 |url-access=limited |year=2006 |publisher=Pearson Education Inc. |location=Upper Saddle River, NJ |page=[https://archive.org/details/conceptsgenetics00klug_804/page/n241 215]|isbn=9780131918337 }}</ref> While working with ''[[Mirabilis jalapa]],'' Correns observed that leaf colour was dependent only on the genotype of the maternal parent.  Based on these data, he determined that the trait was transmitted through a character present in the [[cytoplasm]] of the [[ovule]]. Later research by [[Ruth Sager]] and others identified DNA present in [[chloroplast]]s as being responsible for the unusual inheritance pattern observed. Work on the poky strain of the mould ''[[Neurospora crassa]]'' begun by Mary and [[Hershel Mitchell]]<ref name="pmid16589122">{{cite journal |vauthors=Mitchell MB, Mitchell HK |title=A case of "maternal" inheritance in ''Neurospora crassa'' |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=38 |issue=5 |pages=442–9 |year=1952 |pmid=16589122 |doi=10.1073/pnas.38.5.442 |pmc=1063583|bibcode=1952PNAS...38..442M |doi-access=free }}</ref> ultimately led to the discovery of genetic material in the mitochondria, the [[mitochondrial DNA]].{{citation needed|date=March 2024}}

According to the [[endosymbiont]] theory, mitochondria and chloroplasts were once free-living organisms that were each taken up by a eukaryotic cell.<ref>{{cite journal |last=Embley |first=T. Martin |author-link1=Martin Embley|author2=William Martin  |date=March 2006 |title=Eukaryotic evolution, changes and challenges |journal=Nature |volume=440 |issue=7084 |pages=623–630 |doi=10.1038/nature04546 |pmid=16572163|bibcode=2006Natur.440..623E |s2cid=4396543 |url=https://zenodo.org/record/897869 }}</ref> Over time, mitochondria and chloroplasts formed a [[symbiotic]] relationship with their eukaryotic hosts. Although the transfer of a number of genes from these organelles to the nucleus prevents them from living independently, each still possesses genetic material in the form of double stranded DNA.{{citation needed|date=April 2023}}

It is the transmission of this [[organellar]] DNA that is responsible for the phenomenon of extranuclear inheritance. Both chloroplasts and mitochondria are present in the cytoplasm of maternal gametes only. Paternal gametes ([[spermatozoon|sperm]] for example) do not have cytoplasmic mitochondria{{Citation needed|date=November 2021}}.  Thus, the [[phenotype]] of traits linked to genes found in either chloroplasts or mitochondria are determined exclusively by the maternal parent.

In humans, [[mitochondrial disease]]s are a class of diseases, many of which affect the muscles and the eye.{{citation needed|date=March 2024}}

===Polygenic traits===
Many traits are produced by the interaction of several genes. Traits controlled by two or more genes are said to be [[polygene|polygenic traits]]. ''Polygenic'' means "many genes" are necessary for the organism to develop the trait. For example, at least three genes are involved in making the reddish-brown pigment in the eyes of [[Drosophila|fruit flies]]. Polygenic traits often show a wide range of phenotypes. The broad variety of [[Human skin color|skin colour in humans]] comes about partly because at least four different genes probably control this trait.{{citation needed|date=March 2024}}

=== Non-random segregation ===
[[Non-random segregation of chromosomes]] is a deviation from the usual distribution of chromosomes during meiosis and in some cases of mitosis.

=== Gene conversion ===
[[Gene conversion]] can be one of the major forms of non-Mendelian inheritance. Gene conversion arises during DNA repair via DNA [[Genetic recombination|recombination]], by which a piece of DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. This may occur as a [[mismatch repair]] between the strands of DNA which are derived from different parents. Thus the mismatch repair can convert one [[allele]] into the other. This phenomenon can be detected through the offspring non-Mendelian ratios, and is frequently observed, e.g., in fungal crosses.<ref>Stacey K. A. (1994). Recombination. In: Kendrew John, Lawrence Eleanor (eds.</ref>

=== Infectious heredity ===
Another form of non-Mendelian inheritance is known as infectious heredity. Infectious particles such as [[virus]]es may infect host cells and continue to reside in the cytoplasm of these cells. If the presence of these particles results in an altered phenotype, then this phenotype may be subsequently transmitted to progeny.<ref>{{cite book |last=Klug |first=William S. |author2=Michael R. Cummings |author3=Charlotte A. Spencer  |title=Concepts of Genetics |url=https://archive.org/details/conceptsgenetics00klug_804 |url-access=limited |year=2006 |publisher=Pearson Education Inc. |location=Upper Saddle River, NJ |page=[https://archive.org/details/conceptsgenetics00klug_804/page/n249 223]|isbn=9780131918337 }}</ref> Because this phenotype is dependent only on the presence of the invader in the host cell's cytoplasm, inheritance will be determined only by the infected status of the maternal parent. This will result in a uniparental transmission of the trait, just as in extranuclear inheritance.{{citation needed|date=April 2023}}

One of the most well-studied examples of infectious heredity is the killer phenomenon exhibited in [[yeast]]. Two double-stranded [[RNA virus]]es, designated L and M, are responsible for this phenotype.<ref>{{cite book |last=Russell |first=Peter J. |title=iGenetics: A Mendelian Approach |year=2006 |publisher=Pearson Education, Inc. |location=San Francisco |pages=649–650}}</ref> The L virus codes for the [[capsid]] proteins of both viruses, as well as an [[RNA polymerase]]. Thus the M virus can only infect cells already harbouring L virus particles. The M viral RNA encodes a [[toxin]] that is secreted from the host cell. It kills susceptible cells growing in close proximity to the host.  The M viral RNA also renders the host cell immune to the lethal effects of the toxin. For a cell to be susceptible it must therefore be either uninfected or harbour only the L virus.{{citation needed|date=April 2023}}

The L and M viruses are not capable of exiting their host cell through conventional means. They can only transfer from cell to cell when their host undergoes mating. All progeny of a mating involving a doubly infected yeast cell will also be infected with the L and M viruses. Therefore, the killer phenotype will be passed down to all progeny.{{citation needed|date=March 2024}}

Heritable traits that result from infection with foreign particles have also been identified in ''[[Drosophila]]''. Wild-type flies normally fully recover after being anesthetized with carbon dioxide.  Certain lines of flies have been identified that die off after exposure to the compound. This carbon dioxide sensitivity is passed down from mothers to their progeny. This sensitivity is due to infection with σ (Sigma) virus, a [[rhabdovirus]] only capable of infecting ''Drosophila''.<ref>{{cite journal |last=Teninges |first=Danielle |author2=Francoise Bras-Herreng  |date=July 1987 |title=Rhabdovirus Sigma, the Hereditary CO2 Sensitivity Agent of Drosophila:Nucleotide Sequence of a cDNA Clone Encoding the Glycoprotein |journal=Journal of General Virology |volume=68 |pages=2625–2638 |doi=10.1099/0022-1317-68-10-2625 |pmid=2822842 |issue=10|doi-access=free }}</ref>

Although this process is usually associated with viruses, recent research has shown that the ''[[Wolbachia]]'' bacterium is also capable of inserting its genome into that of its host.<ref>{{cite web |url=http://www.rochester.edu/news/show.php?id=2963 |title=University of Rochester Press Releases |access-date=2007-10-16 }}</ref><ref name="pmid17761848">{{cite journal  |vauthors=Dunning Hotopp JC, Clark ME, Oliveira DC, etal |title=Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes |journal=Science |volume=317 |issue=5845 |pages=1753–6 |year=2007 |pmid=17761848 |doi=10.1126/science.1142490|bibcode=2007Sci...317.1753H |citeseerx=10.1.1.395.1320 |s2cid=10787254 |url=http://www.rifters.com/real/articles/Science_Wolbachia.pdf }}</ref>

=== Genomic imprinting ===
{{Main|Genomic imprinting}}
Genomic imprinting represents yet another example of non-Mendelian inheritance. Just as in conventional inheritance, genes for a given trait are passed down to progeny from both parents. However, these genes are [[epigenetically]] marked before transmission, altering their levels of expression. These imprints are created before gamete formation and are erased during the creation of germ line cells. Therefore, a new pattern of imprinting can be made with each generation.{{citation needed|date=March 2024}}

Genes are imprinted differently depending on the parental origin of the [[chromosome]] that contains them. In mice, the [[insulin-like growth factor 2]] gene undergoes imprinting. The [[protein]] encoded by this gene helps to regulate body size. Mice that possess two functional copies of this gene are larger than those with two mutant copies. The size of mice that are heterozygous at this locus depends on the parent from which the wild-type [[allele]] came. If the functional allele originated from the mother, the offspring will exhibit [[dwarfism]], whereas a paternal allele will generate a normal-sized mouse.  This is because the maternal ''Igf2'' gene is imprinted. Imprinting results in the inactivation of the ''Igf2'' gene on the chromosome passed down by the mother.<ref>{{cite journal |last=Bell |first=A.C. |author2=G. Felsenfeld  |year=2000 |title=Methylation of a CTCF-dependent boundar control imprinted expression of the Igf2 gene |journal=Nature |volume=405 |pages=482–485 |doi=10.1038/35013100 |pmid=10839546 |issue=6785|bibcode=2000Natur.405..482B |s2cid=4387329 }}</ref>

Imprints are formed due to the differential [[methylation]] of paternal and maternal alleles. This results in differing expression between alleles from the two parents. Sites with significant methylation are associated with low levels of [[gene expression]]. Higher gene expression is found at unmethylated sites.<ref>{{cite book |last=Lewin |first=Benjamin |title=Genes VIII |year=2004 |publisher=Pearson Education Inc. |location=Upper Saddle River, NJ |pages=680–684}}</ref> In this mode of inheritance, phenotype is determined not only by the specific allele transmitted to the offspring, but also by the sex of the parent that transmitted it.

===Mosaicism===
Individuals who possess cells with genetic differences from the other cells in their body are termed mosaics. These differences can result from [[mutation]]s that occur in different tissues and at different periods of development. If a mutation happens in the non-gamete forming tissues, it is characterized as [[Somatic (biology)|somatic]]. [[Germline]] mutations occur in the egg or sperm cells and can be passed on to offspring.<ref>{{cite web |url=http://geneticsmodules.duhs.duke.edu/Design/page.asp?CourseNum=2&LessonNum=3 |title=Lesson 3: Mosaicism |access-date=2007-10-16 }}</ref> Mutations that occur early on in development will affect a greater number of cells and can result in an individual that can be identified as a mosaic strictly based on phenotype.

[[Mosaicism]] also results from a phenomenon known as [[X-inactivation]]. All female mammals have two [[X chromosome]]s. To prevent lethal [[gene dosage]] problems, one of these chromosomes is inactivated following [[fertilization]]. This process occurs randomly for all of the cells in the organism's body. Because a given female's two X chromosomes will almost certainly differ in their specific pattern of alleles, this will result in differing cell phenotypes depending on which chromosome is silenced. [[Calico cat]]s, which are almost all female,<ref>{{Cite web|url=http://www.apetsblog.com/pets-journal/calico-kitten-cat-genetics.htm|title=Genetics of Calico Color}}</ref> demonstrate one of the most commonly observed manifestations of this process.<ref>{{cite web |url=http://www.med.uc.edu/embryology/chapter1/updates/mosaic.htm |title=Genetic Mosaicism |access-date=2007-10-28 }}</ref>

===Trinucleotide repeat disorders===
{{main|Trinucleotide repeat disorder}}
Trinucleotide repeat disorders also follow a non-Mendelian pattern of inheritance.  These diseases are all caused by the expansion of [[Microsatellite (genetics)|microsatellite]] [[tandem repeat]]s consisting of a stretch of three [[nucleotide]]s.<ref>{{cite web |url=http://geneticsmodules.duhs.duke.edu/Design/page.asp?CourseNum=2&LessonNum=1 |title=Lesson 1: Triplet Repeat Expansion |access-date=2007-10-16 }}</ref>  Typically in individuals, the number of repeated units is relatively low.  With each successive generation, there is a chance that the number of repeats will expand.  As this occurs, progeny can progress to premutation and ultimately affected status.  Individuals with a number of repeats that falls in the premutation range have a good chance of having affected children.  Those who progress to affected status will exhibit symptoms of their particular disease.  Prominent trinucleotide repeat disorders include [[Fragile X syndrome]] and [[Huntington's disease]].  In the case of Fragile X syndrome it is thought that the symptoms result from the increased methylation and accompanying reduced expression of the fragile X intellectual disability gene in individuals with a sufficient number of repeats.<ref>{{cite web |url=http://www.geneclinics.org/profiles/fragilex/details.html |title=FMR1-Related Disorders |access-date=2007-10-29 }}</ref>

==See also==
* [[Meiotic drive]]
* [[CoRR Hypothesis]]
* [[Epigenetic inheritance]]
* [[Gene drive]]
* [[Intragenomic conflict]]

==References==
{{reflist|2}}

==External links==
* [http://geneticsmodules.duhs.duke.edu/Design/MainMenu.asp?CourseNum=2 non-Mendelian inheritance] at [[Duke University]]

{{Mitochondrial diseases}}
{{Trinucleotide repeat disorders}}
{{Genomic imprinting}}

{{DEFAULTSORT:Non-Mendelian Inheritance}}
[[Category:Extended evolutionary synthesis]]
[[Category:Classical genetics]]