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''''Inbred strains''' (also called '''inbred lines''', or rarely for animals '''linear animals''') are individuals of a particular [[species]] which are nearly identical to each other in [[genotype]] due to long [[inbreeding]]. A strain is inbred when it has undergone at least 20 generations of brother x sister or offspring x parent mating, at which point at least 98.6% of the [[Locus (genetics)|loci]] in an individual of the strain will be [[Zygosity|homozygous]], and each individual can be treated effectively as [[Cloning|clones]]. Some inbred strains have been bred for over 150 generations, leaving individuals in the population to be [[Zygosity|isogenic]] in nature.<ref name="Beck_2000">{{cite journal | vauthors = Beck JA, Lloyd S, Hafezparast M, Lennon-Pierce M, Eppig JT, Festing MF, Fisher EM | title = Genealogies of mouse inbred strains | journal = Nature Genetics | volume = 24 | issue = 1 | pages = 23–5 | date = January 2000 | pmid = 10615122 | doi = 10.1038/71641 }}</ref> Inbred strains of animals are frequently used in laboratories for experiments where for the reproducibility of conclusions all the test animals should be as similar as possible. However, for some experiments, [[genetic diversity]] in the test population may be desired. Thus [[Outbred|outbred strains]] of most laboratory animals are also available, where an outbred strain is a strain of an organism that is effectively [[Wild type|wildtype]] in nature, where there is as little inbreeding as possible.<ref>{{cite web | url = http://isogenic.info/html/outbred_stocks.html | title = Outbred Stocks | date = | website = Isogenic | access-date = 28 November 2017 }}</ref> Certain plants including the genetic [[model organism]] ''[[Arabidopsis thaliana]]'' naturally [[self pollination|self pollinate]], which makes it quite easy to create inbred strains in the laboratory (other plants, including important genetic models such as [[Maize#Genetics|Maize]] require transfer of [[pollen]] from one [[flower]] to another).<ref>{{cite book | editor-last = Green | editor-first = Earl L. |title=Biology of the Laboratory Mouse |year=1966 |publisher=[[McGraw-Hill]] |location=New York |lccn=65-27978 |page=156 | first1 = Thomas H. | last1 = Roderick | first2 = Gunther | last2 = Schlager | name-list-format = vanc |chapter=Multiple Factor Inheritance}}</ref><ref name=mgreen>{{cite book |editor=Green, Margaret C. |title=Genetic Variants and Strains of the Laboratory Mouse |year=1981 |publisher= Gustav Fischer Verlag |location=Stuttgart |isbn=0-89574-152-0 |page=368| first = Mary F. | last = Lyon | name-list-format = vanc | authorlink=Mary F. Lyon |chapter=Rules for Nomenclature of Inbred Strains}}</ref> == Inbred strains in the lab == Inbred strains have been extensively used in research. Several Nobel Prizes that have awarded for work that probably could not have been done without inbred strains. This work includes Medawar's research on [[immune tolerance]], Kohler and Milstein's development of [[monoclonal antibodies]], and Doherty and Zinkernagel's studies of the [[major histocompatibility complex ]] (MHC).<ref name="Beck_2000" /> Isogenic organisms have identical, or near identical [[genotype]]s.<ref>{{cite web | url = https://www.merriam-webster.com/dictionary/isogenic|title=Isogenic | website=Merriam-Webster | access-date=18 November 2017}}</ref> which is true of inbred strains, since they normally have at least 98.6% similarity by generation 20.<ref name="Beck_2000" /> This very uniformity means that fewer individuals are required to produce results with the same level of statistical significance when an inbred line is used in comparison to an outbred line in the same experiment.<ref>{{cite web | url = http://isogenic.info/html/increased_statistical_power.html|title=Increased statistical power|website=isogenic.info|access-date=2017-11-30}}</ref> Breeding of inbred strains is often towards specific [[phenotype]]s of interest such as behavioural traits like alcohol preference or physical traits like aging, or they can be selected for traits that make them easier to use in experiments like being easy to use in [[Transgenic animal|transgenic]] experiments.<ref name="Beck_2000" /> One of the key strengths of using inbred strains as a model is that strains are readily available for whatever study one is performing and that there are resources such as the [[Jackson Laboratory]], and [[FlyBase|Flybase]], where one can look up strains with specific phenotypes or genotypes, from among inbred lines, recombinant lines, and Coisogenic strains. Jackson Laboratory has additional features to maintaining mice, one can order mice that have been altered with genetic tools such as [[GAL4/UAS system|Gal4/UAS]] or [[CRISPR]], meaning that even if the strain does not currently exist, you can still obtain a line of mouse that is useful to your research.<ref>{{Cite web|url=https://www.jax.org/jax-mice-and-services/model-generation-services|title=Model Generation Services|website=Jackson Laboratory|access-date=18 November 2017}}</ref> Additionally, the embryos of lines that are of little interest currently can be frozen and preserved until there is an interest in their unique genotypical or phenotypical traits.<ref>{{cite web | url = http://isogenic.info/html/history_of_inbred_strains.html|title=History of inbred strains|website=isogenic.info|access-date=2017-11-30}}</ref> === Recombinant inbred lines === [[File:QTL_mapping_using_inbred_strains.pdf|thumb|QTL mapping using inbred strains]] For the analysis of the linkage of [[Quantitative trait locus|quantitative traits]], [[Recombinant inbred strain|recombinant lines]] are useful because of their isogenic nature, because the genetic similarity of individuals allows for the replication of a quantitative trait locus analysis. The replication increases the precision of the results from the mapping experiment, and is required for traits such as aging where minor changes in the environment can influence the longevity of an organism, leading to variation in results.<ref name="Dixon_1993">{{cite journal | vauthors = Dixon LK | title = Use of recombinant inbred strains to map genes of aging | journal = Genetica | volume = 91 | issue = 1–3 | pages = 151–65 | year = 1993 | pmid = 8125266 | doi = 10.1007/BF01435995 }}</ref> === Coisogenic strain === One type of inbred strain that either has been altered, or naturally mutated so that it is different at a single [[Locus (genetics)|locus]].<ref>{{cite journal | vauthors = Bult CJ, Eppig JT, Blake JA, Kadin JA, Richardson JE | title = Mouse genome database 2016 | journal = Nucleic Acids Research | volume = 44 | issue = D1 | pages = D840-7 | date = January 2016 | pmid = 26578600 | pmc = 4702860 | doi = 10.1093/nar/gkv1211 }}</ref> Such strains are useful in the analysis of variance within an inbred strain or between inbred strains because any differences would be due to the single genetic change, or to a difference in environmental conditions between two individuals of the same strain,<ref name="Dixon_1993" /> === Gal4 lines === One of the more specific uses of Drosophila inbred strains are the use of [[GAL4/UAS system|Gal4/UAS]] lines in research.<ref name="Duffy_2002">{{cite journal | vauthors = Duffy JB | title = GAL4 system in Drosophila: a fly geneticist's Swiss army knife | journal = Genesis | volume = 34 | issue = 1–2 | pages = 1–15 | date = 2002-09-01 | pmid = 12324939 | doi = 10.1002/gene.10150 }}</ref> Gal4/UAS is a driver system, where Gal4 can be expressed in specific tissues under specific conditions based on its location in the Drosophila [[genome]]. Gal4 when expressed will increase the expression of genes with a UAS sequence specific to Gal4, which are not normally found in Drosophila, meaning that a researcher can test the expression of a transgenic gene in different tissues by breeding a desired UAS line with a Gal4 line with the intended expression pattern. Unknown expression patterns can also be determined by using [[Green fluorescent protein|Green Fluorescent protein (GFP)]] as the protein expressed by UAS. Drosophila in particular has thousands of Gal4 lines with unique and specific expression patterns, making it possible to test most expression patterns within the organism.<ref name="Duffy_2002" /> == Effects == Inbreeding animals will sometimes lead to [[genetic drift]]. The continuous overlaying of like genetics exposes recessive gene patterns that often lead to changes in reproduction performance, fitness, and ability to survive. A decrease in these areas is known as [[inbreeding depression]]. A hybrid between two inbred strains can be used to cancel out deleterious recessive genes resulting in an increase in the mentioned areas. This is known as [[heterosis]].<ref>{{cite web |url=http://isogenic.info/html/inbreeding___it_s_effects.html |title=Inbreeding & it's effects |author=[[Michael Festing]] |date= |accessdate=2013-12-19}}</ref> Inbred strains, because they are small populations of homozygous individuals, are susceptible to the fixation of new mutations through genetic drift, Jackson laboratory in an information session on genetic drift in mice, calculated a quick estimate of the rate of mutation based on observed traits to be 1 phenotypic mutation every 1.8 generations, though they caution that this is likely an under representation because the data they used was for visible phenotypic changes and not phenotype changes inside of mice strains. they further add that statistically every 6-9 generations, a mutation in the coding sequence is fixed, leading to the creation of a new substrain. Care must be taken when comparing results that two substrains are not compared, because substrains may differ drastically<ref>{{cite web | url = http://jackson.jax.org/rs/444-BUH-304/images/Genetic-Drift-Webinar-11May2017.pdf | title = Genetic Drift: What It Is and Its Impact on Your Research | website = The Jackson Laboratory | access-date=18 November 2017}}</ref> == Notable species == === Rats and mice === "The period before World War I led to the initiation of inbreeding in rats by Dr Helen King in about 1909 and in mice by Dr C. C. Little in 1909. The latter project led to the development of the DBA strain of mice, now widely distributed as the two major sub-strains DBA/1 and DBA/2, which were separated in 1929-1930. DBA mice were nearly lost in 1918, when the main stocks were wiped out by murine paratyphoid, and only three un-pedigreed mice remained alive. Soon after World War I, inbreeding in mice was started on a much larger scale by Dr L. C. Strong, leading in particular to the development of strains C3H and CBA, and by Dr C. C. Little, leading to the C57 family of strains (C57BL, C57BR and C57L). Many of the most popular strains of mice were developed during the next decade, and some are closely related. Evidence from the uniformity of mitochondrian DNA suggests that most of the common inbred mouse strains were probably derived from a single breeding female about 150-200 years ago." "Many of the most widely used inbred strains of rats were also developed during this period, several of them by Curtis and Dunning at the Columbia University Institute for Cancer Research. Strains dating back to this time include F344, M520 and Z61 and later ACI, ACH, A7322 and COP. [[Robert Tryon|Tryon's]] classic work on selection for [[Tryon's Rat Experiment|maze-bright and dull]] rats led to the development of the TMB and TMD inbred strains, and later to the common use of inbred rats by experimental psychologists."<ref>{{cite web |url=http://isogenic.info/html/history_of_inbred_strains.html |title=History of inbred strains |author=[[Michael Festing]] |date= |accessdate=2013-12-19}}</ref> ==== Inbred strains of rats ==== * [[Wistar rat|Wistar]] as a generic name for inbred strains such as Wistar-Kyoto, developed from the Wistar outbred strains. * Jackson Laboratory maintains a list of inbred Rat lines and their characteristics on their website [http://www.informatics.jax.org/inbred_strains/rat/STRAINS.shtml?new+window=target= here]<ref>{{Cite web|url=http://isogenic.info/html/rat_strains.html|title=Rat strains|website=isogenic.info|access-date=2017-11-30}}</ref> ==== Inbred strains of mice ==== A [[Genealogy|genealogical chart]] of mouse inbred strains can be found [http://www.informatics.jax.org/downloads/datasets/misc/genealogy/genealogy.pdf here] on the Jackson Laboratory website and is currently being maintained by the laboratory.<ref name="History of inbred strains">{{Cite web|url=http://isogenic.info/html/history_of_inbred_strains.html|title=History of inbred strains|website=isogenic.info|access-date=2017-11-30}}</ref>{{columns-list|colwidth=30em| * [[A/J]] * [[C3H (mouse strain)|C3H]] * [[C57BL/6]] * [[CBA (mouse strain)|CBA]] * [[DBA/2]] * [[BALB/c]] }} === Guinea pigs === G.M. Rommel first started conducting inbreeding experiments on guinea-pigs in 1906. Strain 2 and 13 guinea-pigs, were derived from these experiments and are still in use today. [[Sewall Wright]] took over the experiment in 1915. He was faced with the task of analyzing all of the accumulated data produced by Rommel. Wright became seriously interested in constructing a general mathematical theory of inbreeding. By 1920 Wright had developed his method of path coefficients, which he then used to develop his mathematical theory of inbreeding. Wright introduced the [[inbreeding coefficient]] ''F'' as the correlation between uniting gametes in 1922, and most of the subsequent theory of inbreeding has been developed from his work. The definition of the inbreeding coefficient now most widely used is mathematically equivalent to that of Wright.<ref name="History of inbred strains"/> === Medaka === The Japanese [[Japanese rice fish|Medaka fish]] has a high tolerance for inbreeding, one line having been bred brother-sister for as many as 100 generations without evidence of inbreeding depression, providing a ready tool for laboratory research and genetic manipulations. Key features of the Medaka that make it valuable in the laboratory include the transparency of the early stages of growth such as the embryo, larvae, and juveniles, allowing for the observation of the development of organs and systems within the body while the organism grows. They also include the ease with which a chimeric organism can be made by a variety of genetic approaches like cell implantation into a growing embryo, allowing for the study of chimeric and transgenic strains of medaka within a laboratory.<ref>{{cite journal | vauthors = Kirchmaier S, Naruse K, Wittbrodt J, Loosli F | title = The genomic and genetic toolbox of the teleost medaka (Oryzias latipes) | journal = Genetics | volume = 199 | issue = 4 | pages = 905–18 | date = April 2015 | pmid = 25855651 | doi = 10.1534/genetics.114.173849 | pmc=4391551}}</ref> === Zebrafish === Though there are many traits about zebrafish that are worthwhile to study including their regeneration, there are relatively few inbred strains of [[zebrafish]] possibly because they experience greater effects from [[inbreeding depression]] than mice or Medaka fish, but it is unclear if the effects of inbreeding can be overcome so an isogenic strain can be created for laboratory use<ref>{{cite journal | vauthors = Shinya M, Sakai N | title = Generation of highly homogeneous strains of zebrafish through full sib-pair mating | journal = G3 | volume = 1 | issue = 5 | pages = 377–86 | date = October 2011 | pmid = 22384348 | doi = 10.1534/g3.111.000851 | url = http://www.g3journal.org/content/1/5/377 | pmc=3276154}}</ref> == See also == {{Commons category|Inbred strains}} * [[Backcrossing]] * [[Linebreeding]] * [[Recombinant inbred strain]] * [[Coisogenic strain]] * [[Congenic|Congenic strain]] * [[Inbreeding depression]] * [[Inbreeding]] * [[Jackson Laboratory]] * [[genetic drift]] == References == {{Reflist}} {{DEFAULTSORT:Inbred Strain}} [[Category:Population genetics]] [[Category:Breeding]]'