Inbred strain
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 loci ( in an individual of the strain will be homozygous, and each individual can be treated effectively as clones. Some inbred strains have been bred for over 150 generations, leaving individuals in the population to be Isogenic in nature.[1] Inbred strains of animals are frequently used in laboratories for experiments where for 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 strains of most laboratory animals are also available, where an outbred strain is a strain of an organism that is effectively wildtype in nature, where there is as little inbreeding as possible.[2]
Certain plants including the genetic model organism Arabidopsis thaliana naturally self pollinate, which makes it quite easy to create inbred strains in the laboratory (other plants, including important genetic models such as Maize require transfer of pollen from one flower to another).[3][4]
Laboratory benefits to using inbred strains
As stated by Elizabeth M.C. Fisher et al. in their paper "Genealogies of mouse inbred strains":
Inbred strains have long been used for genetic and immunological studies because of the isogenicity within a strain or F1 hybrid and the genetic heterogeneity between inbred strains. Several Nobel Prizes have been awarded for work which probably could not have been done without inbred strains; examples include Medawar's research of immunological tolerance, Kohler and Milstein's development of monoclonal antibodies, and Doherty and Zinkernagel's studies of major histocompatibility complex (MHC) restriction. The use of inbred strains contributed to the Nobel prize-winning work of George Snell in dissecting the biology of the mouse MHC (ref. 6) and developing the backcrossing methodology, which is now an important tool in genetic mapping studies.[1]
Isogenic organisms have identical, or near identical genotypes.[5] which is certainly true of inbred strains, since they normally have at least 98.6% similarity by generation 20[1]
Breeding of inbred strains is often towards specific phenotypes 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 experiments.[1] 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, 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 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[6]
Coisogenic strains are one type of inbred strain that either has been altered, or naturally mutated so that it is different at a single locus[7]
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.[8]
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[9]
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. Tryon's classic work on selection for 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."[10]
Inbred strains of rats
- Wistar as a generic name for inbred strains such as Wistar-Kyoto, developed from the Wistar outbred strains.
Inbred strains of mice
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.[citation needed]
Medaka
The Japanese 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. As stated in "The Genomic and Genetic Toolbox of the Teleost Medaka (Oryzias latipes)"
Currently >60 wild strains from both the northern and southern populations and ∼14 derived inbred strains are available at the Japanese Medaka Stock Center (National BioResource Project Medaka, NBRP Medaka; http://www.shigen.nig.ac.jp). Apart from genomic polymorphisms, these inbred strains also exhibit strain-specific differences in behavior, body shape, brain morphology, and susceptibility to mutagens (Ishikawa et al. 1999; Kimura et al. 2007). Heritability of craniofacial traits has been demonstrated, indicating that the inbreeding of polymorphic populations in medaka reveals the genetic contribution to variability of these traits (Kimura et al. 2007). To further exploit the tolerance to inbreeding combined with genetic polymorphism, recently a detailed analysis of wild populations has been carried out with the aim to establish a panel of >100 inbred lines derived from a single polymorphic wild population (Spivakov et al. 2014). Such a panel of inbred lines with sequenced genomes will serve as a genetic source for genome-wide association studies (GWAS).[11]
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 over come so an isogenic strain can be created for laboratory use[12]
See also
References
- ^ a b c d Fisher, Elizabeth M.C.; Beck, Jon A.; Lloyd, Sarah; Hafezparast, Majid; Lennon-Pierce, Moyha; Eppig, Janan T.; Festing, Michael F.W. (2000-01-01). "Genealogies of mouse inbred strains". Nature Genetics. 24 (1): 23–25. doi:10.1038/71641.
- ^ "Outbred Stocks". Isogenic. Retrieved 28 November 2017.
{{cite web}}: Cite has empty unknown parameter:|dead-url=(help) - ^ Thomas H. Roderick; Gunther Schlager (1966). "Multiple Factor Inheritance". In Green, Earl L. (ed.). Biology of the Laboratory Mouse. New York: McGraw-Hill. p. 156. LCCN 65-27978.
- ^ Mary F. Lyon (1981). "Rules for Nomenclature of Inbred Strains". In Green, Margaret C. (ed.). Genetic Variants and Strains of the Laboratory Mouse. Stuttgart: Gustav Fischer Verlag. p. 368. ISBN 0-89574-152-0.
- ^ "Isogenic". Merriam-Webster. Retrieved 18 November 2017.
{{cite web}}: Cite has empty unknown parameter:|dead-url=(help) - ^ "Model Generation Servvices". Jackson Laboratory. Retrieved 18 November 2017.
{{cite web}}: Cite has empty unknown parameter:|dead-url=(help) - ^ Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E. (2016-01-04). "Mouse genome database 2016". Nucleic Acids Research. 44 (Database issue): D840–D847. doi:10.1093/nar/gkv1211. ISSN 0305-1048. PMC 4702860. PMID 26578600.
- ^ Michael Festing. "Inbreeding & it's effects". Retrieved 2013-12-19.
- ^ "Genetic Drift: What It Is and Its Impact on Your Research" (PDF). the Jackson Laboratory. Retrieved 18 November 2017.
{{cite web}}: Cite has empty unknown parameter:|dead-url=(help) - ^ Michael Festing. "History of inbred strains". Retrieved 2013-12-19.
- ^ Kirchmaier, Stephan; Naruse, Kiyoshi; Wittbrodt, Joachim; Loosli, Felix (2015-04-01). "The Genomic and Genetic Toolbox of the Teleost Medaka (Oryzias latipes)". Genetics. 199 (4): 905–918. doi:10.1534/genetics.114.173849. ISSN 0016-6731. PMID 25855651.
- ^ Shinya, Minori; Sakai, Noriyoshi (2011-10-01). "Generation of Highly Homogeneous Strains of Zebrafish Through Full Sib-Pair Mating". G3: Genes, Genomes, Genetics. 1 (5): 377–386. doi:10.1534/g3.111.000851. ISSN 2160-1836. PMID 22384348.