Editing Phenotype (section)

==Large-scale phenotyping and genetic screens==
{{See also|Genetic screen|Essential gene}}

Large-scale genetic screens can identify the genes or [[mutation]]s that affect the phenotype of an organism. Analyzing the phenotypes of mutant genes can also aid in determining gene function.<ref>{{cite journal | vauthors = Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N | display-authors = 6 | title = A large-scale insertional mutagenesis screen in zebrafish | journal = Genes & Development | volume = 13 | issue = 20 | pages = 2713–2724 | date = October 1999 | pmid = 10541557 | pmc = 317115 | doi = 10.1101/gad.13.20.2713 }}</ref> Most genetic screens have used microorganisms, in which genes can be easily deleted. For instance, nearly all genes have been deleted in ''[[Escherichia coli|E. coli]]''<ref>{{cite journal | vauthors = Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H | display-authors = 6 | title = Construction of ''Escherichia coli'' K-12 in-frame, single-gene knockout mutants: the Keio collection | journal = Molecular Systems Biology | volume = 2 | issue = 1 | pages = 2006.0008 | date = January 2006 | pmid = 16738554 | pmc = 1681482 | doi = 10.1038/msb4100050 }}</ref> and many other [[bacteria]], but also in several eukaryotic model organisms such as [[baker's yeast]]<ref>{{cite journal | vauthors = Nislow C, Wong LH, Lee AH, Giaever G | title = Functional genomics using the ''Saccharomyces cerevisiae'' yeast deletion collections | journal = Cold Spring Harbor Protocols | volume = 2016 | issue = 9 | page = pdb.top080945 | date = September 2016 | pmid = 27587784 | doi = 10.1101/pdb.top080945 }}</ref> and [[Schizosaccharomyces pombe|fission yeast]].<ref>{{cite journal | vauthors = Kim DU, Hayles J, Kim D, Wood V, Park HO, Won M, Yoo HS, Duhig T, Nam M, Palmer G, Han S, Jeffery L, Baek ST, Lee H, Shim YS, Lee M, Kim L, Heo KS, Noh EJ, Lee AR, Jang YJ, Chung KS, Choi SJ, Park JY, Park Y, Kim HM, Park SK, Park HJ, Kang EJ, Kim HB, Kang HS, Park HM, Kim K, Song K, Song KB, Nurse P, Hoe KL | display-authors = 6 | title = Analysis of a genome-wide set of gene deletions in the fission yeast ''Schizosaccharomyces pombe'' | journal = Nature Biotechnology | volume = 28 | issue = 6 | pages = 617–623 | date = June 2010 | pmid = 20473289 | pmc = 3962850 | doi = 10.1038/nbt.1628 }}</ref> Among other discoveries, such studies have revealed lists of essential genes .

More recently, large-scale [[Phenotypic screening|phenotypic screens]] have also been used in animals, e.g. to study lesser understood phenotypes such as [[Behavioural genetics|behavior]]. In one screen, the role of mutations in mice were studied in areas including learning and [[memory]], [[circadian rhythm]]icity, vision, responses to stress, and response to [[Stimulant|psychostimulants]].
{| class="wikitable"
|+[[doi:10.1016/j.tins.2006.02.006|Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice]]
!Phenotypic domain
!Assay
!Notes
!Software package
|-
|Circadian Rhythm
|Wheel running behavior
|
|ClockLab
|-
|Learning and Memory
|[[Fear conditioning]]
|Video-image-based scoring of freezing
|FreezeFrame
|-
|Preliminary Assessment
|[[Open field (animal test)|Open field activity]] and [[elevated plus maze]]
|Video-image-based scoring of exploration
|LimeLight
|-
|Psychostimulant response
|Hyperlocomotion behavior
|Video-image-based tracking of locomotion
|BigBrother
|-
|Vision
|[[Electroretinography|Electroretinogram]] and [[Fundus photography]]
|
|L. Pinto and colleagues
|}
This experiment involves the progeny of mice treated with [[ENU]], or N-ethyl-N-nitrosourea, which is a potent mutagen that causes [[point mutation]]s. The mice were phenotypically screened for alterations in the different behavioral domains in order to find the number of putative mutants (see table for details). Putative mutants are then tested for heritability in order to help determine the inheritance pattern as well as map out the mutations. Once they have been mapped out, cloned, and identified, it can be determined whether a mutation represents a new gene or not.
{| class="wikitable"
!Phenotypic domain
!ENU progeny screened
!Putative mutants
!Putative mutant lines with progeny
!Confirmed mutants
|-
|General assessment
|29860
|80
|38
|14
|-
|Learning and memory
|23123
|165
|106
|19
|-
|Psychostimulant response
|20997
|168
|86
|9
|-
|[[Neuroendocrinology|Neuroendocrine]] response to stress
|13118
|126
|54
|2
|-
|Vision
|15582
|108
|60
|6
|}
These experiments show that mutations in the [[rhodopsin]] gene affected vision and can even cause retinal degeneration in mice.<ref>{{cite journal | vauthors = Vitaterna MH, Pinto LH, Takahashi JS | title = Large-scale mutagenesis and phenotypic screens for the nervous system and behavior in mice | language = English | journal = Trends in Neurosciences | volume = 29 | issue = 4 | pages = 233–240 | date = April 2006 | pmid = 16519954 | pmc = 3761413 | doi = 10.1016/j.tins.2006.02.006 }}</ref> The same [[amino acid]] change causes [[Blindness|human familial blindness]], showing how phenotyping in animals can inform medical diagnostics and possibly therapy.