Просмотр кода страницы Gene mapping

{{Short description|Process of locating specific genes}}
[[File:Drosophila Gene Linkage Map.svg|right|thumb|300px| [[Thomas Hunt Morgan]]'s ''[[Drosophila melanogaster]]'' [[genetic linkage]] [[map]]. This was the first successful [[gene map]] produced and provides important evidence for the [[Boveri–Sutton chromosome theory]] of [[inheritance]]. The map shows the relative positions of [[allele|allelic]] characteristics on the second Drosophila chromosome. The distance between the genes (map units) are equal to the percentage of [[Chromosomal crossover|crossing-over]] events that occurs between different alleles.<ref>{{cite book | vauthors = Mader S |date=2007 |title=Biology | edition = Ninth |location= New York |publisher= McGraw-Hill |page= 209 |isbn= 978-0-07-325839-3 }}</ref>]]
'''Gene mapping''' or '''genome mapping''' describes the methods used to identify the [[locus (genetics)|location]] of a [[gene]] on a [[chromosome]] and the distances between genes.<ref name="Lister Hill">{{Cite web|title=Gene mapping - Glossary Entry |url=http://ghr.nlm.nih.gov/glossary=genemapping|archive-url=https://web.archive.org/web/20090531062346/http://www.ghr.nlm.nih.gov/glossary=genemapping|archive-date=May 31, 2009|date=2013-09-03|work=Genetics Home Reference]|publisher=Lister Hill National Center for Biomedical Communications, an Intramural Research Division of the [[United States National Library of Medicine|U.S. National Library of Medicine]]|access-date=2013-09-06|location=Bethesda, MD}}</ref><ref name="Genome3">{{cite web |title=Mapping |url=https://www.genome.gov/genetics-glossary/Mapping |website=Genome.gov |access-date=3 May 2023 |language=en}}</ref>  Gene mapping can also describe the distances between different sites within a gene.

The essence of all [[genome]] mapping is to place a collection of [[molecular marker]]s onto their respective positions on the genome. Molecular markers come in all forms. Genes can be viewed as one special type of genetic markers in the construction of genome maps, and mapped the same way as any other markers. In some areas of study, gene mapping contributes to the creation of new recombinants within an organism.<ref name="Maximizing the potential of multi-p">{{cite journal | vauthors = Ladejobi O, Elderfield J, Gardner KA, Gaynor RC, Hickey J, Hibberd JM, Mackay IJ, Bentley AR | display-authors = 6 | title = Maximizing the potential of multi-parental crop populations | journal = Applied & Translational Genomics | volume = 11 | pages = 9–17 | date = December 2016 | pmid = 28018845 | pmc = 5167364 | doi = 10.1016/j.atg.2016.10.002 }}</ref>

'''Gene maps''' help describe the spatial arrangement of genes on a [[chromosome]]. Genes are designated to a specific location on a chromosome known as the [[locus (genetics)|locus]] and can be used as [[molecular markers]] to find the distance between other genes on a chromosome. Maps provide researchers with the opportunity to predict the inheritance patterns of specific traits, which can eventually lead to a better understanding of disease-linked traits.<ref>{{cite book|last1 = Nussbaum|first1 = Robert L.|last2 = McInnes|first2 = Roderick R.|last3 = Wilard|first3 = Huntington F.|title = Thompson & Thompson Genetics in Medicine|date = 2016|publisher = Elsevier|location = Philadelphia, PA|isbn = 978-1-4377-0696-3|pages = 178–187|edition = Eighth|access-date = 13 October 2015|url = https://elsevier.ca/product.jsp?isbn=9781437706963|archive-url = https://web.archive.org/web/20160304104826/https://elsevier.ca/product.jsp?isbn=9781437706963|archive-date = 4 March 2016}}</ref>

The genetic basis to gene maps is to provide an outline that can potentially help researchers carry out [[DNA sequencing]]. A gene map helps point out the relative positions of genes and allows researchers to locate regions of interest in the [[genome]]. Genes can then be identified quickly and [[DNA sequencing|sequenced]] quickly.<ref name="Brown">{{Cite book|title = Genomes|last = Brown|first = Terence, A.|publisher = Garland Science|year = 2002|isbn = 0-471-25046-5|location = Manchester, UK|url = https://www.ncbi.nlm.nih.gov/books/NBK21116/}}</ref>

Two approaches to generating gene maps ('''gene mapping''') include physical mapping and genetic mapping. Physical mapping utilizes molecular biology techniques to inspect chromosomes. These techniques consequently allow researchers to observe chromosomes directly so that a map may be constructed with relative gene positions. Genetic mapping on the other hand uses genetic techniques to indirectly find association between genes. Techniques can include cross-breeding ([[Hybrid (biology)|hybrid]]) experiments and examining [[pedigree chart|pedigrees]]. These technique allow for maps to be constructed so that relative positions of genes and other important sequences can be analyzed.<ref name=Brown />

== Mapping approaches ==
{{Chloroplast DNA|caption=An interactive gene map of [[chloroplast DNA]] from ''[[Nicotiana tabacum]]''. Segments with labels on the inside reside on the B strand of [[DNA]], segments with labels on the outside are on the A strand. Notches indicate [[introns]].}}

There are two distinctive mapping approaches used in the field of genome mapping: genetic maps (also known as linkage maps)<ref name="Genome">{{cite web |title=Genetic Map |url=https://www.genome.gov/genetics-glossary/Genetic-Map |website=Genome.gov |access-date=2 May 2023 |language=en}}</ref> and physical maps.<ref name="Genome3"/> While both maps are a collection of [[genetic markers]] and gene [[Locus (genetics)|loci]],<ref>{{cite journal | vauthors = Aguilera-Galvez C, Champouret N, Rietman H, Lin X, Wouters D, Chu Z, Jones JD, Vossen JH, Visser RG, Wolters PJ, Vleeshouwers VG | display-authors = 6 | title = Two different ''R'' gene loci co-evolved with ''Avr2'' of ''Phytophthora infestans'' and confer distinct resistance specificities in potato | journal = Studies in Mycology | volume = 89 | pages = 105–115 | date = March 2018 | pmid = 29910517 | pmc = 6002340 | doi = 10.1016/j.simyco.2018.01.002 | ref = In Leading women in fungal biology, Studies in Mycology March 2018 89:105-115 }}</ref> genetic maps' distances are based on the [[genetic linkage]] information, while physical maps use actual physical distances usually measured in number of [[base pair]]s. While the physical map could be a more accurate representation of the genome, genetic maps often offer insights into the nature of different regions of the chromosome, for example the genetic distance to physical distance ratio varies greatly at different genomic regions which reflects different recombination rates, and such rate is often indicative of euchromatic (usually gene-rich) vs heterochromatic (usually gene-poor) regions of the genome.{{cn|date=December 2024}}

=== Genetic mapping ===
Researchers begin a genetic map by collecting samples of blood, saliva, or tissue from family members that carry a prominent disease or trait and family members that do not. The most common sample used in gene mapping, especially in personal genomic tests is saliva. Scientists then isolate DNA from the samples and closely examine it, looking for unique patterns in the DNA of the family members who do carry the disease and the DNA of those who do not carry the disease do not have. These unique molecular patterns in the DNA are referred to as polymorphisms, or markers.<ref>{{Cite web | url=https://www.genome.gov/10000715 |title = Genetic Mapping Fact Sheet}}</ref>

The first steps of building a genetic map are the development of [[genetic marker]]s and a mapping population. The closer two markers are on the chromosome, the more likely they are to be passed on to the next generation together. Therefore, the "co-segregation" patterns of all markers can be used to reconstruct their order. With this in mind, the genotypes of each genetic marker are recorded for both parents and each individual in the following generations. The quality of the genetic maps is largely dependent upon these factors: the number of genetic markers on the map and the size of the mapping population. The two factors are interlinked, as a larger mapping population could increase the "resolution" of the map and prevent the map from being "saturated".{{cn|date=December 2024}}

In gene mapping, any sequence feature that can be faithfully distinguished from the two parents can be used as a genetic marker. Genes, in this regard, are represented by "traits" that can be faithfully distinguished between two parents. Their linkage with other genetic markers is calculated in the same way as if they are common markers and the actual gene loci are then bracketed in a region between the two nearest neighboring markers. The entire process is then repeated by looking at more markers that target that region to map the gene neighborhood to a higher resolution until a specific causative locus can be identified. This process is often referred to as "[[positional cloning]]", and it is used extensively in the study of plant species. One plant species, in particular in which positional cloning is utilized is in [[maize]].<ref>{{cite journal | vauthors = Gallavotti A, Whipple CJ | title = Positional cloning in maize (Zea mays subsp. mays, Poaceae) | journal = Applications in Plant Sciences | volume = 3 | issue = 1 | article-number = 1400092 | date = January 2015 | pmid = 25606355 | pmc = 4298233 | doi = 10.3732/apps.1400092 }}</ref> The great advantage of genetic mapping is that it can identify the relative position of genes based solely on their phenotypic effect.{{cn|date=December 2024}}

Genetic mapping is a way to identify exactly which chromosome has which gene and exactly pinpointing where that gene lies on that particular chromosome. Mapping also acts as a method in determining which gene is most likely to recombine based on the distance between two genes. The distance between two genes is measured in units known as centimorgan or map units, these terms are interchangeable. A centimorgan is a distance between genes for which one product of meiosis in one hundred is recombinant.<ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 175–184 | date = 2017-04-01 | pmid = 32166015 | doi = 10.1016/j.cj.2016.06.003 | series = Advances in Crop Science: Innovation and Sustainability | pmc = 7052475 }}</ref><ref name="Maximizing the potential of multi-p"/> The farther two genes are from each other, the more likely they are going to recombine. If it were closer, the opposite would occur.<ref>{{Cite book| vauthors = Goldberg M, Fischer J, Hood L, Hartwell L |title=Genetics: From Genes to Genomes |publisher=McGraw Hill |year=2020 |isbn=978-1-260-24087-0 |location=New York, NY |pages=125–128 }}</ref>

====Linkage analysis====
{{See also|Genetic linkage}}
The basis to [[Genetic linkage#Linkage analysis|linkage analysis]] is understanding chromosomal location and identifying disease genes. Certain genes that are [[Genetic linkage|genetically linked]] or associated with each other reside close to each other on the same chromosome. During [[meiosis]], these genes are capable of being inherited together and can be used as a [[genetic marker]] to help identify the [[phenotype]] of diseases. Because linkage analysis can identify inheritance patterns, these studies are usually family based.<ref>{{cite journal|last1 = Pulst|first1 = Stefan M.|title = Genetic Linkage Analysis|journal = JAMA Neurology|date = June 1999|volume = 56|issue = 6|pages = 667–672|doi = 10.1001/archneur.56.6.667|access-date = 13 October 2015|url = http://archneur.jamanetwork.com/article.aspx?articleid=775035|pmid = 10369304|doi-access = free|url-access = subscription}}</ref>
[[File:First genetic map (Sturtevant, 1913).png|thumb|First genetic map (Sturtevant, 1913). It shows 6 sex-linked genes.]]
[[File:Genetic_map_of_drosophila,_as_of_1926.png|thumb|Genetic map of drosophila, published in ''The theory of the gene'' 1926 edition.<ref>{{Cite book |last=Morgan |first=Thomas Hunt |url=http://archive.org/details/theoryofgene00morg |title=The theory of the gene |date=1926 |publisher=New Haven, Yale University Press; [etc., etc.] |others=MBLWHOI Library}}</ref>]]
The earliest gene maps were done by linkage analysis of fruitflies, in the research group around [[Thomas Hunt Morgan]]. The first was published in 1913.<ref>{{cite journal |last1=Sturtevant |first1=A. H. |date=1913 |title=The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association |url=http://www.esp.org/foundations/genetics/classical/holdings/s/ahs-13.pdf |journal=Journal of Experimental Zoology |volume=14 |issue=1 |pages=43–59 |bibcode=1913JEZ....14...43S |doi=10.1002/jez.1400140104 |s2cid=82583173}}</ref>

==== Gene association analysis ====
Gene association analysis is population based; it is not focused on inheritance patterns, but rather is based on the entire history of a population. Gene association analysis looks at a particular population and tries to identify whether the frequency of an [[allele]] in affected individuals is different from that of a control set of unaffected individuals of the same population. This method is particularly useful to identify complex diseases that do not have a [[Mendelian inheritance]] pattern.<ref name=Hartwell />

===Physical mapping===
Since actual base-pair distances are generally hard or not possible to directly measure, physical maps are actually constructed by first shattering the genome into hierarchically smaller pieces. By characterizing each single piece and assembling back together, the overlapping path or "tiling path" of these small fragments would allow researchers to infer physical distances between genomic features.{{cn|date=December 2024}}

[[Restriction map]]ping is a method in which structural information regarding a segment of [[DNA]] is obtained using [[restriction enzyme]]s. Restriction enzymes are [[enzyme]]s that help cut segments of DNA at specific recognition sequences. The basis to restriction mapping involves digesting (or cutting) DNA with restriction enzymes. The digested DNA fragments are then run on an agarose gel using [[Gel electrophoresis|electrophoresis]], which provides one with information regarding the size of these digested fragments. The sizes of these fragments help indicate the distance between restriction enzyme sites on the DNA analyzed, and provides researchers with information regarding the structure of DNA analyzed.<ref name="Hartwell">{{cite book|last1 = Hartwell|first1 = Leland H.|last2 = Hood|first2 = Leroy|last3 = Goldberg|first3 = Michael L.|last4 = Reynolds|first4 = Anne E.|last5 = Silver|first5 = Lee M.|last6 = Karagiannis|first6 = Jim|last7 = Papaconstantinou|first7 = Maria|title = Genetics: From Genes to Genomes|date = 2014|publisher = McGraw-Hill Ryerson|location = Canada|isbn = 978-0-07-094669-9|pages = 456–459, 635–636|edition = Canadian|access-date = 13 October 2015|url = https://www.mheducation.ca/highereducation/products/9781259030840/connect+online+access+for+genetics/}}</ref> The resulting pattern of DNA migration – its [[genetic fingerprint]] is used to identify what stretch of DNA is in the [[Clone (genetics)|clone]]. By analyzing the fingerprints, [[contig]]s are assembled by automated (FPC) or manual means (pathfinders) into overlapping DNA stretches. Now a good choice of clones can be made to efficiently sequence the clones to determine the [[DNA sequencing|DNA sequence]] of the organism under study.{{cn|date=December 2024}}

In physical mapping, there are no direct ways of marking up a specific gene since the mapping does not include any information that concerns traits and functions. Genetic markers can be linked to a physical map by processes like [[in situ hybridization]]. By this approach, physical map contigs can be "anchored" onto a genetic map. The clones used in the physical map contigs can then be sequenced on a local scale to help new genetic marker design and identification of the causative loci.{{cn|date=December 2024}}

Macrorestriction is a type of physical mapping wherein the high molecular weight DNA is digested with a restriction enzyme having a low number of restriction sites.{{cn|date=December 2024}}

There are alternative ways to determine how [[DNA]] in a group of clones overlaps without completely sequencing the clones. Once the map is determined, the clones can be used as a resource to efficiently contain large stretches of the genome. This type of mapping is more accurate than genetic maps.{{cn|date=December 2024}}

====Restriction mapping====
[[Restriction map]]ping is a method in which structural information regarding a segment of [[DNA]] is obtained using [[restriction enzyme]]s. Restriction enzymes are [[enzyme]]s that help cut segments of DNA at specific recognition sequences. The basis to restriction mapping involves digesting (or cutting) DNA with restriction enzymes. The digested DNA fragments are then run on an agarose gel using [[Gel electrophoresis|electrophoresis]], which provides one with information regarding the size of these digested fragments. The sizes of these fragments help indicate the distance between restriction enzyme sites on the DNA analyzed, and provides researchers with information regarding the structure of DNA analyzed.<ref name="Hartwell"/>

====Fluorescent in situ hybridization====
[[Fluorescence in situ hybridization]] (FISH) is a method used to detect the presence (or absence) of a DNA sequence within a cell.<ref name="Genome2">{{cite web |title=Fluorescence In Situ Hybridization Fact Sheet |url=https://www.genome.gov/about-genomics/fact-sheets/Fluorescence-In-Situ-Hybridization |website=Genome.gov |access-date=3 May 2023 |language=en}}</ref> DNA probes that are specific for chromosomal regions or genes of interest are labeled with [[Fluorophore|fluorochromes]]. By attaching fluorochromes to probes, researchers are able to visualize multiple DNA sequences simultaneously. When a probe comes into contact with DNA on a specific chromosome, hybridization will occur. Consequently, information regarding the location of that sequence of DNA will be attained. FISH analyzes single stranded DNA ([[ssDNA]]). Once the DNA is in its single stranded state, the DNA can bind to its specific probe.<ref name=Brown />

====Sequence-tagged site (STS) mapping====
A [[sequence-tagged site]] (STS) is a short sequence of DNA (about 100 - 500 [[base pair]]s in length) that is seen to appear multiple times within an individual's genome. These sites are easily recognizable, usually appearing at least once in the DNA being analyzed. These sites usually contain genetic [[Single-nucleotide polymorphism|polymorphisms]] making them sources of viable genetic markers (as they differ from other sequences). Sequenced tagged sites can be mapped within our genome and require a group of overlapping DNA fragments. [[Polymerase chain reaction|PCR]] is generally used to produce the collection of DNA fragments. After overlapping fragments are created, the [[Centimorgan|map distance]] between STSs can be analyzed. In order to calculate the map distance between STSs, researchers determine the frequency at which breaks between the two markers occur (see [[shotgun sequencing]])<ref name=Hartwell />

===Mapping mutational sites===
In the early 1950s the prevailing view was that the genes in a [[chromosome]] are discrete entities, indivisible by [[genetic recombination]] and arranged like beads on a string.  During 1955 to 1959, Benzer performed [[genetic recombination]] experiments using [[T4 rII system|rII]] mutants of [[Escherichia virus T4|bacteriophage T4]].  He found that, on the basis of recombination tests, the sites of [[mutation]] could be mapped in a linear order.<ref name="pmid16589677">{{cite journal | vauthors = Benzer S | title = Fine structure of a genetic region in bacteriophage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 41 | issue = 6 | pages = 344–54 | date = June 1955 | pmid = 16589677 | pmc = 528093 | doi = 10.1073/pnas.41.6.344 }}</ref><ref name="pmid16590553">{{cite journal | vauthors = Benzer S | title =  On the topology of the genetic fine structure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 45 | issue = 11 | pages = 1607–20 | date = November 1959 | pmid = 16590553 | pmc = 222769 | doi = 10.1073/pnas.45.11.1607 }}</ref> This result provided evidence for the key idea that the gene has a linear structure equivalent to a length of [[DNA]] with many sites that can independently mutate.{{cn|date=December 2024}}

In 1961, Francis Crick, Leslie Barnett, Sydney Brenner and Richard Watts-Tobin performed genetic experiments that demonstrated the basic nature of the [[genetic code]] for proteins.<ref name="pmid13882203">{{cite journal | vauthors = Crick FH, Barnett L, Brenner S, Watts-Tobin RJ | title = General nature of the genetic code for proteins | journal = Nature | volume = 192 | issue = | pages = 1227–32 | date = December 1961 | pmid = 13882203 | doi = 10.1038/1921227a0 }}</ref> These experiments, involving mapping of mutational sites within the rIIB gene of bacteriophage T4, demonstrated that three sequential [[nucleobase]]s of the gene's DNA specify each successive amino acid of its encoded protein. Thus the genetic code was shown to be a triplet code, where each triplet (called a codon) specifies a particular amino acid. They also obtained evidence that the codons do not overlap with each other in the DNA sequence encoding a protein, and that such a sequence is read from a fixed starting point.{{cn|date=December 2024}}

Edgar et al.<ref name="pmid13889186">{{cite journal | vauthors = Edgar RS, Feynman RP, Klein S, Lielausis I, Steinberg CM | title = Mapping experiments with r mutants of bacteriophage T4D | journal = Genetics | volume = 47 | issue = 2 | pages = 179–186 | date = February 1962 | pmid = 13889186 | pmc = 1210321 | doi = 10.1093/genetics/47.2.179 }}</ref> performed mapping experiments with r mutants of bacteriophage T4 showing that recombination frequencies between rII mutants are not strictly additive. The recombination frequency from a cross of two rII mutants (a x d) is usually less than the sum of recombination frequencies for adjacent internal sub-intervals (a x b) + (b x c) + (c x d). Although not strictly additive, a systematic relationship was demonstrated<ref name="pmid5882191">{{cite journal | vauthors = Fisher KM, Bernstein H | title = The additivity of intervals in the RIIA cistron of phage T4D | journal = Genetics | volume = 52 | issue = 6 | pages = 1127–36 | date = December 1965 | pmid = 5882191 | pmc = 1210971 | doi = 10.1093/genetics/52.6.1127 }}</ref> that likely reflects the underlying molecular mechanism of [[genetic recombination]].

===Genome sequencing===
[[Whole genome sequencing|Genome sequencing]] is sometimes mistakenly referred to as "genome mapping" by non-biologists. The process of [[shotgun sequencing]]<ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 890–898 | date = 2018 | pmid = 32166015 | doi = 10.1080/1828051X.2018.1462110 | pmc = 7052475 | doi-access = free }}</ref> resembles the process of physical mapping: it shatters the genome into small fragments, characterizes each fragment, then puts them back together (more recent sequencing technologies are drastically different). While the scope, purpose and process are totally different, a genome assembly can be viewed as the "ultimate" form of physical map, in that it provides in a much better way all the information that a traditional physical map can offer.{{cn|date=December 2024}}

==Use==
{{more citations|section|date=December 2023}}
Identification of genes is usually the first step in understanding a genome of a species; mapping of the gene is usually the first step of identification of the gene. Gene mapping is usually the starting point of many important downstream studies.

===Disease association===
The process to identify a genetic element that is responsible for a [[disease]] is also referred to as "mapping". If the locus in which the search is performed is already considerably constrained, the search is called the ''fine mapping'' of a gene. This information is derived from the investigation of disease manifestations in large families ([[genetic linkage]]) or from populations-based [[genetic association]] studies.

Using the methods mentioned above, researchers are capable of mapping disease genes. Generating a gene map is the critical first step towards identifying disease genes. Gene maps allow for variant alleles to be identified and allow for researchers to make predictions about the genes they think are causing the [[Mutation|mutant]] phenotype. An example of a disorder that was identified by Linkage analysis is [[Cystic fibrosis|Cystic Fibrosis]]. For example, with Cystic Fibrosis (CF), DNA samples from fifty families affected by CF were analyzed using linkage analysis. Hundreds of markers pertaining to CF were analyzed throughout the genome until CF was identified on the [[Q arm|long arm]] of chromosome 7. Researchers then had completed linkage analysis on additional DNA markers within chromosome 7 to identify an even more precise location of the CF gene. They found that the CF gene resides around 7q31-q32 (see [[Chromosome nomenclature|chromosomal nomenclature]]).<ref name=Hartwell />

== See also ==
* [[Eukaryotic chromosome fine structure]]
* [[Fate mapping]]
* [[G banding]]
* [[Genetic fingerprinting]]
* [[Genome project]]
* [[Human Genome Project]]
* [[Optical mapping]]
* [[Quantitative trait locus]]
* [[Sulston score]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Brown TA |title=Genomes 3 |publisher=[[Garland Science|Garland Science Publishing]] |location= New York, NY |year=2007 |isbn=978-0-8153-4138-3 |oclc=444522997}}
{{refend}}

== External links ==
* {{Cite web|title=Genetic Mapping Fact Sheet|url=https://www.genome.gov/10000715|publisher=[[National Human Genome Research Institute]], [[National Institutes of Health]]|access-date=2013-09-06|location=Bethesda, MD}}
* {{Cite web|title=Canada's Michael Smith Genome Sciences Centre|url=http://www.bcgsc.ca/|access-date=2013-09-06|location=Vancouver, British Columbia}}

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[[Category:Genetics]]