In
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, complete (or absolute) linkage is defined as the state in which two
loci are so close together that
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
s of these loci are virtually never separated by
crossing over. The closer the physical location of two genes on the DNA, the less likely they are to be separated by a crossing-over event. In the case of male
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
there is complete absence of recombinant types due to absence of crossing over. This means that all of the genes that start out on a single chromosome, will end up on that same chromosome in their original configuration. In the absence of recombination, only parental phenotypes are expected.
Linkage
Genetic Linkage
Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separ ...
is the tendency of alleles, which are located closely together on a chromosome, to be inherited together during the process of
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
in sexually reproducing organisms. During the process of meiosis, homologous chromosomes pair up, and can exchange corresponding sections of DNA. As a result, genes that were originally on the same chromosome can finish up on different chromosomes. This process is known as
genetic recombination
Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryo ...
. The rate of recombination of two discrete loci corresponds to their physical proximity. Alleles that are closer together have lower rates of recombination than those that are located far apart. The distance between two alleles on a chromosome can be determined by calculating the percentage or recombination between two loci. These probabilities of recombination can be used to construct a
linkage map, or a graphical representation of the location of genes and gene in respect to one another. If linkage is complete, there should be no recombination events that separate the two alleles, and therefore only parental combinations of alleles should be observed in offspring. Linkage between two loci can have significant implications regarding the inheritance of certain types of diseases.
Gene maps or Qualitative Trait Loci (QTL) maps can be produced using two separate methods. One way uses the frequency of marker alleles and compares them to individuals selected from the two tails of the trait distribution. This is called the Trait-Based approach and strictly uses phenotypic information only to select the individuals for a sample. The other approach is called the Marker-Base approach (MB), and uses both the difference in marker allele frequencies and the phenotypic values of each marker genotype when selecting samples.
(Click here for more information on Linkage Map
Recombination During Meiosis
In diploid eukaryotic cells, recombination can occur during the process of Meiosis. Homologous chromosomes pair up during meiosis before finally splitting, resulting in two haploid daughter cells each with a single copy of every chromosome. While homologous chromosomes are lined up, they are free to exchange corresponding segments of their own DNA with that of their homolog. This results in a chromosomes that carry both maternal and paternal DNA. Through recombination, daughter cells have the greatest amount of genetic diversity.
<
(Click Here for a video tutorial explaining genetic recombination)/u>
Methods of Analysis
Hierarchical Clustering
![Swiss centroid](https://upload.wikimedia.org/wikipedia/commons/2/22/Swiss_centroid.png)
One powerful tool for interpreting and graphing linkage data sets is called
Hierarchical clustering, Hierarchical Clustering. Clustering organizes things into groups based on similarity. In the case of linkage, similarity equates to physical proximity on a chromosome. Hierarchical clustering is a bottom-up approach to cluster analysis, in which the two closest data points are grouped together and are treated as a single data point for later clustering. In complete-linkage Hierarchical Clustering, this process of combining data points into clusters of increasing size is repeated until all date as part of a single cluster. The resulting diagram from a Hierarchical Cluster Analysis is called a
dendrogram
A dendrogram is a diagram representing a tree. This diagrammatic representation is frequently used in different contexts:
* in hierarchical clustering, it illustrates the arrangement of the clusters produced by the corresponding analyses.
...
, in which data are nested into brackets of increasing dissimilarity. Two common issues with Hierarchical Clustering include designating a specific distance of “similarity” between two data points, in order to generate meaningful associations between data points, and also how to merge data points, in a way that will be helpful for further clustering once they have been deemed similar. A cross-clustering algorithm with automatic estimation of the number of clusters has been designed, which helps resolve some of these issues. By fine tuning the number of clusters expected, the possibility of associating two unrelated clusters is minimized. Again, under this type of analysis, a single resultant cluster signifies complete-linkage, since all data points are within the range of assigned similarity.
(Click Here for an interactive Hierarchical Clustering Demo)
History
![Thomas Hunt Morgan](https://upload.wikimedia.org/wikipedia/commons/8/8f/Thomas_Hunt_Morgan.jpg)
The idea of genetic linkage was first discovered by the British geneticists
William Bateson
William Bateson (8 August 1861 – 8 February 1926) was an English biologist who was the first person to use the term genetics to describe the study of heredity, and the chief populariser of the ideas of Gregor Mendel following their rediscove ...
,
Edith Rebecca Saunders
Edith Rebecca Saunders FLS (14 October 1865 – 6 June 1945) was a British geneticist and plant anatomist. Described by J. B. S. Haldane as the "Mother of British Plant Genetics", she played an active role in the re-discovery of Mendel's laws ...
and
Reginald Punnett
Reginald Crundall Punnett FRS (; 20 June 1875 – 3 January 1967) was a British geneticist who co-founded, with William Bateson, the ''Journal of Genetics'' in 1910. Punnett is probably best remembered today as the creator of the Punnet ...
.
Thomas Hunt Morgan
Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role tha ...
expanded the idea of linkage after noticing that in some instances the observed rate of crossing-over events differed from the expected rate of crossing-over events. He attributed the depressed rates of recombination to the smaller spatial separation of genes on a chromosome; Hypothesizing that genes which are more closely positioned on a chromosome will have smaller rates of recombination than those that are spaced farther apart. The unit of measurement describing the distance between two linked genes is the
Centimorgan
In genetics, a centimorgan (abbreviated cM) or map unit (m.u.) is a unit for measuring genetic linkage. It is defined as the distance between chromosome positions (also termed loci or markers) for which the expected average number of intervening ...
, and is named after Thomas Hunt Morgan. A centimorgan is equivalent to the percent of recombination. two loci with 2% recombination frequency are located 2 centimorgans apart.
Uses In Research
Economic Benefits
Being able to determine linkage between genes can also have major economic benefits. Learning about linkage of traits in sugar cane has led to more productive and lucrative growth of the crop. Sugar cane is a sustainable crop that is one of the most economically viable renewable energy sources. QTL analysis for sugarcane was used to construct a linkage map that identified gene clusters and important linked
loci that can be used to predict the response to fungal infection in a specific line of sugar cane.
Medical Benefits
Linkage mapping can also be useful in determining the inheritance patterns of traits such as psychological disease. Linkage studies of
panic disorder
Panic disorder is a mental disorder, mental and Abnormal behavior, behavioral disease#Disorder, disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear th ...
and
anxiety disorder
Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
s have indicated regions of interest on specific chromosomes. Chromosomes 4q21 and 7p are being considered strong candidate regions for panic and fear-associated anxiety disorder loci. Knowing the specific location of these loci and their probability of being inherited together based on their linkage can offer insight into how these disorders are passed down, and why they often occur together in patients.
References
{{reflist
Classical genetics