Complete linkage

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In genetics, complete (or absolute) linkage [1] is defined as the state in which two loci are so close together that alleles 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 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. [2]

Contents

Linkage

Sister chromosomes with recombinant DNA HR in meiosis.svg
Sister chromosomes with recombinant DNA

Genetic Linkage is the tendency of alleles, which are located closely together on a chromosome, to be inherited together during the process of meiosis 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. 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. [3]

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. [4]

(Click here for more information on Linkage Maps )

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. [5]

(Click Here for a video tutorial explaining genetic recombination)

Methods of Analysis

Hierarchical Clustering

Dendrogram of multiple clusters Swiss centroid.png
Dendrogram of multiple clusters

One powerful tool for interpreting and graphing linkage data sets is called 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. [6] The resulting diagram from a Hierarchical Cluster Analysis is called a dendrogram, 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. [7] 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 Thomas Hunt Morgan.jpg
Thomas Hunt Morgan

The idea of genetic linkage was first discovered by the British geneticists William Bateson, Edith Rebecca Saunders and Reginald Punnett. Thomas Hunt Morgan 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. [8] The unit of measurement describing the distance between two linked genes is the Centimorgan, 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. [9]

[10]

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. [11]

Medical Benefits

Linkage mapping can also be useful in determining the inheritance patterns of traits such as psychological disease. Linkage studies of panic disorder and anxiety disorders 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. [12]

Related Research Articles

<span class="mw-page-title-main">Mendelian inheritance</span> Type of biological inheritance

Mendelian inheritance is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularized by William Bateson. These principles were initially controversial. When Mendel's theories were integrated with the Boveri–Sutton chromosome theory of inheritance by Thomas Hunt Morgan in 1915, they became the core of classical genetics. Ronald Fisher combined these ideas with the theory of natural selection in his 1930 book The Genetical Theory of Natural Selection, putting evolution onto a mathematical footing and forming the basis for population genetics within the modern evolutionary synthesis.

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination 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 eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

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 separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked, although the penetrance of potentially deleterious alleles may be influenced by the presence of other alleles, and these other alleles may be located on other chromosomes than that on which a particular potentially deleterious allele is located.

<span class="mw-page-title-main">Homologous chromosome</span> Chromosomes that pair in fertilization

A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci where they provide points along each chromosome which enable a pair of chromosomes to align correctly with each other before separating during meiosis. This is the basis for Mendelian inheritance which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.

In population genetics, linkage disequilibrium (LD) is the non-random association of alleles at different loci in a given population. Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is higher or lower than expected if the loci were independent and associated randomly.

Forward genetics is a molecular genetics approach of determining the genetic basis responsible for a phenotype. Forward genetics provides an unbiased approach because it relies heavily on identifying the genes or genetic factors that cause a particular phenotype or trait of interest.

<span class="mw-page-title-main">Non-Mendelian inheritance</span> Type of pattern of inheritance

Non-Mendelian inheritance is any pattern in which traits do not segregate in accordance with Mendel's laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent contributes one of two possible alleles for a trait. If the genotypes of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of phenotypes expected for the population of offspring. There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.

Genetics, a discipline of biology, is the science of heredity and variation in living organisms.

<span class="mw-page-title-main">Gene mapping</span> Process of locating specific genes

Gene mapping or genome mapping describes the methods used to identify the location of a gene on a chromosome and the distances between genes. Gene mapping can also describe the distances between different sites within a gene.

Genetic association is when one or more genotypes within a population co-occur with a phenotypic trait more often than would be expected by chance occurrence.

A tag SNP is a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium that represents a group of SNPs called a haplotype. It is possible to identify genetic variation and association to phenotypes without genotyping every SNP in a chromosomal region. This reduces the expense and time of mapping genome areas associated with disease, since it eliminates the need to study every individual SNP. Tag SNPs are useful in whole-genome SNP association studies in which hundreds of thousands of SNPs across the entire genome are genotyped.

Marker assisted selection or marker aided selection (MAS) is an indirect selection process where a trait of interest is selected based on a marker linked to a trait of interest, rather than on the trait itself. This process has been extensively researched and proposed for plant- and animal- breeding.

In genetics, a centimorgan or map unit (m.u.) is a unit for measuring genetic linkage. It is defined as the distance between chromosome positions for which the expected average number of intervening chromosomal crossovers in a single generation is 0.01. It is often used to infer distance along a chromosome. However, it is not a true physical distance.

<span class="mw-page-title-main">Tetrad (meiosis)</span>

The tetrad is the four spores produced after meiosis of a yeast or other Ascomycota, Chlamydomonas or other alga, or a plant. After parent haploids mate, they produce diploids. Under appropriate environmental conditions, diploids sporulate and undergo meiosis. The meiotic products, spores, remain packaged in the parental cell body to produce the tetrad.

A doubled haploid (DH) is a genotype formed when haploid cells undergo chromosome doubling. Artificial production of doubled haploids is important in plant breeding.

A recombinant inbred strain or recombinant inbred line (RIL) is an organism with chromosomes that incorporate an essentially permanent set of recombination events between chromosomes inherited from two or more inbred strains. F1 and F2 generations are produced by intercrossing the inbred strains; pairs of the F2 progeny are then mated to establish inbred strains through long-term inbreeding.

Quantitative trait loci mapping or QTL mapping is the process of identifying genomic regions that potentially contain genes responsible for important economic, health or environmental characters. Mapping QTLs is an important activity that plant breeders and geneticists routinely use to associate potential causal genes with phenotypes of interest. Family-based QTL mapping is a variant of QTL mapping where multiple-families are used.

In genetics, the crossover value is the linked frequency of chromosomal crossover between two gene loci (markers). For a fixed set of genetic and environmental conditions, recombination in a particular region of a linkage structure (chromosome) tends to be constant and the same is then true for the crossover value which is used in the production of genetic maps.

This glossary of genetics and evolutionary biology is a list of definitions of terms and concepts used in the study of genetics and evolutionary biology, as well as sub-disciplines and related fields, with an emphasis on classical genetics, quantitative genetics, population biology, phylogenetics, speciation, and systematics. Overlapping and related terms can be found in Glossary of cellular and molecular biology, Glossary of ecology, and Glossary of biology.

References

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  7. Tellaroli, Paola; Bazzi, Marco; Donato, Michele; Brazzale, Alessandra R.; Drăghici, Sorin (2016-01-01). "Cross-Clustering: A Partial Clustering Algorithm with Automatic Estimation of the Number of Clusters". PLOS ONE. 11 (3): e0152333. Bibcode:2016PLoSO..1152333T. doi: 10.1371/journal.pone.0152333 . ISSN   1932-6203. PMC   4807765 . PMID   27015427.
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  11. Palhares, Alessandra C.; Rodrigues-Morais, Taislene B.; Van Sluys, Marie-Anne; Domingues, Douglas S.; Maccheroni, Walter; Jordão, Hamilton; Souza, Anete P.; Marconi, Thiago G.; Mollinari, Marcelo (2012-01-01). "A novel linkage map of sugarcane with evidence for clustering of retrotransposon-based markers". BMC Genetics. 13: 51. doi: 10.1186/1471-2156-13-51 . ISSN   1471-2156. PMC   3443450 . PMID   22742069.
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