Linkage maps

//Linkage maps

Linkage maps

Genetic map or a linkage map or a chromosomal map represents the linkage of genes in a chromosome. Alfred Sturtevant was the first individual to construct a genetic map. He prepared the first genetic map of X- chromosome of Drosophila by using the frequency of crossing over between two genes. The two major aspects of genetic mapping are to determine the linear order (gene order) of genetic units in which they are arranged with respect to one another and to determine the relative distance between these units i.e. gene distance.
As the distance between the two specific gene loci increases recombination frequency also tend to increase, therefore the percentage of recombination can be used to represent a measure of distance between two genes which is called the map distance.
The physical distance between the loci is related directly to the frequency of crossing over between the loci (% recombination).
One unit of map distance is equivalent to one percent crossing over or recombination. Hence, the genetic map of the gene in a linear array can be constructed by analyzing the recombination frequencies among the progeny of parents that are heterozygous for a number of linked genes. The distance between the loci represents the frequency of occurrence of recombination and is not equal to a precise physical distance. The value of percentage recombination and the number of base pairs of DNA can be deduced by correlating physical chromosome maps with genetic maps.
So, Map distance = (Number of recombinant off/springTotal number of offspring) ×100
The unit for the measurement of the genetic linkage is map unit or centiMorgan (cM). One map unit is equal to 1 cM and 1 cM is equal to 1% recombination that means if two genes are recombining with the frequency of 5.5%, they are said to be located 5.5 map unit apart.
Gene mapping from two point cross:
Two point cross is the cross that involve two loci. Test cross progeny is the easiest way to detect cross over gametes in a dihybrid. If, we test cross dihybrid individuals in coupling phase (XY/xy) and find in the progeny phenotypes 37% dominant at both loci, 37% recessive at both loci, 13% dominant at the first locus and recessive at the second and 13% dominant at the second locus and recessive at the first. Obviously, the last two groups (genotypically Xy/xy and Xy/xy) were produced by cross over gametes from the dihybrid parent. Thus, 26% of all gametes (13+13) were of cross over types and the distance between the loci X and Y is estimated to be 26 map units, or 26 cM.

Gene mapping from three point-cross:
Several different types of crossing over products can be obtained by adding a third gene. If we perform a testcross with F1 the expected ratio will be 1:1:1:1:1:1:1:1 ratio. As with the two point crosses, deviation from this expected ratio indicates that linkage is occuring. Let us take an example of gene X, Y and Z. We first make a cross between individuals that are XXYYZZ and xxyyzz. Next, the F1 is test crossed to an individual that is xxyyzz. We will use the following data to determine the gene order and linkage distances. As with the two point data, we will consider the F1 gamete composition.
The best way to solve these problems is to develop a systematic approach. Firstly determine the parental genotypes that are fond most frequently. It is clear from the above table that the XYZ and xyz genotype were the parental genotypes. Next, we need to determine the order of the genes. Once we have determined the parental genotypes, we use the information along with the information obtained from the double-crossover. The double-crossover gametes are always in the lowest frequency. In the above table, the XYz and xyZ genotypes are in the lowest frequency. The next important point is that a double-crossover event moves the middle allele from one sister chromatid to the other. This effectively places the non-parental allele of the middle gene onto a chromosome with the parental alleles of the two flanking genes. It can be easily seen from the table that the Z gene must be in the middle because the recessive c allele is now on the same chromosome as the X and Y alleles, and the dominant Z allele is on the same chromosome as the recessive x and y alleles.

Tetrad Analysis
Certain species of lower eukaryotes that is unicellular algae and fungi, which spend the greatest part of their life cycle in the haploid stage, have been used in mapping studies. Ascomycetes, the sac fungi, have been particularly useful because of their unique type of sexual reproduction. Fungi may be multicellular or unicellular. Fungal cells are typically haploid (1n) and can reproduce asexually. In addition, they can also reproduce sexually by the fusion of two haploid cells which results in diploid zygote (2n). Diploid zygote further proceeds to meiosis and results in the production of 4 haploid cells, known as spores. The group of 4 spores is known as a tetrad. In some species of fungi further mitotic division takes place to produce 8 cells, known as octad. The tetrad and octad cells remain within a sac called as ascus

Mapping with molecular markers:
In the first 70 years of building genetic maps, the markers on the maps were genes with variant alleles producing detectably different phenotypes. As organisms became more and more researched, large numbers of such genes could be used as markers on the maps. However, even in those organisms in which the maps appeared to be ―full‖ of loci of known phenotypic effect, measurements showed that the chromosomal intervals between genes had to contain vast amounts of DNA. These gaps could not be mapped by linkage analysis, because there were no markers in those regions. What was needed were large numbers of additional genetic markers that could be used to fill in the gaps to provide a higher-resolution map. This need was met by the discovery of various kinds of molecular markers. A molecular marker is a site of heterozygosity for some type of silent DNA variation not associated with any measurable phenotypic variation. Such a ―DNA locus‖, when heterozygous, can be used in mapping analysis just as a conventional heterozygous allele pair can be used. Because molecular markers can be easily detected and are so numerous in a genome, when they are mapped by linkage analysis, they fill the voids between genes of known phenotype. Note that, in mapping, the biological significance of the DNA marker is not important in itself; the heterozygous site is merely a convenient reference point that will be useful in finding one‘s way around the chromosomes. In this way, markers are being used just as milestones were used by travelers in previous centuries. Travelers were not interested in the milestones (markers) themselves, but they would have been disoriented without them. The two basic types of molecular markers are those based on restriction-site variation and on repetitive DNA

By | 2018-04-03T09:59:34+00:00 April 3rd, 2018|Molecular Biology|Comments Off on Linkage maps

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