What is the Difference Between Genetic and Physical Mapping

The main difference between genetic and physical mapping is that the distances of genetic maps depend on the genetic linkage information, but physical maps are based on the actual physical distances as measured by the number of base pairs. Furthermore, genetic markers and the size of the mapping population are the two important factors of genetic mapping. But, physical mapping involves the fragmentation of the genome either through restriction digestion or physical shattering of the genome. Moreover, genetic maps often offer insights into the nature of different regions of the chromosome, while physical maps are a more accurate representation of the genome. 

In brief, genetic and physical mapping are two distinctive types of maps used in genome mapping. Both use a collection of molecular markers with respective positions on the genome. 

Key Areas Covered 

1. What is Genetic Mapping
     – Definition, Construction, Importance
2. What is Physical Mapping
     – Definition, Construction, Importance
3. What are the Similarities Between Genetic and Physical Mapping
     – Outline of Common Features
4. What is the Difference Between Genetic and Physical Mapping
     – Comparison of Key Differences

Key Terms 

FISH, Genetic Mapping, Genome Mapping, Markers, Physical Mapping, Restriction Mapping, STS Mapping

What is Genetic Mapping 

Generic mapping is the technique responsible for demonstrating the arrangement of genes and their relative distances on a chromosome with the help of recombination frequencies. In this mapping, the genes serve as markers, and hence, these maps are population specific. Therefore, mapping population becomes an important factor in genetic mapping.

Figure 1: Linkage and Linkage Disequilibrium

Moreover, during genetic mapping, comparing the genes to each other helps to determine their order on the chromosome. Also, this uses the studies the inheritance or assortment of traits by genetic analysis.  

Markers 

In the early decades of the 20th century, genes served as the first-ever markers in genetic mapping of organisms, such as fruit fly. Basically, the gene, being a segment of the DNA, is an abstract entity responsible for the transmission of heritable characteristics from parent to offspring. Also, each gene has at least two alternative forms called alleles, which ultimately produce specific phenotypes. And, these phenotypes served as visual markers, and thus, showed the positions of genes for the body color, eye color, wing shape, and suchlike in the first fruit-fly map.

Figure 2: Thomas Hunt Morgan’s Drosophila melanogaster Genetic Linkage Map

However, later, genetic mapping relied on biochemical phenotypes, such as blood typing. Also, for the larger genomes, such as the genomes of vertebrates and flowering plants, other DNA sequence features are useful. For example, restriction fragment length polymorphisms (RFLPs), simple sequence length polymorphisms (SSLPs), and single nucleotide polymorphisms (SNPs).  

Techniques 

Still, all the techniques of genetic mapping depend on genetic linkage derived from the seminal discoveries in genetics made in the mid 19th century by Gregor Mendel. His discoveries were made from the results of his breeding experiments with peas. In these experiments, the two alleles of a particular gene led to either homozygosity or heterozygosity. Additionally, the complicated situations of this simple dominant-recessive rule include incomplete dominance, codominance, etc. Furthermore, his First Law states that alleles segregate randomly while his Second Law states that pairs of alleles segregate independently. However, in general, chromosomes are the intact units of inheritance and the set of alleles in it will be inherited together, which is partial linkage. Principally, partial linkage explains the behavior of chromosomes in meiosis as described by Thomas Hunt Morgan.

Figure 3: Crossovers

Sometimes, all the alleles in the chromosome may not inherit together with the occurrence of crossing-over during meiosis. In fact, crossing-over is a random event, which can separate two genes on the same chromosome depending on their relative distance. On that account, recombination frequencies can be used to determine the distance between two genes. Hence, a genetic map can be constructed by working out on the recombination frequencies of several pairs of genes. Also, planned breeding in plants and pedigree analysis in humans are the methods to obtain recombination frequencies. 

What is Physical Mapping 

Physical mapping, on the other hand, is the technique used to indicate the physical distance of two genes. Generally, the low resolution of genetic maps due to fewer crossovers as well as their limited accuracy make physical mapping important. Also, it gives the actual distance between markers by means of the number of nucleotides. Basically, the most important forms of physical mapping techniques include restriction mapping, FISH (fluorescent in situ hybridization), and STS (sequence-tagged sites) mapping.  

Restriction Mapping  

In restriction mapping, restriction sites serve as DNA markers. Of these, polymorphic restriction sites used are a few, but non-polymorphic restriction sites used are numerous. Generally, the simplest way to construct a restriction map is to compare the fragment sizes produced by the digestion of a DNA molecule with two different restriction enzymes, having different target sequences. However, restriction mapping is more applicable to short DNA fragments with relatively few cut sites. Still, there is a possibility to analyze entire genomes larger than 50 kb by using rare cutters with infrequent cut sites. Additionally, optical mapping is another technique for constructing ordered, genome-wide, high-resolution restriction maps called “optical maps” from single, stained molecules of DNA. 

Figure 4: Optical Mapping

FISH 

Fluorescent in situ hybridization permits the direct visualization of the position of the marker on the chromosome. For that, it uses the hybridization of either radioactive or fluorescent probes. Also, it uses metaphase chromosomes, which are highly condensed. However, this leads to low-resolution mapping. Hence, the use of mechanically-stretched metaphase chromosomes or non-metaphase chromosomes would increase the resolution.

Figure 5: FISH

STS Mapping 

Sequence tagged mapping is the high resolution, rapid, and less-technically demanding mapping procedure. Therefore, it is the most powerful physical mapping technique and the one that has been responsible for the generation of the most detailed maps of large genomes. Normally, an STS or a sequence-tagged site is a short DNA sequence, between 100 and 500 bp in length and it is easily recognizable and occurs only once in a specific chromosome or genome. Therefore, an STS map can be generated by using a collection of overlapping DNA fragments from a single chromosome. 

Similarities Between Genetic and Physical Mapping  

• Genetic and physical mapping are two types of genome mapping techniques, producing different types of genome maps.  
• They use a collection of molecular markers with respective positions on the genome.  
• Both allow the identification of genes, which give rise to a particular phenotype or a mutation responsible for a specific variant.    
• Also, genome mapping is the initial process of many downstream processes.  
• As an example, it helps to identify genetic elements associated with diseases. 

Difference Between Genetic and Physical Mapping 

Definition 

Genetic mapping refers to the process of determining the order and relative distance between genetic markers on a chromosome from their pattern of inheritance. But, physical mapping refers to the technique used to find the order and physical distance between DNA base pairs by DNA markers. 

Types of Markers 

Genes (genetic markers) are the markers used in genetic mapping, but restriction recognition sites (DNA markers) are the markers used in physical mapping. 

Significance of Markers 

Genetic maps depend on genetic linkage, but physical maps use visual markers that are short DNA sequences.  

Rely on 

Genetic maps rely on recombination and crossing over, while physical maps rely on the DNA sequence of the genome. 

Techniques 

Genetic maps are based on recombination frequencies, but physical maps are based on restriction digestion. 

Purpose 

Genetic maps determine the probabilities of the recombination events between two points, while physical maps determine the number of bases between two points. 

Factors 

Genetic markers and the size of the mapping population are the two important factors of genetic mapping. Meanwhile, physical mapping involves the fragmentation of the genome either through restriction digestion or physical shattering of the genome.  

Accuracy 

Genetic maps are comparatively less accurate than physical maps. 

Importance 

Genetic maps provide firm evidence on genetic disorders associated with one gene (eg: cystic fibrosis and muscular dystrophy) or two genes (eg: diabetes, cancer, and asthma). On the other hand, physical maps are important to identify the origin of diseases, whether they are inherited or arise due to a random mutation. 

Conclusion 

Genetic mapping is a technique, depicting the relative positions of loci depending on the degree of recombination. Therefore, it studies the inheritance or assortment of traits by genetic analysis. Hence, the type of markers used in genetic mapping is the genes. In contrast, physical mapping is another technique, determining the actual distance between loci using the number of nucleotides. For that, it uses the techniques of molecular biology such as restriction digestion and DNA sequencing. Also, restriction recognition sites serve as DNA markers for physical mapping. On that account, the main difference between genetic and physical mapping is the type of markers and the techniques used in the mapping. 

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