genetic marker

A genetic marker is a gene or DNA sequence with a known location on a chromosome and associated with a particular gene or trait. It can be described as a variation, which may arise due to mutation or alteration in the genomic loci, that can be observed. A genetic marker may be a short DNA sequence, such as a sequence surrounding a single base-pair change (single nucleotide polymorphism, SNP), or a long one, like minisatellites.

Background

For many years, gene mapping was limited in most organisms by traditional genetic markers which include genes that encode easily observable characteristics such as blood types or seed shapes. The insufficient amount of these types of characteristics in several organisms limited the mapping efforts that could be done.^[1]

Types

Some commonly used types of genetic markers are

• RFLP (or Restriction fragment length polymorphism)
• AFLP (or Amplified fragment length polymorphism)
• RAPD (or Random amplification of polymorphic DNA)
• VNTR (or Variable number tandem repeat)
• Microsatellite polymorphism
• SNP (or Single nucleotide polymorphism)
• STR (or Short tandem repeat)
• SFP (or Single feature polymorphism)
• DArT (or Diversity Arrays Technology)

They can be further categorized as dominant or co-dominant. Dominant markers allow for analyzing many loci at one time, e.g. RAPD. A primer amplifying a dominant marker could amplify at many loci in one sample of DNA with one PCR reaction. Co-dominant markers analyze one locus at a time. A primer amplifying a co-dominant marker would yield one targeted product.

Uses

Genetic markers can be used to study the relationship between an inherited disease and its genetic cause (for example, a particular mutation of a gene that results in a defective protein). It is known that pieces of DNA that lie near each other on a chromosome tend to be inherited together. This property enables the use of a marker, which can then be used to determine the precise inheritance pattern of the gene that has not yet been exactly localized.

Genetic markers have to be easily identifiable, associated with a specific locus, and highly polymorphic, because homozygotes do not provide any information. Detection of the marker can be direct by RNA sequencing, or indirect using allozymes.

Some of the methods used to study the genome or phylogenetics are RFLP, Amplified fragment length polymorphism (AFLP), RAPD, SSR. They can be used to create genetic maps of whatever organism is being studied.

There was a debate over what the transmissible agent of CTVT (canine transmissible venereal tumor) was. Many researchers hypothesized that virus like particles were responsible for transforming the cell, while others thought that the cell itself was able to infect other canines as an allograft. With the aid of genetic markers, researchers were able to provide conclusive evidence that the cancerous tumor cell evolved into a transmissible parasite. Furthermore, molecular genetic markers were used to resolve the issue of natural transmission, the breed of origin (phylogenetics), and the age of the canine tumor. ^[2]

Genetic Markers have also been used to measure the genomic response to selection in livestock. Natural and artificial selection leads to a change in the genetic makeup of the cell. The presence of different alleles due to a distorted segregation at the genetic markers is indicative of the difference between selected and non-selected livestock. ^[3]

Insulin production

Genetic markers also play a role in genetic engineering, as they can be used to produce normal, functioning proteins to replace defective ones. The damaged or faulty section of DNA is removed and replaced with the identical, but functioning, gene sequence from another source.

This is done by removal of the faulty section of DNA and its replacement with the functioning gene from another source, usually a human donor. These gene sections are placed in solution with bacterial cells, a small number of which take up the genetic material and reproduce the new DNA sequence. Engineers need to know which bacteria have been successful in duplicating these genes so another gene is added, altering the bacteria's resistance to antibiotics. Replica plating or a fermenter is used to grow enough bacteria to test resistance to antibiotics. It is important that the cultures are not mixed.

This process can be used as a treatment for diabetes mellitus. Bacterial DNA often has two resistancy genes: one for tetracycline and one for ampicillin. The insulin gene can be inserted in the middle of the ampicillin gene after it has been removed using restriction endonucleases. If the gene has been taken up, the bacteria both produces insulin and is also no longer ampicillin resistant. The bacteria are then allowed to grow on an agar plate containing a culture medium. The bacteria grow and produce colonies on the agar jelly. A piece of filter paper can be placed onto the top of this agar plate so that the exact positions of the colonies are remembered. This produces a copy which can then be transferred onto a second agar plate containing ampicillin. All of the bacteria that are not resistant to ampicillin will die. These locations on the second plate show the places on the first plate where bacteria are not resistant and, therefore, produce insulin. Another similar method is followed, in which an epitope sequence is added to insert. When the insert is expressed so is the epitope. Then this epitope can be effectively bound using an antibody on a filter paper. And the expressing colonies can be easily selected.

Other references

• de Vicente, C., T. Fulton (2003). Molecular Marker Learning Modules – Vol. 1.. IPGRI, Rome, Italy and Institute for Genetic Diversity, Ithaca, New York, USA.. http://www.bioversityinternational.org/publications/molecular_markers_module_volume_1_en.html. 
• de Vicente, C., T. Fulton (2004). Molecular Marker Learning Modules – Vol. 2.. IPGRI, Rome, Italy and Institute for Genetic Diversity, Ithaca, New York, USA.. http://www.bioversityinternational.org/publications/molecular_markers_module_volume_2_en.html. 
• de Vicente, C., J-C. Glaszmann, editors (2006). Molecular Markers for Allele Mining. AMS (Bioversity's Regional Office for the Americas), CIRAD, GCP, IPGRI, M.S. Swaminathan Research Foundation. http://www.bioversityinternational.org/Publications/pubfile.asp?ID_PUB=1134.  85 p.
• de Vicente, C., T. Metz and A. Alercia (2004). Descriptors for genetic markers technologies. IPGRI. http://www.bioversityinternational.org/Publications/pubfile.asp?ID_PUB=913.  30 p.
• Spooner, S., R van Treuren and M.C. de Vicente (2005). Molecular markers for genebank management. CGN, IPGRI, USDA. http://www.bioversityinternational.org/Publications/pubfile.asp?ID_PUB=1082.  126 p.
• What Is A Genetic Marker?

References