What is a genetic marker and what is it used for?

We explain what types of genetic markers exist, and their applications in medicine and science.

The discovery of new genetic markers that help to identify and, therefore, better prevent multiple diseases is becoming more and more frequent. and, therefore, to better prevent multiple diseases.

These markers are used to relate certain genetic mutations to the risk of onset and development of numerous hereditary disorders. The use of new genome sequencing techniques will be essential in advancing our knowledge of this type of disease and many others.

In this article we explain what a genetic marker is, what types of markers exist, how the different genetic variants are detected and what are the main techniques used in genomic sequencing.

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What is a genetic marker?

Genetic markers are DNA segments located at a known position (a locus) on a given chromosome. These markers are usually associated with specific disease phenotypes and are very useful in identifying different genetic variations in specific individuals and populations.

DNA-based genetic marker technology has revolutionized the world of genetics, making it possible to detect polymorphisms (responsible for the great variability among individuals of the same species) between different genotypes or alleles of a gene for a given DNA sequence in a group of genes.

Those markers that confer a high probability of disease occurrence are more useful as diagnostic tools.. A marker may have functional consequences, such as altering the expression or function of a gene that contributes directly to the development of a disease; and conversely, it may have no functional consequence, but may be located close to a functional variant so that both the marker and the variant tend to be inherited together in the general population.

DNA variations are classified as "neutral" when they produce no change in metabolic or phenotypic traits (the observable traits), and when they are not subject to any evolutionary pressure (whether positive, negative or balancing); otherwise, the variations are called functional.

Mutations in key nucleotides of a DNA sequence can change the amino acid composition of a protein and lead to new functional variants. Such variants may have higher or lower metabolic efficiency compared to the original sequence; they may lose their functionality completely or even incorporate a new one.

Polymorphism detection methods

Polymorphisms are defined as genetic variants in the DNA sequence between individuals of the same species.. They can have consequences on the phenotype if they are found in coding regions of the DNA.

To detect these polymorphisms, there are two main methods: the Southern blotting method, a nucleic acid hybridization technique; and the polymerase chain reaction PCR technique, which allows the amplification of small specific regions of DNA material.

Using these two methods, genetic variations in DNA samples and polymorphisms in a specific region of the DNA sequence can be identified. However, studies show that in the case of more complex diseases it is more difficult to identify these genetic markers, as they are usually polygenic, i.e. caused by defects in multiple genes.

Types of genetic markers

There are two main types of molecular markers: post-transcription markers and molecular markers.There are two main types of molecular markers: post-transcription-translation markers, which are performed by an indirect analysis of DNA; and pre-transcription-translation markers, which allow polymorphisms to be detected directly at the DNA level and are discussed below.

1. RFLP markers

RFLP (Restriction Fragment Length Polymorphism) genetic markers are obtained after extraction and fragmentation of the DNA. are obtained after extraction and fragmentation of the DNA by cutting an endonuclease by restriction enzymes..

The restriction fragments obtained are then analyzed using gel electrophoresis. They are a fundamental tool for genomic mapping and in the analysis of polygenic diseases.

2. AFLP markers

These markers are bi-allelic and dominant.. Variations at many loci (multi-locus naming) can be ordered simultaneously to detect single nucleotide variations of unknown genomic regions, where a given mutation may be frequently present in indeterminate functional genes.

Microsatellites

Microsatellites are the most popular genetic markers in genetic characterization studies.. Their high mutation rate and co-dominant nature allow estimation of genetic diversity within and between breeds, and genetic admixture between breeds, even if they are closely related.

4. Mitochondrial DNA markers

These markers provide a rapid way to detect hybridization between species or subspecies..

Polymorphisms in certain sequences or in the control region of mitochondrial DNA have contributed greatly to the identification of the progenitors of domestic species, the establishment of geographical patterns of genetic diversity and the understanding of domestication behaviors.

5. RAPD markers

These markers are based on the polymerase chain reaction or PCR technique. The fragments obtained by RAPD are amplified in different random regions.

Its usefulness lies in the fact that it is an easy-to-use technique and allows rapid and simultaneous distinction of many polymorphisms. It has been used in the analysis of genetic diversity and the improvement and differentiation of clonal lines.

Genome sequencing techniques

Many of the existing diseases have a genetic basis. The cause is usually determined by the appearance of one or more mutations that cause the disease or, at least, increase the risk of developing it.

One of the most common techniques for detecting these mutations, which has been used until recently, is the genetic association study (GAS).The most common technique for detecting these mutations is the genetic association study, which involves sequencing the DNA of one or a group of genes suspected of being involved in a given disease.

Genetic association studies study the DNA sequences in the genes of carriers and healthy individuals in order to find the gene or genes responsible. These studies have sought to include members of the same family to increase the probability of detecting mutations. However, such studies can only identify mutations linked to a single gene, with the limitations that this entails.

In recent years, new sequencing techniques have been discovered that have made it possible to overcome these limitations, known as next-generation sequencing (NGS) techniques. These make it possible to sequence the genome with less time (and less money). As a result, so-called genome-wide association studies (GWAS) are now being carried out.

Genomic sequencing by GWAS allows all mutations present in the genome to be explored.This has led to the creation of consortiums of researchers and researchers from all over the world who are working together to find the genes responsible for a given disease. This has led to the creation of international consortia with researchers from all over the world sharing chromosomal maps with the risk variants of a multitude of diseases.

Nevertheless, GWAS are not without their limitations, such as their inability to fully explain the genetic and familial risk of common diseases, the difficulties in assessing rare genetic variants, or the small effect sizes obtained in most studies. Undoubtedly problematic aspects that will have to be improved in the years to come.

Bibliographic references:

• Korte, A., & Farlow, A. (2013). The advantages and limitations of trait analysis with GWAS: a review. Plant methods, 9(1), 29.

• Pritchard, J. K., & Rosenberg, N. A. (1999). Use of unlinked genetic markers to detect population stratification in association studies. The American Journal of Human Genetics, 65(1), 220-228.

• Williams, J. G., Kubelik, A. R., Livak, K. J., Rafalski, J. A., & Tingey, S. V. (1990). DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. Nucleic acids research, 18(22), 6531-6535.