HAPLOTYPE: STUDY METHODS, DIAGNOSES, DISEASES, EXAMPLES - BIOLOGY - 2024

A haplotype is a region of the genome that tends to be inherited together through multiple generations; typically it is all on the same chromosome. Haplotypes are the product of genetic linkage and remain intact during genetic recombination.

The word "haplotype" is derived from a combination of the word "haploid" and the word "genotype." "Haploid" refers to cells with a single set of chromosomes and "genotype" refers to the genetic makeup of an organism.

Scheme of the distribution of Y chromosome haplotypes in Asian populations (Source: Moogalord via Wikimedia Commons) Following the definition, a haplotype can describe a pair of genes or more that are inherited together on a chromosome from a parent, or it can describe a chromosome that is inherited entirely from a parent, such as the Y chromosome in males.

For example, when haplotypes share genes for two different phenotypic characters, such as hair color and eye color, individuals who possess the gene for hair color will also possess the other gene for eye color.

Haplotypes are one of the tools most used today for the study of genealogy, to trace the origin of diseases, to characterize genetic variability and the phylogeography of populations of different types of living beings.

There are multiple tools for the study of haplotypes, one of the most used today is "Haplotype map" (HapMap), which is a web page that allows determining which are the genome segments that are haplotypes.

Study methods

Haplotypes represent an opportunity to understand the inheritance of genes and their polymorphism. With the discovery of the “Polymerase Chain Reaction” (PCR) technique, much progress was made in the study of haplotypes.

Currently there are numerous methodologies for the study of haplotypes, some of the most outstanding are:

DNA sequencing and detection of single nucleotide polymorphisms (SNPs)

The development of next-generation sequencing technologies represented a great leap for the study of haplotypes. New technologies make it possible to detect variations of up to a single nucleotide base in specific regions of a haplotype.

In bioinformatics, the term haplotype is also used to refer to the inheritance of a group of single nucleotide polymorphisms (SNPs) in DNA sequences.

By combining bioinformatics programs with haplotype detection using next-generation sequencing, the position, substitution, and effect of each base change in the genome of a population can be accurately identified.

Microsatellites (SSRS)

The microsatellites or SSRS, derive their name from the English “S imple Sequence Repeat and Short Tandem Repeat”. These are short nucleotide sequences that repeat in succession within a region of the genome.

It is common to find microsatellites inside non-coding haplotypes, therefore, through the detection of variations in the number of microsatellite repeats, the different alleles in the haplotypes of individuals can be observed.

Molecular microsatellite markers have been developed for the detection of a myriad of haplotypes, from the sexing of plants such as Papaya (Carica papaya) to the detection of human diseases such as sickle cell anemia.

Amplified fragment length polymorphisms (AFLP)

This technique combines amplification with PCR reactions with digestion of DNA with two different restriction enzymes. The technique detects polymorphic loci in haplotypes according to the different cleavage sites in the DNA sequence.

To better illustrate the technique, let's imagine three fabric fragments of the same length, but cut at different sites (these fragments represent three PCR-amplified haplotype fragments).

By the time the fabric is cut, many pieces of different sizes will be obtained, since each fabric is cut in different places. By ordering the fragments according to the type of fabric they come from, we can see where the differences between the fabrics or in the haplotypes are found.

Diagnoses and diseases

An important advantage of the genetic study of haplotypes is that they remain almost intact or unaltered for thousands of generations, and this allows the identification of remote ancestors and each of the mutations that individuals contribute to the development of diseases.

Haplotypes in humanity vary depending on the races and, based on this first, genes have been detected within the haplotypes that cause severe diseases in each of the human races.

The HapMap project includes four racial groups: Europeans, Nigerians, Yoruba, Han Chinese, and Japanese.

In this way, the HapMap project can cover different population groups and trace the origin and evolution of many of the inherited diseases that affect each of the four races.

One of the diseases most frequently diagnosed using haplotype analysis is sickle cell anemia in humans. This disease is diagnosed by tracking the frequency of African haplotypes in a population.

Being a disease native to Africa, identifying African haplotypes in populations makes it easy to trace people who have the mutation in the genetic sequence for beta globins in sickle-shaped erythrocytes (characteristic of the pathology).

Examples

With haplotypes, phylogenetic trees are constructed that represent the evolutionary relationships between each of the haplotypes found in a sample of homologous DNA molecules or from the same species, in a region that has little or no recombination.

One of the most studied branches through haplotypes is the evolution of the human immune system. Haplotypes encoding the TOll-like receptor (a key component of the innate immune system) have been identified for the Neanderthal and Denisovan genomes.

This allows them to track how genetic sequences in "modern" human populations have changed from haplotype sequences corresponding to "ancient" humans.

By building a network of genetic relationships from mitochondrial haplotypes, how the founder effect occurs in species is studied, since this allows scientists to identify when populations stopped reproducing among themselves and established themselves as separate species.

Distribution of Haplotype R (Y-DNA) in Native Populations (Source: Maulucioni, via Wikimedia Commons) Haplotype diversity is used to track and study the genetic diversity of captive-bred animals. These techniques are used especially for species that are difficult to monitor in the wild.

Animal species such as sharks, birds, and large mammals such as jaguars, elephants, among others, are constantly genetically evaluated through mitochondrial haplotypes to monitor the genetic status of captive populations.

References

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