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Gene copies vs. gene paralogs - what's the difference?

Gene copies vs. gene paralogs - what's the difference?


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I'm trying to get into the theory and practice of gene copy number variation (CNV) analysis, but there is something basic confusing me, which I couldn't yet figure out. Sorry if this is a dumb/trivial question - would appreciate your help anyway.

My confusion is regarding the terms 'gene copy' and 'paralogs'. As far as I understand, paralogs are created when a gene undergoes duplication (never mind by what molecular mechanism), and then starts accumulating mutations as evolution proceeds. So, if gene X was duplicated to create another X, and then X changed to become X', are X and X' considered copies of the same gene, or are they paralogs? Is it a matter of applying some threshold on the sequence similarity between X and X', so they are considered copies up to the point where they diversify enough? Or maybe gene copies are expected to be perfect duplicates? If so, I'd guess that finding such gene pairs is very rare… Maybe it's a matter of function, so once X' gets a different function from X (neo-functionalization), it is considered a paralog? This is a rather complex and difficult to measure definition…
To make things less theoretical and more practical, lets limit the conversation to the context of whole genome sequencing analysis. Let's say that I am annotating a newly-assembled genome, and let's assume that the assembly is good enough so gene copies are not collapsed, but rather are located in their respective genomic positions. How would you look for gene copies and paralogs, and how do you make the classification?

Could anyone clarify this point for me, or refer me to relevant literature?
Thanks a lot!


The general term "copies" has multiple meaning with reference to genes. In diploid organisms for example, we have two copies of each gene (except those on the Y chromosome). However, these copies are called alleles. Copies that are due to duplication are called parlalogs. There is no distance criterion for differentiating copies or parlalogs. Once duplicated, there are two copies. But the consequences of paralogy would depend on differences, so the question is interesting. At the first generation after duplication, if both copies included all of the upstream regulatory elements, it would be hard to identify which of the copies was the original, since they would both be identical. But over time, if one were to evolve a new function or (more likely) accumulate frameshift substitutions, the altered one would be called the paralogous copy (relative to comparisons across species).


5.19: Population Genetics

  • Contributed by CK-12: Biology Concepts
  • Sourced from CK-12 Foundation

Jeans vs. Genes. What's the difference?

Plenty. One you have for life, the other just lasts a few years. One is the basis for the passing of traits from one generation to the next. Some jeans you change frequently. But what happens when you change a gene's frequency? Essentially, evolution is a change in gene frequencies within a population.


Click here to order our latest book, A Handy Guide to Ancestry and Relationship DNA Tests

What is the difference between dominant vs. recessive? Can you tell me what I could do to show my class about this without this being long? Thank you.

-A middle school student from New York

Good question. Remember that for most genes, you have two copies of each gene that you inherited from your mother and your father.

Each copy of the gene could be different. For example one copy may give you blue eyes while another may give you brown.

So, what color are your eyes if you have both the brown and blue eye version of the eye color gene? Brown. This is where the idea of dominant and recessive comes in.

Dominant means that one of the versions trumps the other. In our example here, brown is dominant over blue so you end up with brown eyes.

The way people write out dominant and recessive traits is the dominant one gets a capital letter and the recessive one a lower case letter. So for eye color, brown is B and blue is b.

As I said above, people have two versions of each gene so you can be BB, Bb, or bb--BB and Bb have brown eyes, bb, blue eyes. Versions of genes are often dominant because the recessive version actually does nothing (click here to learn about other ways that gene versions can be dominant).

In the eye color example above, the brown version of the gene makes a pigment that turns your eye brown but the blue version does not make a blue pigment. Instead, it makes no pigment and an eye without pigment is blue.

As you can probably guess, if the blue version of the eye color gene made a pigment, then you'd get some mix of brown and blue. There are some cases like this for people. One of the easiest to understand is hair.

There are two "hair type" genes, curly and straight. If you have two copies of the curly version, you have curly hair and if you have two copies of straight hair version, you have straight hair.

What kind of hair do you have if you have a copy of each? Wavy.

Each of these versions contributes something so that you get a mixture of the two. You would write this out as CC is curly, SS is straight and CS is wavy.

In terms of what to talk about in your class, the hair type example I discussed above is a pretty good one for incomplete dominance. Maybe ask the class what kind of hair they have and what genes that means they have.

You can also ask them about their parent's hair type and whether their results fits the model. For pure dominant and recessive traits, I've listed a bunch below that you could discuss with your class. Hope this helps. Good luck!

The examples listed below are traditionally taught in classes as simple dominant/recessive traits. Upon closer study, many are not. Where available, I have included links to answers that discuss this in more detail for each specific trait. In addition, please click here for more information about other traits not discussed here. These other traits are all not true dominant/recessive traits either.

The dominant version of the gene causes distal segment of pinky finger to bend distinctly inward toward the ring (fourth) finger.

People lacking hair in the middle segments of the fingers have two recessive versions of the gene.

People with a dominant allele can roll their tongues into a tube shape. People with two recessive versions are non-rollers and can not learn to roll their tongues. (Maybe not a great example.)

Ear lobes: Recessives have attached ear lobes. People with a dominant version of the gene have detached ear lobes. (Maybe not a good example.)

In a relaxed interlocking of fingers, left thumb over right results from having 1 or 2 copies of the dominant version of the gene. People with 2 recessives place right thumb over left.


Why are genetics and genomics important to my family's health?

Understanding more about diseases caused by a single gene (using genetics) and complex diseases caused by multiple genes and environmental factors (using genomics) can lead to earlier diagnoses, interventions, and targeted treatments. A person's health is influenced by his/her family history and shared environmental factors. This makes family history an important, personalized tool that can help identify many of the causative factors for conditions that also have a genetic component. The family history can serve as the cornerstone for learning about genetic and genomic conditions in a family, and for developing individualized approaches to disease prevention, intervention, and treatment. (See: My Family Health Portrait).

Understanding more about diseases caused by a single gene (using genetics) and complex diseases caused by multiple genes and environmental factors (using genomics) can lead to earlier diagnoses, interventions, and targeted treatments. A person's health is influenced by his/her family history and shared environmental factors. This makes family history an important, personalized tool that can help identify many of the causative factors for conditions that also have a genetic component. The family history can serve as the cornerstone for learning about genetic and genomic conditions in a family, and for developing individualized approaches to disease prevention, intervention, and treatment. (See: My Family Health Portrait).


Difference Between Transcription and Translation

Purpose

Transcription: Synthesis of RNA copies of the genetic instructions written in the genome is the main purpose.

Translation: The main purpose is the synthesis of proteins from RNA which are copied from genes.

Template

Transcription: Template is the genes in the genome.

Translation: Template is the mRNA.

Location

Transcription: This occurs in the nucleus.

Translation: This occurs in the cytoplasm.

Enzymes

Transcription: RNA polymerase are the enzymes.

Translation: Ribosomes are enzymes.

Initiation

Transcription: Binding of RNA polymerase into the promoter of the gene initiates the formation of transcription initiation complex. RNA polymerase is directed by the promoter to the transcription initiation site.

Translation: The binding methionine carrying tRNA to the AUG start codon initiate the translation.

Precursors

Transcription: The four nitrogenous bases: Adenine, guanine, cytosine and uracil are the precursors.

Translation: The 20 different amino acids carried by tRNAs are the precursors.

Elongation

Transcription: RNA polymerase elongates from 5′ to 3′ direction.

Translation: Incoming aminoacyl tRNA binds to the codon at A-site. The new amino acid binds with the growing chain. Ribosome moves to the next codon position from 5′ to 3′ direction.

Type of Bond Forms

Transcription: A phosphodiester bond between two nucleotides can be observed.

Translation: A peptide bond between two amino acids can be observed.

Termination

Transcription: Transcript is released, the enzyme detaches and DNA rewinds.

Translation: Ribosome dissembles by encountering into one of the three stop codons, and polypeptide chain is detached.

Product

Transcription: Several functional forms of RNA is produced in transcription: mRNA, tRNA, rRNA and non-coding RNA.

Translation: Proteins are the products.

Product Processing

Transcription: Post-transcriptional modifications occur such as addition of 5′ cap, the 3′ poly A tail and splicing out of introns occur.

Translation: Numerous post-translational modifications such as formation of disulfide bridges, phosporylation, farnesylation, etc. occur.

Inhibition by Antibiotics

Transcription: They are inhibited by rifampicin and 8-Hydroxyquinoline.

Translation: They are inhibited by tetracycline, chloramphenicol, streptomycin, erythromycin, anisomycin, cyclohexamide, etc.

Localization

Transcription: They are localised into prokaryotes’ cytoplasm and eukaryotes’ nucleus.

Translation: They are localised into prokaryotes’ cytoplasm and eukaryotes’ ribosomes on the endoplasmic reticulum.

Conclusion

Transcription and the translation are collectively called gene expression. During transcription, nucleotides are utilised to produce a new RNA strand by the RNA polymerase and other associated proteins. On the other hand, amino acids are utilised to produce a polypeptide chain in translation. In eukaryotes, transcription and translation both add modifications into their end products which are referred to as post-transcriptional and the post-translational modifications, respectively. Post-transcriptional modifications involve the addition of 5′ cap, 3′ poly A tail and splicing out of introns. During post-translational modifications, protein maturation is acquired through phosphorylation, formation of the disulfide bridges and carboxylation like reactions. Therefore the key difference between transcription and translation is in their role in the process of gene expression.

Reference:
1. “Transcription (biology)”. Wikipedia, the free encyclopedia, 2017. Accessed 26 Feb 2017
2. “Translation (biology)”. Wikipedia, the free encyclopedia, 2017. Accessed 26 Feb 2017
3. Clancy, S. and Brown, W. “Translation: DNA to mRNA to Protein”. Nature Education, 2008. 1(1):10 . Accessed 26 Feb. 2017
4. “Stages of translation”. KHANACEDAMY. 2017. Accessed 26 Feb. 2017

Image Courtesy:
1. “Process of transcription (13080846733)” By Genomics Education Programme – Process of transcription (CC BY 2.0) via Commons Wikimedia
2. “Ribosome mRNA translation en”By LadyofHats – Own work (Public Domain) via Commons Wikimedia

About the Author: Lakna

Lakna, a graduate in Molecular Biology & Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things


Gene copies vs. gene paralogs - what's the difference? - Biology

  • Two genes are to be orthologous if they diverged after a speciation event,
  • Two genes are to be paralogous if they diverged after a duplication event.


The original quotation is by Walter Fitch (1970, Systematic Zoology 19:99-113):

"Where the homology is the result of gene duplication so that both copies have descended side by side during the history of an organism, (for example, alpha and beta hemoglobin) the genes should be called paralogous (para = in parallel). Where the homology is the result of speciation so that the history of the gene reflects the history of the species (for example alpha hemoglobin in man and mouse) the genes should be called orthologous (ortho = exact)."

This is also well explained in the book "Fundamentals of Molecular Evolution" by Li & Graur 1991, Ed. Sinauer Associates, Inc., Sunderland, Mass., USA.

What terms should be used in the case that there is a speciation event, followed by duplication events in both lineages ? For example:


where () indicates speciation and X indicates gene duplication. So speciation comes here before duplication.

According to Fitch's definition, Mouse_gene_1 and Mouse_gene_2 are paralogous, as are Rat_gene_1 and Rat_gene_2.

But Rat_gene_1 is orthologous both to Mouse_gene_1 and to Mouse_gene_2, since Rat_gene_1 and the ancestor of the 2 mouse genes diverged after a speciation event. Hence we have:

  • Rat_gene_1 is orthologous to Mouse_gene_1 and to Mouse_gene_2
  • Rat_gene_2 is orthologous to Mouse_gene_1 and to Mouse_gene_2
  • Mouse_gene_1 is orthologous to Rat_gene_1 and to Rat_gene_2
  • Mouse_gene_2 is orthologous to Rat_gene_1 and to Rat_gene_2


Hence, it seems acceptable to say that the mouse gene family (that includes Mouse_gene_1 and Mouse_gene_2) is orthologous to the rat gene family (Rat_gene_1 and Rat_gene_2).

Note that many molecular biologists confuse "orthology" and "functional equivalence" . For example Koonin et al. (Trends in Genetics 1996 12:334-336) wrote:

"By definition, orthologs are genes that are related by vertical descent from a common ancestor and encode proteins with the same function in different species. By contrast, paralogs are homologous genes that have evolved by duplication and code for protein with similar, but not identical functions."

Does Rat_gene_1 have the same function as Mouse_gene_1 or as Mouse_gene_2 ?

Indeed, the phylogenetic analysis allows one to determine orthology relationships but not functional equivalence .

In fact, whereas it is likely that two orthologs have similar function, these functions are not necessarily "identical".

Thus it it is important not to confuse "orthology" with "functional equivalence". Now that the importance of comparative genomics is well recognized it is essential to avoid misunderstandings !

The case of lactate dehydrogenase

Let's now take the reverse situation of two closely related genes in one organism that ahve been the result of a duplication before a speciation event occurred, e.g. those of mammalian lactate dehydrogenase isoenzymes. In the case of this tetrameric enzyme the gene products of the liver type (LDH_L) and of the muscle type (LDH_M) may give rise to in total five different isoenzymes: M4, M3L, M2L2, ML3 and L4, respectively, depending on the type of tissue and the level of expression of the two genes. When one now constructs a phylogenetic tree, the result should be something like this:

  • _________ Rat_LDH_L

    LDH_L |

    _______( )

    | |_________ Mouse_LDH_L

    |

    --- X

    | _________ Rat_LDH_M

    | |

    |_______( )

    LDH_M |_________ Mouse_LDH_M

where X indicates gene duplication and ( ) indicates speciation. Here gene duplication came before speciation. In the case someone is not aware of the presence of isoenzymes in the organisms, because only one sequence for each organism (e.g. LDH_L for mouse and LDD_M for rat) is available and isoenzyme data are missing, then the resulting phylogeny would result in an apparent much earlier separation of mouse and rat. This will inevitably lead to erroneous phylogenies.

According to Walter Fitch's definition,

  • Mouse_LDH_M and Mouse_LDH_L are paralogous,
  • Rat_LDH_M and Rat_LDH_L are paralogous,
  • Rat_LDH_M and Mouse_LDH_M are orthologous,
  • Rat_LDH_L and Mouse_LDH_L are orthologous,

Hence, it seems acceptable to say the the LDH_M family is paralogous to the LDH_L gene family.


Difference between Serology Test and PCR

Basics

– So, what is serology testing? Serology is basically the scientific study of serum or plasma, particularly in response to the body’s immune system response. Serology test is a diagnosis for infectious diseases through the use or detection of serum globulins, known as antibodies. It helps identify if an individual has been exposed to a virus. Polymerase Chain Reaction, or PCR, is one of the most frequently used methods in molecular diagnostics that determines if a patient has an active infection. It gives a clean picture of the patient’s clinical status with regard to the virus.

Testing

– Serology test is a diagnostic test that detects an immunologic response specific to an infectious agent in an individual’s serum. It looks for potential traces of pathogens in a person’s blood sample to determine whether or not that person has been exposed to the virus. It helps determine if a person has developed an immune response to the virus and can safely go back to normal life. PCR, on the other hand, is a molecular test that amplifies a specific fragment of DNA in order to increase the target DNA to detectable levels. It looks directly for the genetic material of a virus in a nasal or throat swab, instead of blood.

Procedure

– Serology test is a simple procedure which requires loading a blood sample to be tested into an antibody test device. It looks for antibodies to viruses in the bloodstream. In the device, the antibodies bind to the antigen while the other antibodies do not bind or weakly bind to antigens because they are not trained to attack this specific virus. The device then washes off the weakly bound antigens and looks for remaining antibodies that are specific to a viral infection. If the device detects them, then it determines that the antibodies are present in the bloodstream.

PCR basically makes millions to billions of copies of a particular segment of DNA. It is composed of three steps – the first step is ‘denaturation’, which involves separating the two strands of a DNA sample apart the second step is ‘annealing’, which specifies the region of DNA that will be copied and the final step is ‘extension’, which copies the DNA.

Serology Test vs. PCR: Comparison Chart


Gene editing

This technique inserts, removes, changes, or replaces specific pieces of a person’s existing DNA.

To treat diseases, scientists are exploring ways to edit pieces of DNA at precise spots along the gene. The goal of gene editing is to change the existing gene and correct mutations where they occur.

Gene editing is a lot like editing a movie: different scenes or images (ie, genes) can be added, removed, or put into a different order.

While several types of editing have been developed, the most common is called clustered regularly interspaced short palindromic repeats, or CRISP-R, which is a lot easier to say. It is used to change DNA sequences and gene function.

Gene editing has been studied since the 1980s. Clinical trials with many different kinds of genetic diseases are ongoing to further investigate its safety and efficacy. There are no FDA-approved treatments available at this time.


In sports, business or your personal life, how you respond to stress and aggression may be in your genes, or at least partly so. Let’s take a look at a great documentary and the science behind it.

Human behavior is complex and influenced by our genes, our environment, and our circumstances. One of the most provocative and often controversial of genetic variants has been dubbed the “Warrior Gene.”

Studies have linked the “Warrior Gene” to increased risk-taking and to retaliatory behavior. Men with the “Warrior Gene” are not necessarily more aggressive, but they are more likely to respond aggressively to perceived conflict.

On December 14, 2010, National Geographic Channel’s Explorer: “Born to Rage?” documentary investigated the discovery behind a single “warrior gene” directly associated with violent behavior.

With bullying and violent crime making headlines, this controversial finding stirs up the nature-versus-nurture debate. Now, former Grammy-winning rocker, author and radio/television broadcaster Henry Rollins goes in search of carriers from diverse, sometimes violent backgrounds who agree to be tested for the genetic mutation. Who has the warrior gene? And are all violent people carriers? The results turn assumptions upside down.

A rock band front man. A bullet-scarred Harley rider. A former gang member from East L.A. Even a Buddhist monk with a far-from-peaceful past. Which one carries the gene associated with violence? An extraordinary discovery suggests that some men are born with impulsive, aggressive behavior … but it’s not always who you think.

It’s a hotly debated topic: nature versus nurture. Many experts believe our upbringing and environment are the primary influences on our behavior, but how much are we predisposed by our DNA? The discovery of a single gene variation affecting only men, which appears to play a crucial role in managing anger, argues that nature may have a far bigger influence on behavior. It’s this low-functioning, shortened gene linked to violent behavior that has become known as the “warrior gene,” and one-third of the male population has it.

One of those men, who describes himself as “fairly furious all the time” and agrees to be tested for the gene with a simple cheek swab, is Henry Rollins — a former poster boy of youthful rebellion and the American punk scene. Some of his tattoos are too provocative and socially offensive to show.

In this special Explorer episode, he dives into his own history of rage and searches out others with aggressive behavior from a range of different backgrounds. “If you can think of a stove, and the pilot light is always on, always ready to light all four burners, that is me, all the time,” he says. “I’m always ready to go there.”

Follow Rollins as he meets with former foot soldiers in one of the most violent street gangs in East Los Angeles fighters in the ultraviolent sport of mixed martial arts, and Harley Davidson bikers. He’ll also talk to a Navy SEAL veteran and Buddhist monks whose lives weren’t always so tranquil.

After learning more about the warrior gene, many of the men believe they have it, which could offer an explanation of their past behavior. Their sentiment mimics Rollins as he says, “If I find out that I have the warrior gene, that would be interesting. If I find out I don’t, I must say, I would feel a bit of disappointment.” As the anticipation builds, be there when they receive the surprising outcome of the test.

Then, Explorer takes a look at the original study — on one family with generations of men displaying patterns of extreme physical aggression — that led Dutch geneticist Dr. Han Brunner to the revolutionary discovery of this rare genetic dysfunction. We’ll also take a look at new revelations that warrior gene carriers are significantly more likely to punish when provoked. In one study attempting to demonstrate this, subjects are given permission to administer punishment to their partner (who was secretly instructed to make a nuisance of himself), with unexpected results.

For any man questioning his inner warrior, a simple cheek swab test is available at Family Tree DNA.

So wanna know who, in the documentary, had the warrior gene? Well, hint….it wasn’t the biker…although his lady assured him he would always be her warrior. But I’m not going to tell you who does have it. All I’ll say is that you’ll be amazed at the outcome. The link to watch the video is below. Enjoy!

The Science

Let’s take a look at the actual science behind this most interesting and controversial mutation.

The Warrior Gene is a variant of the gene MAO-A on the X chromosome and is one of many genes that play a part in our behavioral responses. The “Warrior Gene” variant reduces function in the MAOA gene. Because men have one copy of the X-chromosome, a variant that reduces the function of this gene has more of an influence on them. Women, having two X-chromosomes, are more likely to have at least one normally functioning gene copy, and scientists have not studied variants in women as extensively.

Recent studies have linked the Warrior Gene to increased risk-taking and aggressive behavior. Whether in sports, business, or other activities, scientists found that individuals with the Warrior Gene variant were more likely to be combative than those with the normal MAO-A gene. However, human behavior is complex and influenced by many factors, including genetics and our environment. Individuals with the Warrior Gene are not necessarily more aggressive, but according to scientific studies, are more likely to be aggressive than those without the Warrior Gene variant.

This test is available for both men and women, however, there is limited research about the Warrior Gene variant amongst females. Additional details about the Warrior Gene genetic variant of MAO-A can be found in the paper titled “A functional polymorphism in the monoamine oxidase A gene promoter” by Sabol et al, 1998.

When testing for the Warrior Gene, we are looking for an absence of MAOA (monoamine oxidase A) on the X chromosomes. Based on how many times we see the repeat of a certain pattern on the X or Xs we can tell if the MAOA is present or absent (depleted). Three repeats of the pattern indicates that the X chromosome is deficient of MAOA and therefore you have the Warrior Gene. If we see 3.5, 4 or 5 repeats of the pattern, MAOA is present and this is a normal variant of the gene on your X chromosome.

However, women have 2 X chromosomes where men have 1 X and 1 Y. As mentioned above, the gene is carried on the X chromosome, so women can either have it 1) not at all, 2) on only 1 X (therefore making them a carrier), or 3) on both Xs (exhibiting the trait).

Looking at results, with one X-chromosome, men with the “Warrior Gene” will show a value of 3. Other men will have normal variants: 3.5, 4, 4.5 or 5. With two X-chromosomes, women will have two results. For example, a woman might have 3 and 3, 3 and 5, or 4.5 and 5.

This first example is of a female with one copy of the normal variant and one copy of the Warrior Gene indicated by a value of 3.

In the second example, shown below, this female has the Warrior Gene trait, because she carries the Warrior Gene depletion, shown as a value of 3, on both of her chromosomes, the one contributed to her by her father and the one contributed to her by her mother. This also tells us that her father has the Warrior Gene, since he carries only the X chromosome contributed by his mother, which he gave to his daughter. It also tells us that her mother was either a carrier, if she had only the one copy she gave to her daughter, or had the Warrior Gene herself is she carried two copies.

A male’s results would have only one result listed. If he has a value of 3, he had the Warrior Gene. Any other value is NOT indicative of the Warrior Gene.

Happiness Gene in Women

In an unexpected turn of events, in August 2012, another study in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry indicates that while this gene may express as aggression in men, it may be the happiness gene in women. Even women with only one copy of the gene were shown to be happier than women who carry no copies. A study of 193 women and 152 men evaluated their happiness level and women who carried this mutation on one or both X chromosomes rated themselves as significantly happier than women who did not carry this trait. There was no difference in the male participants.

Among the many advances and discoveries of modern DNA and genetics are ‘scientific’ oddities. These genetic wonders make it into popular culture and sometimes develop a life there that far outpaces their academic worth. But they are interesting. These factoids are best used as ‘cocktail party conversation’ starters or maybe a good way to tease Uncle Leo at the family picnic. Family Tree DNA, where you can find out if you have the Warrior Gene, portrays it to their customers as just that, a novelty.

I receive a small contribution when you click on some of the links to vendors in my articles. This does NOT increase the price you pay but helps me to keep the lights on and this informational blog free for everyone. Please click on the links in the articles or to the vendors below if you are purchasing products or DNA testing.


Knock-in and knockout mice are both genetically altered mice that assist researchers in understanding the genetic functions of the human body at a greater level of detail. While doing genetic research directly on humans and modifying genes in human tissues is still not an ethical, viable option, genetically modified mice can present researchers with a window of opportunity that other models may not offer. This is due to the fact that the mouse genome – albeit far simpler – is extremely similar to the human genome. It contains many of the same genes that scientists would need to knock out or knock in, depending on their research goals. Despite both methods being used for genetic research, that’s pretty much where the similarities between knock-in and knockout mice end. In fact, the processes of generating both types of model are quite different. Moreover, the entire approach to the study of knockout mice is very different compared to that of knock-in mice, as outlined below.

The most important difference between the two types of models is that, in the case of knockout mice, a gene is targeted and inactivated, or “knocked out.” On the other hand, generating knock-in mice involves the opposite technique: altering the mouse’s genetic sequence in order to add foreign genetic material in the form of a new gene housed by the specific locus targeted by the researcher. Knockout mice are far older and more vastly researched when compared to knock-in models. The first knockout mouse was generated in 1989, while generating knock-in mice is a process that has only been perfected during the past few years. However, this technique has been growing in popularity at an accelerated rate, as the methods of obtaining knock-in mice continue to increase in number.

Knock-in and knockout technologies are very different. While both can be used on laboratory mice to facilitate genetic research without having to experiment on human subjects, the technology and the specific methods used to delete or inactivate a portion of the DNA sequence are distinct and recognized as such by researchers who are familiar with both gene knockouts and knock-ins. Knock-ins create a one-for-one substitution of the DNA sequence within the genome. In particular, knock-in technology is focused on a specific locus of the sequence, compared to how knockout mouse generating technologies and methods focus on engineering an entirely new DNA sequence, which is very similar to the original one, but made to ensure that the gene becomes inoperable.

It’s also important to take note of what both techniques are designed to achieve. Their uses vary in significant ways, to the extent that researchers tend to use each for different types of studies. Knockout mice are designed to help scientists peer into the details of what makes genes work and what each gene does. Because they are able to stop specific genes from fulfilling their functions, they can be used to study the impact of a specific gene on the entire body’s various functions. This will help medical and genetic researchers study genetic diseases more easily, along with various disorders that are affected by the impairment of a certain gene. In contrast, knock-ins help to study the human genome more closely by introducing human genetic material into a mouse’s genome. The possibilities are endless, but most of the progress done by genetic scientists has been in the field of immunodeficiency and stem cell research, as well as in studying various diseases that required the activation of human genes.