Mutations and Disease

DNA is constantly subject to mutations, accidental changes in its code. Mutations can lead to missing or malformed proteins, and that can lead to disease.

We all start out our lives with some mutations. These mutations inherited from your parents are called germ-line mutations. However, you can also acquire mutations during your lifetime. Some mutations happen during cell division, when DNA gets duplicated. Still other mutations are caused when DNA gets damaged by environmental factors, including UV radiation, chemicals, and viruses.

Few mutations are bad for you. In fact, some mutations can be beneficial. Over time, genetic mutations create genetic diversity, which keeps populations healthy. Many mutations have no effect at all. These are called silent mutations.

But the mutations we hear about most often are the ones that cause disease. Some well-known inherited genetic disorders include cystic fibrosis, sickle cell anemia, Tay-Sachs disease, phenylketonuria and color-blindness, among many others. All of these disorders are caused by the mutation of a single gene.

Most inherited genetic diseases are recessive, which means that a person must inherit two copies of the mutated gene to inherit a disorder. This is one reason that marriage between close relatives is discouraged; two genetically similar adults are more likely to give a child two copies of a defective gene.

Diseases caused by just one copy of a defective gene, such as Huntington’s disease, are rare. Thanks to natural selection, these dominant genetic diseases tend to get weeded out of populations over time, because afflicted carriers are more likely to die before reproducing.

Scientists estimate that every one of us has between 5 and 10 potentially deadly mutations in our genes-the good news is that because there’s usually only one copy of the bad gene, these diseases don’t manifest.

Cancer usually results from a series of mutations within a single cell. Often, a faulty, damaged, or missing p53 gene is to blame. The p53 gene makes a protein that stops mutated cells from dividing. Without this protein, cells divide unchecked and become tumors.

Method to find bad mutations may improve maize crops

This deformed ear of corn results from bad mutations that occur randomly each generation. When bad mutations are not removed from breeding populations, they can cause dramatic losses in yield. Credit: Jason Wallace, Buckler Lab

Cornell researchers have developed a way to predict bad mutations in the maize genome, addressing a major challenge for breeders trying to grow better crops and feed rising populations. The researchers found regions of the genome that were riddled with such unwanted DNA.

For every gene that contains a desirable trait, many undesirable mutations come along for the ride – a common hindrance for breeders focused on improved varieties. By knowing exactly where the bad mutations are in the genome, researchers can apply new genome editing technologies that allow precise cuts and fixes to be made.

“The technology is now moving forward for us to recognize these bad mutations and edit them out of the genome,” said Edward Buckler, a Cornell and U.S. Department of Agriculture (USDA) research geneticist, and senior author of a March 9 paper in Proceedings of the National Academy of Sciences.

With genome editing, undesired genes can be replaced with a healthy common variant of the gene found within the species, Buckler said.

The study focused on recombination, a natural gene shuffling process in which sections of genomes from each parent are swapped into the offspring.

“If recombination does not occur in a region of DNA, good mutations do not have the opportunity to join together,” said Eli Rodgers-Melnick, the paper’s co-lead author and a postdoctoral researcher in Buckler’s lab. “At the same time, bad mutations can be dragged along with the good, like a rusted trailer with flat tires attached to a souped-up sports car.”

Much like a deck of cards that is split in half and shuffled, clumps of cards can stick together in the process. Using this analogy to describe recombination, each half of the deck represents DNA from each parent, but during mating when genetic material is combined and reshuffled, clumps or regions of DNA stick together.

One reason for sex among any species is to break up chromosomes and swap regions of the genome to create new combinations, but “about 40 percent of the genome doesn’t do this well,” said Buckler, who is a USDA–Agricultural Research Station (ARS) scientist in Cornell’s Institute for Genomic Diversity and an adjunct professor in Cornell’s Department of Plant Breeding and Genetics.

In the study, the researchers analyzed markers in the genomes of 7,000 maize varieties – representing the diversity of maize – to determine where crossovers occur and which regions of the genome might stay together as a group. It turned out the junctions where the genome breaks during recombination are very similar across all varieties, making these regions stable and highly predictable.

The researchers also found that the regions of the maize genome with the lowest recombination rates also harbor the largest number of bad mutations. This means the portions of the maize genome most burdened with undesirable mutations will also be the most difficult to improve using conventional, more time-consuming breeding techniques, in which breeders repeatedly cross parents with agriculturally desirable traits to get offspring with the right features.

The researchers note that genome editing is different from genetic engineering, which might introduce foreign genes randomly in the genome. “We are not introducing new genes but precisely fixing bad mutations,” Buckler said. Every variety has a few hundred to thousands of bad mutations.

Explore further

Sex has another benefit: It makes humans less prone to disease over time More information: Recombination in diverse maize is stable, predictable, and associated with genetic load, Journal information: Proceedings of the National Academy of Sciences Provided by Cornell University Citation: Method to find bad mutations may improve maize crops (2015, March 11) retrieved 1 February 2020 from This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

The gene-editing method CRISPR has transformed biology, giving scientists the ability to modify genes to treat or prevent genetic diseases by correcting dangerous mutations and to create a host of new genetically modified plants and animals. But the technique, which involves using an enzyme called a nuclease that acts as molecular scissors to “cut” DNA, can cause unintended effects. Making such double-stranded breaks in DNA can result in unwanted genetic material being inserted or deleted, which can have consequences including activating genes that cause cancer. Most mutations cannot be corrected easily without creating these undesirable genetic by-products.

In 2016 a team led by David Liu at the Broad Institute of Harvard University and the Massachusetts Institute of Technology developed another method, called base editing, which allows scientists to make precise edits to single DNA letters without relying on double-stranded breaks. This technique, however, can only be used to fix four out of the 12 types of “point” genetic mutations, which include insertions, deletions and combinations of the two.

Now Liu, Andrew Anzalone—a postdoctoral researcher in Liu’s laboratory—and their colleagues have developed a new gene-editing tool that avoids these double-stranded breaks and can correct all 12 types of point mutations. The researchers used their new technique, dubbed “prime editing,” in lab-grown human cells to correct the genetic defects that cause sickle cell disease and Tay-Sachs disease, they report in a study published Monday in Nature. They say their method is more efficient than traditional CRISPR (except for in certain cell types) and has fewer off-target effects. In principle, it could correct about 89 percent of known human genetic defects that cause diseases, although it is still a very new technique and requires much more study before it can be used to treat humans.

“In the big picture, the invention of prime editing is a moment for all gene editors to stand up and cheer,” says Fyodor Urnov, a professor of molecular and cell biology at the University of California, Berkeley, and scientific director for technology and translation at the Innovative Genomics Institute, a partnership between U.C. Berkeley and the University of California, San Francisco. “Prime editing is potentially an exceptionally powerful way to do repair,” says Urnov, who was not involved in the study but was a reviewer on the paper. Yet he cautions that “in practical terms, these are very early days.”

Credit: S. Hamilton & K. Zusi Broad Institute of M.I.T. and Harvard

Prime editors consist of two components, a protein and an RNA molecule. The first is an engineered form of the common CRISPR enzyme Cas9 combined with a second enzyme called a reverse transcriptase. The second is an engineered guide RNA, called a pegRNA, which both specifies the target site in the DNA and serves as a template for the desired edit. At the target site, the engineered Cas9 makes a nick in one strand of DNA, and the reverse transcriptase directly copies the pegRNA into a new DNA strand attached at that point, letter by letter. This creates an extra “flap” of DNA with the edited sequence. The prime editor then cuts the unedited strand and replaces it with the edited one.

“If nucleases are like scissors, and base editors are like pencils, prime editors are like word processors,” Liu says. They serve a kind of “search and replace” function for DNA.

Anzalone and his colleagues compared prime editing with CRISPR’s usual DNA repair mechanism, finding that the new method was more efficient (meaning it successfully edited a higher proportion of cells) and that it produced far fewer insertions and deletions. With prime editing, the team was able to achieve an efficiency of about 20 to 50 percent—and in some cases, as high as 78 percent, depending on the cell type. For certain diseases, such as sickle cell, even 25 to 30 percent efficiency could alleviate some of the symptoms. Others, such as cystic fibrosis, will require much greater efficiency.

The CRISPR enzyme Cas9 is known to have unintended, or off-target, effects at a number of sites in the genome. The researchers showed that prime editing causes fewer off-target effects at these locations. They think this occurs because whereas Cas9 requires only one instance of DNA pairing, prime editing requires three, which means there is a lower likelihood of random pairings that could have unwanted effects.

Other researchers praised the new approach, although they noted that the technique is still in its early stages. Feng Zhang, one of several CRISPR pioneers, who is also at the Broad Institute but was not involved in the study, calls it “a creative approach further expanding the range of genetic changes that can be made.” (Zhang is a co-founder of the companies Editas Medicine and Beam Therapeutics, which are developing CRISPR-based therapies.)

Jussi Taipale, a professor of biochemistry at Cambridge University, calls it a “major advance” that “moves from a genome cutting tool toward a true genome-editing tool.”

“It’s exciting to see another tool in the CRISPR-Cas9 toolbox!” adds Jennifer Doudna, a CRISPR pioneer at U.C. Berkeley, who was not a co-author on the study but collaborates with Liu’s lab. (Doudna is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics and Mammoth Biosciences—all companies working on CRISPR technology.)

Like every new technique, prime editing has its limitations, which will have to be overcome before scientists can contemplate using it in humans. For one, researchers have to figure out how to deliver the tool to cells in the body in a way that reaches the intended cells safely and effectively. Anzalone and his colleagues explored both viral and nonviral delivery methods in their study, and they plan to do additional studies in animals.

Another issue is whether the engineered enzyme and RNA could activate the body’s immune system, Urnov says. The RNA is originally from bacteria and the enzyme is from a virus, so the two are “a chimaera the likes of which we’ve never seen,” he adds. (Classical CRISPR faces similar challenges, too.)

The introduction of a reverse transcriptase enzyme could also copy other RNA in the cell into DNA that could then be incorporated into the genome, causing unwanted effects, Zhang says.

Finally, there is the efficiency. Zhang says the results they achieved are promising but will need to be improved in certain disease-specific cell types.

Prime editing is not likely to replace techniques such as CRISPR or base editing. “Nuclease editors , base editors and prime editors all have strengths and weaknesses,” Liu notes. “We anticipate all three classes will have roles in therapeutics and research,” he says.

Urnov likens the different gene-editing tools to dog breeds—each have their own specialized functions. For example, border collies are great at herding sheep, whereas German shepherds make good police dogs. When it comes to gene editing, he says, “I honestly think we do not have enough data on what will be most widely used ‘dog.’”

Disposable parts of plants mutate more quickly

While new mutations in DNA are the fuel for evolution, most of them are bad for you — some can indeed cause cancer or genetic disease. Because of this, natural selection usually acts to reduce the mutation rate. But preventing mutations from happening is costly, so one might expect that the extent of mutation limitation depends on a balance between the future impact of any mutation and the costs of preventing mutation.

This hypothesis predicts, for example, that in animals the cells that contribute to sperm and eggs (germline cells) should have a lower mutation rate than ones that don’t (somatic cells), as the latter don’t have an evolutionary future, just a short-term future in the body they find themselves in. We take our somatic mutations with us to our grave, but our germline mutations can live on in our sons and daughters. Similarly, short-lived organisms would be expected to have a higher mutation rate in their somatic cells than longer lived organisms. These ideas are hard to test but limited data from animals are currently supportive.

Unlike animals, plants may not have a well-defined germline, so the researchers reasoned that cells in plant stems should have a lower mutation rate than in roots, as the latter has no prospect of giving rise to seeds. Similarly, leaves might have lower mutation rates than petals, as petals are so short-lived. Also branches that had grown over one growing season should have the same mutation rate. By sequencing over 750 genomes from 8 different plant species the authors find that all three predictions are upheld.

Closer examination of the differences between roots and shoots further reinforced this conclusion; the team noticed that the ratio of the number of mutations in shoots to that in roots was higher for long-lived (perennial) species than for species with just one growing season before they die (annuals). This made perfect sense when they also discovered that mutations in the shoots of annuals are very rarely transmitted to the next generation, while the same is not true for perennials. Thus, the greater the future prospects of mutations in stems, the lower the relative mutation rate.

Another observation that at first appeared odd, turned out to be the exception that proves the rule. Strawberry plants send out runners that can then sprout new plants. At first sight, the runners might be expected to have a low rate of mutation accumulation, as all new plants — and hence seeds — come from the runner. But the researchers found that runners have a rather high rate compared to the plants that sprout from them. By tracking mutations, they worked out why this is: most cells of the runner never develop into the new plants, making the bulk of runner more like root than shoot. If we want to know if plants ever have a germline — itself a contentious question — this system, they suggest, would be a great model organism.

Before concluding that the theory works, the team also caution that there is probably more to mutation rate variation than the potential longevity of mutations. Prior evidence had suggested that just stressing plants can increase the mutation rate. The team also observed that if we grow plants artificially in the lab they have much higher mutation rates than field-grown comparators. The mutation rate, they suggest, is possibly fragile and easily affected by local conditions. Indeed, the authors caution that the difference between petal and leaf may reflect nothing more than different microenvironments rather than necessarily natural selection shaping the mutation rate. Either way, the new evidence points to the possibility that plants don’t have one mutation rate but many. How these different rates of mutation accumulation in different body parts comes about has yet to be resolved.

Professor Hurst commented, “This confirmation of the theory potentially has relevance to many fields but especially to understanding cancers. Cancers develop in older individuals in all mammals, but this means that mice develop tumours aged 2, we get them around 50 and blue whales much later. Our results support the idea that one of the reasons for this trend is that different species have different mutations rates with longer lived species investing more into keeping their somatic mutation rate down. Helping us to do this would be a sensible preventative measure.”

Special Issue “Advances in Plant Mutagenesis Research”

Dear Colleagues,

Induced mutagenesis, one of the most efficient tool for the crop improvement, has been utilized extensively to create genetic variation for economically important traits. Induced mutagenesis has also been proven to be a convenient tool for the identification of key regulatory genes and molecular mechanism involved in the trait development. Conventionally, the induced mutagenesis is performed by means of physical, chemical, and insertional mutagen treatment methods. Besides achieving numerous benefits, these methods are less preferred due to random and slow process. In addition, localization of casual mutation using the conventional methods is tedious and costly. However, due to the recent advancements in next-generation sequencing (NGS) techniques, detection of millions of mutations in short period of time has become convenient and cost efficient. Several mutation mapping approaches utilizing NGS such as MutMap, MutChromSeq and whole genome sequencing based mapping have been recently developed. The cost-effectiveness and high applicability make these approaches a choice of method to identify desired genes in lesser time. Furthermore, induced mutagenesis coupled with whole genome sequencing has provided a robust platform for forward and reverse genetic applications. Apart from the advances in mutation mapping, excellent tools have been recently invented to induce at precise location in the genome. Increasing availability of whole genome sequence information for large number of crops have enabled target specific genome editing techniques such as ZFNs (Zinc Finger Nucleases), transcription activator like effector nucleases (TALENS), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease. The CRISPR/Cas9 has instigated paradigm shift in the entire biology field including crop science. The special issue of Plants will highlight the advances in mutagenesis techniques, high-throughput mutation mapping, identification of novel genes using mutagenesis approaches and mutation breeding efforts.

Dr. Rupesh Deshmukh
Dr. Juhi Chaudhary
Dr. Humira Sonah
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Plants is an international peer-reviewed open access monthly journal published by MDPI.

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How do mutations affect species diversity?

Mutations increase the amount of diversity within a population/species.

Mutations are the primary source of genetic diversity. By introducing new alleles into the population, the population becomes more heterogeneous.

For example, if you have all white shirts, you have no diversity in the color of your shirts. Then let’s say you get a red shirt for your birthday and someone else gives you a blue shirt as a thank you gift. The diversity of your shirts has increased. You can choose whether you want to wear white, blue, or red. This is the same principle with mutations and populations different species.

****Note: if you mean “species diversity,” which is defined as the number of species in a region and the abundance of each species, the answers differs.

A species with a higher mutation rate and therefore greater genetic diversity may do better than a species with lower diversity. The more diverse species may out-compete another, lowering the abundance of the second species and lowering the species diversity of the area.

For example, you have a population of turtles with high diversity and a population of birds with low diversity, and both species are hunted by humans. The genetic diversity of the turtles means that they have multiple ways of adapting to hunting, some work and some may not. The birds, with lower diversity, have one strategy to adapt to hunting, and it doesn’t work very well.

Over time, the population of birds will drop but the population of turtles may stay the same or even increase, as those with successful adaptations survive and breed and their adaptations are passed on to offspring. The species diversity of the area may decrease because the number of birds dropped. However, species diversity is very complex and we still have much to learn.

What is a mutation?

  • Over a lifetime our DNA can undergo changes or ‘mutations’ in the sequence of bases, A, C, G and T.
  • This results in changes in the proteins that are made. This can be a bad or a good thing.
  • Mutations can occur during DNA replication if errors are made and not corrected in time.
  • Mutations can also occur as the result of exposure to environmental factors such as smoking, sunlight and radiation.
  • Often cells can recognise any potentially mutation-causing damage and repair it before it becomes a fixed mutation.
  • Mutations contribute to genetic variation within species.
  • Mutations can also be inherited, particularly if they have a positive effect.
  • For example, the disorder sickle cell anaemia is caused by a mutation in the gene that instructs the building of a protein called haemoglobin. This causes the red blood cells to become an abnormal, rigid, sickle shape. However, in African populations, having this mutation also protects against malaria.
  • However, mutation can also disrupt normal gene activity and cause diseases, like cancer
  • Cancer is the most common human genetic disease; it is caused by mutations occurring in a number of growth-controlling genes. Sometimes faulty, cancer-causing genes can exist from birth, increasing a person’s chance of getting cancer.

An illustration to show an example of a DNA mutation.
Image credit: Genome Research Limited

This page was last updated on 2016-01-25

Changes in genes

Gene mutations

Mutations are abnormal changes in the DNA of a gene. The building blocks of DNA are called bases. The sequence of the bases determines the gene and its function. Mutations involve changes in the arrangement of the bases that make up a gene. Even a change in just one base among the thousands of bases that make up a gene can have a major effect.

A gene mutation can affect the cell in many ways. Some mutations stop a protein from being made at all. Others may change the protein that is made so that it no longer works the way it should or it may not even work at all. Some mutations may cause a gene to be turned on, and make more of the protein than usual. Some mutations don’t have a noticeable effect, but others may lead to a disease. For example, a certain mutation in the gene for hemoglobin causes the disease sickle cell anemia.

Cells become cancer cells largely because of mutations in their genes. Often many mutations are needed before a cell becomes a cancer cell. The mutations may affect different genes that control cell growth and division. Some of these genes are called tumor suppressor genes. Mutations may also cause some normal genes to become cancer-causing genes known as oncogenes (oncogenes and tumor suppressor genes are discussed in more detail later).

We have 2 copies of most genes, one from each chromosome in a pair. In order for a gene to stop working completely and potentially lead to cancer, both copies have to be “knocked out” with mutations. That means for most genes, it takes 2 mutations to make that gene stop working completely.

Types of mutations

There are 2 major types of gene mutations, inherited and acquired:

An inherited gene mutation is present in the egg or sperm that formed the child. After the egg is fertilized by the sperm, it created one cell called a zygote that then divided to create a fetus (which became a baby). Since all the cells in the body came from this first cell, this kind of mutation is in every cell in the body (including some eggs or sperm) and so can be passed on to the next generation. This type of mutation is also called germline (because the cells that develop into eggs and sperm are called germ cells) or hereditary. Inherited mutations are thought to be a direct cause of only a small fraction of cancers.

An acquired mutation is not present in the zygote, but is acquired some time later in life. It occurs in one cell, and then is passed on to any new cells that are the offspring of that cell. This kind of mutation is not present in the egg or sperm that formed the fetus, so it cannot be passed on to the next generation. Acquired mutations are much more common than inherited mutations. Most cancers are caused by acquired mutations. This type of mutation is also called sporadic, or somatic.

Mutations and cancer

Experts agree that it takes more than one mutation in a cell for cancer to occur. When someone has inherited an abnormal copy of a gene, though, their cells already start out with one mutation. This makes it all the easier (and quicker) for enough mutations to build up for a cell to become cancer. That is why cancers that are inherited tend to occur earlier in life than cancers of the same type that are not inherited.

Even if you were born with healthy genes, some of them can become changed (mutated) over the course of your life. These acquired mutations cause most cases of cancer. Some acquired mutations can be caused by things that we are exposed to in our environment, including cigarette smoke, radiation, hormones, and diet. Other mutations have no clear cause, and seem to occur randomly as the cells divide. In order for a cell to divide to make 2 new cells, it has to copy all of its DNA. With so much DNA, sometimes mistakes are made in the new copy (like typos). This leads to DNA changes (mutations). Every time a cell divides, it is another opportunity for mutations to occur. The numbers of gene mutations build up over time, which is why we have a higher risk of cancer as we get older.

It is important to realize that gene mutations happen in our cells all the time. Usually, the cell detects the change and repairs it. If it can’t be repaired, the cell will get a signal telling it to die in a process called apoptosis. But if the cell doesn’t die and the mutation is not repaired, it may lead to a person developing cancer. This is more likely if the mutation affects a gene involved with cell division or a gene that normally causes a defective cell to die.

Some people have a high risk of developing cancer because they have inherited mutations in certain genes. To learn more about this, see Family Cancer Syndromes.


For dominant genes and mutations, the term penetrance is used to indicate the proportion of those carrying a mutation who will have the trait, syndrome, or disease. If all of the people who inherit the mutation have the disease, it is called complete penetrance. If not all of the people who have the mutation get the disease, it is called incomplete penetrance. In general, inherited mutations leading to cancer have incomplete penetrance, meaning not everyone with the mutation will get cancer. That is in part because although the person has a mutation in one copy of the gene, he or she needs to acquire at least one more mutation for the gene to stop working completely and cancer to occur. Since not everyone gets the second mutation, not everyone gets cancer. Incomplete penetrance can also be because even if the mutation makes it so that a gene doesn’t function, other factors may be needed for the cancer to start.

High vs. low penetrance

Gene mutations can cause large changes in the function of a gene. They may even cause that copy of the gene to stop working altogether. When an inherited mutation has a large enough effect on the function of a gene to cause a disease or noticeable problem in most of the people who have it, that mutation is called “high penetrance.”

High-penetrance mutations in cancer susceptibility genes can lead to many people in a family getting certain kinds of cancers – a family cancer syndrome. These are thought to cause only a small fraction of cancers that run in a family. For example, only about 1/5 of the breast cancer that runs in families is thought to be caused by high-penetrance mutations in genes like BRCA1 and BRCA2.

Some inherited mutations, though, don’t seem to affect gene function very much and don’t often cause obvious problems. These mutations are called “low-penetrance.” Low-penetrance mutations can affect cancer risk through subtle effects on things like hormone levels, metabolism, or other things that interact with risk factors for cancer. Low-penetrance mutations, together with gene variants (discussed below) are thought to be responsible for most of the cancer risk that runs in families.

Gene variants

People can also have different versions of genes that are not mutations. Common differences in genes are called variants. These versions are inherited and are present in every cell of the body. The most common type of gene variant involves a change in only one base (nucleotide) of a gene. These are called single nucleotide polymorphisms (SNPs, pronounced “snips”). There are estimated to be millions of SNPs in each person’s DNA.

Other types of variants are less common. Many genes contain sequences of bases that are repeated over and over. A common type of variant involves a change in the number of these repeats.

Some variants have no apparent effect on the function of the gene. Others tend to influence the function of genes in a subtle way, such as making them slightly more or less active. These changes don’t cause cancer directly, but can make someone more likely to get cancer by affecting things like hormone levels and metabolism. For example, some gene variants affect levels of estrogen and progesterone, which can affect the risk of breast and endometrial cancers. Others can affect the breakdown of toxins in cigarette smoke, making a person more likely to get lung and other cancers.

Gene variants can also play a role in diseases that impact cancer risk – like diabetes and obesity.

Variants and low-penetrance mutations can be similar. The main difference between the two is how common they are. Mutations are rare, while gene variants are more common.

Still, since these variants are common and someone can have many of them, their effect can add up. Studies have shown that these variants can influence cancer risk and, together with low penetrance mutations, they may account for a large part of the cancer risk that runs in families.

Other ways cells change genes and gene activity

Although all of the cells of your body contain the same genes (and DNA), different genes are active in some cells than in others. Even within a certain cell, some genes are active at some times and inactive at others. Turning on and off of genes in this case isn’t based on changes in the DNA sequence (like mutations), but by other means called epigenetic changes.

DNA methylation: In this type of epigenetic change, a molecule called a methyl group is attached to certain nucleotides. This changes the structure of the DNA so that the gene can’t start the process of making the protein for which it codes (this process is called transcription). This basically turns off the gene. In some people with a mutation in one copy of a cancer susceptibility gene, the other copy of the gene becomes inactive not by mutation, but by methylation.

Histone modification: Chromosomes are made up of DNA wrapped around proteins called histones. Histone proteins can be changed by adding (or subtracting) something called an acetyl group. Adding acetyl groups (acetylation) can activate (turn on) that part of the chromosome, while taking them away (deacetylation) can deactivate it (turn it off). Methylation is also used to activate and deactivate parts of chromosomes. Histone proteins can also be changed by adding or subtracting methyl groups (methylation and demethylation). Although abnormal histone modification isn’t known to cause cancer, drugs that alter histone modifications can help in the treatment of cancer by turning on genes that help control cell growth and division.

RNA interference: RNA (ribonucleic acid) is important inside cells as the middle step that allows genes to code for proteins. But some small forms of RNA can interfere with gene expression by attaching to other pieces of RNA, or even affecting histones or DNA itself. Drugs are being developed that affect abnormal genes in cancer cells through RNA interference.

7 beautiful mutations: Which one do you have?

Image zoom Kazzakova/iStock/Getty Images

If I wasn’t a writer, I think I’d like to be a genetic researcher. I know, they seem like totally unrelated fields, but hear me out. The thing that interests me most in the entire world is why people (or characters) are who they are, and what makes them tick. And one of the things at the very bottom of what makes people tick is in their genes, and I think that’s why I find genetics so interesting. I love picking out the features that I inherited from my parents (my dad’s eyes, my mum’s cheekbones) as well as those that haven’t appeared for several generations (my hair texture).

Since humans are around 99.9% genetically identical, it’s amazing to think that such a tiny percentage difference can result in such incredible variation in our species. And one of the vehicles for that variation is genetic mutation.

Unfortunately, we’re not yet mutating the power of flight or telepathy—sorry, Professor X. A mutation is a permanent change in the DNA structure of a gene. They can be inherited or acquired, and they can be beneficial, neutral or pathogenic (seldom are they superpowers). Some mutations eventually become so common that they’re considered “normal,” and then we call them polymorphs, whereas others remain rare and unusual in the human population.

Because this is a beauty site, I’ve picked seven physical mutations to write about. Some of them are considered polymorphs and some aren’t, but they all make us uniquely beautiful. And who knows—maybe someday I’ll get that adamantium skeleton I’ve been asking Santa for since I was 6.

1 Heterochromia

I never thought much about my eyes growing up. They were very much like my dad’s, and I figured that having blue, yellow, and green all mixed up together was just what green eyes looked like.

Imagine my surprise to find out that this is actually quite atypical, and all thanks to a mutation called heterochromia iridum. It refers to eyes that have multiple colours in them, and you’ve probably heard of it if you’ve seen X Men: First Class; young Professor X calls it “a very groovy mutation.”

via giphy

There are three types of heterochromia:

  • Complete (each eye a different color).
  • Sectoral (a segment of contrasting color in the iris).
  • Central (a different colour radiating out from the pupil).

These three categories are pretty fluid, though, and they can combine in weird and wonderful ways. My left eye is far lighter and more yellow than my right, while my right eye has The Blotch. Both have rings of gray and yellow around the pupil.

I guess this is why I always get attitude at the DMV when I tell them my eyes are green.

If you’re born with heterochromia, it’s probably because one of your parents had it—it’s a dominant autosomal trait. Though you could also be a chimera (two fertilised eggs fusing into one zygote, each with a different gene for eye colour) or a mosaic (someone with two or more different genetic codes in their cells; in this case, a slightly altered gene responsible for eye colour).

It’s also possible to acquire heterochromia, although you probably don’t want to. It’s almost always the result of a serious illness or injury. Certain medications have been known to deposit brown pigment in eyes—a pretty rare side-effect, and one that usually only happens in hazel eyes, but certainly one worth mentioning.

Most sources I consulted say that heterochromia is super-rare, but from my very scientific study of both readers and writers, I’ve determined that it really isn’t rare at all. It seems like most of us have some form of this, with central being the most popular. Multicolored eyes, unite!

2 Double eyelashes

Image zoom API/GAMMA/Gamma-Rapho via Getty Images

I had to include this after this outstanding Elizabeth Taylor tutorial, because Taylor was famous for her super-dark, gorgeous double eyelashes.

It’s called distichiasis, and if you’re born with it, it’s because one of your parents had it (it’s a dominant trait, so you’re welcome, future offspring). It’s the result of a transcription error on your 16th chromosome, and can also be a symptom of some pretty serious heart-related disorders.

This is another fun mutation expressed in my phenotype. It’s not as obvious on me as it is on some people, because my eyelashes are blonde. But man, do I ever have a lot of them.

There is a difference, though, between having “lots of eyelashes” and a double row, and it can difficult to figure out if you have this particular mutation or not. Google is very little help, except to be absolutely disgusting (seriously, is there anything grosser than gross eye pictures?). So today I’m going to be better than Web MD.

Here’s how you can tell: Lift up the lashes on your upper eyelid and peek underneath where the waterline is. If your eyelashes stop and then your waterline starts, you have beautiful thick lashes. If, however, you can see lashes sprouting out of your waterline where they should not be (I find this incredibly distressing), then congratulations, you have distichiasis.

Anecdotally, this isn’t always the super-gorgeous advantage that it sounds like. I had to have seven eyelashes that were growing in towards my eye removed when I was a kid, which, thankfully, I only have vague memories of now.

Another way to tell is to go to a new eye doctor for a checkup. If they say “Damn, what’s going on HERE?” then congratulations, and may the spirit of Liz Taylor be with you.

3 Red hair

I think most people know that red hair is a recessive trait; meaning that if you’re a ginger (term used with lots of love), you have two variant copies of a gene called MC1R on each of your 16th chromosomes. This mutation results in generally fairer skin, freckles (we’ll get to them), light-coloured eyes, issues dealing with UV light and, recent studies have suggested, a unique pain tolerance.

That’s all pretty neat, but I want to talk about a totally false idea that regains popularity every couple of years: that redheads are going extinct, and that there will be no more gingers as early as 2060.

No. Just no.

How Stuff Works debunked this very, very thoroughly: “Recessive genes can become rare but don’t disappear completely unless everyone carrying that gene dies or fails to reproduce. So while red hair may remain rare, enough people carry the gene that, barring global catastrophe, redheads should continue to appear for some time.”

So the next time your Facebook friends all start posting nonsense about the looming Gingerpocalypse, just send them a link to this article and settle their hash. Then reread Anne of Green Gables and feel pleased that all is right with the world.

4 Freckles

I have a few freckles, and I think they are the cutest. I always wished that I had more, probably because a lot of my friends growing up had them.

And guess what causes them? Or rather, guess what partially causes them?

That’s right: mutations.

And it all has to do with cells in the skin that make pigment called melanocytes. When exposed to UV light, melanocytes produce melanin, which makes skin darker to protect our DNA. There are two main types of melanin–eumelanin and pheomelanin. Pheomelanin is less common, and it’s what gives red hair and freckles their orangey tone.

Remember a second ago when we were talking about red hair and the MC1R gene? That guy is coming back into play again here. When the MC1R gene is working normally, it turns all pheomelanin into eumelanin. This means skin tans instead of freckles, and hair is a colour other than red. But when the MC1R gene isn’t working, you get red hair and freckled skin thanks to all that lovely pheomelanin floating around.

“But Alle,” I hear you saying. “Not all people who have freckles also have red hair.”

You’re so right! Remember how we know that being a ginger is a recessive trait that needs two copies of a gene—one from each parent—to be expressed?

MCR1 is that gene! Some people have a single mutated copy of it and have no idea—but it means that not all their pheomelanin changes to eumelanin, and they still get freckles when exposed to UV light. My family hasn’t ever had any redheads in it—we’re generally either dark blondes or have black Irish hair—but I, and a few of my cousins, still have freckles. It could be that we’re carrying a single redhead gene, makin’ pheomelanin like it’s our jobs.

Or it could be something else entirely, because this only applies sometimes. Not all people with red hair have freckles (though it’s more likely) and, as we know, not all people with freckles also have red hair. Something else is afoot, but scientists don’t know what it is yet. Another gene doing something? Environment? Epigenetics? No idea!

This is a super-weird result, because it tells us that freckles are a dominant trait, being expressed even when there’s only one copy of the gene in question, but red hair itself is recessive–even though they’re both caused by the same gene. Genetics is really cool and complicated, guys.

5 Blue eyes

I know: what? Blue eyes aren’t exactly rare! But mutations don’t have to be rare—this one now appears in so much of the population that it’s considered a polymorph. But really, blue eyes are the result of a pretty recent mutation. You know, 10,000 years ago. Practically yesterday.

The first thing you gotta know is that blue eyes aren’t technically a color—they’re a lack of color. Eye colour is determined by pigments in the part of the iris called the stroma, and if there is a tiny amount of pigment there (or none at all), eyes will appear blue. A bit more pigment gives us green eyes. And if there’s heaps of pigment, eyes are brown.

The gene that’s responsible for this is called OCA2, and it controls melanin. Back in the day, all humans had brown eyes—eyes with lots of melanin pigment. One day, a nearby gene mutated and started to limit OCA2’s ability to produce melanin in the iris. This stopped melanin from coloring the eyes, leaving the stroma blue, and voila! Blue eyes appeared in the population.

In fact, scientists currently think that everyone who has blue eyes is descended from a single common individual who lived around the Black Sea 6,000 to 10,000 years ago. How’s that for neat?

6 Cleft chin

Cleft chins are caused when the two halves of the jaw bone (or muscle) don’t quite fuse properly during development. A lot of really attractive people have cleft chins, so please excuse me while I indulge in some eye candy.

Common wisdom—and also Wikipedia—states that this is a primarily dominant genetic trait.

Allow me to bust this myth.

First: not all cleft chins are exactly the same. There’s heaps of variation when it comes to size (round dimples, eg: Kirk Douglas, vs Y-shaped clefts, eg: Aaron Ekhart) and depth (very subtle vs very deep). So it’s sometimes harder than you’d think to say which chin is smooth and which isn’t.

Second: men are more frequently butt-chinned than women are, which doesn’t fit the simple dominant-recessive genetic model. A really old study (from 1939)recorded that 9.6% of German men and 4.5% of German women had cleft chins. That’s a really big difference between sexes for a trait that isn’t supposed to be sex-linked.

Another study (from 1960) found that even when two parents had smooth chins, they could still have cleft-chinned offspring. It didn’t happen often (11% of the time), but it happened. If cleft chins truly are dominant, this should have been impossible.

So basically, if Alexander Skarsgard and I ever had a kid, there’s a chance it would have a cleft chin—but it’s not a certainty.

That’s a little disappointing, honestly.

7 No-show wisdom teeth

If there’s one thing I wish would just die out of the human population, it would be wisdom teeth. Mine popped up when I was 20, all four completely on their sides, two of them poking through the gums like painful little islands in a sea of pink gum.

There’s a lot of variation when it comes to how people recover after wisdom teeth surgery–I did not have a great time. I honestly hope that not many of you guys know what dry sockets are, because they are the worst and most horrible things.

When I cursed my horrible teeth to my dad, he got really quiet and said “I never had those.”

Yep. My dad is one of the lucky ones who was born without wisdom teeth.

As things are right now, we aren’t totally sure that this is a mutation, because we’re not sure why wisdom teeth don’t show up (even though it happens in an estimated 35% of the population). Is there a gene that says “No, wisdom teeth do not grow here?” A bunch of genes? Is it due to environmental factors? Some kind of physical injury in childhood that prevents them from forming? Nobody knows for sure!

There’s some recent evidence that the suppression of wisdom teeth was a mutation that popped up in China three to four hundred THOUSAND years ago. This doesn’t prove anything, but it sure is interesting to think that my dad is possibly the beneficiary of a four-hundred-thousand-year-old mutation.

Although if the point of variation like this is to pass them down to your children, that didn’t work out very well. Both my brother and I had fully impacted wisdom teeth followed by painful surgeries and long recoveries. Womp womp.

This article originally appeared on xoJane by Alle Connell

A gene mutation is a change that occurs in our DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental factors. However, technically speaking, we’re all mutants because everything that makes us human from our nails to our brain is a cause of mutations spread in our evolutionary history.


Genetic mutations are such a complex phenomenon that they sometimes produce amazing results. The beauty of some mutations is extremely unique and captures our attention faster than we blink our eyes.

In this post, we have listed up 30 beautiful Genetic mutations in humans due to rare genetic anomalies. Their eye-catching beauty is like a magnet that attracts everyone.

Scroll on peeps to witness the miracles of genetic mutations yourself!

  1. 1 Ocular albinism: When we see children from a primarily dark-eyed family having blue or green eyes, they are most likely ocular albinos.

  2. 2 Each eye more beautiful than the other

  3. 3 A natural carrot top of African descent “Red Hair”

  4. 4 Waardenburg Syndrome gives gives people beautiful, wide set, blue eyes

  5. 5 The best way to age through life

  6. 6 God has gifted her skin with patterns

  7. 7 Britain’s ‘first black and white twins’ born from same egg

  8. 8 Don’t stare or you’ll be hypnosis

  9. 9 Piebaldism, white fringe hair

  10. 10 Don’t let others be a barrier for you

  11. 11 The most perfect imperfections

  12. 12 Freckle queen

  13. 13 Magical eyes

  14. 14 The adorable Snow White

  15. 15 They’re more than just regular freckles

  16. 16 Cleft chin

  17. 17 Vitiligo: Causes the skin, hair, and even nails to lose colour.

  18. 18 Beauty lies in the eyes of the beholder

  19. 19 Multi colored eyes are such a treat to the eyes

  20. 20 Gigantism: The world’s tallest girl at 6’-8” Elisany da Cruz Silva, 17 of Brazil, with her 1’-6” shorter boyfriend

  21. 21 The bodybuilder Ia Östergren has disproportionately long legs. Her height is 5’8″, and the length of her legs is 3’5″.

  22. 22 An African American girl with albinism

  23. 23 This beyond stunning albino

  24. 24 A bright example of heterochromia

  25. 25 a unibrow model who tinted her naturally blond eyebrows black to highlight her unique appearance instead of hiding it.

  26. 26 Alexandria Genesis – the Most Beautiful Mutation

  27. 27 Girl with Cat eyes / Reptilian eyes

  28. 28 Beautiful Little Girl with Ice Blue Eyes

  29. 29 Double pupils used to be know as the “evil eye”. Medical term: Polycoria

  30. 30 Vitiligo Model

Do you or does someone you know have different-colored eyes? When you meet someone with one blue and one brown eye, for example, it sometimes takes a minute to register why they may seem a little “not quite right.” But then, when you look a little closer, you see how beautiful and unique this trait is. It’s a rare phenomenon called heterochromia. So is it always DNA-caused or can it happen for other reasons? Let’s have a look.

Where Eye Color Comes From

First, a little bit about eye color. A pigment called melanin determines hue, and eye color develops in the eight or so weeks following birth.

  • People with a lot of melanin in their irises have brown eyes.
  • People with very little melanin in their irises have blue or grey eyes.
  • People with middling amounts of melanin sport hazel or green eyes.

Newborns’ eyes all look blue because it takes weeks for the genetically-designated amount of melanin to ‘color in’ their irises. Today’s scientists believe that two genes control eye color (not just one), and it is how these genes interact that provides the full range of colors in people’s peepers. Which brings us to folks who have two different-colored eyes.

FUN FACT: Did you know that blue eyes were originally caused by a genetic mutation some 6,000 to 10,000 years ago? Scientists believe that everyone originally had brown eyes. That original mutation ended up greatly affecting the world’s DNA pool, didn’t it? READ MORE ABOUT IT HERE.

Different Types of Heterochromia

‘Heterochromia’ is a Latin term meaning ‘different colors,’ which perfectly describes this trait. There are actually three distinct categories of heterochromia, although some people may have a combination of two or three:

  1. Complete (each eye is a different color).
  2. Sectoral (a segment of one or both irises is a different color).
  3. Central (a different color surrounds the pupil).

How Does Heterochromia Happen and Why?

There are lots of different reasons! In the vast majority of cases, people are born with different-colored eyes, but there are times when heterochromia is caused by something else. Do you or someone you know have different-colored eyes? If so, this unique characteristic most likely happened from one of the reasons listed below.

Family DNA: Usually, if the trait is apparent from babyhood, then it came from the family gene pool. In fact, since it’s a dominant autosomal trait, chances are good one of the person’s parents has it too.

Trauma during Birth: If facial trauma occurs around the time birth, it may prevent melanin from ‘coloring’ the eye in the affected area of the face.

Genetic Mutation: Sometimes, a mutation in one of the genes regulating eye color may occur during embryonic development.

Disease: There are certain diseases such as Horner Syndrome that may cause heterochromia during a person’s lifetime.

Injury: Heterochromia that happens later in life is usually caused by eye injuries or specific types of medication.

Chimera: Under extremely rare circumstances, a person could be a chimera (when they contain separate DNA from an undeveloped twin) and have eyes with different colors as a result.

The Bottom Line

Keep in mind that traits like heterochromia or other physical characteristics are never absolute proof of paternity-a DNA paternity test is a much more scientific and reliable resource for determining a biological relationship. Too often, a mother might say, “But my child looks just like this man I slept with and not like the other one,” only to find out through DNA testing that the child is the biological offspring of the man he/she looks nothing like! So be very careful about making assumptions about a biological relationship based only on heterochromia.

Our bodies are wonderful things, and little blips in our DNA can sometimes have physical consequences-like double eyelashes! Over time, genetic mutations are no longer mutations at all, but are considered ‘normal’-like blue eyes. If you or someone you know is lucky enough to have different-colored eyes, embrace its unique look!


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