Glossary

This is the whole set of genes and DNA pairs in each one of our cells. The sequence of these DNA molecules determines how our cells will respond to any given environment, which ultimately determines what materials the cell will produce.

It only takes four types of DNA molecules, A, G, C, and T, to make the the genome. You can think about this like we think about computer files. Each file is, at its most basic level, made of sequences of ones and zeroes (corresponding to on and off, or electrons present and electrons not present). Fortunately for us, we have four separate possibilities, allowing a lot more complexity to be coded by our genes.

There are three billion of these DNA molecules in our genome sequence, but less than 1% of the DNA molecule differences account for all the variation in our bodies. When scientists talk about the human genome, oftentimes we're only referring to the fraction of DNA molecules that make the difference between people's genome sequences.

Our genotype is the sequence of DNA molecules in our genes that determines what our cells produce. When my hair produces the proteins to make a brown color, that's because my genotype codes for brown hair.

This is the outcome of our genotype. The brown color of my hair is the phenotype of my hair color genotype.

Occasionally, certain genetic sequences are frequently inherited together. Most often, these will arrive to an offspring from only one parent, which helps explain why they are inherited together. For example, we can suppose that the genes for blonde hair and blue eyes are inherited together. Then, if we sequence the genes of a person whose parent had blonde hair and blue eyes, we might find the blond hair/blue eyes haplotype.

Most human cells contain a set of 46 chromosomes, 23 each from mom and dad. The autosomal chromosomes are the ones that don't determine sex. That is to say, every chromosome is autosomal except for the X and Y chromosomes. Notably, this means that we all have two copies of each gene, except for the genes that are on the X and Y chromosomes.

This term indicates that a person only has one copy of an allele, which is a possible sequence of a gene. Remembering that we have two sets of each gene (except for sex genes), we might have two different variants of a gene. For example, I would be mono-allelic for brown eyes if I had a copy of a brown-eyes gene, but my other gene was for blue eyes. Here, if brown eyes are a dominant gene, then I would have brown eyes.

A recessive gene is one that isn't expressed in an organism. Because we have two copies of each gene, our cells can choose to use one, both, or none of them. The recessive gene is the one that our cells don’t use.

When our cells use only one of our two copies of genes, the gene that gets used is the "dominant" gene. That means that the cell uses that gene as the map to make proteins, such as the proteins for brown hair – even if we have a different copy of the gene, like the one for blonde hair.

Sometimes recessive genes can appear to be dominant. The best example of this is when a gene is related to the sex chromosomes. Men have X and Y sex chromosomes, and women have two X sex chromosomes. So, even if a gene on the X chromosome is recessive, it will be expressed in a man no matter what. This helps explain why men are colorblind more often than women – the gene for colorblindness is on the X chromosome, and men don't have a backup copy to use for their eye cells.

Just like computers use groups of ones and zeroes to represent a larger set of numbers (an 8-bit number can have 256 values, called a "byte"), our genes use groups of DNA molecules to indicate the right amino acid to use in a protein. Three DNA molecules can produce 64 different combinations, and this cluster of three molecules is called a "codon".

This is a gene that encodes for the "Pendrin" protein. "SLC" stands for "solute carrier", which explains what the Pendrin protein does. Some studies report that up to 40% of EVA cases are associated with this mutation.

Before understanding Pendrin, though, we'll have to learn a little bit about cellular biology. Cells are defined by a membrane that separates the outside-cell (extracellular) environment from the inside-cell (intracellular) environment. This is a crucial function, and you'll find that a lot of biology depends on membranes to separate compartments.

Pendrin is a protein that is embedded in the cellular membrane, and serves to selectively transport certain atoms across the membrane. Each of our cells has needs, one of which is a proper intracellular and extracellular environment. Pendrin allows cells to maintain these needs by transporting chloride (half of chlorine) with bicarbonate (one of the components of baking soda). Just like we make sure to eat food we like, our cells maintain close control over their insides.

Besides maintaining individual cells' needs, Pendrin also serves functions in whole tissues. One of the best-known functions of Pendrin is its contribution to intracellular/extracellular environments required for cells to form thyroid hormones. If Pendrin doesn't function, then thyroid hormones aren't formed as efficiently.

But we're interested in hearing--not hormones! So, how does Pendrin relate?

Researchers hypothesize that the Pendrin gene is used to control vestibular aqueduct growth during human development. This makes sense because different concentrations of atoms produce different pressures (as an example, red blood cells will swell and burst when placed in distilled water because the intracellular concentration is higher than the extracellular concentration). When atom transportation goes haywire, these pressures can't be effectively regulated.

Because Pendrin actually serves several functions, we find that Pendrin mutations are sometimes associated with more than one symptom! This is called "Pendred syndrome", and is characterized by both thyroid malfunction and vestibular anatomy malformation.

Still, not everyone with EVA has Pendred syndrome. How does that work? Well, it turns out that there are different mutations that can happen in the SLC26A4 gene. Some of these mutations make a bigger difference than others, and sometimes these mutations affect Pendrin to the extent that we find EVA without Pendred syndrome.

The "Gap Junction Beta 2" gene encodes for a protein called Connexin 26. Over 100 different mutations have been associated with GJB2 mutation, and it's estimated that up to 50% of patients with autosomal recessive non-syndromic hearing loss have a mutation in this gene.

Connexin 26 serves a different function than Pendrin, but the underlying cause is a bit similar. In the SLC26A4 section, we discussed how membranes play an important role in keeping cells healthy. Unlike Pendrin, which impacts individual cells, Connexin 26 forms part of a link between cells. We can think of Connexin 26 as a hand that reaches out to hold hands with its neighbor. When several of these hands hold each other, they can form a channel that allows solutes to move across one cell membrane and into another – this is called a "gap junction". Note, however, that Connexin 26 isn't the only connexin, and it may serve purposes besides forming gap junctions.

Connexin 26 is necessary for hearing because it allows the formation of gaps between cells that change intracellular potassium concentration. These gaps allow potassium to be moved away from a cell whose intracellular concentration has just changed, which essentially recharges the cell so it can be stimulated again.

You may have heard of these cells that change potassium concentration. They're called "hair cells", and they have a long hair that vibrates when the surrounding environment vibrates at a similar rate. When hair cells change potassium concentrations, that's a sign that the hair has just vibrated. If the hair cell can't share this sign with its neighbor – that is, if the hair cell isn't holding its neighbor's hand--then the sound signal stops right there. This is one form of what is called "sensorineural hearing loss".

Remember, though, that these explanations are not necessarily correct. That's the goal of science – finding out what is correct using clear evidence. An alternative hypothesis to the potassium hand-shaking hypothesis presented above proposes that a different molecule, not potassium, is the one that moves across Connexin 26 gap junctions.

This is one of the "forkhead" family genes. Unfortunately, its specific function is still unknown, but there is a lot of information about how the gene affects the body.

One of the most prominent features of this gene is that it is essential for normal development of hearing, sense of balance, and kidney function. These functions may seem wildly different, but the association makes sense when considering that the kidney is responsible for filtering different atoms for excretion. This means that, along with impacting atom exchange in the ear during human development, this gene can affect the kidney!

While the specific function isn't known, this gene is likely a "transcription factor". That means that when the FOXI1 gene is used to make proteins, those proteins in turn affect how other genes are regulated.

Notably, some cells require a properly-functioning FOXI1 gene before they can produce Pendrin. This may help scientists find the link between FOXI1 and EVA.

SNHL is defined according to where a malfunction occurs. If there is a malfunction of the inner ear or its associate nerves in the brain, then hearing loss is called SNHL. This represents approximately 90% of hearing loss cases.

Also known as "magnetic resonance imaging", this technique takes advantage of the fact that some atoms have a characteristic direction that they spin. By applying the right magnetic waves, these atoms can be manipulated towards higher-energy states (like a compass needle). Radio waves are then generated to further excite the atoms, where different atoms absorb the radio waves at different rates. When the radio waves are shut down, the atoms release the radio wave energy that they absorbed (like how a heat dissipates from a cup of coffee). This energy release is recorded, and an image of the inside of a body is generated by correlating energy release to the atoms we would expect to be present in different tissues. These machines were first conceived of in the early 1970s, and produced soon thereafter. Because they are so complex, there are several variations that can be used to identify different attributes of human tissue.

This is when a radio-opaque chemical is injected into a person for the purpose of increasing the difference in visibility across types of tissue. As an example of contrast agent use, a cardiologist might inject a contrast agent near the heart's blood supply as a way to better identify the site of a heart attack.

This inner-ear malformation sometimes accompanies EVA. It is defined according to the cochlea, and how many turns the cochlea can do before it ends. Normally, a person would have a cochlea that turns in on itself two-and-a-half times. For someone with Mondini Malformation, however, the cochlea would only turn inwards one-and-a-half times. Mondini malformation is associated with hearing loss.

There are two ways that sound vibrations can reach our inner ear sensory organs: first, via pressure waves in air that are transmitted through the ear, second, via vibrations in cranial bones. If there is a difference in a person's ability to perceive sound between these two ways, then there might be something wrong with the pressure wave transmission that occurs in the ear. Often, this is associated with the middle ear, which houses three small bones called the malleus, incus, and stapes.

This is when only one side of the body is affected by a condition. In the context of EVA, it would mean that a person has EVA on either the left or the right side, but not both.

This is when both sides of the body are affected by a condition. In the context of EVA, it would mean that a person has EVA in both ears.

This syndrome occurs with some mutations of the SLC26A4 gene, where Pendrin deficiency leads to thyroid deficiency and goiter. This is called a "syndrome" because it involves several symptoms that are commonly observed together.

This is when scientists or researchers look at events that have already happened. For example, when scientists look at medical records that have already been made, this would be called a retrospective chart review.

This is when scientists or researchers observe events that haven't happened yet, or that may not happen at all. For example, a researcher might get approval to periodically record a patient's status after an operation. This could involve examining medical records, or it might require using special forms for the condition of interest. Either way, this sort of study would be a prospective study.

This is the inner ear system that senses balance. It is comprised of three semi-circular chambers that are each oriented in one of three dimensions, similar to a gimbal system.