Genetic Kidney Disease Jargon Busters
This glossary features more than 130 terms explained in an easy-to-understand way to overcome the common Genetic Kidney Disease jargon, acronyms and abbreviations.
Type CTRL-F to find a word or phrase in this section
A
Acute Kidney Injury
AKI
This term describes a sudden reduction in kidney function. AKI can occur due to stress on the kidneys from illnesses, infections, dehydration or exposure to certain medications. Acute kidney injury can get better in a few days or weeks, but sometimes it causes ongoing problems.
Albumin
Alb
This is the major protein in blood. Large amounts of this protein in your urine may be a sign of chronic kidney disease. See albuminuria below.
Albuminuria
A condition in which your urine has more than the normal amounts of albumin. This may be a sign of kidney disease.
Allele
An allele is one of two or more versions of DNA sequence (a single base or a segment of bases) at a given genomic location. An individual inherits two alleles, one from each parent, for any given genomic location where such variation exists. If the two alleles are the same, the individual is homozygous for that allele. If the alleles are different, the individual is heterozygous.
Amino Acid
AA
These form the basic building blocks of proteins. Many amino acids occur in nature. Only 22 are used as the building blocks of proteins. Nine of these are "essential" amino acids, meaning that we need to get them from our food as we cannot make them ourselves. They link to each other to create chains of amino acids (peptides) that are folded or joined to other peptides to make proteins.
The body's ability to line up amino acids in the right order to make a protein is governed by genes, and the process of making a peptide from a gene is called translation. This is why a fault in a gene can lead to the production of a faulty protein. This in turn gives rise to a structural or functional change in the body, sometimes a disease.
Amniotic Fluid
This is the fluid that surrounds an unborn baby during pregnancy. It contains protein and carbohydrates which help the baby to grow. The fluid allows the baby to move about in the womb and protects it from injury by cushioning sudden movements. The amount of fluid in the womb increases as the baby grows. A lack of amniotic fluid can impair the development of the baby’s lungs, and this can cause breathing difficulties once the baby is born.
Autosomal Dominant Polycystic Kidney Disease
ADPKD or PKD
This is a genetic disorder involving the growth of numerous cysts in the kidneys. ADPKD cysts can slowly replace much of the mass of the kidneys, reducing function and leading to kidney failure.
About one person in every 1,000 has ADPKD, meaning approximately 25,000 Australians will be affected by ADPKD in their life. ADPKD occurs equally in males and females of all ethnic origin. As its name suggests, this is an autosomal dominant inherited kidney disease. This means that a single copy of the mutated gene (from one parent) is enough to cause the disorder. A biological child of a person affected by an ADPKD has a 50% chance of being affected by that condition.
Symptoms can vary in severity. Most people start developing symptoms between the ages of 30 and 40. ADPKD is a progressive disease, which means the symptoms tend to get worse over time.
The most common symptoms of ADPKD are pain in the back and the sides from kidney cysts, and headaches from high blood pressure. Other features may include blood in urine, urinary tract infections, kidney stones, liver and pancreatic cysts, abnormal heart valves, and brain aneurysms.
For more information see: https://pkdaustralia.org/adpkd/
Autosomal Dominant Tubulointerstitial Kidney Disease
ADTKD or Medullary cystic kidney disease or MCKD
This is a group of genetic kidney diseases that cause progressive loss of kidney function. Signs and symptoms of all forms of ADTKD include slowly worsening kidney disease. Kidney ultrasound examination is generally normal early in the disease course, but some people with ADTKD have cysts in the centre of the kidneys (medullary cysts) that may be seen on an ultrasound. Inheritance of ADTKD is autosomal dominant, as the name implies. Most people with ADTKD have a family history of "kidney disease" (if not a family history of ADTKD specifically) or some of the other symptoms. The diagnosis of ADTKD may be suspected based on family history, symptoms, and laboratory tests, and it can be confirmed by genetic testing.
Autosomal Recessive Polycystic Kidney Disease
ARPKD
This is a genetic condition that is characterised by the growth of cysts in the kidneys (which lead to kidney failure) and liver and problems in other organs, such as the blood vessels in the brain and heart. The severity varies from person to person. The signs of ARPKD frequently begin before birth, so it is often called infantile PKD but some people do not develop symptoms until later in childhood or even adulthood. The condition is caused by a genetic change in the PKHD1 gene and is inherited in an autosomal recessive manner.
Audiologist
A medical professional who specialises in hearing loss.
Alport Syndrome
AS
This is a genetic disorder that affects the collagen protein genes. Collagen is an important protein that is needed to maintain normal function of cell membranes of your kidneys, eyes and ears. It usually develops during early childhood. Symptoms are chronic blood and protein in urine. This progressive condition can lead to kidney failure, hearing loss and abnormalities of the eyes.
For more information see https://alport.org.au/awareness/
A condition in which the number of red blood cells is lower than average. Anaemia reflects low level of haemoglobin in the blood. This results in less oxygen being carried to the body’s cells and can cause reduced energy levels, breathlessness, and feeling of weakness.
Aneuploidy
Aneuploidy is an abnormality in the number of chromosomes in a cell due to loss or duplication. In humans, aneuploidy would be any number of chromosomes other than the usual 46.
Angiotensin Converting Enzyme Inhibitors
ACE inhibitors or RAS blockade
This group of medications were originally prescribed to reduce blood pressure. ACE inhibitors also reduce the scarring process in the glomeruli, slowing the progression of kidney disease. It is normally prescribed as a pill to be taken once a day. Brand names include Ramipril and Enalapril. A blood test is usually performed before starting treatment to record the level of kidney function. Side effects of the treatment are uncommon but may include persistent irritating cough.
ACE inhibitors may be used in conditions where there are high levels of protein in the urine.
In Alport syndrome for example, this group of medications is found to slow the progression of kidney disease.
Angiotensive Receptor Blocker
ARB
Similar to ACE inhibitors, this is another form of medication designed to reduce blood pressure. It is often prescribed if ACE inhibitors have caused side effects such as a persistent cough. Brand names often end in ’sartan’ such as Losartan and Irbesartan. As with ACE inhibitors a blood test is usually performed before starting treatment. ARB medication is used like ACE inhibitors to slow the progression of certain types of kidney disease.
Antidiuretic Hormone
ADH
A natural body chemical that slows down the body’s production of urine. In nephrogenic diabetes insipidus, the kidney tubules do not respond to ADH as expected and are therefore, not able to concentrate the urine appropriately.
Atypical Haemolytic Uraemic Syndrome
aHUS
This is a very rare and life-threatening genetic condition. In those living with aHUS, part of the immune system (known as the complement system) is uncontrolled. As a result, the immune system is always active, attacking the body’s cells. This can lead to serious problems such as blood vessel damage, abnormal blood clotting, and damage to major organs, including the kidneys, brain and heart.
Audiogram
This is a test to measure the range of an individual’s hearing. Sounds are presented through a set of headphones and the individual is required to indicate when they hear a sound. Usually, individuals are asked to press a button the moment they hear the sound. The sounds vary in volume and frequency (high pitch to low pitch) to represent the full range of human hearing. This test may be required for genetic kidney conditions that also affect hearing such as Alport Syndrome.
Autosomal Dominant
AD
Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the mutated gene is enough to cause the disorder. A biological child of a person affected by an autosomal dominant condition has a 50% chance of being affected by that condition via inheritance of a dominant allele. Autosomal Dominant Polycystic Kidney Disease is an example of an autosomal dominant genetic disorder.
It is important to remember that chance has no memory and the 50% chance of inheriting the altered gene for the condition applied to each child, irrespective of whether or not the parents already have children with, or without the condition.
In autosomal dominant conditions, males and females are affected in roughly equal proportions, and both affected males and females are both able to pass the conditions to their sons or daughters.
Sometimes autosomal dominant conditions can develop for the first time in the affected individual’s family, this is called “de novo”.
Autosomal Dominant Polycystic Kidney Disease is an example of an autosomal dominant genetic disorder.
Autosomal Recessive
AR
Autosomal recessive is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Recessive” means that two copies of the mutated gene (one from each parent) are required to cause the disorder. In a family where both parents are carriers and do not have the disease, roughly a quarter of their biological children will inherit two disease-causing alleles and have the disease. Nephronophthisis is an example of an autosomal recessive genetic disorder.
B
Bardet Biedel Syndrome
BBS
This is an inherited condition that affects many parts of the body. People with this syndrome have progressive visual impairment due to cone-rod dystrophy; extra fingers or toes (polydactyly); truncal obesity; decreased function of the male reproductive organs (hypogonadism); kidney abnormalities (nephronophthisis); and learning difficulties. Genetic changes in many genes are known to cause Bardet-Biedl syndrome and inheritance is usually autosomal recessive.
Bartter Syndrome
Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body. In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the baby (amniotic fluid). Polyhydramnios increases the risk of premature birth. Beginning in infancy, babies with Bartter syndrome often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterised by low levels of potassium in the blood, which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness). One form begins before birth (antenatal) and is often more severe. The other form, often called the classical form, begins in early childhood and tends to be less severe.
Base Pair
A base pair consists of two complementary DNA nucleotide bases that pair together to form a “rung of the DNA ladder.” DNA is made of two linked strands that wind around each other to resemble a twisted ladder — a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), cytosine (C), guanine (G) or thymine (T). The two strands are held together by hydrogen bonds between pairs of bases: adenine pairs with thymine, and cytosine pairs with guanine.
Benign variant
This involves changes to the DNA sequence that have no impact on health or development.
Bioinformatics
Bioinformatics, as related to genetics and genomics, is a scientific subdiscipline that involves using computer technology to collect, store, analyse and disseminate biological data and information, such as DNA and amino acid sequences or annotations about those sequences. Scientists and clinicians use databases that organise and index such biological information to increase our understanding of health and disease and, in certain cases, as part of medical care.
Blood Pressure
BP
This is the force of blood exerted on the inside walls of blood vessels. Blood pressure is expressed as two numbers. For example, a blood pressure result of 120/80 is said as “120 over 80.” The first number is systolic pressure, or the pressure when the heart pushes blood out into the arteries. The second number is the diastolic pressure, or the pressure when the heart rests.
C
Carrier
A genetic carrier is an individual who does not show any symptoms of a disease, but “carries” a genetic variant which is associated with disease. The carrier has inherited the variant allele from one parent and a normal allele from the other parent. A carrier can also pass on this genetic variant to their biological children in an autosomal recessive or X-linked manner.
Carrier Screening
Carrier screening involves testing to see if a person “carries” a genetic variation (allele) associated with a specific disease. A carrier has inherited a normal allele and a variant allele for a disease-associated gene, one from each parent. Most typically, carrier screening is performed to look for autosomal recessive inherited diseases when the suspected carrier has no symptoms of the disease, but that person’s biological children could have the disease if the other parent is a carrier of a genetic variant in the same gene.
Chromosome
Chr
Chromosomes are threadlike structures made of protein and a single molecule of DNA that serve to carry the genomic information from cell to cell. Humans have 22 pairs of numbered chromosomes (autosomes) and one pair of sex chromosomes (XX or XY), for a total of 46. Each pair contains two chromosomes, one coming from each parent, which means that children inherit half of their chromosomes from their biological mother and half from their biological father.
Chronic Kidney Disease
CKD
A progressive reduction in kidney function or kidney damage which is present for at least three months. CKD may develop over many years and may lead to kidney failure, which requires dialysis or a kidney transplant to keep you alive.
Ciliopathies
These comprise a group of disorders associated with genetic mutations which produce defective proteins. This results in abnormal formation and function of cilia. As cilia are a component of almost all cells, their abnormal function can result in anomalies in the kidneys, eyes and brain. Also see Bardet-Biedl syndrome, Joubert Syndrome, nephronophthisis, Meckel-Gruber Syndrome and Senior-Loken syndrome.
Collagen
The main protein in your skin, which gives strength and support for your tendons, cartilage, bone and connective tissue which surround many of your organs.
Codon
A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide) that forms a unit of genetic information to build a particular amino acid or stop signals which indicate the termination of protein development.
Congenital
Congenital refers to a condition or trait that exists at birth. Congenital conditions or traits may be genetically inherited, or may result from an event occurring during pregnancy or at birth, or they may be due to a combination of these factors.
Congenital Anomalies of the Kidney and Urinary Tract
CAKUT
More commonly known by the acronym CAKUT, this describes a group of anomalies (abnormalities) affecting the kidneys and other parts of the urinary tract, which consist of the ureter, bladder and urethra. The ureters are tubes that carry urine from the kidneys to the bladder and the urethra is the tube that carries the urine from the bladder to outside of the body.
CAKUT is caused by a combination of environmental and genetic factors that affect the formation and development of the kidneys and urinary tract prenatally (during pregnancy).
CAKUT is one of the most common groups of abnormalities diagnosed in newborns and is the most common cause of developing kidney failure in childhood.
Congenital Nephrotic Syndrome
CNS
This is a genetic condition of the kidney that begins early in development during pregnancy or within the first three months of life. The syndrome is characterised by a group of symptoms, including protein in the urine (proteinuria), low blood protein levels, high cholesterol levels, and swelling (nephrotic syndrome), which progresses rapidly to kidney failure. Infants with congenital nephrotic syndrome may have failure to thrive and frequent infections.
Copy Number Variation
CNV
This refers to a circumstance in which the number of copies of a specific segment of DNA varies among different individuals’ genomes. The individual variants may be short or include thousands of bases. These structural differences may have come about through duplications, deletions or other changes and can affect long stretches of DNA.
Creatinine
Cr
This is a marker of kidney function, being a waste product of muscular activity. It is usually removed from your blood by your kidneys and passes out in your urine. When your kidneys aren’t working properly, creatinine stays in your blood, and creatinine levels in your blood tests can be higher than normal.
Cystinosis
A genetic disease caused by the body's inability to process cystine, which is a by-product of protein metabolism. This leads to a buildup of cystine in the body's organs and tissues and ultimately to severe organ damage. This is an autosomal recessive inherited disorder, which occurs when a person receives an abnormal copy of the cystinosin gene from each parent. There are three forms of the illness: infantile, juvenile, and adult cystinosis. The infantile form of the disease is the most common and the most severe. Cystinosis can impact many parts of the body, including the eyes, muscles, brain, heart, white blood cells, thyroid, and pancreas as well as causing serious kidneys problems.
For more information see:
https://australiancystinosisfoundation.com.au/what-is-cystinosis/
Cysts
A fluid filled sack, that can vary in size and may occur anywhere in the body. Often, they do not cause any problems and can be left untreated. Problems can develop if the cysts grow very large or when multiple cysts develop in the same organ such as the kidneys, stopping them from working properly.
Cystinuria
This is a condition in which urine contains high levels of the amino acid cystine. If cystine does not dissolve in the urine, it can build up to form kidney stones.
D
Deletions
This is a type of mutation that involves the loss of one or more nucleotides from a segment of DNA. A deletion can involve the loss of any number of nucleotides, from a single nucleotide to an entire piece of a chromosome.
Dense Deposit Disease
DDD or Membranoproliferative glomerulonephritis type 2
This is a condition that primarily affects kidney function. The major symptoms are due to kidney malfunction, and often include protein leak in the urine (proteinuria); blood in the urine (haematuria); reduced amounts of urine; low levels of protein in the blood; and swelling in many areas of the body. Dense Deposit Disease can have genetic or non-genetic causes. It can be caused by genetic changes in the C3 and CFH genes. Dense Deposit Disease may develop as a result of both genetic risk factors and environmental triggers. It can also result from the presence of autoantibodies that block the activity of proteins needed for the body's immune response. Most cases are occur by chance in people with no history of the disorder in their family.
Denys-Drash syndrome
DDS or Drash syndrome or Wilms tumour-DSD syndrome
Denys-Drash syndrome is a condition that affects the kidneys and genitalia. Kidney disease typically begins in the first few months of life. In addition, up to 90 percent of people with this condition develop a rare form of kidney cancer known as Wilms tumour. Males with Denys-Drash syndrome have gonadal dysgenesis, a condition in which their external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. The testes are also undescended, meaning that they remain in the pelvis, abdomen, or groin. Affected females usually have normal genitalia. For this reason, females with this condition may be diagnosed with isolated nephrotic syndrome. Denys-Drash syndrome is caused by genetic changes in the WT1 gene. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, most cases result from new genetic changes in the gene and occur in people with no history of the disorder in their family.
Deoxyribonucleic Acid
DNA
Deoxyribonucleic acid (abbreviated DNA) is the molecule that carries genetic information for the development and functioning of an organism. DNA is made of two linked strands that wind around each other to resemble a twisted ladder — a shape known as a double helix.
Dialysis
When the kidneys stop working properly, machines are used to take over some of their function. There are two different kinds of dialysis - haemodialysis and peritoneal dialysis. Both systems control the amount of water and salt in the body and help to remove some of the waste products that our bodies produce. Dialysis can take over the function of the kidneys but does not make them better.
DNA sequencing
DNA sequencing refers to the general laboratory technique for determining the exact sequence of nucleotides, or bases, in a DNA molecule. The sequence of the bases (often referred to by the first letters of their chemical names: A, T, C, and G) encodes the biological information that cells use to develop and operate. Establishing the sequence of DNA is key to understanding the function of genes and other parts of the genome.
Duplication
This refers to a type of mutation in which one or more copies of a DNA segment is produced. This can be as small as a few bases or as large as a major region on a chromosome.
E
F
End Stage Renal Disease / End Stage Kidney Disease
ESRD / ESKD
At this stage there is total and permanent kidney failure. When the kidneys fail, the body retains fluid. Harmful wastes build up. A person with ESRD needs treatment with dialysis or transplantation to replace the work of the failed kidneys. (Also see Kidney Failure)
Enzymes
Substances which cause chemical changes to take place in the body.
Epigenetics
This is a field of study focused on changes in DNA that do not involve alterations to the underlying sequence. The DNA letters and the proteins that interact with DNA can have chemical modifications that change the degrees to which genes are turned on and off. Certain epigenetic modifications may be passed on from parent cell to daughter cell during cell division or from one generation to the next. The collection of all epigenetic changes in a genome is called an epigenome.
Erythropoietin
EPO
This is a hormone that is made mostly in the kidneys. The cells that make it are found in the lining of the capillary blood vessels. EPO is released into the blood stream and is picked up by the developing immature red blood cells and allows red cell development to continue. Without EPO, red cell production stops. This way EPO controls the production of red cells and therefore the red cell composition of blood.
In chronic kidney disease the ability of the kidneys to produce EPO falls, and this leads to anaemia.
Estimated Glomerular Filtration Rate
eGFR
This is a blood test result based on creatinine and your age and indicates how well the kidney’s function. The result is like a percentage of your kidney function compared to normal. It helps work out the stage of CKD.
Exome
Each gene has protein-coding regions that are referred to as exons. The human genome contains about 180,000 exons, which are collectively called an exome.
Exon
This is a region of the genome that ends up within an mRNA molecule. Some exons are called “coding” exons containing information to make a protein, and others are “non-coding”.
Fabry Disease
Fabry disease is a rare genetic disease where the gene that controls the body's ability to make the enzyme, alpha GAL, is abnormal. This results in a deficiency or absence of this enzyme that breaks down globotriaosylceramide, a fatty material that can accumulate in blood and blood vessel walls, leading to decreased blood flow. Kidney complications due to Fabry disease are common and serious. Kidney failure typically occurs in the third decade of life. Patients affected by Fabry Disease are also at greater risk of heart attacks and strokes. Enzyme replacement and oral chaperone therapy is used to slow down build-up of this fatty material and may slow the progression of disease.
Familial Focal Segmental Glomerulosclerosis
Familial FSGS or Genetic FSGS
This is a type of kidney disorder, which is characterised by scar tissue that forms in some of the kidney filters (glomeruli) in the kidney. Genetic FSGS is a rare form of FSGS and is suspected when several members of a family show signs of FSGS. Familial FSGS can also occur when neither parent has the disease but each one carries a copy of an altered gene that can be passed on to the next generation. Familial FSGS may cause non-specific signs and symptoms, including protein in the urine, elevated levels of creatinine, and swelling.
See also steroid resistant nephrotic syndrome.
Family History
FH
This is a record of the health conditions of an individual and that person’s biological family members, both living and deceased. A family history can help determine whether someone has an increased genetic risk of having or developing certain conditions. It is often recorded by drawing a pedigree (a family tree) that illustrates the relationships among individuals.
Frameshift mutation
This refers to the insertion or deletion of nucleotide bases in numbers that are not multiples of three. This is important because a cell reads a gene’s code in groups of three nucleotides when making a protein. Each of these three nucleotides corresponds to one of 20 different amino acids used to build a protein. If a variant disrupts the normal 3-nucleotide reading frame, the entire gene sequence following this variant will be incorrectly read. This can result in the addition of the wrong amino acids to the protein and or the creation of a stop codon that signals a halt to protein development in the cell.
Frasier Syndrome
This is a rare genetic syndrome that affects the kidneys and genetalia. Typically, children have protein in urine (proteinuria). There is slow progression to kidney failure which typically occurs between 20-30 years of age. Males with Frasier syndrome have gonadal dysgenesis, a condition in which their external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. Internal reproductive organs (gonads) are typically underdeveloped and are non-functional and often can become cancerous. These tumours that develop are called gonadoblastomas.
G
Gamete
This is a reproductive cell. Female gametes are called ova or egg cells, and male gametes are called sperm. Ova and sperm are haploid cells, with each cell carrying only one copy of each chromosome. During fertilization, a sperm and ovum unite to form a new diploid organism.
Gene
The gene is considered the basic unit of inheritance. Genes are passed from parents to their biological children and contain the information needed to code specific proteins which have their individual functions within the body.
Gene Panels
Investigates a defined number of genes, that could include tens to thousands of genes.
Gene Therapy
Gene therapy is a technique that uses a gene(s) to treat a medical disorder. Often, gene therapy works by adding new copies of a gene that is broken, or by replacing a defective or missing gene in a patient’s cells with a healthy version of that gene. Both inherited genetic diseases (e.g., haemophilia and sickle cell disease) and acquired disorders (e.g., leukemia) have been treated with gene therapy
Genetic Counselling
GC
This refers to the guidance relating to genetic disorders that a specialised healthcare professional (genetic counsellor) provides to an individual or family. A genetic counsellor might provide information about how a genetic condition could affect an individual or family and/or interpret genetic tests designed to help estimate the risk of a disease. The genetic counsellor conveys information to address the concerns of the individual or family, helps them make an informed decision about their medical situation and provides psychological counselling to help them adapt to their condition or risk.
Genetics
This is the study of inheritance, including the interplay of genes, DNA variation and their interactions with environmental factors.
Genetic Testing
Genetic testing is the use of a laboratory test to examine an individual’s DNA for variations. In a medical setting, the results of a genetic test can be used to confirm or rule out a suspected genetic disease. Results may also be used to determine the likelihood of parents passing on a genetic mutation to their biological children. Genetic testing may be performed before or after birth.
Genetic Steroid Resistant Nephrotic Syndrome
Genetic SRNS
This is a rare, inherited form of nephrotic syndrome characterised by protein in the urine, low blood levels of protein, swelling (oedema) and high level of cholesterol in the blood. People typically do not respond to an initial trial of steroids (i.e. steroid-resistant nephrotic syndrome; SRNS) and this follows a complicated course involving decline in kidney function and kidney failure.
Genomics
This is the study of all the DNA of a person – the genome. Genomics involves identifying all the genes and functional elements in a person’s genome and how they interact.
Genotype
A genotype is an individual’s genetic makeup. It is a scoring of the type of variant present at a given location (i.e., a locus) in the genome. It can be represented by symbols.
Germline variant
Germline mutation
These are changes to the DNA sequence (variant) that occur in eggs and sperm cells. The resulting embryo and baby will have the variant in every cell of their body that contains a copy of the genome. These variants are also present in the cells that produce their own sperm or eggs and therefore can be passed on to their biological children.
When considering inheritance of a genetic condition, it is those that are the result of a germline variant that have implications for the patient’s relatives.
Gitelman Syndrome
This is an autosomal recessive inherited disorder which occurs when a person receives an abnormal copy of the SLC12A3 or CLCNKB genes from each parent. Gitelman syndrome is a kidney function disorder that causes an imbalance of salts in the body, including ions of potassium, magnesium, and calcium. It is usually diagnosed during late childhood or adulthood. The most common symptoms of Gitelman syndrome include fatigue, salt craving, thirst, frequent urination, muscle cramping, muscle weakness, dizziness, tingling or numbness, low blood pressure and heart palpitations.
Glomerular Basement Membrane
GBM
A mesh of proteins found in the kidneys which forms the boundary between the blood and urine. Water and other small molecules are filtered across this membrane from the blood to pass out of the body in the urine.
Glomerular Filtration Rate
GFR
This is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute.
Glomerulus (singular) Glomeruli (plural)
Tiny filters found in the outer part of the kidneys which are responsible for filtering the blood stream. Glomeruli are actually tiny arteries folded up into a ball, and tucked inside a capsule which collects the filtered fluid. These microscopic blood vessels are thin walled and very permeable to water and small molecules. They are commonly known as glomerular capillaries. Each capillary is a tiny tube with blood flowing inside it. The wall of the tube has a perforated lining like a colander. This is surrounded by a strong membrane called the Glomerular Basement Membrane.
Glyoxylate
A chemical produced in the liver which controls the production of oxalate inside the body.
H
Haematuria
This is when blood is found in the urine. This occurs when the kidneys aren’t filtering well and red blood cells leak into the urine. Sometimes it can be obvious and the urine changes colour to red or brown (called Macroscopic Haematuria), or it may only be a small amount found when the urine is tested (called Microscopic Haematuria).
Haemodialysis
HD
This is a form of dialysis treatment that takes over the role of the kidneys. Haemodialysis is a way of treating the blood by passing it through an artificial filtering system. Blood is pumped through a filter and cleaned before being returned to the body. Most patients require at least three sessions of haemodialysis a week, with each session lasting around four hours. Treatment usually takes place in hospital but can be set-up at home.
Haploid
Haploid refers to the presence of a single set of chromosomes in an organism’s cells. Sexually reproducing organisms are diploid (having two sets of chromosomes, one from each parent). In humans, only the egg and sperm cells are haploid.
Heterozygous
This term refers to having different versions (alleles) of a genomic marker for a particular trait from each biological parent. An individual who is heterozygous for a genomic marker has two different versions of that marker. By contrast, an individual who is homozygous for a marker has identical versions of that marker.
Homozygous
This refers to having inherited the same versions (alleles) of a genomic marker for a particular trait from each biological parent. An individual who is homozygous for a genomic marker has two identical versions of that marker.
Hypercalciuria
Abnormally large amounts of calcium in the urine.
Hyperoxaluria
Unusually large amounts of oxalate in the urine, leading to kidney stones.
Hypertension
HTN
This describes the state of high blood pressure. Blood pressure measures the force of the blood on the walls of the blood vessels. Blood pressure is measured as two numbers: the systolic blood pressure (when the heart contracts), and the diastolic blood pressure (when the heart relaxes). A blood pressure reading of 130/85 means a systolic BP of 130 and a diastolic BP of 85. These two numbers show how hard the heart is working. The harder it is for the blood to flow through the vessels, the higher the blood pressure will be. High blood pressure is one of the major risk factors of kidney disease and kidney failure.
I
IgA Nephropathy
IgA nephropathy is a kidney disorder that occurs when IgA (immunoglobulin A), a protein that helps the body fight infections, settles in the kidneys. In the early stages, IgA nephropathy has no symptoms. The first sign of this condition may be blood in the urine. Kidney failure may develop. In most instances, the cause of this condition is unknown; however, several cases of familial IgA nephropathy have been reported. Familial IgA nephropathy is suspected to run through families in an autosomal dominant manner and is linked to genetic material on the long arm of chromosome 6 (6q22-23).
Inherited
This refers to a trait passed on to you by your biological parents. This can include your personality, traits, physical appearance and some health conditions.
In genetics, this term refers to a trait or variant encoded in DNA and passed from biological parent to children during reproduction. Inheritance is determined by the rules of Mendelian genetics.
Intron
This is a region within a gene that does not remain in the final mature mRNA molecule following transcription of that gene and does not code for amino acids that make up the protein encoded by that gene.
J
Joubert Syndrome
This is a rare, autosomal recessive inherited genetic disorder. It is characterised by abnormal brain development that includes the absence or underdevelopment of the cerebellar vermis (an area of the brain that controls balance and coordination) and a malformed brain stem. It can be inherited (both parents must have a copy of one of the many the gene mutations that causes the disorder) or sporadic (happening on its own).
Symptoms and features of Joubert Syndrome include, decreased muscle tone, abnormal eye movements, impaired intellectual development, involuntary muscle movements, abnormally rapid breathing, physical deformities (polydactyly, cleft lip or palate, and tongue abnormalities), kidney and liver abnormalities and seizures.
The kidney abnormalities are known as nephronophthisis, which can lead to increased urine production, excessive thirst, general weakness, and extreme tiredness. Fluid-filled cysts develop in the kidneys, and people also have a shortage of red blood cells, a condition known as anaemia. These changes may lead to kidney failure.
K
Karyotype
This is an individual’s complete set of chromosomes. The term also refers to a laboratory-produced image of a person’s chromosomes isolated from an individual cell and arranged in numerical order. A karyotype may be used to look for abnormalities in chromosome number or structure.
Kidney Biopsy
This is a routine medical test for a wide number of kidney conditions. It is usually done using local anaesthetic, although in younger children sedation or general anaesthesia is often preferred. Mostly biopsies can be done as a day case. Using an imaging technique, usually an ultrasound scan, the doctor steers a needle to the position of one of the kidneys. Thin cores of kidney tissue are taken from the body to be examined under a microscopy to provide a diagnosis.
Kidney Failure
KF or End Stage Kidney Disease (ESKD)
At this stage there is total and permanent kidney failure. When the kidneys fail, the body retains fluid. Harmful wastes build up. A person with KF needs treatment with dialysis or transplantation to replace the work of the failed kidneys. (Also see End Stage Kidney Disease)
Kidney Function
The amount of work done by the kidneys. A decline in kidney function means the kidneys are not filtering wastes and fluid from the blood as well as they should.
Kidneys
Two bean shaped organs that filter wastes from the blood. The kidneys are located near the middle of the back, one on each side of the spine. They create urine, which is delivered to the bladder through tubes called ureters.
Kidney Stone
(AKA calculus, nephrolithiasis)
A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. Kidney stones include calcium oxalate stones, cystine stones, struvite stones and uric acid stones.
L
Locus
This is the physical site or location within a genome of a gene or another DNA segment of interest. It is like a street address.
Lowe Syndrome
Lowe Oculocerebrorenal dystrophy or Oculocerebrorenal syndrome of Lowe or OCRL
This is a rare condition that primarily affects the eyes, central nervous system and kidneys. Some of the signs and symptoms associated with the condition are often present from birth, including congenital cataracts and other eye abnormalities including reduced muscle tone and feeding difficulties. Affected people may also experience kidney problems (such as Fanconi syndrome – abnormal kidney tubules lead to excessive urination and drinking during childhood and growth restriction), infantile glaucoma, impaired vision, developmental delay, intellectual disability, behavioural problems, seizures and short stature. Lowe syndrome occurs almost exclusively in males. The condition is inherited in an X-linked recessive manner.
M
Meckel-Gruber Syndrome
Meckel syndrome
This is a very severe genetic disorder that is characterised by multiple cysts on the kidneys, protrusion of a portion of the brain through an opening in the skull (occipital encephalocele), and extra fingers or toes (polydactyly). Affected children may also have abnormalities affecting the head and face, liver, lungs, genitals, and urinary tract. Meckel-Gruber syndrome inherited in an autosomal-recessive manner.
Mendelian genetics
This refers to certain patterns of how traits are passed from parents to their biological children. These general patterns were established by the Austrian monk Gregor Mendel, who performed thousands of experiments with pea plants in the 19th century. Mendel’s discoveries of how traits are passed down from one generation to the next introduced the concept of autosomal dominant and autosomal recessive modes of inheritance.
Messenger RNA
mRNA
This is a type of single-stranded RNA involved in protein development. As DNA cannot leave the cell nucleus, relevant sections of DNA are transcribed into mRNA. The role of mRNA is to carry protein information from the DNA in the cell’s nucleus to the cell’s cytoplasm where the protein-making machinery reads the mRNA sequence and translates each three-base codon into its corresponding amino acid in a growing protein chain.
Microarray
This laboratory approach uses technology that looks for extra or missing segments of DNA known as copy number variants.
Missense Mutation
A missense mutation is a DNA change that results in different amino acids being encoded at a particular position in the resulting protein. Some missense mutations alter the function of the resulting protein.
Mutation
A mutation is a change in the DNA sequence of an individual. Mutations that occur in eggs and sperm are called “germline mutations”, will be present in every cell that develops from that egg or sperm and can be passed on to affect biological children. “Somatic mutations” occur in the body cells and can only affect the cell where the mutation occurred and cells that grow from that cell. These somatic mutations are not passed on to biological children.
N
Nephrocalcinosis
Nephrocalcinosis is a disorder that occurs when too much calcium is deposited in the kidneys. It commonly occurs in premature infants. Individuals may not have symptoms, or their symptoms may relate to the condition causing nephrocalcinosis. If kidney stones are present, symptoms may include blood in the urine, fever and chills, nausea and vomiting, and severe pain in the belly area, sides of the back (flank), groin, or testicles. Later symptoms may be associated with chronic kidney failure. It may be caused by use of certain medications or supplements, infection, or any condition that leads to high levels of calcium in the blood or urine including hyperparathyroidism, renal tubular acidosis, Alport syndrome, Bartter syndrome, and a variety of other conditions. Some of the underlying disorders that can cause nephrocalcinosis are genetic, with the inheritance pattern depending on the specific disorder.
Nephrogenic Diabetes Insipidus
Nephrogenic DI
A condition in which the kidney tubules do not respond to antidiuretic hormone as expected and are therefore, not able to concentrate the urine appropriately. Individuals have constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow.
Nephron
This is the basic structure in the kidney that filters the blood. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. The term is derived from the Greek word Nephros meaning kidney.
Nephronophthisis
NPHP
This is an autosomal recessive inherited disorder characterised by inflammation and scarring of the kidneys and reduced kidney function. Most of the nephronophthisis genetic abnormalities occur in the cilium. This is a hairlike structure found in many cell membranes and play a role in transmitting information between the inside and outside of a cell. Because these structures can be found all over the body, when they don’t function properly, they can cause a wide variety of diseases. This group of diseases are called “ciliopathies.”
Nephronophthisis is a leading genetic cause of kidney failure in children and young adults. This condition can lead to increased urine production, excessive thirst, general weakness, and extreme tiredness.
People with nephronophthisis develop fluid-filled cysts in the kidneys, and have a shortage of red blood cells, a condition known as anaemia.
Nephronophthisis often leads to kidney failure. There are 3 subtypes which are characterised by the age of onset of kidney failure, these include infantile (1 year of age), juvenile (13 years of age) and adolescent (19 years of age).
This condition can be combined with other health problems other than kidney disease, such as liver fibrosis or cardiac malformations. Nephronophthisis may occur together with a group of other abnormalities. These are known as the following syndromes:
Nephrotic Syndrome
NS
A collection of symptoms that result from high levels of protein being leaked in the urine. This leads to reduced blood protein levels, and fluid retention which causes swelling. This is usually first noticed as swollen eyelids or a puffy face that is worse first thing in the morning. Later in the day, after being upright, the fluid collects in the legs and appears as swollen ankles.
Nonsense Mutation
A nonsense mutation is a change in the DNA sequence that causes a protein to terminate or end its translation earlier than expected. This change gives rise to a stop codon, which results in the production of a shortened protein that is likely non-functional.
Nucleotide
A nucleotide is the basic building block of nucleic acids. Long chains of nucleotides make RNA and DNA. A nucleotide consists of a sugar molecule attached to a phosphate group and a nitrogen-containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, the base uracil (U) takes the place of thymine (T).
O
Ophthalmologist
A medical doctor who specialises in diagnosing and managing conditions of the eyes.
Oxalate
A salt-like chemical formed by the breakdown of proteins and vitamin C during digestion. Its production is controlled by enzymes found in the liver. Oxalate is normally absorbed into the small intestine and leaves the body in the urine. If too much oxalate is allowed to build-up inside the body, it can combine with calcium to form kidney stones.
P
Panel
Gene panel sequencing
Gene panels are collections of genes that have been grouped for testing. This enables DNA sequencing of all the genes with variants known to cause a particular disease, syndrome, or a collection of clinical features.
Pathogenic variant
Pathogenic mutation
This involves a change in the DNA sequence that results in the formation of a non-functioning or faulty gene. It is this gene defect that is known to cause a certain health or developmental condition.
Pedigree
This is a diagram that illustrates the inheritance of a trait or health condition through generations of a family. The pedigree particularly shows the relationships among family members and, when the information is available, indicates which individuals have traits of interest.
Peritoneal Dialysis
PD
This is a form of dialysis treatment that takes over the role of the kidneys. In peritoneal dialysis, fluid is passed in and out of the abdomen through a catheter to remove waste products. The peritoneal dialysis catheter is inserted under a general anaesthetic and dialysis takes place every day in order to be effective. This can take place at home either automatically during the night or manually several times a day following training.
Phenotype
Phenotype refers to an individual’s observable traits, such as height, eye colour and blood type. A person’s phenotype is determined by both their genomic makeup (genotype) and environmental factors.
Point Mutation
This occurs in a genome when a single base pair is added, deleted or changed. While most point mutations are benign, they can also have various functional consequences, including changes in gene expression or alterations in encoded proteins.
Precision / Personalised Medicine
This is an innovative approach that uses information about an individual’s genomic, environmental and lifestyle information to guide decisions related to their medical management. The goal of precision medicine is to provide more a precise approach for the prevention, diagnosis and treatment of disease.
Primary Distal Renal Tubular Acidosis
dRTA or distal RTA or RTA type 1
This is a rare genetic disorder that affects the ability of the kidneys to remove acid from the blood. This leads to metabolic acidosis. Metabolic acidosis is a condition in which the circulating chemical acids and bases are out of balance. The blood of affected individuals contains too much acid and the urine contains too little acid. Chronic metabolic acidosis can lead to a variety of symptoms. The specific signs, symptoms, and severity of this disorder can vary from one person to another. There are different forms of primary distal renal tubular acidosis. They are caused by variants in one of at least three different genes, and inherited in an autosomal dominant or autosomal recessive pattern.
Primary Hyperoxaluria
PH or oxalosis
This is a rare genetic disorder that affects the body’s ability to regulate the production of oxalate which can result in kidney damage. The liver normally makes proteins, called enzymes, that prevent the body from making too much oxalate. In primary hyperoxaluria, the liver doesn’t create enough of this enzyme, or the enzyme doesn’t work properly. There are 3 types of primary hyperoxaluria which are caused by different defects in liver enzymes. It follows an autosomal recessive inheritance pattern.
Some people with primary hyperoxaluria may not show any symptoms until later in life, while others may experience severe symptoms at a young age. Kidney failure can occur as early as infancy while others with PH never develop kidney failure. Kidney stones presenting in childhood are the most common first symptom of primary hyperoxaluria. However, there is great variation in how severe the disease can be and not all individuals with primary hyperoxaluria will have kidney stones.
For more information see: https://ohf.org/primary-hyperoxaluria/
Proband
A proband is an individual who is affected by a genetic condition or who is at risk of developing a genetic condition. Usually, the proband is the first person in a family who brings the concern of a genetic disorder to the attention of healthcare professionals.
Protein
Proteins are large, complex molecules that play many important roles in the body. They are critical to most of the work done by cells and are required for the structure, function and regulation of the body’s tissues and organs. A protein is made up of one or more long, folded chains of amino acids, whose sequences are determined by the DNA sequence of the protein-encoding gene.
Proteinuria
This is when protein is found in the urine usually because the kidney filters (nephrons) are damaged and leaking. The most common protein found is called albumin (see Albuminuria)
Q
R
Renal
Of or relating to the kidneys. A renal disease is a disease of the kidneys. Renal failure means the kidneys are damaged.
Renal Tubular Acidosis
RTA
This is a group of disorders affecting the function of the kidney tubules. Primarily, this affects the acid-base exchange in the kidneys, and can result in blood that is more acidic than normal. In these groups of disorders, the function of other parts of the kidney and the glomerular filtration rate remains relatively normal.
Ribonucleic Acid
RNA
This is a nucleic acid present in all living cells. RNA is most often single-stranded. An RNA molecule has a backbone made of alternating phosphate groups and the sugar ribose, rather than the deoxyribose found in DNA. Attached to each sugar is one of four bases: adenine (A), uracil (U), cytosine (C) or guanine (G).
Risk
In genetics, this refers to the probability that an individual will be affected by a particular genetic disorder. Both a person’s genome and environmental exposures can influence risk. An individual’s risk may be higher because they inherit a genetic variant (orallele) in one gene or a combination of many variants in different genes that increases susceptibility to a particular condition.
S
Secondary Genomic Finding
This term refers to a genomic variant found through the analysis of a person’s genome, that is unrelated to the initial reason for examining the person’s genome. This secondary genomic finding might have potential medical importance by offering the chance to identify a previously unrecognized risk for disease that could change the medical management of that patient and potentially prevent or more effectively treat the disease.
Senior-Loken syndrome
SLS
This is a rare syndrome that mainly affects the kidneys and eyes. It is inherited in an autosomal recessive pattern. SLS causes a cystic kidney disease called nephronophthisis. The kidneys develop cysts, inflammation, and scarring, which progressively impair kidney function. Symptoms of nephronophthisis may include increased production of urine, excessive thirst, weakness, and severe fatigue. SLS affects the eyes by causing varying degrees of retinal dystrophy, which is progressive wasting of the retina (the part of the eye that senses light and sends images to the brain). Some children with SLS have a severe type of retinal dystrophy called Leber congenital amaurosis (LCA). Symptoms of LCA include severe farsightedness, light sensitivity (photophobia), and nystagmus. Other children with SLS do not have LCA but develop symptoms of a retinal dystrophy called retinitis pigmentosa (RP). Symptoms of RP range in age of onset and severity and may include night blindness and progressive loss of peripheral vision and central vision. In rare cases, additional symptoms such as liver fibrosis or skeletal abnormalities have been reported. SLS may be caused by genetic changes in any of several genes, and inheritance is autosomal recessive. The syndrome can be diagnosed based on symptoms, kidney and eye evaluations, and genetic testing.
Sex Chromosome
This is a type of chromosome involved in sex determination. Humans have two sex chromosomes, X and Y, that in combination determine the sex of an individual. Females have two X chromosomes (XX) in their cells, while males have one X and one Y (XY).
Sex-Linked
This term refers to traits that are influenced by genes carried on the sex chromosomes. This term often refers to traits influenced by genes on the X chromosome, as it contains many more genes than the smaller Y chromosome. Males, who have only a single copy of the X chromosome, are more likely to be affected by a sex-linked disorder than females, who have two copies. In females, the presence of a second, non-mutated copy may cause different, milder, or no symptoms of a sex-linked disorder. (refer to X-linked)
Single Nucleotide Polymorphism
SNP or Pronounced Snip
Is a genomic variant at a single base position in the DNA. Scientists use SNPs to study certain areas of the genome amongst those with same diseases, or other trait to search for similarities.
Somatic variants
Somatic mutations
These are changes to the DNA sequence that occur in body cells and can only affect the cell where the mutation has occurred and the cells that grow from that cell. Therefore, somatic variants are not present in every cell in the body, and are not passed from parent to biological children.
A somatic variant can be present in a large number of cells in the body or just a few. This depends on when in a person’s lifetime the new variant occurs. If this change occurs early in embryo development, a large proportion of the individual’s cells may contain this variant. If the change occurs later in development, then it may only be present in a particular tissue type or only part of a tissue. This results in different cells in the body having slight differences in their genetic make-up, some with the variant and some without, this is known as mosaicism.
Splice site variant
Splice site mutation
This is a genetic alteration in the DNA sequence that occurs at the boundary of an exon and an intron. This boundary is known as the splice site. This genetic change can result in loss of exons or inclusion of introns and an altered protein-coding sequence.
Stop Codon
This is a sequence of three nucleotides (a trinucleotide) in DNA or messenger RNA (mRNA) that signals a halt to protein development in the cell.
Syndrome
In genetics, related to a group of traits or conditions that tend to occur together and characterise a recognisable disease. Some syndromes have a genetic cause.
T
Trait
A specific characteristic of an individual. These can be determined by genes, environmental factors or by a combination of both. Traits can be descriptive (i.e. eye colour) or numerical (i.e. blood pressure). A given trait is part of an individual’s overall phenotype.
Transcription
This is the process of making an RNA copy of a gene’s DNA sequence. This copy, called messenger RNA (mRNA), carries the gene’s protein information encoded in DNA used to develop the encoded protein.
Transfer RNA
tRNA
This is a small RNA molecule that plays a key role in protein development. Transfer RNA serves as a link between the messenger RNA (mRNA) molecule and the growing chain of amino acids that make up a protein. Each time an amino acid is added to the chain, a specific tRNA pairs with its complementary sequence on the mRNA molecule, ensuring that the appropriate amino acid is inserted.
Translation
This is the process through which information encoded in messenger RNA (mRNA) directs the addition of amino acids during protein synthesis.
Transplant
A medical operation involving inserting a donated healthy organ into a recipient in need. Most transplants come from people who have died in hospital on life support machines. They can also come from living people like a close relative or friend. Transplanted organs are carefully chosen to give the best possible chance of success. It can take months or even years for a right match to become available.
Trinucleotide
A sequence of three nucleotides.
Tuberous Sclerosis Complex
TSC or TS
This is an autosomal dominant inherited genetic disorder, which occurs when a person receives an abnormal copy of the TSC gene from one parent. Symptoms of Tuberous Sclerosis Complex begin before birth and might be noted on ultrasound, such as tumours in the brain and heart. Seizures, intellectual disability, and developmental delay usually appear in childhood. Other symptoms that might develop in childhood include skin changes and kidney symptoms caused by tumours. Brain tumours usually grow during childhood and in teen years, which may lead to other concerns, such as hydrocephalus. In adulthood, kidney and pulmonary symptoms become more common.
Tubulopathy
This is an umbrella term which encompasses various diseases which affect the kidney tubules. Some of these include Renal Tubular Acidosis, Cystinosis, Bartter and Gitelman Syndromes, and Nephrogenic Diabetes Insipidus. These diseases can have a genetic origin and present in early childhood, for others, they develop as a result of another disease process which damages the renal tubules.
Kidney tubules are responsible for maintaining fluid, salt and acid-base balance of the blood. When the renal tubules are damaged, people may have more acidic blood, and have an imbalance of salts in the blood. People affected may find that they have high volumes of urine output and are increasingly thirsty.
V
Variant
Gene variant
This is any difference between the DNA sequence of two individuals’ genomes. Some variants can be harmless and will have no impact on health, others can account for physical differences or can be disease-causing. This type of genetic change used to be known as a gene mutation, but because changes in DNA do not always cause disease, it is thought that gene variant is a more accurate term. Variants can affect one or more DNA building blocks (nucleotides) in a gene.
Most variants do not lead to development of disease, and those that do are uncommon in the general population. Some variants occur often enough in the population to be considered common genetic variation. Several such variants are responsible for differences between people such as eye colour, hair colour, and blood type. Although many of these common variations in the DNA have no negative effects on a person’s health, some may influence the risk of developing certain disorders.
Variant of Uncertain Significance
VUS or VOUS
When an individual has undergone genomic testing and it has identified a variant, but it is unclear whether that variant is actually connected to the health condition in question. In many cases, these variants are so rare in the population that little information is available about them. Typically, more information is required to determine if the variant is disease related. Such information may include more extensive population data, functional studies, and tracing the variant in other family members who have or do not have the same health condition.
W
Whole Exome Sequencing
WES
The exome is the protein-coding section of DNA and makes up about 1-2% of a person’s entire genome. Exome sequencing uses a technique that allows many overlapping small sections of DNA to be sequenced at the same time. The exome is thought to contain most pathogenic variants. Analysing only 1-2% of the genome greatly reduces the amount of information to be filtered (sorted) and resources needed to do the test. In this test, the non-protein coding regions of the genome are not tested.
Whole Genome Sequencing
WGS
This is a similar type of test to Whole Exome Sequencing but instead looks at the whole of a person’s genome. This includes all the genes in both the protein-coding and non-protein coding regions. Whole genome sequencing is the most comprehensive form of genetic testing in current clinical use. It allows a wide range of variant types in a large number of genes to be tested for simultaneously.
U
X
X-Chromosome
The X chromosome is one of the two sex chromosomes that are involved in sex determination. We have two sex chromosomes (X and Y) that in combination determine the sex of an individual. Females have two X chromosomes in their cells (XX), while males have one X and one Y (XY).
X-linked inheritance
This refers to traits that are influenced by genes on the X chromosome. X-linked conditions occur when a pathogenic variant in a gene on the X chromosome leads to disease. Males, who have only a single copy of the X chromosome, are more likely to be affected by an X-linked disorder than females, who have two copies. In females, the presence of a second, non-mutated copy may cause different, milder, or no symptoms of an X-linked disorder.
Males with X-linked conditions cannot pass their pathogenic variant on to their sons, but they always pass their affected X chromosome to their daughters. Sons of females with a pathogenic variant on one of their X chromosomes have a 1-in-2 or 50% chance of being affected by the condition.
Y
Y-Chromosome
The Y chromosome is one of the two sex chromosomes that are involved in sex determination. We have two sex chromosomes (X and Y) that in combination determine the sex of an individual. Females have two X chromosomes in their cells (XX), while males have one X and one Y (XY).