A cell is a small container of chemicals, smaller structures, and water that is wrapped in a membrane.

Cells are the basic building blocks of all living things. Cells have many parts that work together to give living things their structure (how they look) and function (how they work). Our bodies are made up of trillions of cells, and different cells have different functions.

Most cells in the human body have a nucleus. The nucleus holds most of the genetic information (called DNA) needed to build and run a human body.

Some of our DNA is held in a different part of the cell called the mitochondria. Most of the cell’s energy is made in mitochondria. Genetic conditions involving mitochondrial DNA have a special way of being inherited.

DNA is the set of genetic instructions that tells your body how to grow and how to work.

DNA stands for deoxyribonucleic acid.

DNA forms a structure called a DNA double helix. The double helix is made up of 2 matching DNA strands. Each DNA strand is itself made up of a code using 4 small units called bases or nucleotides. The names of these bases are adenine (A), guanine (G), cytosine (C), and thymine (T).

Each base forms a chemical bond with a second base. Adenine (A) always matches up with thymine (T), and guanine (G) always matches up with cytosine (C). A set of 2 bases is called a base pair. Once each base has a match, the set of base pairs on the 2 strands of DNA twist around and form the double helix.

We all have differences in our DNA that make us different from each other. We call these differences variants. Genetic variation can be as small as a change from 1 base pair to another or can be as large as an entire chromosome being deleted or duplicated.

Most variants do not cause any health problems. These are called benign variants.

Sometimes, a variant can cause health concerns or increase someone’s chance to develop a health concern. These variants are called pathogenic variants. Alternative terms for pathogenic variants include mutations or disease-causing variants. Pathogenic variants are the cause of genetic conditions.

Variants can be inherited from parents, or they can happen for the first time in a person with a genetic condition. When a variant happens for the first time, it is called a “de novo” variant (“de novo” means “new” in Latin). Learn more about inheritance.

Our DNA is organized as units of instructions called genes. We have about 20,000 genes in total. There are thousands of genes that are important for health.

Each gene is a specific instruction, which is carried out by creating a protein. There are many types of proteins that our cells need, like:

• enzymes for chemical reactions
• proteins for structure, transportation, defence, and communication
• motor proteins for muscle contraction

You have 2 copies of almost every gene. One copy comes from the egg and one from the sperm that formed you. When you have children, you pass down only 1 copy of each of your genes.

DNA is packaged into structures called chromosomes. You have 2 copies of most chromosomes. One copy comes from the egg and one from the sperm that formed you. We typically have 23 pairs of chromosomes, giving a total of 46 chromosomes in each cell.

One of the pairs of chromosomes is called the sex chromosomes. Sex is what people are assigned at birth based on the appearance of their external genitals. Usually, individuals assigned female at birth have two X chromosomes, and individuals assigned male at birth have one X chromosome and one Y chromosome. Though they often match, sex assigned at birth is a different concept than gender. Learn more about gender and gender identity.

There are many variants that affect chromosomes that can cause genetic conditions, including:

• Having an extra copy of a whole chromosome. For example, Down syndrome happens when there is an extra copy of chromosome 21. Klinefelter syndrome happens when a male has an extra X chromosome.
• Missing an entire copy of a whole chromosome. For example, Turner syndrome happens when there is only one X chromosome in a cell, and a second sex chromosome is missing.
• A small piece of a chromosome is duplicated or deleted. For example, 22q11.2 deletion syndrome is caused by a small part being missing (having been deleted) on chromosome 22.
• Part of a chromosome breaks off and re-attaches to a different chromosome. This is called translocation. For example, the 11;22 translocation or a Robertsonian translocation.
• Part of a chromosome breaks off, turns around, and re-attaches to the same chromosome. This is called an inversion.

The effect of a chromosome variant can include:

• No impact on the health or development of the person with the chromosome variant. However, a person with a chromosome variant might have a higher chance of not being able to have children, having a miscarriage (for themselves or their partner), having a child who is stillborn, or having a child born with serious health, developmental, or learning concerns.
• Some mild impacts on health, development, and learning of the person with the chromosome variant, along with the fertility concerns described above.
• Serious impacts on health, development, and learning.
• Early miscarriage or stillbirth due to problems in the early development of an embryo.

The effect of a chromosome variant is determined by what specific genes are involved and by the type of variant. A single gene may be involved in causing a genetic condition, or many genes may be involved.

Many people do not know that they have a genetic variant affecting their chromosomes. About 1 in every 500 people have a sex chromosome variant, and about 1 in every 1,000 people have a chromosome rearrangement.

Genetic conditions caused by chromosome variants are also called chromosome disorders. They can be inherited from a parent, most often through autosomal dominant inheritance, or they can happen as a de novo variant. Chromosome translocations have a different way of being passed down. Learn more about balanced translocations and unbalanced translocations.

Genome is the term for all of the DNA in a person. The human genome is made up of the DNA in the 46 chromosomes and the DNA in the mitochondria. Most of the DNA that makes up the genome is not used to make proteins. DNA that isn’t used to make proteins is called non-coding DNA. We are still learning about the different purposes for non-coding DNA.

Exome refers to the smaller amount of DNA that is contained within our genes and is used to make proteins. The DNA that is used to make proteins is called coding DNA. The exome is only about 1% to 3% of all the DNA in the genome. Most of the genetic conditions that have been identified to date are caused by pathogenic variants in the exome.

Congenital anomalies (previously called birth defects) are differences present at birth. Congenital anomalies can be structural (how the body is built) or functional (how the body works). They can cause physical disability, developmental or learning concerns, or other health concerns.

About 3 out of every 100 babies born in Alberta each year will have a congenital anomaly. Examples of structural congenital anomalies include:

• cleft lip or cleft palate
• heart defects, such as missing or misshaped valves
• limbs that are in a different position than usual, such as a clubfoot
• neural tube defects, such as spina bifida, and problems related to the growth and development of the brain and spinal cord

Different congenital anomalies have different causes, and the causes of many congenital anomalies remain unknown. Some of the causes we do know are:

• a genetic condition or genetic syndrome
• amniotic bands causing a missing limb or the position of the baby leading to clubfoot
• infection during a pregnancy, such as measles or Zika virus
• exposure of a pregnancy to high-risk medicines, chemicals, or other substances (such as thalidomide, tobacco, alcohol, or pesticides)

Genetic conditions (also called genetic disorders) are health, developmental, or learning concerns caused by DNA variants in a person’s genetic instructions. There are over 7,000 different genetic conditions, with more being identified each year.

Different genetic conditions can affect different parts of the body, like the brain and nervous system, heart, muscles, or kidneys. Some genetic conditions cause a higher chance to develop specific health problems like cancer, high cholesterol, inherited arrhythmias or cardiomyopathies, or early-onset dementia.

If a genetic condition causes a higher chance of a specific health problem, but a person may never develop that health problem, it is called having a genetic predisposition.

Some genetic conditions are always caused by a specific variant in a specific gene. For example, sickle cell disease is always caused by the same variant in the beta-globin gene. Other variants in the beta-globin gene can cause a different genetic condition called beta thalassemia. Cystic fibrosis, on the other hand, can be caused by many different variants in the CFTR gene. Other conditions, like hypertrophic cardiomyopathy, can be caused by variants in many different genes. However, for each person, they will have one variant in one gene that causes the condition for them.

Genetic conditions that are caused by variants in one gene are called monogenic conditions.

Genetic conditions can be inherited from parents, or they can happen for the first time in a person with a genetic condition. When a genetic condition happens for the first time, it is called a “de novo” variant (“de novo” means “new” in Latin). Learn more about inheritance.

Genetic syndromes refer to a group of health concerns and sometimes specific physical traits that are often seen together. These may include congenital anomalies, developmental and learning concerns, and a chance for specific health concerns in the future. An example of a genetic syndrome is Down syndrome (also called trisomy 21).

Genetic syndromes can be inherited from parents, or they can happen for the first time in a person with a genetic syndrome. When a genetic syndrome happens for the first time, it is caused by a “de novo” variant (“de novo” means “new” in Latin). Learn more about inheritance.

Some health concerns have complex causes that can include genetics, lifestyle, environment, age, and chance. These are called complex disorders.

Health, developmental, or learning concerns that are impacted by genes can be monogenic or polygenic.

• Monogenic means that a variant in a single gene is causing a health, developmental, or learning concern.
• Polygenic means that there may be many variants in many different genes involved in creating risk for a health concern.

Genetic testing is possible for many monogenic conditions. Genetic testing for polygenic or complex disorders is much more complicated, and there are currently no accurate tests for these conditions available in Alberta.

While some genetic conditions affect many people around the world, other genetic conditions are very rare, affecting only a small number of people. However, when we combine all these rare conditions together, about 1 in every 12 Canadians lives with a rare disease.

Diagnosing a rare genetic condition can be hard, and it can take many appointments and tests to come up with the right diagnosis. This is called the “diagnostic odyssey.” Unfortunately, some people may never know what caused their genetic condition. Learn more about a negative genetic test result when you have a genetic condition.

The Clinical and Metabolic Genetics program has partnered with programs around the world to improve rare disease diagnosis and to bring new treatments for genetic conditions to people in Alberta. These partnerships have brought new advancements to Alberta, like:

• new genetic testing technologies, like exome and genome sequencing
• new treatments for conditions like urea cycle disorders and spinal muscular atrophy
• being able to describe new genetic conditions like Au-Kline syndrome and Beaulieu-Boycott-Innes syndrome
• participating in national programs like Care4Rare and the Canadian Rare Disease Network