Genetic diseases or disorders are caused by a change in our DNA. These changes can be inherited from our parents, arise randomly or be triggered by an environmental exposure. A disease can be caused by a change in one gene (monogenic), changes to chromosomes (chromosomal) or by the small effects of many mutations or variations in combination with environmental factors (complex/multifactorial).
Monogenic
Monogenic disorders are diseases caused by a mutation in one specific gene such as sickle cell disease (hemoglobin-beta gene), cystic fibrosis (CTFR gene), Huntington disease (HD gene), or Duchenne muscular dystrophy (dystrophin gene). Genes code for proteins so a mutation in a gene can result in a truncated protein, a protein that can’t fold properly or the protein prevented from being made entirely. When a protein is missing or can’t perform its function, this can lead to disease.
Even though these diseases are caused by faulty versions of specific single genes, it is now recognised that their age of onset and severity depends on the actions of many genes and environmental factors.
Phenylketonuria (PKU)
All newborn babies in Australia are given a heel prick test soon after birth to screen for multiple rare diseases such as phenylketonuria. PKU is a rare disorder caused by mutations in the gene that codes for the enzyme that breaks down phenylalanine, an amino acid. Phenylalanine is found in all proteins in our diet, and if not removed by the enzyme, builds up to harmful levels in the body, causing permanent intellectual disability.
By testing at birth, babies diagnosed with PKU can be immediately placed on a diet low in phenylalanine to reduce their health risks.
Chromosomal
Chromosomal diseases occur when someone is born with changes to their usual 46 chromosomes. These changes can be numerical, meaning there is an additional or absent chromosome, or structural – part of an individual chromosome is missing, duplicated or moved to another chromosome. These changes occur when the egg and sperm are forming or during the very early stages of foetal development.
Down Syndrome
Down syndrome is caused by abnormal cell division early in development leading to a full or partial extra copy of chromosome 21. Down syndrome is also called trisomy 21, referring to the three copies of chromosome 21. This extra genetic material causes intellectual disabilities and developmental delay of varying severity.
Other chromosomal disorders include trisomy 13, trisomy 18 and changes in the sex chromosomes (XXX, XXY, XYY instead of the expected XX (female) and XY (male)).
Complex (multifactorial)
Most diseases – including the biggest killers such as cancer, coronary heart disease and type 2 diabetes – do not have a single cause. Instead, they are influenced by many genes in combination with environmental factors such as stress, exposure to chemicals and behaviours like diet and smoking.
The genetic contribution to these diseases has long been recognised through looking at family histories and how their risk runs in families. But as we investigate our genome in ever-greater detail, we are uncovering direct signals from DNA associated with common diseases. IMB researchers are developing statistical methods and software to analyse genetic and genomic data from millions of participants. These methods and software are used by researchers all over the world, extending their impact and amplifying the benefit of our research.
Building our knowledge about these complex diseases brings us closer to understanding them and devising ways to diagnose and treat some of the world’s leading causes of death.
Heart disease
Heart disease is a classic example of a multifactorial/complex disease. There are many factors with a genetic component that contribute to heart disease, like faults in the heart muscle, rhythm or high cholesterol. Your inherited risk is set at birth, but whether you develop the disease will also be influenced by environmental factors, such as whether you smoke, exercise and eat a healthy diet.
A person who lives very healthily but has a high genetic risk may still experience heart disease, while someone who smokes, eats poorly and doesn’t exercise might still manage to avoid it, thanks to good genes. Ultimately, we can’t control our genes, so living healthily is the best way to minimise our risk.
