Genomics and Disease

Many factors contribute to human health and disease. Our environment and our biology are two factors that strongly influence our health. For a long time, it was believed that diseases resulted entirely from our environment (such as a tuberculosis [TB] infection) or entirely from our biology (such as an inherited disease like cystic fibrosis). Now, we are seeing that many human diseases are a result of a complex interaction between our biology and our environment, and many other factors.

The key to human variation is mutation. A mutation is simply a change in the genetic information. Our genome consists of more than three billion nucleotides that can acquire a mutation at any time throughout our lives. Understandably, every human being carries at least several mutations in their genome. Most of these mutations are "silent" and harmless and never have an effect on our health. Others may make us more susceptible to other diseases and whether or not we develop those diseases depends on many other factors, including the rest of our genes and our environment. Still others can predispose us to a disease that may develop later in life, which is also influenced by other factors. Finally, some mutations result directly in disease if they interrupt an essential function in our body.


  • Normal variation: brown and blonde eye/hair colour;
  • Susceptibility: TB infection - a person needs to be exposed to be susceptible;
  • Predisposition: breast cancer (BRCA1/BRCA2); and
  • Disease: Cystic Fibrosis.

Inheritance patterns

Mutations can happen during someone's lifetime, in which case they are known as acquired mutations. These are often in one cell or group of cells - they are not in every cell of the body. Mutations can also be passed on from parents to children. In this case, they are known as inherited mutations. Inherited mutations are present in the first embryonic cell and so they are found in every cell of the body. This can happen in two ways - either one of the parents also has the inherited mutation or has an acquired mutation in their sperm or egg cells.

Genetic traits and diseases caused by inherited mutations can be passed on from parents to children in several different ways. Everyone inherits two copies of most genes - one from their mother and one from their father. Some diseases or traits will develop if only one gene has a mutation in it, but others will develop only if both copies have a mutation. By looking at large family trees and finding out who has the trait and who does not, we can figure out the inheritance pattern for the trait or disease. Although there are other inheritance patterns, the four main ones are autosomal recessive, autosomal dominant, X-linked and mitochondrial.

Autosomal recessive inheritance

The word "autosomal" means the gene involved is located on one of the autosomes (chromosome pairs 1 to 22). Autosomal recessive traits or diseases develop when both copies of a gene have a mutation that interrupts the gene's normal function.

The parents of a person with an autosomal recessive trait or disease would both be carriers and have a mutation in only one of their copies of the gene, but they would not have the trait or disease. The chance that a couple who are both carriers will have a child with the trait or disease associated with the mutation is 1 in 4, or 25%. There is a 1 in 2, or 50%, chance that they will have a child who is also a carrier, and a 1 in 4, or 25%, chance that they will have a child who does not inherit either mutation. An example of a disease that is inherited in an autosomal recessive way is cystic fibrosis, a relatively common condition in the Caucasian population.

Autosomal dominant inheritance

Autosomal dominant traits or diseases develop when only one gene of a pair has a mutation that interrupts the gene's normal function.

One of the parents of a person with a dominant trait or disease will also have the trait or disease, except in rare cases where a new mutation occurs. The chance that a person with a dominant trait or disease will have a child with the same trait or disease is 1 in 2, or 50%. There is therefore also a 1 in 2, or 50%, chance that they will have a child who does not have the trait or disease. An example of a disease that is inherited in an autosomal dominant way is Huntington's disease, an adult-onset neurologic disorder affecting movement, behaviour and thought.

X-linked inheritance

The sex chromosomes are different from the autosomes. The X and Y (sex) chromosomes do not carry the same genetic information. In a male, who has one X and one Y chromosome, there are genes on the X chromosome that he has only one copy of. A female has two because she has two X chromosomes. Disease or traits that are associated with a mutation in a gene on the X chromosome are inherited differently by women and men.

If a woman inherits a recessive mutation on one of her X chromosomes, she most likely will not develop the disease or trait because she has another X chromosome that can still do its job. However, a man who inherits a recessive mutation on his X chromosome will develop the disease or trait because he does not have another copy of that gene that can take over. There can also be dominant mutations on the X chromosome, in which case both the male and the female can develop the trait or disease.

Mitochondrial inheritance

A more recently discovered inheritance pattern occurs via the mitochondria, whose job it is to produce energy for the cell. Mitochondria have their own DNA, in which mutations can also occur. Everyone inherits mitochondria from their mother, because they are present in egg cells but not in the sperm. A disease or trait that is associated with a mutation in the mitochondrial DNA can be passed on only from a mother to her children. This rare mode of inheritance has been associated with mitochondrial disorders that affect energy metabolism.

Genetic testing

Genetic testing involves the analysis of a person's chromosomes or DNA to look for specific changes. Genetic tests are very specific and look only at one or two genes at a time. No universal genetic test is available which can look at all of a person's genes for mutations. There are many reasons why genetic tests are used, including the following:

  • Diagnostic testing is used to confirm or rule out a suspected genetic disease in a person with symptoms of the disease;
  • Predictive testing is offered to a person who has a family history of a genetic disease, but has not yet developed symptoms;
  • Carrier testing is done to identify if a person carries a mutation for an autosomal recessive disease in their family or is common in the individual's ethnic group;
  • Prenatal testing is performed during pregnancy to test the fetus for a genetic disease when there is indication of increased risk;
  • Preimplantation testing is done on embryos produced through in vitro fertilization that are at increased risk of having a serious genetic disease; and
  • Newborn screening is performed on all newborn babies to look for common childhood genetic diseases that can benefit from early intervention.

Biotechnology techniques used in genetic testing

The following techniques are the ones most often used in genetic testing:

  • Southern blot is used to find a gene and look for large molecular defects like deletions and rearrangements;
  • Northern blot is used to look at the size and quantity of the mRNA product from the gene in question;
  • Allele-specific oligonucleotide probes (Short chain fragments of DNA) are used to detect specific single nucleotide changes;
  • Polymerase chain reaction (PCR) is used to quickly amplify a gene of interest for sequencing or testing with an allele-specific oligonucleotide probe; and
  • DNA sequence analysis is used to determine the exact sequence of the gene to look for changes.

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