The blueprint for an entire human is stored in every single cell in our body. The instructions for our eye colour, gender and the design of a human heart all reside in tiny stretches of DNA called genes. The information in our genes can be used to diagnose and predict disease, determine our ancestry and familial relationships and predict how are bodies may respond to medicines and diet.
DNA
All the information for an entire human being is contained in short stretches of DNA code.
Deoxyribonucleic acid (DNA) is composed of two polynucleotide chains that form a double helix. Each chain is made up of the bases adenine, guanine, cytosine, and thymine. These bases combine into complementary pairs that form stretches of DNA called genes.
Combinations of base pairs code for every single structure and function within the human body. The sum of all our genes is called the genome. Genes can be transcribed into ribonucleic acid (RNA) and then processed and edited. The RNA is then translated into a protein or it becomes a non-coding RNA (ncRNA) which there are a variety of types and function.
Each cell within the body contains approximately 3 billion base pairs of DNA neatly wrapped inside the nucleus, with the exception of most of the mitochondrial DNA which is stored separately. Stretches of DNA are wrapped around proteins called histones with longer stretches forming chromosomes. There are usually 46 chromosomes in each cell with 23 coming from each parent. There are 23 pairs of chromosomes, 22 are known as autosomes and the 23rd pair is made of the X and Y sex chromosome.
Genetic regulation
Genetic regulation is the process of turning genes off and on, allowing the cell to respond to any change in their environment. Genes are either always on regardless of the environment or turned on and off as required by the cell.
In the off-state genes are often tightly wrapped around their respective histone and are not readily accessible to the cellular transcription machinery.
In response to an internal or external cellular signal the DNA can be unwound by adding chemical tags to the histones or the DNA which may be temporary or permanent. There are also specific proteins that can bind the DNA causing it to unwind. Once the DNA is unwound the relative gene is bound by a transcription factor and is transcribed into either a protein or a non-coding RNA. Once the transcription signal ceases or a competing stop signal appears, the gene is effectively turned off.
There is also regulation at the product level with cellular processes designed to control the availability of gene products to maintain homeostasis.
The genes we inherit from our parents can change within our lifetime, and how they are regulated also changes due to lifestyle and the aging process. Genetic regulation is an exquisite process allowing the body to effectively control how we progress from conception to adulthood and maintain all our systems throughout life.
Genetic alterations
A test usually compares a single gene or group of genes to parts of a reference genome. The reference genome is made up of multiple individual part genomes and is considered what constitutes normal genes. A change in DNA sequence may involve a single or multiple bases in a gene. The change in the gene (genotype) and how that relates to observable changes within the body (phenotype) are variable.
It is yet not known what all changes in genotype has on phenotype.
The change in DNA sequence may be referred to as a mutation, variant or simply a change. For simplicity and accuracy an observed change from the reference genome is preferrable referred to as a variant. There are a variety of DNA variants. Bases may be changed, deleted, added or the amount amplified. The end-product may then be missing, excessively produced or a non-functional variant is produced. A variant may also not have any effect on the end-product and phenotype.
A variant may be disease causing, beneficial to health, have an unknown effect on function or have a non-disease phenotype like eye or hair colour.
Reporting of a variant and the resulting impact on function maybe categorized as follows,
- Affects function
- Probably affects function
- Unknown
- Probably does not affect function
- Does not affect function
Changes in the number of chromosomes and their structure may also impact health. Each chromosome usually has two copies one inherited from each parent sometimes there is an additional chromosome (trisomy) or a single copy (monosomy). Changes in chromosome number has a variety of potential pathology.
Chromosomes may also have structural aberrations where parts of the chromosome may be missing, duplicated, or mixed with another chromosome.