Genetic Carrier Screening Technology & Science

There's a lot of science and technology behind carrier screening. In the past 40 years, heaps of research has gone into developing and improving prenatal testing.

When carrier screening was first introduced several decades ago, labs could only scan for a single gene at a time. The process was slow, expensive, and was hard to obtain for patients with no family history of a condition.

Luckily, these days carrier screening is usually a quick, non-invasive, simple, and – when covered by Medicare – often quite an inexpensive process for patients.

But what does carrier screening actually involve?

Carrier screening is performed through the collection, extraction and analysis of certain parts of your genetic information. To access this information, samples collected go through a variety of laboratory processes.

Let's take a deeper dive into the process.

Step 1: DNA Extraction

After you collect your sample, the first step at the lab is to extract DNA from the sample. DNA extraction is the process of isolating DNA from cells, tissues, or organisms.

Extraction is important since the lab only wants to examine the DNA, not any of the other microscopic things that could be in your sample. This extracted "pure" DNA can then be used for analysis, such as genome sequencing or to identify gene variations.

To separate the DNA from the other components, the laboratory adds a variety of solutions under various temperature conditions to isolate pure DNA.

DNA Extraction Steps

1. Cell lysis

   "Lysis" is a scientific term which refers to separation. This first step involves breaking open the cell membranes to release the DNA.

   There's several ways a lab might perform cell lysis, some of which are physical and some chemical. This can include: "grinding" the cells to break the membranes (mechanical disruption), using detergents to break down cell membranes (chemical methods), or using enzymes to break down proteins (enzymatic digestion).

   Some labs might even combine several of these methods when performing cell lysis.

2. Removal of proteins and other cellular components

   Once the cells are lysed, there's still more than just DNA remaining. The solution will still contain proteins, lipids, carbohydrates, and other cellular debris.

   To isolate the DNA, these contaminants need to be removed. This is often done by adding substances like magnetic beads, salt and alcohol to precipitate the DNA while leaving other components behind.

   When using beads, the DNA will attach to the magnetic beads leaving the other components behind to be discarded.

3. DNA purification

   After the previous step is complete, the DNA is ready to be purified. The DNA goes through a series of washes to clean off any remaining materials. The magnetic beads are also removed, leaving a solution containing the pure DNA.

Step 2: Exome Sequencing

After the DNA has been extracted from a sample and isolated, it can now undergo a process called "sequencing". This is the process labs use to turn a DNA sample into data that can actually be used to produce a report.

The reason why it's called sequencing is because the process involves figuring out the order of the DNA "building blocks", known as or nucleotides, in the patient's DNA.

By itself, a DNA sample won't tell a lab much. But when sequenced, depending on the type of sequencing performed, it can provide a large amount of data that can then be used to create scientific reports about a patient's health.

Exome sequencing is a genomic technique that focuses on sequencing a small part of the DNA known as the "exome". The exome makes up all the "protein-coding" regions of DNA – the parts that provide instructions for cellular processes in the body.

Like extraction, there are multiple steps involved.

Exome sequencing steps

1. Isolation of Exome

   Isolating the exome begins after DNA extraction. "Free floating" DNA is processed to separate protein coding regions (exomes) from non-protein coding regions (introns).

   The exome only makes up about 1-2% of the larger "genome" in DNA, however this section is where most disease-causing mutations are found within the genome. This is particularly important for carrier screening which relates to autosomal recessive conditions.

   The exome is isolated using target enrichment techniques, separating and capturing the specific DNA regions that encode proteins.

2. Sequencing

   Next-generation sequencing (NGS) technologies are employed to sequence the exome. This involves determining the order of the nucleotides (adenine, thymine, cytosine, and guanine - A, T, C, G) that make up the DNA molecules within the exome.

Step 3: Analysing Genetic Data for Reports

At this point, we've extracted the DNA from a sample and created a bunch of raw data. But we still can't learn much from this data until we do some analysis.

This is where a clinical geneticist trained in a field called "bioinformatics" can help. They use a special type of computer software known as bioinformatics tools to analyse the sequenced data.

These tools let the geneticist compare the obtained exome data to a "reference genome" – an example set of genes developed from a lot of research. When comparing the patient's exome data to the reference genome, they can identify any variations and mutations within the exome.

A clinical geneticist reads the genome sequence and writes the report. As part of the report for carrier screening, clinical geneticists determine if the variations in your DNA sequence will result in gene changes that have a chance of causing inherited genetic conditions. They are typically classified as low chance, increased chance, or of unknown significance.

The reported options for each gene are then collated to form one report that can be compared with your reproductive partners report. This report provides the combined chance of passing on the genetic condition to your children.