Repeat DNA and Forensic DNA Analysis

This episode of 'Dr. DNA Dan' hosted by Professor Dan Handley from Southern California University of Health Sciences delves into genetics, specifically focusing on short tandem repeats (STRs). 

The podcast explains the significance of STRs in forensic DNA testing and paternity tests by measuring the number of repeated sequences in different individuals' genomes. STRs, found across all human chromosomes, are used to match DNA samples in criminal investigations through the CODIS database maintained by the FBI. 

The accuracy and real-world challenges of STR analysis, including potential sample contamination and degradation, are discussed to provide a comprehensive understanding of forensic DNA testing.

Tune in each month as DNA Dan dives into the evolving world of genetics, from ancestry and health testing to genetics in mental health and forensics. With over 30 years of experience in genomics, SCU Professor Dan Handley, M.S., Ph.D., brings unique insights into how genetics shapes our lives and the future of precision medicine.

Please visit our website for more information about Southern California University of Health Science's Master of Science Program in Human Genetics & Genomics. https://bit.ly/SCU-DNA_Dan

Transcript

I’m Dr. Dan Handley, professor of human genetics and genomics at Southern California University of Health Sciences. This is a podcast about all things related to human genetics, genomics, and the future of precision medicine.

In the last episode, I discussed repeat DNA sequences. To recap, our genomes consist of dozens of different categories of repeated sequences of nucleotides As, Cs, Ts, and Gs. Some are very simple, just repeats of two nucleotides such as ATATATAT. Others are much longer, perhaps hundreds, thousands, or millions of nucleotides long.

In this episode I’m going to discuss a particular type of repeat DNA called short tandem repeats, or STRs. They’re important for using DNA samples to identify someone whether used in a forensic DNA test for a crime or a paternity test.

So by the time you finish this podcast, next time you watch some kind of true crime show in which they use DNA as evidence, you will understand the basic science behind what they are doing. And it all starts with repeat DNA in our genomes, specifically short tandem repeats or STRs.

STRs are an interesting category of repeat DNA in the human genome, and their characteristics are what makes them useful in distinguishing one person from another. STRs are repeats of between one to six nucleotides, or bases. Since they are repeated over and over again in a chain, then this is known as being in tandem. Both of these characteristics are why they are called short tandem repeats. What makes them interesting is that the number of repeats is often different in different people. They can vary between around six to well over fifty. Since the number of tandem repeats differs between unrelated people, determining the number of repeats in an STR on a chromosome can show whether two people are related or not. By the way, the number of DNA sequence repeats in an STR determines its length, so the term STR repeat number or STR length can be used interchangeably. 

Further, STRs are found on all of the 23 pairs of human chromosomes including the X and Y chromosomes. Each STR can differ in the number of repeats independently. So by measuring the number of repeats in STRs from different locations on different chromosomes, we can use that information to test DNA samples to see if any of the STR lengths from each location match. If the samples came from the same person, all of the lengths of each STR at each location in the genome would match precisely. If the DNA samples came from two related people, some of the number of repeats would likely be the same and some different from others. This is because STRs are inherited, so the more closely the length of the STRs match, the higher the likelihood that the DNA came from closely related people. This is how STR length measurement is used in paternity testing or identifying relatives. If none of the STR lengths match, then that is extremely strong evidence that the DNA samples came from two entirely unrelated people.

You can now see what a powerful technique this is in determining the relationship between people from which DNA samples are tested.

The FBI in the US created a list of specific STR locations spanning a number of chromosomes. The FBI maintains a database of these standard locations, called loci, for forensic DNA testing. It’s called the Combined DNA Index System or CODIS for short. Originally it contained 13 standard loci but was upgraded to 20 loci in 2017 to increase accuracy and decrease the likelihood of misidentification, even though that likelihood is still very small with only 13 loci.

The CODIS database has three levels. First it has the local DNA index system, then the state DNA index system, and then a national DNA index system. These databases contain STR profiles from DNA samples tested from such sources as people who have been arrested, convicted criminals, samples from crime scenes, DNA samples if available from missing persons, and unidentified human remains.

The CODIS database does not contain any personal identifying information such as names. However, the laboratory that obtained the sample does. So when investigating a crime scene and a DNA sample is recovered and tested, it is put into a search against the CODIS database. If a match is found, then investigators can go to the original laboratory that provided the database sample. Going through proper legal procedures, investigators can then obtain the identity of the person whose sample was found in the CODIS database. To help prevent mistakes, the person has their DNA re-tested.

If the STR lengths from all 20 loci match exactly between a DNA sample taken at a crime scene and the DNA sample taken from the suspect, that is pretty powerful evidence to be presented in court. The statistically calculated odds of an exact match from all 20 loci coming from different individuals has been calculated to be about one in one septillion, or 1 in 10 to the 24th power. Conversely, if the STR lengths do not match, that again is powerful evidence towards exonerating the suspect. 

These core loci do not include the Y chromosome. However, forensic analysts sometimes examine STRs on the Y chromosome—known as Y-STRs—in specific cases such as sexual assault investigations, because detecting an STR on the Y chromosome indicates that the DNA sample came from a male.

Despite what you see on TV shows and in the movies, forensic DNA testing is very labor intensive and takes many people with different areas of expertise to be involved. It cannot be done by a lone genius providing results within hours. 

What is not often shown in crime shows is the meticulous attention to obtaining high quality DNA samples, avoiding contaminating samples, carefully maintaining a proper chain of custody for evidence including the samples to be tested. Often, for technical reasons, it could take weeks or months to get results. As careful as the technicians, forensic scientists, and statistical geneticists are to make sure they get the most accurate results, there are inherently a number of complicating factors involved. Sometimes the samples contain mixed substances from two or more individuals. Samples can be contaminated with foreign substances or chemicals, making laboratory analysis difficult or impossible. And the DNA in samples can be degraded for many reasons, again making it difficult for reliable analysis. So although forensic DNA testing may seem like rock solid proof in a criminal proceeding, there are complexities involved that may make the results unreliable. So the high statistical accuracy of STR testing in principle has to be balanced against real-world challenges in sample collecting, analysis, and interpretation of laboratory results.

STR forensic DNA testing is not just useful for law enforcement but also many other uses. Paternity testing as previously mentioned and identifying the remains of the deceased also use these principles. 

I hope this introduction to STRs and how they can be used to identify individuals gives you a bit more insight about how forensic DNA testing is done.

It is important to know that STRs also are involved in a number of diseases such as Huntington disease and Fragile X syndrome. I’ll be discussing more on Huntington disease and related conditions in a future episode, and more about fragile sites such as those involved in Fragile X syndrome in the next episode.