Our bodies are built from a detailed instruction book, DNA, which is almost identical among all humans. However, tiny sections within this genetic blueprint show remarkable differences between individuals. These unique segments are called short tandem repeats, or STRs, which are like genetic stutters within our DNA. An STR is a short sequence of DNA, typically 2 to 6 base pairs long, that is repeated multiple times in a row, such as “GATA GATA GATA”. While the specific sequence of these repeats is the same for many people, the number of times it repeats varies significantly from one person to another, making these regions highly polymorphic.
The Biological Blueprint of STRs
Short tandem repeats are found throughout the human genome, with many located in the non-coding regions of DNA, meaning they do not directly contribute to protein synthesis. Despite their non-coding nature, these repetitive sequences are prone to changes in their repeat count during DNA replication. This variability primarily arises from a process called polymerase slippage. During DNA replication, the DNA polymerase enzyme, which builds new DNA strands, can “slip” or dissociate from the template strand. When it reattaches, it may do so out of alignment, either adding or subtracting repeat units. This slippage mechanism leads to the high degree of polymorphism observed in STRs, where the number of repeats at a specific location, or locus, can differ from person to person. For example, at a locus like D7S280 on human chromosome 7, individuals might have anywhere from 6 to 15 copies of the “GATA” sequence. The unique combination of repeat numbers at various STR loci forms a distinctive genetic signature for each individual, laying the groundwork for their use in identification.
Application in Forensic DNA Profiling
The unique variability of STRs makes them powerful tools in forensic science for identifying individuals from biological evidence. The process begins with collecting a sample, such as blood, saliva, or skin cells, from a crime scene. DNA is then extracted from this sample, followed by a technique called Polymerase Chain Reaction (PCR). PCR amplifies, or makes millions of copies of, specific STR regions, even from very small or degraded DNA samples. This amplification uses short DNA primers that target the non-varying regions flanking the STRs. After amplification, the DNA fragments are separated by size using a method like capillary electrophoresis, which allows scientists to determine the exact number of repeats at each chosen STR locus. This information is then used to create a DNA profile, sometimes referred to as a “DNA fingerprint”. The Federal Bureau of Investigation (FBI) utilizes a database called the Combined DNA Index System (CODIS), which currently uses 20 core STR loci for criminal investigations. By comparing the STR profile from a crime scene to profiles in the CODIS database, which includes profiles from convicted offenders and other crime scenes, law enforcement can link suspects to crimes or identify victims with a high degree of statistical certainty, often as high as 1 in many billions.
Establishing Family Relationships
Beyond forensic applications, STR analysis is widely used to establish biological relationships between individuals, such as in paternity testing. Since a child inherits half of their DNA from each parent, their STR profile is a combination of alleles from both biological parents. To determine parentage, DNA samples are collected from the child and the alleged parents, typically through saliva or oral cells. The STR markers from these samples are then analyzed and compared, often using techniques like capillary gel electrophoresis. Scientists examine multiple STR loci to see if the child’s alleles, particularly those not inherited from the known mother, match the alleles of the alleged father. A match across a sufficient number of these highly variable STR markers provides a very high probability of a biological relationship. For instance, using 15 to 20 STR markers can achieve a paternity determination accuracy often exceeding 99.99%. This application relies on the same principles of STR variability and inheritance, allowing for accurate confirmation of direct parent-child links.
Connection to Genetic Disorders
While many STRs are found in non-coding DNA and serve as neutral genetic markers, some are located within or near genes and can directly cause genetic disorders. In these cases, an abnormal expansion of the number of repeats, known as an STR expansion, can disrupt gene function. For example, Huntington’s disease is caused by an excessive number of CAG trinucleotide repeats within the HTT gene on chromosome 4. This expansion leads to a mutated huntingtin protein, resulting in the degeneration of specific brain regions and neurological symptoms. Another example is Fragile X syndrome, the most common inherited cause of intellectual disability, which results from an expansion of CGG repeats in the FMR1 gene. When these CGG repeats become excessively long, the gene’s expression is silenced, leading to the absence of a protein important for brain development. These repeat expansion disorders often show a phenomenon called genetic anticipation, where the disease may become more severe or have an earlier onset in successive generations due to further expansion of the repeats. Over 40 human neurological diseases are linked to such STR expansions, illustrating a distinct and impactful role for these repetitive DNA sequences.