Short Tandem Repeat (STR) analysis is a core technology in modern genetics used for individual identification. This technique focuses on specific segments of non-coding DNA that contain short, repetitive sequences. The fundamental principle involves measuring the length of these repeating units at various locations across the human genome. The utility of this analysis spans from diagnosing inherited diseases to establishing identities in forensic and legal contexts, replacing older methods due to its speed and sensitivity.
The Genetics of Short Tandem Repeats
Short Tandem Repeats are segments of DNA where a sequence of two to seven base pairs is repeated multiple times in a row. These sequences are found scattered throughout the genome, often in regions that do not code for proteins. The name “tandem repeat” describes the head-to-tail arrangement of the repeated units, such as “GATA-GATA-GATA”.
The high degree of polymorphism means the number of times a sequence repeats at a specific chromosomal location, or locus, varies significantly among individuals. For example, one person might have 10 repeats of a sequence at a given locus, while another might have 12. These differences in repeat number are inherited, with an individual receiving one allele (repeat number) from each biological parent for every STR locus.
A person possesses a combination of two repeat numbers at each locus, which together form their genotype. Because there are many STR loci across the genome, and the number of repeats is highly variable at each one, the probability of two unrelated individuals sharing the exact same combination across multiple loci is exceedingly small. This makes STRs highly effective individual identity markers.
Analyzing STR Variability
The process of analyzing STR variability involves laboratory steps designed to translate the number of repeats into a measurable data point used to create a DNA profile. The first step requires isolating a small DNA sample, which is often degraded or limited in quantity. To overcome this challenge, the Polymerase Chain Reaction (PCR) technique is used to selectively amplify the target STR regions.
During PCR, specific molecular primers bracket the STR region of interest, copying the DNA exponentially to create millions of identical fragments. These primers are often tagged with fluorescent dyes, allowing the amplified fragments to be visualized later. A single reaction can amplify multiple STR loci simultaneously, a method known as multiplexing, which increases the speed and efficiency of the analysis.
Once the STR regions have been amplified, the resulting DNA fragments are separated and measured using capillary electrophoresis. In this technique, an electric current draws the fragments through a thin tube containing a gel-like polymer. Smaller fragments move faster than larger ones, separating the DNA based on its exact length. A laser detects the fluorescent dye on each fragment, and software converts the travel time into a precise size corresponding to the number of STR repeats.
Clinical and Diagnostic Applications
STR analysis plays a specialized role in medical and diagnostic settings, particularly for certain inherited conditions. Some genetic disorders are caused by an abnormal expansion of repeat sequences, known as trinucleotide repeat disorders. Examples include Huntington’s disease and Fragile X syndrome, where the length of the repeat sequence is directly correlated with the presence and severity of the disease.
The technology is also a standard tool for monitoring patients who have received a bone marrow or stem cell transplant (allogeneic transplantation). Doctors must track chimerism, the presence and proportion of donor cells versus recipient cells in the patient’s blood. By comparing the STR profiles of the donor and the recipient, the analysis quantifies the success of the engraftment. This monitoring helps detect potential complications like relapse or graft-versus-host disease.
Forensic and Identity Determination
STR analysis is widely recognized for its application in forensic science and personal identity determination. In forensics, a DNA profile is generated from biological evidence collected at a crime scene, such as blood, saliva, or hair. This profile, a unique numerical representation of the individual’s STR alleles, can then be compared against the profiles of suspects or victims.
This technique allows investigators to link a suspect to a crime scene, identify human remains, or exonerate individuals who were wrongly accused. Forensic profiles are stored and searched against national repositories, such as the Combined DNA Index System (CODIS) in the United States. CODIS uses a standardized set of core STR loci, ensuring that DNA profiles generated by different laboratories can be reliably compared and matched.
STR analysis is the standard method for establishing biological relationships, such as in paternity or kinship testing. Since children inherit half of their STR alleles from each parent, a match at all tested loci offers strong statistical support for a claimed biological relationship. This application is also used in missing persons cases, comparing the profile of unidentified remains to the STR profiles of family members to achieve a positive identification.