Single nucleotide polymorphisms (SNPs) can be associated with genetic disorders, and researchers use them as powerful genetic markers to identify disease-related regions in the genome. Through genome-wide association studies (GWAS), scientists compare the genomes of individuals affected by a particular disorder with those of healthy individuals and look for SNPs that occur more frequently in patients. Genetic markers are not limited to DNA changes that directly alter the phenotype; they also include neutral variations that can serve as landmarks across the genome. This makes them extremely useful for identifying genetic variants at the molecular level, especially when the disease-causing mutation has known phenotypic effects but the specific gene and its product remain unknown. Many severe human diseases have historically fallen into this category.
For example, Cystic Fibrosis exhibits recessive Mendelian inheritance, but the molecular basis of the disorder remained unknown until researchers identified and characterized the responsible gene.
Through genome-wide association studies, researchers can identify SNPs that are more frequently found in patients with a particular disorder.
Because SNPs are distributed throughout the genome, some are likely to occur near or within virtually any gene of interest. Researchers can exploit this close linkage to identify markers associated with disease-causing genes. When DNA from patients is compared with DNA from unaffected individuals, certain SNPs may consistently appear or be absent in affected individuals. GWAS uses this principle by scanning entire genomes to detect SNPs associated with a disorder. The disorder under investigation does not need to be caused by a single gene; GWAS can also reveal genetic contributions to polygenic and multifactorial disorders that involve both genetic and environmental influences. Although some associated SNPs may have no direct functional role in the disease, others may influence susceptibility or disease progression.
The identification of disease-associated SNPs has two major consequences. First, it can provide a diagnostic tool for detecting a disorder or estimating an individual’s susceptibility to developing it. Some inherited diseases are difficult to diagnose at the molecular level, but if a specific SNP is strongly associated with the phenotype, healthcare providers can use its presence to assess the probability that a person will develop the disorder. Second, associated SNPs can guide researchers to the genes that contribute to the disease, facilitating gene isolation and characterization.
The abundance of polymorphic sites means that every individual carries a unique combination of SNPs. The specific pattern of SNPs in a defined genomic region is known as a haplotype, which represents a small portion of an individual’s complete genotype. The term haplotype was originally introduced to describe the genetic composition of the Major Histocompatibility Complex, a genomic region encoding proteins essential for immune function. Today, the term refers more broadly to any particular combination of alleles or genetic markers within a specified region of the genome. By analyzing SNPs, researchers have constructed a detailed haplotype map of the human genome, greatly improving the ability to locate disease-causing genes.
Highly polymorphic regions of the genome also form the basis of techniques used to establish biological relationships and identify individuals. In cases where parentage is uncertain, comparing haplotypes between a child and potential parents can confirm or exclude a biological relationship. DNA analysis can also associate a DNA sample with a specific person, a process known as DNA profiling or DNA forensics. These methods often rely on the examination of highly variable minisatellite sequences, which provide a distinctive genetic signature for each individual.
