How is DNA sequencing used in diagnosing diseases?

DNA sequencing is a laboratory method used to determine the order of the bases within the DNA. Differences in the sequence of these 3 billion base pairs in the human genome lead to each person's unique genetic makeup. In medicine, DNA sequencing is used for a range of purposes, including diagnosis and treatment of diseases. In general, sequencing allows healthcare practitioners to determine if a gene or the region that regulates a gene contains changes, called variants or mutations, that are linked to a disorder.

While methods for DNA sequencing have evolved over the years, the technique generally consists of breaking long strands of DNA into many small pieces, using one of several types of tests to determine the order of the nucleotide bases that make up those pieces, and then reassembling the data back in the order of the original DNA strand.

The arrays of DNA based tests currently available for diagnosis of human genetic disease include tests designed to search for mutations in a single gene, gene panel tests designed to search for disease causing mutations in any one of a number of genes that are known to be mutated in a specific type of disease, e.g., diseases associated with ataxia. In addition, second generation sequencing techniques have facilitated analysis of the entire exome or the entire genome in a particular individual.

Through collection of data from large numbers of healthy individuals in populations and through archiving of data in publications, bioinformatics resources have been established that facilitate assessment of the likelihood that a particular genomic variant or sequence variant found in a particular patient is of pathologic significance.