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Overview of genetic variation

Benjamin A Raby, MD, MPH
Section Editor
Anne Slavotinek, MBBS, PhD
Deputy Editor
Jennifer S Tirnauer, MD


The human genome is rich in variation. Until recently, only a handful of common variants, termed polymorphisms (chromosome or sequence variants found in more than 1 percent of the population), have been implicated in common disease, although the majority of heritable phenotypic variation is due to alterations in DNA sequence. In contrast, the genetics of Mendelian conditions caused by rare mutations that occur sporadically or that are inherited have been better characterized.

The Human Genome Project, completed in 2003, elucidated the complete sequence of the human reference genome [1]. This sequence, together with the availability of DNA genotyping and sequencing methods capable of surveying variation in large numbers of individuals on a genome-wide scale, has led to rapid expansion of the list of common genetic variants that contribute to disease susceptibility, disease progression, and variability in treatment response.

This topic will review the types of genetic variation implicated in health and disease, with a particular focus on common genetic variants, including short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), and copy number variants (CNVs).

A glossary of genetic terms is available separately. (See "Glossary of genetic terms".)


Chromosomal abnormalities that are visible using light microscopy can be classified into those due to aberrant chromosome number and those due to abnormal chromosome structure. These variants can result in well-characterized syndromes, although many structural abnormalities are rare or unique. Chromosome aberrations typically result from either chromosome recombination errors during meiosis (for germline mutations) or aberrant chromosomal segregation during meiosis or mitosis. Large-scale variants can be evaluated using a variety of cytogenetic approaches, including karyotyping, fluorescence in-situ hybridization (FISH), and array comparative genome hybridization (array CGH) applications. (See 'Aneuploidy' below and 'Structural chromosome abnormalities' below and "Tools for genetics and genomics: Cytogenetics and molecular genetics".)


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Literature review current through: Sep 2016. | This topic last updated: Oct 14, 2016.
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