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Genomic disorders: An overview

Carlos A Bacino, MD, FACMG
Section Editors
Helen V Firth, DM, FRCP, DCH
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD


Genomic disorders are diseases that result from the loss or gain of chromosomal/DNA material. The most common and better-delineated genomic disorders are divided in two main categories: those resulting from copy number losses (deletion syndromes) and copy number gains (duplication syndromes).

An overview of genomic disorders is presented here. Specific syndromic disorders are reviewed separately.


Structural genetic variation refers to a class of sequence alterations spanning more than 1000 bases (one kilobase or kb) [1]. This class includes quantitative variations such as copy number variations (CNVs), sequence rearrangements (such as those observed among immunoglobulins), and other less common variations, including chromosomal rearrangements that may or may not alter the genome contents and in some cases result in disease.

CNVs, the most prevalent type of structural variation, are DNA segments spanning thousands to millions of bases whose copy number varies between different individuals [2,3]. These submicroscopic genomic differences in the number of copies of one or more sections of DNA are the result of DNA gains or losses. Copy number gains can be the result of duplications, triplications, or even multiple copy number gains. Most deletions are one copy loss (heterozygous), but in some instances the loss can affect both copies (homozygous deletions).

CNVs are most commonly inherited but can occur de novo (ie, as a new event). These were initially thought to be rare events resulting from sporadic mutation and correlated with specific Mendelian diseases [4,5]. These misperceptions about their rarity and absolute disease linkage were primarily due to technical limitations precluding genome-wide assessments in large cohorts. Advances in technology have shown that deviation from the diploid state is widespread and contributes substantially to genetic diversity. Some studies have suggested that CNV differences in the human genome are as extensive as 20 percent, although this may be an overestimation [6,7]. It is estimated conservatively that most individuals carry an average of three large-scale CNVs [3]. The number of known CNVs that contribute to disease pathogenesis continues to increase.


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Literature review current through: Sep 2016. | This topic last updated: Aug 31, 2015.
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