Deletion (genetics)

Types

Types of deletion include the following:

• Terminal deletion – a deletion that occurs towards the end of a chromosome.
• Intercalary/interstitial deletion – a deletion that occurs from the interior of a chromosome.
• Microdeletion – a relatively small amount of deletion (up to 5Mb that could include a dozen genes).

Micro-deletion is usually found in children with physical abnormalities. A large amount of deletion would result in immediate abortion (miscarriage).

Nomenclature

The International System for Human Cytogenomic Nomenclature (ISCN) is an international standard for human chromosome nomenclature, which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations include a minus sign (−) for chromosome deletions, and del for deletions of parts of a chromosome.

Effects

Small deletions are less likely to be fatal; large deletions are usually fatal – there are always variations based on which genes are lost. Some medium-sized deletions lead to recognizable human disorders, e.g. Williams syndrome.

Deletion of a number of pairs that is not evenly divisible by three will lead to a frameshift mutation, causing all of the codons occurring after the deletion to be read incorrectly during translation, producing a severely altered and potentially nonfunctional protein. In contrast, a deletion that is evenly divisible by three is called an in-frame deletion.

Deletions are responsible for an array of genetic disorders, including some cases of male infertility, two thirds of cases of Duchenne muscular dystrophy, and two thirds of cases of cystic fibrosis (those caused by ΔF508). Deletion of part of the short arm of chromosome 5 results in Cri du chat syndrome. Deletions in the SMN-encoding gene cause spinal muscular atrophy, the most common genetic cause of infant death.

Microdeletions are associated with many different conditions, including Angelman syndrome, Prader-Willi syndrome, and DiGeorge syndrome. Some syndromes, including Angelman syndrome and Prader-Willi syndrome, are associated with both microdeletions and genomic imprinting, meaning that same microdeletion can cause two different syndromes depending on which parent the deletion came from.

Recent work suggests that some deletions of highly conserved sequences (CONDELs) may be responsible for the evolutionary differences present among closely related species. Such deletions in humans, referred to as hCONDELs, may be responsible for the anatomical and behavioral differences between humans, chimpanzees and other varieties of mammals like ape or monkeys.

Recent comprehensive patient-level classification and quantification of driver events in TCGA cohorts revealed that there are on average 12 driver events per tumor, of which 2.1 are deletions of tumor suppressors.

Detection

The introduction of molecular techniques in conjunction with classical cytogenetic methods has in recent years greatly improved the diagnostic potential for chromosomal abnormalities. In particular, microarray-comparative genomic hybridization (CGH) based on the use of BAC clones promises a sensitive strategy for the detection of DNA copy-number changes on a genome-wide scale. The resolution of detection could be as high as >30,000 "bands" and the size of chromosomal deletion detected could as small as 5–20 kb in length. Other computation methods were selected to discover DNA sequencing deletion errors such as end-sequence profiling.

Mitochondrial DNA deletions

In the yeast Saccharomyces cerevisiae, the nuclear genes Rad51p, Rad52p and Rad59p encode proteins that are necessary for recombinational repair and are employed in the repair of double strand breaks in mitochondrial DNA. Loss of these proteins decreases the rate of spontaneous DNA deletion events in mitochondria. This finding implies that the repair of DNA double-strand breaks by homologous recombination is a step in the formation of mitochondrial DNA deletions.