Deletion (genetics)

In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome.^[1] Deletions can be caused by errors in chromosomal crossover during meiosis. This causes several serious genetic diseases. Deletion also causes frameshift.

Causes

Causes include the following:

• Losses from translocation
• Chromosomal crossovers within a chromosomal inversion
• Unequal crossing over
• Breaking without rejoining

For synapsis to occur between a chromosome with a large intercalary deficiency and a normal complete homolog, the unpaired region of the normal homolog must loop out of the linear structure into a deletion or compensation loop.

Types

Types of deletion include the following:

• Terminal Deletion - a deletion that occurs towards the end of a chromosome.
• Intercalary Deletion / Interstitial Deletion - a deletion that occurs from the interior 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.

Deletion of a number of base 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.^[2]

Deletions are responsible for an array of genetic disorders, including some cases of male infertility and two thirds of cases of Duchenne muscular dystrophy.^[1] Deletion of part of the short arm of chromosome 5 results in a syndrome called Cri du chat,^[1] French for "cry of the cat" syndrome. It is found in approximately 1 in 50,000 live births. The surviving infants have a distinctive cry, severe mental retardation, and shortened life span.

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 are referred to as hCONDELs may be responsible for the anatomical and behavioral differences between humans ,chimpanzees and other mammals^[3] .

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 as high as >30,000 "bands" and the size of chromosomal deletion detected could as small as 5–20 kb in length.^[4]

See also

• Indel
• Chromosome abnormalities
• Null allele
• List of genetic disorders
• Medical genetics

References

1. ^ ^{a b c} Lewis R. 2005. Human Genetics: Concepts and Applications, 6th Ed. McGraw Hill, New York.
2. ^ LSDB - Controlled vocabulary terms at The GEN2PHEN Knowledge Centre. Posted Fri, 08/01/2010.
3. ^ McLean, C. Y.; Reno, P. L.; Pollen, A. A.; Bassan, A. I.; Capellini, T. D.; Guenther, C.; Indjeian, V. B.; Lim, X. et al. (2011). "Human-specific loss of regulatory DNA and the evolution of human-specific traits". Nature 471 (7337): 216–219. doi:10.1038/nature09774. PMC 3071156. PMID 21390129. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3071156.  edit
4. ^ Ren, H (May 2005). "BAC-based PCR fragment microarray: high-resolution detection of chromosomal deletion and duplication breakpoints". Human Mutations 25 (5): 476–482. PMID 15832308.