What is gene deletion?

Deletion is one of the most common events of genetic mutation. It occurs when any portion of genetic information is lost. Deletion can be variable in the number of lost nucleotides, the location within a chromosome, the severity of the disease it ensues, etc. The size of the lost segment can range from a single nucleotide, a codon, a gene, to an entire chromosome. The diversity of deletion makes it a popular topic for scientists. And its tight connection with diseases attracts medical professionals to devote themselves to it. The rest of the article will be organized based on the size of the lost segment and will put emphasis on the correlation between each deletion and its corresponding diseases.

Single nucleotide loss, the smallest unit of a deletion event, though not seeming like a big deal, is actually harmful when it occurs inside a gene. The loss of one nucleotide causes the entire reading frame to shift by one nucleotide, thus, making the translation go wrong from that position. The resulting genetic product would not function at all. Of all the diseases resulting from single nucleotide loss, the most well-known and also the most notorious one is Duchenne muscular dystrophy, an X-linked recessive disease. In Duchenne muscular dystrophy, the culprit is the deletion of a protein named dystrophin, which is responsible for anchoring actin filament to the cell membrane of muscle fiber. A milder form of Duchenne muscular dystrophy called Becker muscular dystrophy, though having mutation of the same gene, usually involves only a missense mutation, therefore, the impaired dystrophin still retains most of its structural integrity and only compromises a part of its function.

Deletion of a codon obviously would cause an amino acid to be lost in a protein genetic product, and thus, disrupt the normal function of that protein. Cystic fibrosis, an autosomal recessive disease, is mostly due to a deletion of a codon in the CFTR gene, which encodes CFTR protein, a chloride ion channel that is widespread throughout exocrine glands. Once CFTR is impaired, digestive juice or sweat secreted by those glands would be so thick that it forms a mucus plug and blocks the outflow tract of the glands. No doubt that patients with cystic fibrosis present with respiratory infection due to sticky secretion, infertility in males due to the absence of vas deferens, malabsorption, abdominal pain due to obstructed exocrine glands, etc.

Deletion of an entire gene either diminishes the expression of a genetic product when only one locus is affected or completely shuts down its production when both loci are affected. The lack or loss of a certain genetic product reflects the presentation of patients. More interestingly, the presence of a disease may depend on another genetic phenomenon called imprinting. Take Prader-Willi syndrome and Angelman syndrome for example. Both diseases are autosomal recessive and have a deletion at the same locus on chromosome 15. However, a deletion on one locus is enough to precipitate the disease in some cases. In Prader-Willi syndrome, the locus on the maternal chromosome is imprinted, thus, deletion of the same locus on the paternal chromosome is enough to cause the disease. Likewise, Angelman syndrome involves maternal deletion and paternal imprinting of that same locus. Other examples are Cri-du-chat syndrome (deletion at 5p), DiGeorge syndrome (deletion at 22q11), and Williams syndrome. Of note, deletion of less than 2-5 Mb is termed microdeletion since it is not visible under high-resolution karyotyping. However, there is no absolute criteria/definition for microdeletion which is often used in textbooks to describe a certain class of diseases.

Last but not the least, the most severe type of deletion is the loss of an entire chromosome or multiple chromosomes. Since each chromosome carries hundreds of genes if not thousands (in the case of humans), no life can tolerate such a great loss. Loss of any chromosome is incompatible with life except for the X chromosome. Turner syndrome, an example of monosomy, is due to the loss of one X chromosome, resulting in a genotype of 45, X. Patients with Turner syndrome are characteristic of a webbed neck, low-set ears, infertility, a short stature, etc.