Mutation acquired during an organism's lifespan
A postzygotic mutation (or post-zygotic mutation) is a change in an organism's genome that is acquired during its lifespan, instead of being inherited from its parent(s) through fusion of two haploid gametes. Mutations that occur after the zygote has formed can be caused by a variety of sources that fall under two classes: spontaneous mutations and induced mutations. How detrimental a mutation is to an organism is dependent on what the mutation is, where it occurred in the genome and when it occurred.
Causes.
Postzygotic changes to a genome can be caused by small mutations that affect a single base pair, or large mutations that affect entire chromosomes and are divided into two classes, spontaneous mutations and induced mutations.
Spontaneous mutations.
Most spontaneous mutations are the result of naturally occurring lesions to DNA and errors during DNA replication without direct exposure to an agent. A few common spontaneous mutations are:
Induced mutations.
Induced mutations are any lesions in DNA caused by an agent or mutagen. Mutagens often demonstrate mutational specificity, meaning they cause predictable changes in the DNA sequence. A few common mutagens that induce mutations are:
Consequences.
A large determinant of the severity of consequences caused by postzygotic mutations is when and where they occur. As a result, consequences can range from being negligible to incredibly detrimental.
Mosaicism.
When an individual has inherited an abnormality it is usually present in all of their cells. However some mutations like DNA code change, epigenetic alterations and chromosomal abnormalities, can occur later in development. This would result in one progeny cell line to be normal while the other cell line(s) to be abnormal. As a result, the individual is considered to be a mosaic of normal and abnormal cells.
Mosaicism is the occurrence of two or more cell lines with different genotypes within a single individual. It is different from chimerism which is the fusion of two zygotes, causing a new single zygote with two genotypes.
Loss of chromosome Y.
The loss of chromosome Y (LOY) in blood cells is the most common human postzygotic mutation. It is highly associated with age, being detectable in at least 10% of blood cells for 14% and 57% of males around 70 and 94 years of age, respectively. Men with LOY have a higher all-cause mortality and cancer mortality compared with unaffected males. Additionally, LOY is associated with greater risk for Alzheimer's disease and cardiovascular disease. Smoking increases the risk of inducing LOY more than three times and has a dose-dependent effect on LOY-status.
Trisomy 21 mosaicism.
Trisomy 21 (Down syndrome) is one of the most prevalent chromosomal abnormalities amongst live births. Of all trisomy 21 pregnancies, approximately 80% end in spontaneous abortions or still-births. 1–5% of people diagnosed with having Down Syndrome are actually in fact "high-grade" trisomy 21 mosaics. The rest of trisomy 21 mosaics are marked as "low-grade" mosaics, meaning the chromosomal mutation occurs in less than 3–5% of respective tissue. While high-grade trisomy 21 mosaics, demonstrate similar features to full Down Syndrome, low-grade mosaics have a tendency to show milder features; however, the effects are quite variable depending on the distribution of the trisomic cells.
Somatic mutations.
Somatic mutations are the result of a change in the genetic structure after fertilization. This type of mutation also involves cells outside of the reproductive group and thus is not transmitted to future descendants.
Germ-line mutations.
Germ-line mutations are the result of a change in the genetic structure of germ cells. These mutations are able to be transmitted to the offspring and give rise to a constitutional mutation. Constitutional mutations is a mutation that when present in one cell, is also present in all other cells associated with the organism.
References.
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