Postzygotic mutation

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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. [1]

Contents

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. [2]

Spontaneous mutations

Depurination mutation results in one normal strand and one shortened strand after replication. Depurination.jpg
Depurination mutation results in one normal strand and one shortened strand after replication.

Most spontaneous mutations are the result of naturally occurring lesions to DNA and errors during DNA replication without direct exposure to an agent. [2] 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. [5] 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. [7]

Mosaicism

Mosaicism arises after the zygote has formed and a mutation occurs during development. The mutated cell line can be passed down to offspring if the germ cells are affected. Parental Mosaicism.svg
Mosaicism arises after the zygote has formed and a mutation occurs during development. The mutated cell line can be passed down to offspring if the germ cells are affected.

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. [7]

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. [7]

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. [8] [9] Men with LOY have a higher all-cause mortality and cancer mortality compared with unaffected males. [10] Additionally, LOY is associated with greater risk for Alzheimer's disease and cardiovascular disease. [11] Smoking increases the risk of inducing LOY more than three times and has a dose-dependent effect on LOY-status. [12]

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. [13]

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. [14] [15]

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. [15]

Related Research Articles

<span class="mw-page-title-main">Genetics</span> Science of genes, heredity, and variation in living organisms

Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

Mutagenesis is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. A mutagen is a mutation-causing agent, be it chemical or physical, which results in an increased rate of mutations in an organism's genetic code. In nature mutagenesis can lead to cancer and various heritable diseases, and it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Karyotype</span> Photographic display of total chromosome complement in a cell

A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by determining the chromosome complement of an individual, including the number of chromosomes and any abnormalities.

<span class="mw-page-title-main">Aneuploidy</span> Presence of an abnormal number of chromosomes in a cell

Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any number of complete chromosome sets is called a euploid cell.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

A minisatellite is a tract of repetitive DNA in which certain DNA motifs are typically repeated two to several hundred times. Minisatellites occur at more than 1,000 locations in the human genome and they are notable for their high mutation rate and high diversity in the population. Minisatellites are prominent in the centromeres and telomeres of chromosomes, the latter protecting the chromosomes from damage. The name "satellite" refers to the early observation that centrifugation of genomic DNA in a test tube separates a prominent layer of bulk DNA from accompanying "satellite" layers of repetitive DNA. Minisatellites are small sequences of DNA that do not encode proteins but appear throughout the genome hundreds of times, with many repeated copies lying next to each other.

<span class="mw-page-title-main">Mosaic (genetics)</span> Condition in multi-cellular organisms

Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is one of several possible causes of chimerism, wherein a single organism is composed of cells with more than one distinct genotype.

<span class="mw-page-title-main">Point mutation</span> Replacement, insertion, or deletion of a single DNA or RNA nucleotide

A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences that are moderately predictable based upon the specifics of the mutation. These consequences can range from no effect to deleterious effects, with regard to protein production, composition, and function.

<span class="mw-page-title-main">Transversion</span> DNA point mutation that exchanges a purine (A or G) for a pyrimidine (C or T) or vice versa

Transversion, in molecular biology, refers to a point mutation in DNA in which a single purine is changed for a pyrimidine, or vice versa. A transversion can be spontaneous, or it can be caused by ionizing radiation or alkylating agents. It can only be reversed by a spontaneous reversion.

<span class="mw-page-title-main">Germline mutation</span> Inherited genetic variation

A germline mutation, or germinal mutation, is any detectable variation within germ cells. Mutations in these cells are the only mutations that can be passed on to offspring, when either a mutated sperm or oocyte come together to form a zygote. After this fertilization event occurs, germ cells divide rapidly to produce all of the cells in the body, causing this mutation to be present in every somatic and germline cell in the offspring; this is also known as a constitutional mutation. Germline mutation is distinct from somatic mutation.

Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. It adheres to Mendelian inheritance, with information coming from two parents, one male and one female—rather than matrilineally as in mitochondrial DNA.

Genetics, a discipline of biology, is the science of heredity and variation in living organisms.

<span class="mw-page-title-main">Genetic analysis</span>

Genetic analysis is the overall process of studying and researching in fields of science that involve genetics and molecular biology. There are a number of applications that are developed from this research, and these are also considered parts of the process. The base system of analysis revolves around general genetics. Basic studies include identification of genes and inherited disorders. This research has been conducted for centuries on both a large-scale physical observation basis and on a more microscopic scale. Genetic analysis can be used generally to describe methods both used in and resulting from the sciences of genetics and molecular biology, or to applications resulting from this research.

Mitotic recombination is a type of genetic recombination that may occur in somatic cells during their preparation for mitosis in both sexual and asexual organisms. In asexual organisms, the study of mitotic recombination is one way to understand genetic linkage because it is the only source of recombination within an individual. Additionally, mitotic recombination can result in the expression of recessive alleles in an otherwise heterozygous individual. This expression has important implications for the study of tumorigenesis and lethal recessive alleles. Mitotic homologous recombination occurs mainly between sister chromatids subsequent to replication. Inter-sister homologous recombination is ordinarily genetically silent. During mitosis the incidence of recombination between non-sister homologous chromatids is only about 1% of that between sister chromatids.

A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individual's karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.

The following outline is provided as an overview of and topical guide to genetics:

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

References

  1. ↑ Acuna-Hidalgo, Rocio; Bo, Tan; Kwint, Michael P.; van de Vorst, Maartje; Pinelli, Michele; Veltman, Joris A.; Hoischen, Alexander; Vissers, Lisenka E. L. M.; Gilissen, Christian (2015-07-02). "Post-zygotic Point Mutations Are an Underrecognized Source of De Novo Genomic Variation". The American Journal of Human Genetics. 97 (1): 67–74. doi:10.1016/j.ajhg.2015.05.008. PMC   4571017 . PMID   26054435.
  2. 1 2 3 4 5 Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (2000-01-01). "Spontaneous mutations". An Introduction to Genetic Analysis.[ dead link ]
  3. 1 2 Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2002-01-01). "DNA Repair". Molecular Biology of the Cell (4th ed.). Garland Science.
  4. ↑ "Documents – All Documents". faculty.ksu.edu.sa. Retrieved 2015-12-02.
  5. 1 2 3 4 5 6 Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (2000-01-01). "Induced mutations". An Introduction to Genetic Analysis.[ dead link ]
  6. ↑ Cooke, Marcus S.; Evans, Mark D.; Dizdaroglu, Miral; Lunec, Joseph (2003-07-01). "Oxidative DNA damage: mechanisms, mutation, and disease". The FASEB Journal. 17 (10): 1195–1214. CiteSeerX   10.1.1.335.5793 . doi: 10.1096/fj.02-0752rev . ISSN   0892-6638. PMID   12832285. S2CID   1132537.
  7. 1 2 3 Youssoufian, Hagop; Pyeritz, Reed E. (2002-10-01). "Mechanisms and consequences of somatic mosaicism in humans". Nature Reviews. Genetics. 3 (10): 748–758. doi:10.1038/nrg906. ISSN   1471-0056. PMID   12360233. S2CID   6355589.
  8. ↑ Forsberg, Lars A. (May 2017). "Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men". Human Genetics. 136 (5): 657–663. doi:10.1007/s00439-017-1799-2. ISSN   0340-6717. PMC   5418310 . PMID   28424864.
  9. ↑ Forsberg, Lars A.; Halvardson, Jonatan; Rychlicka-Buniowska, Edyta; Danielsson, Marcus; Moghadam, Behrooz Torabi; Mattisson, Jonas; Rasi, Chiara; Davies, Hanna; Lind, Lars; Giedraitis, Vilmantas; Lannfelt, Lars (January 2019). "Mosaic loss of chromosome Y in leukocytes matters". Nature Genetics. 51 (1): 4–7. doi:10.1038/s41588-018-0267-9. ISSN   1546-1718. PMID   30374072. S2CID   53093907.
  10. ↑ Forsberg, Lars A; Rasi, Chiara; Malmqvist, Niklas; Davies, Hanna; Pasupulati, Saichand; Pakalapati, Geeta; Sandgren, Johanna; Ståhl, Teresita Diaz de; Zaghlool, Ammar (June 2014). "Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer". Nature Genetics. 46 (6): 624–628. doi:10.1038/ng.2966. ISSN   1546-1718. PMC   5536222 . PMID   24777449.
  11. ↑ Haitjema, Saskia; Kofink, Daniel; Setten, Jessica van; Laan, Sander W. van der; Schoneveld, Arjan H.; Eales, James; Tomaszewski, Maciej; Jager, Saskia C. A. de; Pasterkamp, Gerard (2017-08-01). "Loss of y Chromosome in Blood is Associated with Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy". Circulation: Cardiovascular Genetics. 10 (4): e001544. doi: 10.1161/circgenetics.116.001544 . ISSN   1942-325X. PMID   28768751.
  12. ↑ Dumanski, Jan P.; Rasi, Chiara; Lönn, Mikael; Davies, Hanna; Ingelsson, Martin; Giedraitis, Vilmantas; Lannfelt, Lars; Magnusson, Patrik K. E.; Lindgren, Cecilia M. (2015-01-02). "Smoking is associated with mosaic loss of chromosome Y". Science. 347 (6217): 81–83. Bibcode:2015Sci...347...81D. doi:10.1126/science.1262092. ISSN   0036-8075. PMC   4356728 . PMID   25477213.
  13. ↑ Hultén, Maj A.; Jonasson, Jon; Nordgren, Ann; Iwarsson, Erik (2010-09-01). "Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?". Current Genomics. 11 (6): 409–419. doi:10.2174/138920210793176056. ISSN   1389-2029. PMC   3018721 . PMID   21358985.
  14. ↑ "Somatic mutation – Glossary Entry". Genetics Home Reference. 2015-11-09. Retrieved 2015-11-14.
  15. 1 2 Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (2000-01-01). "Somatic versus germinal mutation". An Introduction to Genetic Analysis.[ dead link ]
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