Germline mosaicism

Genetic mosaicism is a condition where more than one set of genetic information is found within cells in an organism. Germline mosaicism is a type of genetic mosaicism where more than one set of genetic information is found specifically within the gamete cells. Somatic mosaicism (a type of genetic mosaicism found in somatic cells) and germline mosaicism can be present at the same time or individually depending on when the condition occurred in development. When the mosaicism is only found in the gametes and not in any somatic cells, it is referred to as pure germline mosaicism. Germline mosaicism can be caused two different ways. It can be the result of a mutation that occurs after conception, early in the develpment of a somatic cell. That somatic cell can then pass the mutated allele on to its daughter cells that later specialize as gametes. It can also be caused by a sporadic mutation in a gamete cell. If the germline mosaicism causing mutation occurs in the somatic cell, it never results in pure germline mosaicism because it will be present in somatic cells as well.^[1][2] Some studies show support that germline mosaicism may also be the result of Epigenetic regulation (alterations to DNA, such as methylation, that do not involve changes in the genetic code).^[3]

Inheritance

Genetic diseases and conditions carried in germline cells can be passed onto offspring even if the mutation is not present in the parents' phenotype. A diseases caused by germline mosaicism can be difficult to diagnose as a genetically inherited disease because the mutant alleles would not likely be present in the somatic cells, such as skin tissue, that are more commonly examined for genetic analysis. Somatic cells are more commonly used for genetic analysis because they are easier to obtain than gametes. If the disease is a result of pure germline mosaicism, then the disease causing mutant allele would never be present in the somatic cells. This is a source of uncertainty for genetic counselling. An individual may still be a carrier for a certain disease even if the disease causing mutant allele is not present in the cell that was analyzed because it could still exist in some of the individual's gametes.^[4]

Germline mosaicism may contribute to the inheritance of many genetic conditions. Conditions that are inherited by means of germline mosaicism are often mistaken as being the result of de novo mutations. Various diseases are now being re-examined for presence of mutant alleles in the germline of the parents in order to further our understanding of how they can be passed-on.^[5] The frequency of germline mosacism is not known due to the sporadic nature of the mutations causing it and the availability of the gametes that must be tested to diagnose it.

Recurrence Rate

The recurrence rate of conditions due to germline mosaicism varies greatly between subjects. Recurrence is proportional to the number of gamete cells that carry the particular mutation with the condition. If the mutation occurred earlier on in the development of the gamete cells, then the reoccurrence rate would be higher because a greater number of cells would carry the mutant allele.^[6]

Notes

1. Orva, Rosa; Orva, David (April 1998). "Germ line Mosaicism". Human Genetics 4 (102): 381. Retrieved December 3, 2015.
2. Nussbuam, McInnes, Willard. Genetics In Medicine. Elsevier. pp. 123–125. ISBN 978-1-4377-0696-3.
3. Laurentino, S.; Beygo, J.; Nordhoff, V.; Kliesch, S.; Wistuba, J.; Borgmann, J.; Buiting, K.; Horsthemke, B.; Gromoll, J. (21 October 2014). "Epigenetic germline mosaicism in infertile men". Human Molecular Genetics 24 (5): 1295–1304. doi:10.1093/hmg/ddu540.
4. Chi Hyan, Cho; et al. (2015). "A Case Report of a Fetus with Mosaic Autosomal Variegated Aneuploidies and Literature Review". Annals of Clinical & Laboratory Science. Retrieved December 3, 2015.
5. Armaroli, Annarita; Trabanelli, Cecilia; Scotton, Chiara; Venturoli, Anna; Selvatici, Rita; Brisca, Giacomo; Merlini, Luciano; Bruno, Claudio; Ferlini, Alessandra (2015-09-01). "Paternal germline mosaicism in collagen VI related myopathies". European Journal of Paediatric Neurology 19 (5): 533–536. doi:10.1016/j.ejpn.2015.04.002.
6. EDWARDS, J. H. (January 1989). "Familiarity, recessivity and germline mosaicism". Annals of Human Genetics 53 (1): 33–47. doi:10.1111/j.1469-1809.1989.tb01120.x.