Germline mosaicism

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Germline mosaicism, also called gonadal 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 conditions occur. 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 either by a mutation that occurs after conception,[1][2] or by epigenetic regulation,[3] alterations to DNA such as methylation that do not involve changes in the DNA coding sequence.

A mutation in an allele acquired by a somatic cell early in its development can be passed on to its daughter cells, including those that later specialize to 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.


Genetic mutations, including those that cause disease, can be carried in gamete cells and passed on to offspring even if the mutation is not present (expressed) in the parents' phenotype. Diseases caused by germline mosaicism can be difficult to diagnose as genetically-inherited because the mutant alleles are not likely be present in the somatic cells. 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 cells that were analyzed because the causative mutation 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 difficulty in obtaining the gametes that must be tested to diagnose it.

Recurrence rate[edit]

The recurrence rate of conditions caused by 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 recurrence rate would be higher because a greater number of cells would carry the mutant allele.[6]


  1. ^ Orva, Rosa; Orva, David (April 1998). "Germ line Mosaicism". Human Genetics. 102: 381–6. PMID 9600231. doi:10.1007/s004390050708. 
  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. PMID 25336341. 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.