If made from stones, could two pieces of a mosaic ever be exactly the same? Of course, the answer is no: although certain pieces of the mosaic may appear similar from a distance, a closer look would reveal that no two stones composing the mosaic were exactly the same.
Like stones in a mosaic, our cells may vary. Specifically, they may undergo changes during development such that one group of cells differs from a neighboring group. This phenomenon is known as mosaicism, and it can be caused by spontaneous DNA mutations, spontaneous reversion of an existing DNA mutation, epigenetic changes in chromosomal DNA, and chromosomal abnormalities. Furthermore, mosaicism can be associated with changes in either nuclear or mitochondrial DNA. The phenotypes associated with mosaicism depend on the extent of the mosaic cell population. Mosaicism has important consequences with respect to human disease, and it also results in variations among all humans at the molecular level, even among identical twins.
Germ Line Mosaicism versus Somatic Mosaicism
![Diagnostic methods for somatic and germ line mosaicism](javascript:dispOrigImg("/scitable/content/36165/10.1038_nrg906-f2_large.jpg", "Diagnostic methods for somatic and germ line mosaicism", "true", "Figure 1", "(A) Hypothetical pedigree of Segmental neurofibromitosis type 1, and (below) molecular analysis showing somatic mosaicism. The three-generation pedigree illustrates the occurrence of a sporadic mutation (shown in red) in a second-generation male (represented as squares) manifested as a cafe-au-lait skin lesion that is typical of NFI. Although this disorder is typically inherited as an autosomal-dominant trait, none of the offspring of the affected individual show the abnormality. Moreover, molecular analysis reveals a putative deletion (MUT) in the NF1 gene in DNA obtained from the abnormal skin of the affected patient. By contrast, only wild-type (WT) DNA is noted in the other tissues. The combination of the clinical information and the molecular information supports the diagnosis of a somatic mosaic state in the affected patient. (B) Hypothetical pedigree and molecular analysis showing germ-line mosaicism in tuberous sclerosis. Although this disorder is inherited as an autosomal-dominant trait, the pedigree is more consistent with either autosomal-recessive inheritance or germ-line mosaicism for a mutation in one of the tuberous sclerosis genes in one of the parents. DNA analysis reveals that the father's germ cells, but not other tissues, harbour the mutation (MUT). Due to the inaccessibility of female germ cells, the molecular analysis in such instances frequently remains incomplete.", "true", "All rights reserved.", '700', '342', 'http://www.nature.com');)
Figure 1: Diagnostic methods for somatic and germ line mosaicism© 2002 Nature Publishing Group Youssoufian, H. et al. Mechanisms and consequences of somatic mosaicism in humans. Nature Reviews Genetics 3, 750 (2002). All rights reserved. 
If the event leading to mosaicism occurs during development, it is possible that both somatic and germ line cells will become mosaic. In this case, both somatic and germ line tissue populations would be affected, and an individual could transmit the mosaic genotype to his or her offspring. Conversely, if the triggering event occurs later in life, it could affect either a germ line or a somatic cell population. If the mosaicism occurs only in a somatic cell population, the phenotypic effect will depend on the extent of the mosaic cell population; however, there would be no risk of passing on the mosaic genotype to offspring. On the other hand, if the mosaicism occurs only in a germ line cell population, the individual would be unaffected, but his or her offspring could be affected.
Figure 1a shows how pedigrees and molecular analyses can be combined to determine whether somatic mosaicism or germ line mosaicism is responsible for disease phenotypes. The first three-generation pedigree shows the inheritance of café au lait spots associated with neurofibromatosis type I, which is typically an autosomal dominant disorder associated with mutations in the NF1 gene. As you can see, two unaffected parents have one son with a café au lait skin lesion. The affected male does not pass on the disorder to any of his four offspring. Molecular analysis of blood and normal skin samples show that these samples carry a wild-type copy of the NF1 gene, whereas the café au lait skin lesion of the affected male contains a wild-type and a mutant copy of the NF1 gene, which is suggestive of a somatic mosaic mutation in this population of skin cells.
The second pedigree (Figure 1b) shows the inheritance of tuberous sclerosis, which is typically an autosomal disorder associated with mutations in the TSC1 or TSC2 gene. In this pedigree, you can see that unaffected parents have one affected son, one affected daughter, and one unaffected son. This pattern of inheritance is consistent with an autosomal recessive disorder in which both parents are carriers, or with germ line mosaicism in one parent. Molecular analysis of blood samples shows that both parents are homozygous for the wild-type TSC1 allele, suggesting that they are not typical heterozygous carriers. Blood samples from the affected children show that both are heterozygous for the mutant TSC1 allele, whereas the unaffected son carries only the wild-type TSC1 allele. Analysis of germ line (sperm) cells from the males in the pedigree shows that the father and the affected son carry the mutant TSC1 allele. Taken together, these results suggest that the father has undergone a germ line mosaic mutation such that some of his sperm cells carry the mutant TSC1 allele.
