How mutations occur in DNA?
Environmental exposure to certain chemicals, ultraviolet radiation, other genetic insults, or even errors that occur during the process of replication can alter the DNA in any cell.
What are somatic and germline mutations?
Germline mutation is one that occurs in a germ-line cell (cells which give rise to gametes, i.e., egg or sperm cells). These mutations can be passed on (inherited) to an organism’s offspring. This means that every cell in the developing embryo will carry the same mutation.
Somatic mutations occur in cells found elsewhere in an organism’s body. Such mutations are passed to daughter cells during one type of cell division known as mitosis (Figure 1), but they are not passed to offspring conceived via sexual reproduction (1). Most cancers are good examples of somatic mutations. Generally, cancer cells form clones as each successive division leads to two daughter cells that carry the same mutation. Recently it has been found that most solid tumors are actually heterogeneous mixtures of multiple clones with various mutations. But within the same tumor if we study a single colony of clonally proliferating cells we will find that all of them are carrying the same mutation which can be traced all the way back to the original parent cell (cancer stem cell) (2).
Can a somatic mutation be inherited?
Somatic mutations can presumably occur at any time, but the majority are said to be phenotypically silent, if, for instance, the mutation is in a non-coding part of the genome, or a gene that is not expressed in the particular cell. Such a mutation could theoretically pass into the germline if it occurred in a cell which would give rise to gametes. However, since germ-line cells are formed very early in development, it seems unlikely.
What is the difference between mutations and polymorphisms?
While a mutation is defined as any alteration in the DNA sequence, biologists use the term “single nucleotide polymorphism” (SNP) to refer to a single base pair alteration that is common in the population (3). SNPs are important as markers, or signposts, for scientists to use when they look at populations of organisms in an attempt to find genetic changes that predispose individuals to certain traits, including disease. On average, SNPs are found every 1,000–2,000 nucleotides in the human genome, and scientists participating in the International HapMap Consortium have mapped millions of these alterations (4).
How do we get these somatic mutations?
DNA interacts with the environment, and sometimes that interaction can be detrimental to genetic information. In fact, every time you go outside, you put your DNA in danger, because ultraviolet (UV) light from the Sun can induce mutations in your skin cells. In addition to ultraviolet light, organisms are exposed to more energetic ionizing radiation in the form of cosmic rays, gamma rays, and X-rays. Ionizing radiation induces double-stranded breaks in DNA, and the resulting repair can likewise introduce mutations if carried out imperfectly. Unlike UV light, however, these forms of radiation penetrate tissue well, so they can cause mutations anywhere in the body. That is why protective lead garments are used by x-ray technicians and people working in places with high risk of radiation exposure.
Does Genomepatri analysis distinguish germline and somatic mutations?
Currently, we are not reporting this feature as most of the markers included in Genomepatri are germline mutations only. However, we are currently providing a separate list of inherited conditions and traits which mainly contain germline mutations and our genetic counselors will cover these topics during the counseling session and provide meaningful inferences based each individual’s family history and pedigree analysis.
1. Pierce, B. A. Genetics: A Conceptual Approach (Freeman, New York, 2000)
2.Greenblatt, M. S., et al. Mutations in the P53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Research 54, 4855–4878 (1994)
3. Twyman, R. Mutation or polymorphism? Wellcome Trust website, (2003)
4. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)
5. Seidl, H., et al. Ultraviolet exposure as the main initiator of P53 mutations in basal cell carcinomas from psoralen and ultraviolet A-treated patients with psoriasis. Journal of Investigative Dermatology 117, 365–370 (2001)

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