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What are inherited, sporadic and acquired mutations and how can they affect my fertility?

2 fertility expert(s) answered this question

Hereditary, sporadic and acquired mutations – how do they impact my fertility?

Inherited (hereditary or germline) mutations, as the name suggests, are inherited from our parents and we are born with them. They include mutations that cause, for example, cystic fibrosis, hemophilia, and sickle cell disease. Other types of mutations that can surface during a person’s life are called sporadic, spontaneous, or new mutations.

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Answer from the fertility expert:
Maria José Mendiola, Gynaecologist in Reproductive Medicine & Reproductive Genetics, Clínica Monterrico

There are two major types of mutations inherited and acquired. First, an inherited gene mutation is present in the egg or a sperm that forms the child. After the egg is fertilized by the sperm it creates what’s still called a zygote so that it is then divided into a fetus which becomes a baby. Since all the cells in the body came from the first cells, this kind of mutation is in every cell in the body including some eggs or sperm so, can be passed on to the next generation. This type of mutation is also called germline because the cells that develop into eggs and the sperms are called germ cells or hereditary. Inherited mutations are thought to be a direct cause of only small fractions of cancers, for example, or some problems regarding my fertility. On the other hand, there has been an acquired mutation that is not present in the zygote that is acquired sometime later in life. It occurs in one cell and then is passed on to any new cells that are the offspring of that cell so, design mutation is not present in the egg or a sperm that form the fetus so, it cannot be passed on to the next generation. Acquire mutations are much more common than inherited mutations. That’s important. Most, for example, cancers by acquiring mutations so, this type of mutation is also called the sporadic or somatic. Regarding fertility, it is more common to have, for example, inherited mutations.

Answer from the fertility expert:
Douglas Lester, Co-Founder & Chief Scientific Officer, Fertility Genomics

Mostly genes that affect fertility are often known as recessive genes. This means you generally need to have inherited two bad copies of a particular sperm or ovum gene before you experience infertility. Such mutations or variations are often present in both your mother’s and your father’s side of the family. But these family members will be unaffected as they possess one good and one bad copy of the gene, which is enough to have a normal fertility phenotype. It’s only if you have the two bad ones together, you get the bad phenotype. Occasionally, however, you might have one bad copy of the variant form of a gene that is present in several individuals from one side of the family, say from your mother’s side. Unfortunately, you might also have a bad copy of the same gene from the other parent, say your father, where no individuals have a family history of a bad gene. In Latin, this mutation is called the Novo or the New or Sporadic Mutation; it has just occurred in the father’s sperm. It is in the development of the father/mother sperm or the father/mother ovum. Early on, there’s been a mutation that’s not in any other cells of the parents. It just happened in the progenitor cells of the sperm or ovum. So this mutation is then passed on and is present in all the chromosomes of the infertile patient.

An example of this is the chromosome 15 deletion that I mentioned earlier that causes deafness and male infertility. In this case, some may inherit the deletion of one of his chromosome 15s through his unaffected mother. The other would be chromosome 15 can be shown not to be present in DNA extracted from his father’s blood or saliva, but why is he got two bad copies of chromosome 15. The only explanation is inheriting a bad chromosome 15 from the father is that there’s been a new, de novo mutation during the father’s sperm production. Unfortunately, they end up with two mutated chromosomes 15, despite this mutation not being found in any of the father’s relatives. Novo and new mutations are much more likely to occur in older fathers. The older the sperm-making cells, the more likely a new mutation will come to arise. You get many more genetic mutations, the older the father, maybe over 40,50, and 60.

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