sChromosomal abnormalities like Down’s syndrome are common in children born to mothers who have conceived at a late age.
Generalizing this condition, all of us tend to believe that it is the mother’s age which is responsible for the development of most of the genetically linked disorders in children. However, in a new study, which turns conventional wisdom on its head, researchers have found that:
It is the father’s age which plays an important role in deciding a child’s risk of developing genetic disorders like autism and schizophrenia.
The study, which was carried out by a private firm deCODE Genetics based in Reykjavik, and has been published in a recent issue of the journal Nature, sequenced the entire genomes of 78 families from Iceland. The children from these families had been diagnosed with autism (in 44 cases) or schizophrenia (in 21 cases). The whole genome sequences of the father, the mother and the child were compared. The entire genome sequence of 1,859 other people from Iceland was also done in order to compare the results.
In the largest study of its kind, the researchers tried to look for those mutations in the child which were not present in the genome sequence of either of the parent. These mutations could have developed spontaneously in the sperm, the egg, or the embryo. In such cases, although there will be no family history of a particular disease, all the cells in the child would be carrying the genetic mutation linked to the disease.
Mutations increase with father's age
The researchers observed that for every one year of increase in the father’s age, an average of two new mutations appeared in the offspring. In other words, the number of new mutations in an offspring for which the father can be held accountable doubles every 16.5 years after the onset of puberty. Even women are responsible for transmitting some of the mutations.
But the number of mutations passed from a father to his child far exceeds the number of mutations passed from the mother.
Two defective genes –EPHB2 and CUL3, transmitted from the fathers, were found in children suffering from autism related disorders.
According to Kari Stefansson, the chief executive of deCODE Genetics, one can safely conclude from the recent study that as the fathers age, there are more mutations taking place inside their sperms, which are then getting transmitted to their children. Sperms are more likely to show mutations in comparison to eggs because, unlike eggs, they are constantly produced by dividing precursor cells, and begin to show error as the man ages.
Childhood Autism Rates Are Rising Around The World
It has been noted that the rate of autism related diseases in children is rising throughout the world. In the United States alone, there has been a 78% increase in patients of autism in 2011 compared to 2007.
Researchers have pointed out that this can be attributed to the fact that men are having children at a later age now compared to earlier times. This demographic trend has been seen worldwide. In Iceland, in 2011, the average age of fathers at the time of conceiving was 33 years. In contrast, in 1980, the average age of fathers was 27.9 years.
As the age of fathers at the time of conception has increased, so has the risk of schizophrenia and autism in their children.
Studies done in the past, also found an association between the advanced age of father at the time of conception and a rise in de novo mutations in the children. However, those studies were based on the analysis of just 1% of the genome. This is the first time that the entire genome sequence was decoded and studied.
Studies related to late fatherhood
A similar study done in 2009 found that late fatherhood was associated with a poor performance of the children in intelligence tests. Another study found that children born to a man over 40 years of age were six times more likely to suffer from autism related disorders compared to children born to a father under 30 year of age. Similar researches done in the past have revealed a link between late fatherhood and diseases like schizophrenia, bipolarity, cancer and epilepsy in children. In these cases, three genes were identified as the culprits, namely AKT3, PIK3R2 and PIK3CA.
According to scientists, a child can expect around 25 mutations when the age of his father is 20. Compared to this, a man of 40 is likely to pass an average of 65 mutations to his child.
This means that with every one year increase in the age of father at the time of conception, two extra mutations are passed to the child.
Compared to this, an average of 14 mutations is transmitted from a mother to her children, irrespective of her age at the time of conception.
Three other independent American researches have shown the link between spontaneous mutation in parents’ egg or sperm cells and risk of autism in children. These studies also found that these mutations have a four times higher chance of being inherited from the father rather than the mother.
The symptoms of autism related disorders may vary from mild to severe mental retardation, with difficulty in communication. These patients also face difficulties in socializing. Every 1 in 88 children born in the United States suffers from autism related disorders, whereas in Europe, this figure is about 1 in 100. Although scientists believe that the increase in rate of children diagnosed with autism may be attributed to better diagnosis and recognition, increased paternal age has also emerged as a leading cause of these disorders. Environmental factors, especially at the time of conception also play an important role in causing autism.
Harmful mutations passed from a parent to a child have a high probability of affecting the proper functioning of the brain. This is partly because of the fact that the maximum number of genes is expressed in the brain compared to other organs of the body.
Scientists have stressed that not all mutations are bad. Genetic mutations form the basis for the process of natural selection. It may be harmful for the next generation, but on the whole, beneficial for the evolution of species.