Definition
Radiation induced mutations are alterations in the genome - either a change in chromosomes or individual genes. If they occur in gametic cells then the mutation may be passed on to future generations.
Importantly, radiation induced mutations have not been shown to create bizarre mutations (a la the Uncanny X-Men) but instead increase the rates of hereditary diseases that occur naturally in the population.
Types of Hereditary Diseases
Mendelian Diseases
These are the 'classical' inheritable genetic disorders, either autosomal dominant, autosomal recessive or X-linked.
- Autosomal dominant conditions are expressed if a single abnormal copy of the gene is present in the cell. They are typically late onset and have minimal effect on fertility. Examples include Huntingdon's Disease and adult onset polycystic kidneys.
- Autosomal recessive conditions only develop if there are abnormal copies of the gene in every cell. They may often present earlier in life and may impact fertility. Heterozygous individuals only possess one abnormal gene, and may be completely normal or have minimal problems. Autosomal recessive conditions include cystic fibrosis or beta thalassaemia.
- X-linked conditions are due to mutation of genes on the X-chromosome. In men this behaves as an autosomal dominant condition, as they only possess a single X chromosome. In women it behaves in an autosomal recessive manner as they possess two X chromosomes. X linked disorders vary in severity, from colour blindness to haemophilia.
The mutations leading to Mendelian disorders may be point mutations, where a single base of DNA is altered, to deletions of varying sizes.
Chromosomal Abnormalities
Chromosomal abnormalities are changes in the structure or number of chromosomes. Most of these changes are fatal to the cell or in embryogenesis, but some may be inherited.
- Trisomy of chromosome 21 is one of the few viable exceptions to the non-viable nature of aneuploidy. Trisomy 13 and 18 may survive until birth but are rapidly fatal ex-utero.
- Translocation of chromosomes occurs when part of an arm is swapped with that of differently numbered chromosome. If only one of the translocated chromosomes is passed on to children then there may be an imbalance of genetic material. This frequently leads to congenital abnormalities or mental retardation.
Multifactorial Effects
Some other conditions may have a genetic component but are not due to chromosomal alterations or subject to classical Mendelian inheritance. This group of conditions is broad, and includes the genetic inheritance of common conditions such as Type II diabetes and cardiovascular disease. Congenital birth defects such as neural tube and cleft lip/palate problems are also multifactorial.
Aside from the congenital birth defects multifactorial conditions present later in life.
Studies of Hereditary Effects
Mouse Studies
Large mouse studies were used to investigate hereditary effects. The largest, the 'megamouse project', studied the increase in hereditary effects seen following radiation exposure. In summary:
- Information is limited to male mice, as female mice are rendered sterile at very low doses
- The development of mutations is highly variable due to differences in gene size
- Hereditary effects are reduced in likelihood as the gap between exposure and conception - mature sperm seem less able to repair abnormalities than those in earlier stages of development.
- The dose required to double the rate of ordinarily observed hereditary effects is about 1 Sv.
