There are total 22 pairs of autosomes in humans. The non-sex chromosomes are known as autosomes. The anomalies associated with the autosomes are known as autosomal anomalies or autosomal abnormalities. The mutations in the genes present on these autosomes decide the inheritance of a particular disease. An autosome consists of a mutant gene in autosomal disorders. The mutant gene expresses the disorder even though present in a single dose. Autosomal diseases involve the presence of a mutant gene on one of the chromosomes in a pair. Consider a mating between a normal individual and an affected individual. The normal individual has a normal genotype. The affected individual has a mutant gene. Hence, 50% of the progeny will express the dominant mutant gene. The remaining 50% of progeny will be normal. The individuals showing a dominant mutant gene are known as heterozygotes. Consider another case of mating between both the affected parents. 25% of the offspring will show both the mutant genes. Hence, they are known as severely affected individuals. 50% of the progeny will show one mutant gene. Hence, they are known as affected individuals. The remaining 25% of individuals show a normal genotype.
Following are the characteristics of an autosomal dominant inheritance:
1. Both the sexes equally get affected with the autosomal dominant traits.
2. The genes or the traits get transmitted in four possible ways such as male to male, male to female, female to female and female to male types of transmissions.
3. Follows no skipping of generations
4. Mostly seen in all the generations
5. In most of the cases, the proband has at least one affected parent
6. New autosomal dominant mutations occur newly in a generation due to some error in the gametogenesis in the parent. The child having new mutations passes on the traits to the next generations
7. Those having the abnormal genes on the autosomes only pass on the trait to the next generation
8. Those having normal genes and exhibiting normal phenotype do not pass on the trait
9. The proportion of the normal and the affected individuals in a population is almost the same.
10. An autosomal dominant gene mostly affects one part of the body. However, it may also lead to a disorder where many parts of the body get affected. One mutated gene can affect many phenotypes. A phenomenon in which one gene produces many phenotypes is known as pleiotropy. Hence, the autosomal dominant gene may exhibit pleiotropy.
11. The expression of the autosomal dominant gene varies from person to person. The phenotype also varies.
12. Sometimes a heterozygous individual does not show or express the dominant phenotype. Such a condition is known as penetrance. It occurs due to the influence of the genes at other loci.
Image: Autosomal dominant inheritance
Following are the examples of autosomal dominant disorders
Huntington’s chorea:
It involves a complete penetrance. Such a type of autosomal dominant disorder leads to nerve cell death and affects the central nervous system. It is a movement disorder mainly known to affect a person in the middle age. Hence, this type of movement is known as chorea. The mutated gene is present on the short of the 4th chromosome. The gene shows the presence of an abnormally large CAG nucleotide repeat at 5’ end. A series of CAG repeats result in the production of glutamine chains. A glutamine chain is also known as a polyglutamine tract. This gene encodes Huntington protein. The altered form of Huntingtin protein is known as mutant Huntingtin. It increases the rate of neuronal cell death. Huntington’s chorea affects 1 in 15,000 individuals. It leads to the breakdown of the nerve cells in the brain. Hence, such individuals experience a diminished ability to walk, speak, and carry out other activities. Involuntary movements in the face, muscles, hands, and legs occur in this condition. Jerks are very common in them. The intellectual ability also starts diminishing.
Familial hypercholesterolemia:
Familial hypercholesterolemia majorly involves heterozygous individuals and rarely involves homozygotes. Such a type of autosomal dominant disorder leads to high serum cholesterol level. Mutation in the LDL receptor gene leads to the disease. As the word suggests familial hypercholesterolemia, the defective gene gets inherited. The mutated gene responsible for the disease is present on chromosome number 19. An important clinical feature of familial hypercholesterolemia involves the progression of atherosclerosis. Cholesterol gets deposited in the arterial walls. Hence, it results in narrowing of the lumen. Three main types of cholesterols include LDL, HDL, and VLDL. LDL or low-density lipoprotein is known as bad cholesterol. HDL or high-density lipoprotein is also known as good cholesterol. Due to the defective LDL receptor, the patients suffering from familial hypercholesterolemia always show an increased level of blood cholesterol. The LDL cholesterol does not get eliminated from the blood. Xenthomata or the subcutaneous deposition of lipid occurs in familial hypercholesterolemia. Such individuals have an increased risk of myocardial infarction or heart attack. This type of autosomal dominant disorder affects 1 in 500 individuals.
Neurofibromatosis:
It shows complete penetrance and variable expression. The mutated gene is present on the 17th chromosome. The gene encodes for neurofibromin protein. It is known as a tumor suppressor gene. A mutated tumor suppressor gene enhances the cancer cell growth. Loss of both the alleles leads to tumor development. Neurofibromatosis leads to pea-sized benign tumors on the skin. Apart from tumors, epilepsy also manifests. 1 in 3000 people suffers from neurofibromatosis.
Here are some more examples of Autosomal dominant disorders:
Examples of autosomal dominant disorders
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Gene mutations
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Myotonic dystrophy
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An abnormal gene on the 19th chromosome with a large CTG repeats 3’ end.
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Achondroplasia
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An abnormal gene is present on the short arm of the 4th chromosome.
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Polycystic kidney disease
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Abnormal PKD1 gene on chromosome 16 and PKD2 gene on chromosome 4.
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Congenital cataract
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PITX3 gene mutation
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Polydactyly
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A mutated GLI 3 gene on the 7th chromosome
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Table: Autosomal dominant disorders and related gene mutations
Codominance:
Both the traits get expressed fully in the heterozygous state. Example of codominance involves ABO blood groups. Presence of both A and B alleles leads to codominance.
[1] Medical genetics, G.P. Pal
[2] Human Genetics, 3/e, Gangane
[3] Vogel and Motulsky's Human Genetics: Problems and Approaches, Friedrich Vogel, Gunter Vogel, Arno G. Motulsky
[4] Biology for the IB Diploma: Standard and Higher Level, Andrew Allott
[5] Principles of Medical Genetics, Thomas D. Gelehrter,
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