Autosomal dominant, autosomal recessive, X linked dominant and X linked recessive inheritance.
“An alternative form of the gene is called as an allele”.
It is possible that many alleles are present for one particular genotype. An allele which is expressed is called as a dominant allele and an allele which cannot be expressed is called as a recessive allele.
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“A pattern of inheritance in which the inheritance of trait depend on the presence and absence of certain allele on autosome are called as an autosomal inheritance”.
It is categorized into autosomal dominant and autosomal recessive inheritance.
Autosomal dominant inheritance
In autosomal dominant inheritance, a single dominant allele is responsible for the occurrence of a phenotype.
Take a look at the example,
Here A gene is present on two different autosomal chromosomes with allele “A” is dominant and allele “a” is recessive.
Four different types of the phenotype are possible,
AA is homozygous dominant which shows the phenotype of dominant allele “A”, two Aa is heterozygous dominant which shows the phenotype of dominant allele “A” and a single aa genotype which has recessive phenotype.
Depending upon the type of inheritance different diseases are categorized into autosomal dominant disorders or autosomal recessive disorders.
Huntington disease and Myotonic muscular dystrophy are the two most common types of autosomal dominant disorders prevalent in the world.
The Huntington’s disease caused by the autosomal dominant inheritance of HTT (huntingtin gene) present on chromosome number 4. The disease is cognitive brain disorder in which a person is suffered from walking, thinking and swallowing problems.
Increased size of CAG triple repeat number of HTT gene causes Huntington’s disease hence it is often called as triple repeat expansion disorder.
The normal range of CAG triplet repeats on HTT gene is 27 to 35. Though the disorder is autosomal dominant there are three different types of condition observed.
- <26 triple repeats of CAG- normal
- 27 to 35 triple repeats of CAG – intermedia
- 36 to 39 triple repeats of CAG – penetrance
- Above 40 triple repeats of CAG- affected
The Huntington’s disease follows the inheritance pattern as shown in figure 1.
Another type of autosomal inheritance is an autosomal recessive inheritance,
Autosomal recessive inheritance
“Two homozygous recessive alleles are responsible for the occurrence of the phenotype.”
Autosomal recessive disorders are inherited into progeny when both recessive alleles are present. Hence the heterozygous individuals remain unaffected.
Genetic carriers are those individuals which have the heterozygous genotype and can inherit a disorder in their next generation.
Cystic fibrosis, Sickle cell anaemia and Tay-Sachs disease are some of the classical examples of autosomal recessive disorders.
Let us understand the mechanism of autosomal recessive inheritance by an example,
Sickle cell anaemia
Atypical haemoglobin (called as haemoglobin S) causes red blood cell to become sickle-shaped. The affected individual has fewer numbers of red blood cells and suffered from anaemia and systemic infections throughout the life.
Sickle cell is not curable and it is most prevalent throughout the world. It affects an estimated 1 out of 500 children worldwide.
Normal HBB gene is responsible for the production of normal haemoglobin. However, the HbS is the mutant allele of the HBB gene, causes sickle cell anaemia. In the homozygous recessive condition, two mutant copy of the HBB gene (HbS) causes sickle cell anaemia.
Another common autosomal recessive inherited disorder is Cystic fibrosis.
Cystic fibrosis is a single gene disorder which is caused by the CFTR gene located on chromosome number 7. Cystic fibrosis transmembrane conductance regulator gene is coded for cell membrane channel which produces mucus, tear and saliva.
Additionally, it regulates the transportation of chloride ions across the membrane. Mutation in the CFTR gene results in accumulation of thick mucus in lung and the ion channel across the membrane is disturbed.
Thick sputum, wheezing and coughing are the most common symptoms of CF. Due to the law immunity, a patient may suffer from repeated lung infections.
A pair of a sex chromosome is present in human, XX in a female and XY in a male. Genes presents on X chromosome are said to be X linked and on Y said to be Y linked. Both types of the gene have different inheritance pattern.
The human sex is decided by the presence or absence of Y chromosome. If a Y chromosome is present along with the X chromosome, the embryo develops into a male. If Y is absent the embryo will develop into a female.
Sex-determining region on Y (SRY) is responsible for the development of the embryo into the male sex. However, genes on X chromosomes are homologous and genes on the Y chromosome are non-homologous.
X linked inheritance
Genes present on X chromosome said as an X linked genes. X linked genes inherited just like autosomes. However, the phenotypic effect of X linked inheritance is different in both males and females.
As males contain only single X chromosomes, the chance of inheritance of disease is higher in male as compared to female.
In the case of X lined disorders males are remained always affected in almost all cases. Even if the condition is X linked dominant or recessive, male suffers from the disease because of the presence of a single X chromosome.
Three different types of the phenotype are possible during X linked inheritance in a female, One with homozygous dominant normal (AA), heterozygous normal (carrier) (Aa) and homozygous recessive mutant (disease) (aa).
Hence for a particular X linked dominant disorders 1 out of 4 offspring become affected, 2 carrier and one remains normal.
In contrast, only one possible phenotype is occurred during X linked inheritance in the male. Hence male become always remain affected in X linked inheritance.
X linked dominant inheritance
When the phenotype is occurred due to the presence of an only single dominant allele of X linked gene, this type of inheritance is called as X linked dominant inheritance.
An only single mutant allele is responsible for the inheritance of disease. Ratt syndrome and fragile X syndrome are comment type of X linked dominant disorders.
Fragile X syndrome
Mutation is the FMR1 gene is responsible for the development of fragile X syndrome. Developmental delay, cognitively impaired and learning disabilities are common symptoms of fragile X syndrome.
Additionally, individual may suffer with wide ranges of mental disorders like delayed speech development, delayed language and lower intelligence.
Fragile X is also a triple repeat expansion disorder in which abnormal CGG repeats results in the mutant phenotype. The normal range of CGG repeats in the FMR1 gene is 5-40 repeats.
The range of CGG repeats in humans are:
- 1-40 range of CGG repeats is a normal state
- 40- 200 pre-mutation
- More than 200 CGG repeats disease state
Pre-mutation is a condition in which the individual may carry the mutant FMR1 gene. The heterozygous individuals have also become affected.
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X linked recessive inheritance
In X linked recessive inheritance, the presence of two recessive alleles produces a mutant phenotype. Hence in X linked recessive disorders, only one out of 4 female become affected all males of the progeny become affected.
However, two heterozygous individuals become a carrier. Carrier is a condition in which the individual remains normal but carries the mutant allele and this mutant allele can be inherited in subsequent generations.
Haemophilia and Duchenne muscular dystrophy are two common type of X linked recessive disorders.
Haemophilia A and haemophilia B are X linked bleeding disorders. People with haemophilia experience prolonged bleeding.
Even a minor cut results in heavy blood loss. The condition becomes even worse in case of internal bleeding in joints, brain and internal organs.
In females, the chance of disorder is fewer due to the presence of two X chromosome. However, males with a mutant allele always remain affected.
Haemophilia is most frequent in males as compared to female. Haemophilia A is even most common disorder and affects 1 in 5000 males as compared to haemophilia B (1 in 20,000 female) worldwide.
Y linked inherited disorder
Y linked disorders are very rare in nature as Y chromosome is present only in males. However, some of the genes present on Y chromosomes are inherited from male to male.
Y chromosome is the smallest chromosome and contains only a few genes on it. Most of the Y chromosomal genes are related to fertility and maleness. If the mutation occurs in Y chromosomal genes as, like the SRY gene, the individual suffering from infertility.
It indicates that if the person is suffered from infertility, it cannot reproduce and cannot produce offsprings. Hence Y linked disorders are rarest among rare.
Genes present in mitochondria and chloroplast inherited in a non-mendelian pattern. Extrachromosomal genes do not follow any distinct pattern of inheritance. Mutant gene inherited randomly.
For more detail on extrachromosomal inheritance please read the articles:
Aricle written and reviewed by: Tushar Chauhan