An autosomal recessive gene or the mutant allele is present in the double dose (homozygous state). A heterozygous individual does not express the gene. A heterozygous individual with an autosomal recessive trait is known as a carrier. Consider a mating between an affected individual and a carrier individual. 50% of the progeny get affected with the trait. The remaining 50% become carriers. An unaffected individual exhibits a normal phenotype. Both the copies of the gene are normal and functional. However, if an individual shows one normal gene and one mutated gene, the individual exhibits a normal phenotype but becomes a carrier. Individuals showing both the mutated gene copies get affected with the condition.
Consider the following characteristics of autosomal recessive inheritance:
1. The trait may involve skipping of generations.
2. It affects both males and females equally.
3. Pseudo-dominant inheritance: 50% of the progeny gets affected.
Image: Autosomal recessive inheritance
Spinal muscular atrophy:
It arises due to degeneration of spinal motor neurons. These individuals suffer from hypotonia. The mutated gene is present on the long arm of chromosome 5. Mainly the SMN1 gene gets mutated. The SMN1 gene encodes a protein known as SMN protein. It helps in motor neuron function. Hence, in the spinal muscular atrophy, an SMN1 gene mutation leads to the degenerated function of motor neurons. The voluntary muscle movements get affected. The word atrophy indicates small muscle size due to lack of activity. SMA affects 1 in 10,000 people. A Musculo-genetic disorder affecting the muscle power of an individual is known as spinal muscular atrophy. It affects the muscle movement and nerve function. Motor neurons get affected leading to difficulty in walking, sitting, standing, and other movements. The word atrophy indicates weakness and wasting of the muscles. These individuals also have breathing and swallowing difficulties. There are three types of spinal muscular atrophies as follows:
Type I spinal muscular atrophy: These individuals show developmental defects, breathing difficulties, and problems associated with swallowing. Infants show difficulty in sitting.
Type II spinal muscular atrophy: These individuals show muscle weakness. It affects the children between ages 6 and 12 months. These children do not have sitting problems. However, they need help in balancing their body. Hence, these children are unable to walk properly.
Type III spinal muscular atrophy: These individuals cannot walk or stand properly. They require a wheelchair for the entire lifetime.
· Genetics:
Multiple gene mutations result in spinal muscular atrophies. Genes such as SMN1, SMN2, UBA1, and many other gene mutations cause the atrophy. SMN genes encode a protein for the neuronal health. It is known as survival motor neurons (SMN) protein and plays an important role in the maintenance of motor neurons. The spinal cord and brain stem require motor neurons coordinating the muscle movements. The SMN1 and SMN2 gene play a crucial role in synthesizing SMN protein product. Mutated genes give rise to faulty protein products. SMN gene mutations lead to different types of spinal muscular atrophies depending on the molecular situation. SMN gene mutations leading to the shortage of SMN protein result in the death of the neurons, nerve impulses, and muscle weakness.
Cystic fibrosis:
Mucus helps in trapping the microbes and foreign particles. The linings of the airways, stomach, intestine, and other body systems possess mucous membranes. Mucous protects our body from microbial infections. It helps in protecting the stomach from high acidity. Respiratory and digestive systems get affected by the mucus build-up. Individuals with cystic fibrosis suffer from a chronic cough and lung infection. It may also lead to permanent lung damage and fibrosis (scar tissue) accompanying cysts. Children with cystic fibrosis also experience digestive problems. A condition known as meconium ileus involves blockage of the intestine. It is common in the newborn babies. The sticky mucus also builds up in the pancreas and harms the glucose-insulin cycle. Individuals with cystic fibrosis also experience poor growth, malnutrition, weight loss, and gastric disturbances. Imbalanced insulin hormone leads to cystic fibrosis-related diabetes mellitus (CFRDM).
Cystic fibrosis is a fatal childhood disease. Mens affected with cystic fibrosis show an absence of vas deferens. Hence, they are infertile. Women experience complications in the pregnancy.
· Genetics:
Cystic fibrosis shows an autosomal recessive mutation. The gene known as CFTR gets mutated. The mutant gene is present on the long arm of the 7th chromosome. 1 in 2000 individuals gets affected by the disease. The CFTR gene encodes for CFTR protein. It indicates the cystic fibrosis transmembrane conductance regulator (CFTR). The protein has two hydrophobic segments spanning the plasma membrane. It has an ATP binding site. Patients with severe cystic fibrosis show three nucleotide pair deletion in the gene. The mutated gene results in abnormal CFTR protein. CFTR gene also provides instructions for making ion channels. Chloride ions help in flowing the mucus. Mutated gene disrupts the chloride channel functioning. Thus, it impairs the ion transport across the membrane. It leads to an abnormal mucus secretion.
Sickle cell anemia:
It is a hemoglobinopathy arising due to an autosomal recessive inheritance. Individuals with sickle cell anemia have sickle-shaped RBCs. The hemoglobin of these individuals is different from that of the normal individuals. Hemoglobin of these individuals is known as HbS. The solubility of the hemoglobin of the individuals suffering from sickle cell anemia is very less. Under deoxygenated conditions, HbS gets crystallized. Sickling of RBCs leads to anemia and arterial obstruction. The clinical features of the sickle cell anemia include splenomegaly, weakness, bone marrow hypertrophy, heart defects, spleen infarct, and hematuria. Splenomegaly occurs due to the destruction of the sickle-shaped RBCs in the spleen. The oxygen-carrying capacity of the blood gets reduced. Hence, it results in anemia.
· Genetics:
It involves a mutation in the gene encoding beta-polypeptide chain. It is 146 amino acid long. The glutamic acid, which is a sixth amino acid changes to valine. A heterozygous individual for the trait becomes a carrier. The condition is known as a sickle-cell trait.
References:
[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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