It was only a few decades ago that precise genetic diagnosis could not be achieved by analysing chromosomes or conducting biochemical studies. Today, this is no longer the case. In recent years, however, as the field of genetics has grown in scope, it has become possible to perform direct analysis on gene defects, increasing the likelihood of correcting the defects. As our understanding of the molecular patterns of various diseases has grown exponentially, new patterns of inheritance have also emerged, some of which are in direct opposition to the generally accepted theories of inheritance.
Principles of Mendelian Disorders
Johann Gregor Mendel was a scientist who lived in the nineteenth century (1822-1884)
Through his research on pea plants, genetics’ Father Gregor Mendel discovered the fundamental laws of inheritance that are still in use today. He came to the conclusion that genes are passed down in pairs and as separate entities, one from each parent, and that this is how they work. When Mendel studied the segregation of parental genes, he was interested in how they manifested themselves in the offspring as dominant or recessive characteristics. He was well-versed in the mathematical patterns of hereditary inheritance that had been passed down through the generations to him.
Gregor Mendel’s studies on pea plants to determine inheritance patterns laid the groundwork for our current understanding of single-gene diseases in humans, which is still being built upon today. Mendelian diseases, also known as monogenic diseases, are caused by mutations in a single gene. Sometimes they are passed down through families. Mendelian disorders are caused by a single genetic mutation that occurs at a single genetic locus. An autosome or a sex chromosome could contain this gene’s coding sequence. Either a dominant or recessive model can be used to describe the disorder’s manifestation. In large families with many affected individuals, we can determine whether a disease-associated gene is present on an autosome or on a sex chromosome by performing pedigree analysis on the genes involved in the disease. It is also used to determine whether a particular phenotype is dominant or recessive in nature.
Mendel’s Law of Segregation
The law of segregation states that during the process of gamete formation, each gene is separated so that each gamete will carry only one allele for each of the genes in the population.
Mendel’s Law of Independence
This law states that at the time of gamete formation, the segregation of each gene pair occurs independently of the segregation of the other gene pairs in the same cell. For lack of a better term, the allele received by a gamete for one gene is unrelated to the allele received by the gamete for another gene.
Mendelian Disorders in Humans
Genetic disorders are caused by abnormalities in the genome or mutations in a single gene, and they are contagious. Symptoms of these disorders are visible from the time of a child’s birth, and they can be predicted based on a child’s family history. Pedigree analysis is the term used to describe this process. Genetic disorders are extremely rare, affecting only one person in every thousand or one in every million people. They could be heritable or non-heritable, depending on the situation. In most cases, inheritable genetic disorders manifest themselves in the germline, with the defects resulting from new mutations.
Types of Mendelian Disorders
According to Mendel’s laws of inheritance, there are several different types of Mendelian disorders, which are as follows:
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
Mitochondrial
Examples of Mendelian Disorders in Humans
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Sickle cell anaemia
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Thalassemia
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Cystic fibrosis
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Colour blindness
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Haemophilia
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Skeletal dysplasia
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Muscular dystrophy
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Phenylketonuria
Cystic Fibrosis
Cystic fibrosis is a chronic lung disease that primarily affects the digestive system and the lungs. A person suffering from this disease produces an abnormally large amount of sticky mucus, which can clog the lungs and pancreas, causing them to become blocked. Cirrhosis fibrosis (CF) is a genetically transmitted disease that causes lung damage and premature death. It manifests itself in a variety of clinical symptoms and has a poor prognosis. There has been significant progress in understanding the role of genetic and nongenetic variables in cystic fibrosis. Some aspects of the disease are linked to allelic variation in the CFTR gene, which is responsible for the condition.
CFTR, on the other hand, has no effect on lung function, newborn intestinal obstruction, diabetes, or anthropometry, despite the fact that candidate gene investigations have discovered genetic modifiers underpinning these characteristics. The application of genome-wide methods has a great deal of potential for identifying specific genetic variants that are responsible for the heritable characteristics and consequences of cystic fibrosis. Patients suffering from this disease typically have a short life expectancy. In this case, it is an example of an autosomal recessive condition.
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Thalassemia
X-linked recessive diseases, such as thalassemia, are examples of such diseases. The body produces an abnormal amount of the protein haemoglobin in the presence of this disorder. Due to the fact that it is caused by a single allele mutation in the HBA1 and HBA2 genes, which are inherited in a Mendelian recessive manner, thalassemia is classified as a Mendelian disorder. Symptoms: Thalassaemia patients produce less haemoglobin and circulating red blood cells than healthy people, resulting in mild to severe anaemia, depending on the severity of the disease. In both and -thalassemias, autosomal recessive inheritance is the most common mode of inheritance, though this is not always the case.
Thalassaemias are a group of diseases that are caused by errors in the production of globin polypeptides. One of the globin chains has an overabundance because the other has been absent or synthesis has been reduced. Due to this, an excessive amount of red blood cells are destroyed, ultimately resulting in anaemia. Dark urine, swelling in the abdomen, deformities of the facial bones, and other symptoms of thalassemia can be seen in some people.
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Sickle Cell Anaemia
It is possible to develop sickle cell anaemia when the glutamic acid present in the sixth position of haemoglobin’s beta-globin chain is replaced by the amino acid valine. The haemoglobin molecule undergoes physical transformation. In the presence of oxygen, the biconcave shape of haemoglobin is transformed into a sickle shape, reducing its oxygen-carrying capacity significantly.
It is possible to develop anaemia if red blood cells sickle and break down prematurely. Anaemia in children manifests itself in a variety of ways, including shortness of breath, fatigue, and slowed growth and development. The rapid breakdown of red blood cells, which manifests itself as yellowing of the eyes and skin and is a symptom of jaundice, can cause this yellowing. Chronically sickled red blood cells, which are stiff and inflexible, can become entangled in small blood vessels, causing excruciating episodes of pain. It is a recessive genetic disorder, and it is a good example of one.
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Haemophilia
As a result of its first observation in a royal family, haemophilia is sometimes referred to as the “royal disease.” It is an example of a recessive disorder that is X-linked. This disorder is passed from mother to son by a carrier mother who is not affected by the disorder, as she passes the hemophilic genes to sons. Females are much less likely than males to be affected by haemophilia because, in order to contract the disease, the mother must either be a carrier of the disease or the father must be affected by the disease.
Because of this disorder, the clotting of the blood does not occur in a normal manner because it affects the protein that aids in the clotting of the blood. In this case, a person suffering from this disease may experience excessive bleeding as a result of cuts and injuries. Because the mutant gene is located on the X chromosome, males are more likely to be affected than females.
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Phenylketonuria
The amino acid phenylalanine has a low metabolism level, which leads to the development of this condition. A person who has phenylketonuria does not have the enzyme necessary to convert phenylalanine to tyrosine in their body. This results in an accumulation of phenylalanine in the body. It decomposes into many different derivatives and causes mental retardation. PKU manifests itself in a number of different ways, ranging from mild to severe. Classic PKU is the most severe form of this illness. It is also the most difficult to treat. Up until the age of a few months, infants with classic PKU appear to be completely normal. They will develop a permanent intellectual handicap if they do not receive treatment for their condition. Epilepsy, developmental delays, behavioural issues, and psychiatric illnesses are all common in children with Down syndrome. Untreated excess phenylalanine in the body can produce a musty or mouse-like odour in those who are exposed to it. In this case, it is an example of an autosomal recessive condition.
Conclusion: –
Mendelian disorder is a type of genetic disorder that affects humans that is caused primarily by mutations in a single gene or as a result of structural abnormalities in the genome. In some cases, a condition like this can be seen from birth and can be deduced from family history by looking at the family tree. Pedigree analysis is the term used to describe the type of analysis that was performed as a result of this.
These genetic disorders are extremely rare, affecting one person in every thousand or one person in every million. Genetic disorders may or may not be passed down through families. While inheritable genetic disorders usually manifest themselves in germline cells, non-heritable genetic disorders are characterised by defects that are caused by new mutations or by changes in the DNA. For example, cancer may be caused by an inherited genetic condition, or by a new mutation caused by environmental factors or other factors, such as smoking.