What are monogenic diseases

What are monogenic diseases??

It is a pure genetic diseases are caused by a single error in a single gene in the human DNA. The nature of disease depends on the functions performed by the modified gene. The single-gene or monogenic diseases can be classified into three main categories:

Monogenic diseases result from modifications in a single gene occurring in all cells of the body. Though relatively rare, they affect millions of people worldwide. Scientists currently estimate that over 10,000 of human diseases are known to be monogenic. 1) Dominant

·         2) Recessive

·         3) X-linked

WE are aware from our undergraduate class that all human beings have two sets or copies of each gene called “allele”; one copy on each side of the chromosome pair. Recessive diseases are monogenic disorders that occur due to damages in both copies or allele. Whereas dominant diseases are monogenic disorders that involve damage to only one gene copy. But X linked diseases are monogenic disorders that are linked to defective genes on the X chromosome which is the sex chromosome.

However the  X linked alleles can also be dominant or recessive. These alleles are expressed equally in men and women, more so in men as they carry only one copy of X chromosome (XY) whereas women carry two (XX).

Monogenic diseases are responsible for a heavy loss of life. The global prevalence of all single gene diseases at birth is approximately 10/1000.

The common disease of our interst are 1) Thalassaemia 
2) Fragile X syndrome 3) Sickle cell anemia 4) Cystic Fibrosis .The other monogenic diseases are Haemophilia, Tay sachs disease &Huntington's disease

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Thalassaemia

Thalassaemia is a blood related genetic disorder which involves the absence of or errors in genes responsible for production of haemoglobin, a protein present in the red blood cells. Each red blood cell can contain between 240 and 300 million molecules of haemoglobin. The severity of the disease depends on the mutations involved in the genes, and their interplay.

A haemoglobin molecule has sub-units commonly referred to as alpha and beta. Both sub-units are necessary to bind oxygen in the lungs properly and deliver it to tissues in other parts of the body. Genes on chromosome 16 are responsible for alpha subunits, while genes on chromosome 11 control the production of beta subunits. A lack of a particular subunit determines the type of thalassaemia (eg. a lack of alpha subunits results in alpha-thalassemia). The lack of subunits thus corresponds to errors in the genes on the appropriate chromosomes.

There can be various gradations of the disease depending on the gene and the type of mutations.

Prevalence:

The alpha and beta thalassaemias are the most common inherited single-gene disorders in the world with the highest prevalence in areas where malaria was or still is endemic. The burden of this disorder in many regions is of such a magnitude that it represents a major public health concern. For example in Iran, it is estimated that about 8,000 pregnancies are at risk each year. In some endemic countries in the Mediterranean region, long-established control programs have achieved 80-100% prevention of newly affected births.

·         Map of global distribution of haemoglobin disorders*
pdf, 143kb

Diagnosis/ prognosis:

Diagnosis of thalassaemia can be made as early as 10-11 weeks in pregnancy using procedures such as amniocentesis and chorionic villi sampling. Individuals can also be tested for thalassaemia through routine blood counts. Thalassaemic patients may have reduced fertility or even infertility. Early treatment of thalessaemia has proved to be very effective in improving the quality of life of patients. Currently, genetic testing and counselling, and prenatal diagnosis play an increasingly important role in informing individual as well as professional decisions around the prevention, management and treatment of this disease.