How do changes in gene structure lead to different syndromes?

It has become evident that genes are somewhat responsible for diseases. The word we have heard frequently is ‘heredity’. It has been the most perplexing phenomenon of nature. The complexity of the sex cells has been the root of its mystery. Those cells were invisible to the naked eye. The invention of the microscope acted as a catalyst for the discovery of sex cells and subsequently heredity.

Before this, there were rudimentary theories and speculations about heredity. It was believed that blood could be used for heredity even by scientists like Charles Darwin. It seems like folklore for scientific biological. All the popular phrases like “royal blood” are the outcome of this belief. Parents transmit only one-half of the genes they have to each child, and they transfer different sets of genes to further children. Would it be wrong to wonder that disease could be the outcome of heredity? Well, this idea is very much sane and proven time and again.

Now, what is a gene?!


Genes could be understood as the instructor that supervises the protein synthesis mechanism and tells to make specific kinds of protein for the body. From a more scientific perspective, Genes constitute promoter regions and alternating regions of introns and exons. The fabrication method of functional protein comprises modifying the gene from DNA into RNA and other biological processes. 

How can disease be hereditary?!!!!!

Every cell depends on numerous proteins to make the biological processes function correctly. Sometimes, gene variants (or mutant genes) prevent the proteins from working correctly. It is just like changing the recipe of a dish and getting an entirely different one. Similarly, it could enterprise protein to malfunction. This alteration can disrupt standard functions and are usually incompatible with life. 

A condition caused by variants in one or more genes is called a genetic syndrome

There are mainly three kinds of genetic syndromes:

1. Single-gene 

Single-gene syndromes can be passed on to subsequent generations in several ways. They are classified into 4 kinds: recessive, autosomal, X-linked types, and dominant types. Recessive and Dominant types are sometimes used interchangeably. X-linked and autosomal are distinguished purely based on the chromosomal location of the gene. Such single-gene defects decrease the fitness of affected people.  

2. Multifactorial syndrome

Genetic syndromes may also be polygenic (associated with the effects of multiple genes in combination). Multifactorial syndromes consist of heart disease and diabetes. Even with the fact that complex syndromes often cluster in families, they have an ambiguous inheritance. This makes them challenging to study, track and treat because the specific factors are also yet not discovered.  

3. Chromosomal syndrome 

A chromosomal syndrome is an abnormal portion of chromosomal DNA. It could arise from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. An example of these syndromes is trisomy 21 (Down syndrome), in which there is an extra copy of chromosome 21.

There are many genes yet let’s look at the most prominent one.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene

The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein is a helpful membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel created by this protein transports negatively charged particles called chloride ions throughout the cells. It is necessary to produce mucus (a slippery substance that lubricates and protects the lining of organs and tissues). Its alterations can lead to syndromes like cystic fibrosis, congenital bilateral absence of vas deferens, hereditary pancreatitis, etc.

Cystic fibrosis Due to CFTR Mutations

Humans with cystic fibrosis are found to have more than 1000 CFTR mutations. These mutations change single protein building blocks (amino acids) in the CFTR protein or delete a small amount of DNA from the CFTR gene. Disease-causing mutations in the CFTR gene alter the production, structure, or stability of the chloride channel. The passage of the lungs, pancreas and other organs produces mucus that is abnormally thick and sticky. The abnormal mucus obstructs the airways and glands, leading to characteristic signs and symptoms of cystic fibrosis.

Some Myths and Facts about Genetic Syndromes

Contrary to general belief, most cancers, although they involve genetic mutations to a small proportion of cells in the body, are acquired diseases. Some family cancer syndromes, such as BRCA mutations, are hereditary genetic syndromes.

Out of 6000 genetic syndromes, more than 600 of these syndromes are treatable. Let’s see a crazy number. Out of 50 people, 1 person is affected by a known single-gene syndrome, while 1 in 263 is affected by chromosomal syndrome. Hereditary genetic mutations affect 65% of people in the world. After looking at the above ratios, it could seem plausible that 1 out of 21 people is affected by a genetic syndrome classified as “rare”.

In conclusion, many studies are being conducted to cure these genetic syndromes through technologies like CRISPR, DNA splicing, etc. They could change the way we see genetics entirely.


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