Miscellaneous

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1.Introduction:

The human body is made up of millions of cells each performing a particular function. In the nucleus of each cell there are subcellular structures called chromosomes. There are 23 pairs of chromosomes which are responsible for transferring genetic information from one generation to another. In humans these chromosomes are of two types- autosomes and sex chromosomes (22 pairs of autosomal chromosomes and one pair of sex chromosome). Sex chromosomes (X and Y chromosome) determine the sex of the individual. Females have two X chromosomes, while males have one X and one Y chromosome.

A male child inherits a Y chromosome from his father and X chromosome from the mother, whereas a female child inherits X chromosomes from both her parents. Each chromosome contains many genes and each gene has a specific function. All human beings have two sets or copies of each gene called “allele”; one copy on each side of the chromosome pair.  Any abnormality in the genetic makeup may result into genetic disease. Dysfunctional gene behaviour is commonly termed as a mutation.

Genetic disorders:

Genetic disorders can be caused by damage to chromosomes (changes in the number or structure of entire chromosomes), or by a mutation in one gene (monogenic disorder), or by mutations in multiple genes (multifactorial inheritance disorder), or by a combination of gene mutations and environmental factors.

Some diseases are inherited from the parents and are present in an individual at birth, like sickle cell disease, whereas other diseases are not inherited from the parents, but occur either randomly or due to some environmental exposure (such as cigarette smoke) during a person's life.  These include many cancers.

Abnormality in the genes can occur in following ways-

1.Genes and chromosomal diseases: Chromosomal diseases may occur when the entire chromosome, or large segments of a chromosome, is missing, duplicated or otherwise altered such as found in following diseases:

Down Syndrome (trisomy 21): Cells contain 3 copies of the 21st chromosome by the process called nondisjunction, in which genetic materials fail to separate during the formation of gametes, resulting in an extra chromosome (called trisomy 21).

Turner syndrome: In Turner syndrome, one of the 2 sex chromosomes is not transferred in the female child and she does not have the usual pair of two complete X chromosomes but has 45 total chromosomes (instead of 46).

 

2. Monogenic diseases or single-gene disorders: All human beings have two sets or copies of each gene called “allele”; one copy on each side of the chromosome pair. Monogenic diseases occur due to changes in one gene in all cells of the body. Scientists currently estimate that over 10,000 of human diseases are monogenic.

The single-gene or monogenic diseases can be classified into three main categories:

  • Dominant diseases are monogenic disorders that involve damage to only one gene copy. Dominant inheritance means an abnormal gene from one parent can cause disease. If one parent has the disease, each child has a 50% chance of inheriting the mutated gene. If someone is diagnosed with an autosomal dominant disease, their parents should also be tested for the abnormal gene. Examples of dominant diseases include Huntington disease, neurofibromatosis, and polycystic kidney diseases
  • Recessive diseases are monogenic disorders that occur due to damages in both copies or allele, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not have the disease themselves and each child has a 25% chance of having the disease. Some examples of recessive diseases include: sickle cell disease, cystic fibrosis, Tay-Sachs disease, thalassemia.
  • X linked diseases are monogenic disorders that are linked to defective genes on the X chromosome which is the sex chromosome. 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). Example: Haemophilia, fragile X syndrome

Haemophilia –It is a hereditary bleeding disorder, in which there is a partial or total lack of an essential blood clotting factor. This illness is a sex-linked recessive disorder.

 

A. When father has haemophilia XY and mother is unaffected XX (affected shown in red and unaffected in blue colour), offsprings will be XY, XY, XX, XX –none of the sons (XY, XY) will have hemophilia, while all of the daughters (XX, XX) will carry the genes.

 

B. When mother carries the genes causing haemophilia (XX) and father is unaffected (XY), offsprings will be XY, XY, XX, XX. There are 50% chances (XY, XY) at each birth that a son will have hemophilia, and 50 % chances at each birth that a daughter (XX, XX) will carry the gene.

 

3. Multifactorial disorders: Non-communicable diseases may occur as a result of mutations in multiple genes, frequently coupled with environmental factors. An individual may not be born with a disease but may be at high risk of acquiring it. This is called as genetic predisposition or susceptibility.

This is not always true that the genetic susceptibility to a particular disease due to the presence of one or more gene mutations, and/or a combination of alleles is abnormal. Understanding genetic predisposition to disease and knowledge of lifestyle modifications that either exacerbate the condition or that lessen the potential for diseases (i.e., no smoking or drinking) is necessary for the public to make informed choices.

Mitochondrial disorders are rare disorders caused by mutations in non-chromosomal DNA located within the mitochondria. (The mitochondria are subcellular organelles.)

Genes and communicable diseases: Genes are also known to play a role in the occurrence of infectious diseases like tuberculosis and AIDS and can be treated with genetic based interventions.

Some Definitions:

Genetics is the study of heredity and of the mechanisms by which genetic factors are transmitted from one generation to the next (WHO). (Hereditary means passing of traits or characteristics through genes from one generation to the other generation).

What is genome?

Genome is the operating manual containing all the instructions that helps development of an organism. It is unique for an individual though lifestyle and environmental factors also play a critical role in development and health.

Genomics is defined as the study of genes and their functions, and related techniques.

The main difference between genomics and genetics is that genetics is the functioning and composition of the single gene whereas genomics addresses all genes and their inter relationships in order to identify their combined influence on the growth and development of the organism.

Genetic testing:  

Genetic testing is done to learn about some genetic inheritance patterns. Prenatal testing can also be done during pregnancy to check the baby for problems. Each parent's DNA may need to be checked. Testing may include:

  • Ultrasound. This test uses sound waves to see growth and any abnormality in the growing foetus.  
  • Chorionic villus sampling (CVS). This test uses a sample of tissues around the foetus to look for problems.
  • Amniocentesis. This test uses a sample of the amniotic fluid from the sac around the baby to check for problems. 
  • Noninvasive prenatal screening. This test involves taking a blood sample from the mother to look for chromosome differences, such as aneuploidy.
  • Carrier screening. This test uses a sample of blood from each parent to check if they carry genetic changes for certain genetic conditions.

The risk of having a baby with a birth defect increases if:

  • The parents have another child with a genetic disorder.
  • There is a family history of a genetic disorder.
  • One parent has a chromosome abnormality.
  • Abnormalities seen on an ultrasound during pregnancy

Family history-comprehensive family medical history is probably the most useful "genetic test." By collecting your family's health history, you can learn whether you may be at increased risk for health problems in the future and whether you can reduce your risks.

For instance, if your family has a history of heart disease, you can reduce your risk by not smoking, regular exercise and a healthy diet. Finding out your family history can benefit both you and your relatives and it can be fun too.

References-

https://www.who.int/topics/genetics/en/

https://www.who.int/genomics/public/geneticdiseases/en/

https://www.cdc.gov/genomics/about/basics.htm

https://ghr.nlm.nih.gov/primer/hgp/genome

https://www.genome.gov/About-Genomics/Introduction-to-Genomics#one

https://www.haemophilia.org.au/about-bleeding-disorders/haemophilia/inheritance#MainContent