Question

Why doesn't having a gene variant associated with a particular illness or disorder guarantee a person will develop the condition?

Answer 1

Genetic variation is defined as the variation in the DNA sequence in each of the genomes. Both large and small changes in DNA sequences causes genetic variation and they cause some diseases. But these variants always do not guarantee a person of developing the disease, the level of penetrance and expressivity are responsible for the person developing that particular condition.

Example of this is breast cancer, in this case people have a variation in a particular gene (that is in BRCA1 gene) have a higher tendency to develop cancer. In this case, cancer is the trait or condition. But it is mentioned that it has a higher tendency, leading towards cancer but do not guarantee, because DNA variations which affects the BRCA1gene increase the risk of getting cancer, but it do not guarantee it. This is known as incomplete penetrance.

Genetic disorder is a genetic problem which occurs due to abnormalities in the genome, it is a condition which is usually present since birth (also called congenital). Most genetic disorders are rare and affect only one or two person in millions of people.

Environment plays an important role in the expression of the variant genes, responsible for a particular trait or condition.

There are various genetic inheritance patterns of these genetic variants they are I) Autosomal dominant, 2) Autosomal recessive 3) Sex-linked dominant 4) Sex-linked recessive 5) Y linked 6) multiple genes also responsible for development of a certain disease.

In Autosomal disorders the mutation which causes variation are present in autosomal chromosomes , in case of autosomal dominant cases, the presence of a single mutated copy of the gene can cause the disorder Each affected person has one affected parent. The chance a child to inherit the mutated gene is 50%. Sometimes autosomal dominant conditions have reduced penetrance, it means though it needs only one mutated copy of the gene, but all individuals who inherit that mutation do not develop the disease. Examples of this type of disorder is Huntington's disease.

In Autosomal recessive:- In this type of genetic disorder , the mode of inheritance is autosomal recessive , In this type two copies of the mutated gene is required for a person to get affected by this disorder. An affected person usually has unaffected parents, both the parents are the carriers of the disorder having a single copy of the mutated gene. Two unaffected people who carry one copy of the mutated gene have a 25% risk in each pregnancy of having a child affected by the disorder. Examples of this type of disorder is Albinism.

X- Linked dominant disorder:-

This type of disorder, is caused by mutations in genes on the X chromosome (these are linked to sex chromosomes). Example of this disorder is X-linked hypophosphatemic rickets. Males and females are both affected by these disorders, males are usually severely affected by this disease than females. In this The sons of a man with an X-linked dominant disorder will all be unaffected (because they receive their father's Y chromosome), and his daughters will all inherit the condition, because the daughters receive a X chromosome from their father, and a woman with an X-linked dominant disorder has a 50% chance of having an affected foetus in each pregnancy.

X-linked recessive disorder:-

In this type of disorder, it is caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing the disorder varies between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will be the carriers as they have one copy of the mutated X-gene from their father. A woman who is a carrier of an X-linked recessive disorder (X^A X^a ) has a 50% chance of having sons who are affected and a 50% chance of having daughters who will be the carriers have one copy of the mutated gene. Examples of X-linked recessive condition is haemophilia. It needs two mutated copy if the gene to express itself.

Y-Linked inheritance:-

Y-linked disorders are caused by mutations on the Y-chromosome. These conditions gets transmitted from the heterogametic sex (from male individuals) to offspring of the same sex. More simply, this means that Y-linked disorders in humans only pass from men to their sons, as males contain both X & Y chromosome , but not to females because they have only X chromosomes.

Example is infertility in man like azoospermia or oligozoospermia. But the person always do not have the defect as several other factors also control this trait.one in a million case is reported having Y-infertility.

Multiple genes responsible for a trait or condition:- In this case a single disorder is linked to many genes.

Genetic disorders are sometimes completely, controlled by many factors or genes called polygenic, it means they are linked, with the effects of multiple genes in combination with lifestyles and environmental factors. Examples of these disorders are heart disease and diabetes. Though these multifactorial disorders usually found in families, but they do not have a clear-cut pattern of inheritance, that is why they do not give the guarantee that the offspring will have the disease.