LGMD2I is a disease caused by a mutation in ONE gene. The inheritance of this kind of pathogenic mutations follows the rules explained below and in many other websites (see “More Information” below).
LGMD2I is a recessive disease:
An important aspect of the inheritance of LGMD2I mutations is that it is recessive. Recessive inheritance is opposed to dominant inheritance. The most known example of recessive versus dominant inheritance is the color of our irises, the circular structure in the eye that controls the diameter of the pupil. The colors blue and green are said to be recessive traits. The brown color is said to be the dominant trait.
We all have 2 copies of our genome, and therefore 2 copies of the FKRP gene. One copy comes from the father and the other copy comes from the mother.
LGMD2I arises when BOTH copies of the FKRP gene are mutated (the copy from the father and the copy from the mother). It is called “Recessive” inheritance because BOTH parental copies need to be altered (see diagrams below).
[In rare cases, the pathogenic mutation is not coming from any of the parents but it is created anew during the development of the embryo. Still, a person needs both copies of the FKRP gene mutated to have LGMD2I.]
Our 2 copies of the FKRP gene are continuously expressed, creating a pool of FKRP protein, that is, to simplify, 50% coming from gene copy 1 and 50% coming from gene copy 2. Any significant mutation in the FKRP gene will create a change in the FKRP protein.
Probability and the inheritance of a mutation:
Below are cartoons to explain the relationship between inheritance and probability. They answer the question: what is the likelihood for the progeny to have LGMD2I knowing the genetics make up of the parents?
Each parent has 2 copies of a gene
Each parent gives 1 copy of the gene to their kids.
Consequently, each kid carries one of 4 possible gene combinations.
If each pairing of the parental copies has the same chance of occurrence, each pairing will happen 1 time out of 4 or 25% of the time.
What about “recessive” inheritance versus “dominant” inheritance?
As explained in the text above, in the recessive inheritance both copies of the gene need to be altered.
Diagram below: Imagine that each of the parents carries an altered copy 1 of the gene (marked by a red-colored “y” in the word copy)