Genetics of Alpha-1

Updated June 14, 2010

The gene for alpha-1 antitrypsin deficiency (A1AD) resides near the end (teolmere) of chromosome 14. At the genetic level, a grossly simplified explanation of A1AD is that it is similar to a spelling mistake on this strand of the individual’s DNA. This ‘spelling mistake’ can be transmitted from parent to child.

Genetics

As has already been mentioned, A1AD is a genetically transmitted disorder. It is something one is born with and can do nothing about. However, there are varying degrees of disorder depending on what is passed on from parents to children. The range is from normal to severely deficient. MM is normal, ZZ is severely deficient and the others (MZ, MS, SS, SZ, etc) are intermediate. If a child inherits one normal gene and one defective gene, for example MZ or MS, each gene will express its specific protein that can be identified in the blood (codominance). In order to inherit full-blown A1AD (usually ZZ), an individual must inherit two defective ZZ genes, one from each parent.

Inheriting Genes

Each parent has two genes for A1AD but can pass on only one to the child. Thus, out of a possible four genes, the child will receive two, one from the mother and one from the father. If both parents have two M (normal) genes, then all their children must also have two M genes. If both parents have two Z (deficient) genes then all their children are destined to have two Z genes. Similarly if one parent is ZZ and the other parent is MM, they, of necessity, must produce children who are all MZ (intermediate level). There are no other possibilities with these genotypes.

Other variations in genetic make-up come into play when the parents are not homozygotes, that is, not MM nor ZZ. The following can result:

While inheriting two ZZ genes means that a person may be predisposed to develop A1AD, it is not a simple cause and effect equation. People who are diagnosed as ZZ have been known to never develop clinical disease. Individuals who inherit only one defective gene are considered to be at little risk for developing A1AD disease, especially if they do not smoke. Individuals who inherit no defective genes are, of course, at no risk for developing AATD or its associated disease.