GENETICS OF G6PD DEFICIENCY
GENETICS OF G6PD DEFICIENCY
t is important to learn about the genetics of G6PD deficiency since this
determines whether someone will be affected by this condition. In humans,
there are 23 pairs of chromosomes which direct various physical and
metabolic traits. One of the 23 pairs of chromosomes is the X and Y-
chromosome pair (also known as the sex chromosomes) which determine
what sex an individual will be, among other things. The X-chromosome is especially important
because it carries genes that are critical to human survival. An important
gene located on the X-chromosome is the gene for the G6PD enzyme (Scriver
et al., 1995). The general location of the G6PD gene on the X-chromosome
is shown in
figure 1
; it is located at the q28 locus (Pai et al., 1980).
Any gene located on the X-chromosome is called an X-linked gene (Pai et al., 1980). All X-linked genetic conditions, such as G6PD deficiency, are more likely to affect males than females. G6PD deficiency will only manifest itself in females when there are two defective copies of the gene in the genome. As long as there is one good copy of the G6PD gene in a female, a normal enzyme will be produced and this normal enzyme can then take over the function that the defective enzyme lacks. When a certain heritable trait is expressed in such a manner, it is a called a recessive trait. In males, however, where there is only one X-chromosome, one defective G6PD gene is sufficient to cause G6PD deficiency.
G6PD deficiency is known to have over 400 variant alleles, or different forms of the same gene (Beutler et al., 1990). Ernest Beutler, one of the leading researchers on G6PD deficiency, provides an up-to-date list of all known G6PD variants in the journal which he edits: Blood, Cells, Molecules, and Diseases(BCMD). A mutant G6PD enzyme may be different from person to person; mutations can be in the form of point mutations or can range from one to several base pair deletions as well as replacements in the DNA (Scriver et al., 1995). Different populations have different types of mutations, but within a specific population, common mutations are usually shared. For example, in Egypt there exists only one type of allele, called the "Mediterranean" variant, among the population, whereas in Japan there is a different variant with a different type of mutation prevalent within that population, this one called the "Japan" variant (Scriver et al., 1995).
With regards to the demographics of G6PD deficiency, figure 2 shows that most of the affected individuals reside in Africa, the Middle East, and Southeast Asia. African Americans and some isolated tribes in Africa and Southeast Asia exhibit the highest frequency of incidence for any given population; a defective enzyme can be found in as many as one in four people among these populations (Scriver et al., 1995).
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