All of the following statements about the genetics of G6PD deficiency are true, except -
Ans. is 'c' i.e., Contradicts Lyon Hypothesis [Ref: Multiple references\o Glucose (-phosphate dehydrogenase (G6PDI deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting more than 400 million people worldwide.Genetics of G6PDo The gene for G6PD is located on the X chromosome (band X q28) [8j and has been cloned and sequenced.o Even though females have two X chromosomes per cell, normal males and females have the same enzyme activity in their red cells because one of the X chromosomes in each cell of the female embryo is inactivated and remains inactive throughout subsequent cell divisions (Lyon hypothesis).o G6PD deficiency is expressed in males carrying a variant gene, while heterozygous females are usually clinically normal.o However, the mean red blood cell enzyme activity in heterozygous females may be normal, moderately reduced, or grossly deficient depending upon the degree of lyonization and the degree to which the abnormal G6PD variant is expressed.G6PD supports Lyon % hypothesisy According to Lyon s hypothesis one of the two chromosomes in each cell of the female embryo is inactivated and remains inactive throughout subsequent cell division.y G6PD is inherited as an X-linked (recessive) disorder, it is more common in males.y Heterozygous Female may also be affected depending on the extent of lyonization (inactivation of one X- chromosome) but the overall average degrees of hemolysis in the heterozygous female is less.o A heterozygous female with 50 percent normal G6PD activity has 50 percent normal red cells and 50 percent G6PD-deficient red cells.o The deficient cells are as vulnerable to hemolysis as the enzyme-deficient red blood cells in males.Maleo Males, who have only one copy of the X chromosome, are either normal or hemizygous for the variant glucose 6- phosphate dehydrogenase (G6PD) gene.o Thus, G6PD deficiency is expressed in males carrying a variant gene on their X chromosome that produces sufficient enzyme deficiency to lead to symptoms. All of the red cells in affected males are vulnerable to hemolysis.Femaleo Females, who have two copies of the X chromosome, are either normal, heterozygous, or homozygous for the variant gene.y Heterozygous females are usually clinically normal.y However, their mean red blood cell enzyme activity may be normal, moderately reduced, or grossly deficient depending upon the degree of X chromosome inactivation (lyonization) and the degree to which the abnormal G6PD variant is expressed.y A female with 50 percent normal G6PD activity, due to 'inactivation of one X chromosome in each cell via lyonization. has 50 percent normal red cells and 50 percent G6PD-deficient red cells.y The deficient cells are as vulnerable to hemolysis as the enzyme-deficient red blood cells in males.y Homozygous females are as severely affected clinically as hemizygous males. All of their red cells are vulnerable to hemolysis
X-linked inheritance
More severe in Men
Contradicts Lyon Hypothesis
May affect Heterozygous females