Question

Human female heterozygotes are unaffected carriers of autosomal recessive diseases. Explain in one paragraph (4-6 sentences) why human female heterozygotes can express mild-to-moderate forms of recessive X-linked disorders.

Answer 1

The chromosomal difference between men and women lies in their sex chromosomes (XY in men and XX in women). Men have just a single X chromosome, whereas, women have two X chromosomes. In order to compensate for the single X chromosome present in males, one of the X chromosomes in female is inactivated (X-inactivation). Thus, only one X chromosome in female is transcriptionally active, while the other one remains silenced. This X-inactivation is a random process, therefore, it may happen that one X-chromosome remains active in some groups of cells, while the other X-chromosome remains active in other cells. Now, when a human female carries a defective allele on a single X-chromosome (that is, when she is heterozygous), the other X-chromosome makes all the proteins, to keep her unaffected. Mild to moderate symptoms may appear when the normal X-chromosome gets inactivated in most of the cells, so that enough proteins are not made to keep the woman healthy.