Chapter 10, Problem 1CS

A researcher was asked if his work on human telomere replication was related to any genetic disorders. He replied that one might think that any such mutations would be lethal during early development, but in fact a rare human genetic disorder affecting telomeres is known. This disorder, dyskeratosiscongenita (DKC), is associated with mutations in the protein subunits of telomerase, the enzyme responsible for replicating the ends of eukaryotic chromosomes. Initial symptoms appear in tissues derived from rapidly dividing cells, including the skin, nails, and bone marrow, and first affect children between the ages of 5 and 15 years.

How could such individuals survive?

Summary Introduction

To review:

The survivability of people with Dyskeratosis congenita (DKC).

Introduction:

Dyskeratosis congenital (DKC) is a rare genetic X chromosome-linked disease. Initial symptoms of this disease show up between the age of 5 to 15 years. People with DKC has the mutation on telomerase gene thus has non-functional telomerase. This disease affects the tissues with rapidly growing cells like skin, nails, and bone marrow.

Explanation of Solution

The tail region of the eukaryotic chromosome is known as the telomere. This region does not contain any functional genes but only guanine and a cytosine-rich tandem repeat of nucleotides. DNA (deoxyribonucleic acid) polymerase responsible for DNA replication cannot replicate the telomere region efficiently. Thus telomerase play a crucial role in replication of telomere. Here in case of persons withDyskeratosis congenita (DKC), after every successful cell division, a part of the telomere region gets lost in the newly divided cell. This problem is known as end replication problem.

The eukaryotic cells use telomerase to replicate telomere, which can successfully replicate the telomere region without losing any of its regions. The whole telomere region of the people with non-functional telomerase gets lost after a few early cell division. However, as this telomere region does not has any functional genes that could affect the cell functionality, early cell divisions can occur smoothly.

The patients can survive early development. Once the whole telomere region gets lost and functional genes present near the telomere region starts getting lost due to further cell division, only then, the patients show symptoms of DKC. That occursnormally between 5- 15 years of age.

Conclusion

Dyskeratosis congenita (DKC) appears among people who have mutated loss-in-function telomerase. Therefore, it can be concluded that the people with non-functional telomerase can survive early development. After that, they will start showing symptoms ofDKC, which includes nail dystrophy, abnormal skin pigmentation, and bone marrow failure.