Go to the OMIM website (https://www.ncbi.nlm.nih.gov/omim) and type 'dyskeratosis congenita autosomal dominant 1' (DKCA1) into the search bar. The result will include a clickable link to the disorder that has an OMIM number of 127550. Review the OMIM information you retrieve and notice that this disorder is caused by a mutation of a telomerase gene that results in abnormally rapid shortening of telomeres and the appearance of disease symptoms at progressively younger ages in successive generations of the affected families. Use this and other information on OMIM to assist with this problem. Go to reference number 15 at the bottom of the OMIM page for a link to a 2004 paper by Tom Vulliamy and colleagues that appeared in the journal Nature Genetics. Click on the 'Full text' option and download a copy of the paper. Look at Table 1 of the paper on page 448. This table lists the lengths of telomeres measured in members of the families in this study. Telomeres shorten with age, and the telomere lengths in Table 1 are age-adjusted. The negative numbers for telomere lengths in the table indicate that telomeres are shorter than average for age, and the more negative the number, the shorter the telomere. Based on Table 1, the the discussion in the Vulliamy et al. (2004) paper, and information available on OMIM, answer the following:
Why are telomeres of people with DKCA1 shorter than average?

Question

Go to the OMIM website (https://www.ncbi.nlm.nih.gov/omim) and type 'dyskeratosis congenita autosomal dominant 1' (DKCA1) into the search bar. The result will include a clickable link to the disorder that has an OMIM number of 127550. Review the OMIM information you retrieve and notice that this disorder is caused by a mutation of a telomerase gene that results in abnormally rapid shortening of telomeres and the appearance of disease symptoms at progressively younger ages in successive generations of the affected families. Use this and other information on OMIM to assist with this problem. Go to reference number 15 at the bottom of the OMIM page for a link to a 2004 paper by Tom Vulliamy and colleagues that appeared in the journal Nature Genetics. Click on the 'Full text' option and download a copy of the paper. Look at Table 1 of the paper on page 448. This table lists the lengths of telomeres measured in members of the families in this study. Telomeres shorten with age, and the telomere lengths in Table 1 are age-adjusted. The negative numbers for telomere lengths in the table indicate that telomeres are shorter than average for age, and the more negative the number, the shorter the telomere. Based on Table 1, the the discussion in the Vulliamy et al. (2004) paper, and information available on OMIM, answer the following:
Why are telomeres of people with DKCA1 shorter than average?

Why are telomeres of people with DKCA1 shorter than average?

Accepted Answer

Hi, everyone. Welcome back. Let's look at our next problem. It says the shelter complex is a multi protein complex involved in regulation and protection of telomeres. The shelter complex consists of six proteins T R F one T R F two P O T one T P P one R A P one and T I N two defects in the shelter and complex can lead to telomere dysfunction which has been associated with a variety of diseases including cancer, bone marrow failure and premature aging syndromes. One such disorder caused by due to a mutation in the gene of TINF two associated with the sheltering complex can lead to a plastic anemia. Mutations in TINF two can disrupt the function of the shelter and complex and lead to telomere shortening and dysfunction. Which of the following statements help explain the consequence of TINF two mutation that leads to a plastic anemia. We have choice. A telomere shortening can lead to the exhaustion of the stem cell pool and the development of bone marrow failure choice. B telomeres become critically short cells can undergo Sene senescence or cell death. C both A and B or D, none of the above. So just keep in mind that we have those C and D choices that both A and B may be correct or both may be incorrect. So let's think through what is involved in this question. We're throwing a lot of information, but we don't need all the information in our problem. We're focusing in on the consequences of the mutation to this gene involved in the proper function of the sheltering complex and how that might lead to a places anemia. Well, a plastic anemia is a condition in which the body stops producing enough new blood cells as a result of bone marrow damage. So we know that the condition involves damage to the bone marrow where the stem cells are made that produce the blood cells. And we know from what our problem tells us that the mutation that causes this condition disrupts the function of the complex that protects the telomeres. So it causes premature te telomere shortening and dysfunction. So with that in mind, let's evaluate these answer choices. So a says telomere shortening can lead to the exhaustion of the stem cell pool and the development of bone marrow failure. Well, this is true. We're gonna put a little dot here since we have that potential of more than one correct answer rather than picking this as our answer right away when telomeres shorten prematurely. So obviously, all of us are telomeres shorten as we age. But when you have this premature telomere shortening, that impairs the ability of stem cells to divide and differentiate properly when that's not happening. And the body can't generate these new stem cells. The stem cell pool in the bone marrow gets depleted and that can lead to bone marrow failure. So that's why choice A is correct. Then we look at B it says telomeres become critically, short cells can undergo senescence or cell death. And that is correct. And with the cells that are happening to the cells that further contributes to that bone marrow failure. And of course, when the bone marrow is failing, the body can no longer produce enough blood cells producing the symptoms of a plastic anemia. So that means that choice B is also correct. So our correct answer must be choice C, both A and B obviously choice D, none of the above is not our answer and neither A nor B by itself is our correct answer. So which of the following statements, it helps explain the consequence of T I N F two mutation that leads to a plastic anemia. Choice C, both A and B is our answer. See you in the next video.

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Key Concepts

Telomeres

Telomerase

Genetic Inheritance