A non-genetic, epigenetic-like mechanism of telomere length inheritance?

Meyer, Tim De; Vandepitte, Katrien; Denil, Simon; Buyzere, Marc L. De; Rietzschel, Ernst; Bekaert, Sofie

doi:10.1038/ejhg.2013.255

Cited by 27 publications

(24 citation statements)

References 15 publications

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“…Both heritable variation in the base telomere sequence and the telomere‐maintenance mechanisms can help produce correlations between parents and offspring. If we were to measure TL in chicks soon after hatching, the influence of the base telomere sequence inherited from the parents would dominate any inherited similarity based on shared telomere‐maintenance genes (De Meyer et al, ). In contrast, if chicks are measured when they are older, the environment will have had a chance to decrease the chick's TL, and inborn repair mechanisms can act on any such erosion.…”

Section: Discussionmentioning

confidence: 99%

The environmental and genetic determinants of chick telomere length in Tree Swallows (Tachycineta bicolor)

Belmaker

Hallinger

Glynn

et al. 2019

Ecology and Evolution

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Conditions during early life can have dramatic effects on adult characteristics and fitness. However, we still know little about the mechanisms that mediate these relationships. Telomere shortening is one possibility. Telomeres are long sequences of DNA that protect the ends of chromosomes. They shorten naturally throughout an individual's life, and individuals with short telomeres tend to have poorer health and reduced survival. Given this connection between telomere length (TL) and fitness, natural selection should favor individuals that are able to retain longer telomeres for a greater portion of their lives. However, the ability of natural selection to act on TL depends on the extent to which genetic and environmental factors influence TL. In this study, we experimentally enlarged broods of Tree Swallows ( Tachycineta bicolor ) to test the effects of demanding early‐life conditions on TL, while simultaneously cross‐fostering chicks to estimate heritable genetic influences on TL. In addition, we estimated the effects of parental age and chick sex on chick TL. We found that TL is highly heritable in Tree Swallow chicks, and that the maternal genetic basis for TL is stronger than is the paternal genetic basis. In contrast, the experimental manipulation of brood size had only a weak effect on chick TL, suggesting that the role of environmental factors in influencing TL early in life is limited. There was no effect of chick sex or parental age on chick TL. While these results are consistent with those reported in some studies, they are in conflict with others. These disparate conclusions might be attributable to the inherent complexity of telomere dynamics playing out differently in different populations or to study‐specific variation in the age at which subjects were measured.

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Section: Discussionmentioning

confidence: 99%

The environmental and genetic determinants of chick telomere length in Tree Swallows (Tachycineta bicolor)

Belmaker

Hallinger

Glynn

et al. 2019

Ecology and Evolution

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“…It has also been proposed that this atypical, epigenetic-like mechanism of TL inheritance may account for a significant proportion of the heritability of TL in the general population. 49 In summary, this study highlights the complexity in categorizing telomerase variants, documents new mechanisms involved in generating human telomeropathies, and demonstrates that thorough investigation is necessary to assess the pathogenic contribution of newly identified telomerase variants. This will become increasingly important and difficult as exome-based diagnostic reports are generated without reference to the many nuances that may be encountered.…”

Section: Discussionmentioning

confidence: 99%

Triallelic and epigenetic-like inheritance in human disorders of telomerase

Collopy

Walne

Cardoso

et al. 2015

Blood

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Key Points• Telomerase variants in patients with bone marrow failure syndromes are difficult to categorize as diseasecausing or otherwise.• DC can derive from triallelic mutations in 2 telomerase genes and epigenetic-like inheritance of short telomeres.Dyskeratosis congenita (DC) and related diseases are a heterogeneous group of disorders characterized by impaired telomere maintenance, known collectively as the telomeropathies. Disease-causing variants have been identified in 10 telomere-related genes including the reverse transcriptase (TERT) and the RNA component (TERC) of the telomerase complex. Variants in TERC and TERT can impede telomere elongation causing stem cells to enter premature replicative senescence and/or apoptosis as telomeres become critically short. This explains the major impact of the disease on highly proliferative tissues such as the bone marrow and skin. However, telomerase variants are not always fully penetrant and in some families disease-causing variants are seen in asymptomatic family members. As a result, determining the pathogenic status of newly identified variants in TERC or TERT can be quite challenging. Over a 3-year period, we have identified 26 telomerase variants (16 of which are novel) in 23 families. Additional investigations (including family segregation and functional studies) enabled these to be categorized into 3 groups: (1) disease-causing (n 5 15), (2) uncertain status (n 5 6), and (3) bystanders (n 5 5). Remarkably, this process has also enabled us to identify families with novel mechanisms of inheriting human telomeropathies. These include triallelic mutations, involving 2 different telomerase genes, and an epigenetic-like inheritance of short telomeres in the absence of a telomerase mutation. This study therefore highlights that telomerase variants have highly variable functional and clinical manifestations and require thorough investigation to assess their pathogenic contribution. (Blood. 2015;126(2):176-184)

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“…In the case of direct transmission of TL to the offspring through the germ cell TLs, random variability of the germ cell TL might dilute the correlations between blood TL measured in parents and offspring. 11 Sperm cell progenitors keep dividing throughout life, whereas more limited numbers of primary oocytes are available from birth. Stochastic effects, for example, associated with androgen fluctuations influencing testicular telomerase activity, 13 might therefore lead to more random fluctuations in sperm cell TL than in oocyte TL.…”

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confidence: 99%