Telomere length analysis in goat clones and their offspring

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Abstract
Incomplete epigenetic reprogramming of the donor genome is believed to be the cause behind the high rate of developmental mortality and post-natal anomalies observed in animal clones. It appears that overt phenotypic abnormalities are not transmitted to their progeny suggesting that epigenetic errors are corrected in the germline of clones. Here, we show variation in telomere lengths among Nigerian dwarf goat clones derived from different somatic cell types and that the offspring of two male clones have significantly shorter telomere lengths than age-matched noncloned animals. Telomere lengths were significantly shorter in skin biopsies of goat clones derived from adult granulosa cells compared to those measured for controls. Telomere lengths were highly variable in male goat clones reconstructed from fetal fibroblasts but their mean terminal repeat fragment (TRF) length was within normal range of normal goats. However, in the progeny of two male clones, mean TRF lengths were considerably shorter than age-matched controls for both skin and leukocyte samples. Evidence for possible inheritance of shortened telomeres was obtained by measuring telomere lengths in testicular biopsies obtained from the clones, which when compared with those from noncloned animals of a similar age were significantly shorter. The offspring exhibited telomere lengths intermediate to the TRF values obtained for their cloned fathers' and age-matched control testes. These results demonstrate that telomere length reprogramming in clones is dependent on the type of donor cell used and that the progeny of clones may inherit telomere length alterations acquired through the cloning procedure. Mol. Reprod. Dev.