The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish

Wellcome Open Research

article

Catherine M. Scahill¹  Zsofia Digby¹  Ian M. Sealy¹  Richard J. White¹  Neha Wali¹  John E. Collins¹  Derek L. Stemple¹  Elisabeth M. Busch-Nentwich¹ 

[1] Wellcome Trust Sanger Institute, Wellcome Genome Campus;Department of Veterinary Medicine, University of Cambridge;Department of Medicine, University of Cambridge

关键词: telomerase;    telomere length;    zebrafish;    age;    sex;    Tert;   

DOI  :  10.12688/wellcomeopenres.12530.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Mutations in proteins involved in telomere maintenance lead to a range of human diseases, including dyskeratosis congenita, idiopathic pulmonary fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the ends of chromosomes, however non-canonical roles of components of telomerase have recently been suggested. Methods: Here we use a zebrafish telomerase mutant which harbours a nonsense mutation intert to investigate the adult phenotypes of fish derived from heterozygous parents of different ages. Furthermore we use whole genome sequencing data to estimate average telomere lengths. Results: We show that homozygous offspring from older heterozygotes exhibit signs of body wasting at a younger age than those of younger parents, and that offspring of older heterozygous parents weigh less irrespective of genotype. We also demonstrate thattert homozygous mutant fish have a male sex bias, and that clutches from older parents also have a male sex bias in the heterozygous and wild-type populations. Telomere length analysis reveals that the telomeres of younger heterozygous parents are shorter than those of older heterozygous parents. Conclusions: These data indicate that the phenotypes observed in offspring from older parents cannot be explained by telomere length. Instead we propose that Tert functions outside of telomere length maintenance in an age-dependent manner to influence the adult phenotypes of the next generation.

【 授权许可】

CC BY