4.5 Article

Single-Nucleotide Polymorphisms in the LEPR Gene Are Associated with Divergent Phenotypes for Age at Onset of Puberty in Davisdale Ewes

Journal

BIOLOGY OF REPRODUCTION
Volume 90, Issue 2, Pages -

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod.113.115923

Keywords

domestic animal reproduction; genetics; puberty

Funding

  1. New Zealand Ministry of Business, Innovation and Employment, New Zealand [C10X0810]
  2. Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India
  3. New Zealand Ministry of Business, Innovation & Employment (MBIE) [C10X0810] Funding Source: New Zealand Ministry of Business, Innovation & Employment (MBIE)

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Attainment of puberty is a key developmental event influenced by genetic and environmental factors. In examining age at attainment of puberty, we observed closely related rams from the Davisdale line whose daughters differed in age at which they attained puberty. A candidate gene approach was used to identify mutations that may underlie these observed differences. Four rams with divergent phenotypes for their daughter's age at onset of puberty were selected for whole-genome sequencing. The coding regions of genes with known roles in regulating reproductive function were searched for single-nucleotide polymorphisms (SNPs) that altered the amino acid sequence of the protein. Of interest were three SNPs in the leptin receptor gene (LEPR). A Sequenom assay was developed to determine the genotype of these SNPs in daughters of 17 sons of a founding sire. A higher percentage of ewe lambs homozygous for the LEPR mutations failed to undergo puberty before 1 yr of age, and those that did undergo puberty during the first breeding season on average were approximately 17 days older than homozygous wild-type ewes. Heterozygous ewes were intermediate for both measurements. Given the predicted change in protein function produced by the mutation in LEPR and the strong associations between the genotype and onset of puberty phenotypes, we propose that this mutation in LEPR underlies the observed difference in age at onset of puberty in the Davisdale line. Furthermore, these animals will likely provide a useful model to better understand the role of leptin in the regulation of puberty.

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