Endocrine Abstracts

Background: The return to active long bone growth in puberty is a distinctly human event¹ and occurs ~2 years earlier in girls compared to boys. Evolutionarily conserved networks of genes are associated with the developmental phases of childhood in multiple tissues², implying the existence of a genetic program that controls the pubertal return to growth.

Objectives: To identify biological functions associated with gender and age-related gene expression in puberty.

Methods: We conducted gene expression (GE) analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Array express databases. A primary data set was generated using cells of lymphoid origin (n=87, 43 boys and 44 girls). For analysis in other tissue data sets were available from muscle (n=14), brain (n=30) and conjunctival epithelium (n=18). GE associated with puberty was assessed using ANOVA (P<0.01) with hierarchical clustering. Age-related GE associated with gender was defined using rank regression (P<0.01). Human interactome network modules associated with GE were identified using the WEB-based GEne SeT AnaLysis Toolkit (WebGestalt)³.

Results: A cluster of 626 gene probes were associated with puberty independent of gender (P<0.01). Age-related differential GE was identified related to gender (813 gene probes). An overlap of 235 gene probes were both associated with gender and puberty (28.9%). Interactome network modules were mapped to this overlap and were associated with the growth hormone signalling pathway (P=2.0×10⁻⁴) and histone demethylase activity (P=8.1×10⁻²). These observations were confirmed in pubertal associated GE in muscle, brain and conjunctival epithelium.

Conclusions: Specific GE profiles were identified in relation to gender differences in puberty. Network analysis showed that biological pathways involved in puberty included growth and epigenetic related clusters of genes. The genes identified in this study could potentially act as markers of the timing and tempo of puberty.

References: 1. Bogin B. Evolutionary perspective on human growth. Annu Rev Anthropol 1999 28 109–153.

2. Stevens A, Hanson D, Whatmore A, Destenaves B, Chatelain P & Clayton P. Human growth is associated with distinct patterns of 3 gene expression in evolutionarily conserved networks. BMC Genomics 2013 14 (1) 547.

3. Wang J, Duncan D, Shi Z & Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res 2013 41 W77–W83.