Identification of novel genetic variants associated with short stature in a Baka Pygmies population
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ORIGINAL INVESTIGATION
Identification of novel genetic variants associated with short stature in a Baka Pygmies population Matteo Zoccolillo1 · Claudia Moia2 · Sergio Comincini2 · Davide Cittaro3 · Dejan Lazarevic3 · Karen A. Pisani1 · Jan M. Wit4 · Mauro Bozzola5 Received: 1 April 2020 / Accepted: 30 May 2020 © The Author(s) 2020
Abstract Human growth is a complex trait determined by genetic factors in combination with external stimuli, including environment, nutrition and hormonal status. In the past, several genome-wide association studies (GWAS) have collectively identified hundreds of genetic variants having a putative effect on determining adult height in different worldwide populations. Theoretically, a valuable approach to better understand the mechanisms of complex traits as adult height is to study a population exhibiting extreme stature phenotypes, such as African Baka Pygmies. After phenotypic characterization, we sequenced the whole exomes of a cohort of Baka Pygmies and their non-Pygmies Bantu neighbors to highlight genetic variants associated with the reduced stature. Whole exome data analysis revealed 29 single nucleotide polymorphisms (SNPs) significantly associated with the reduced height in the Baka group. Among these variants, we focused on SNP rs7629425, located in the 5′-UTR of the Hyaluronidase-2 (HYAL2) gene. The frequency of the alternative allele was significantly increased compared to African and non-African populations. In vitro luciferase assay showed significant differences in transcription modulation by rs7629425 C/T alleles. In conclusion, our results suggested that the HYAL2 gene variants may play a role in the etiology of short stature in Baka Pygmies population.
Introduction
Matteo Zoccolillo and Claudia Moia share first authorship and contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00439-020-02191-x) contains supplementary material, which is available to authorized users. * Mauro Bozzola [email protected] 1
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy
2
Department of Biology and Biotechnology “Lazzaro Spallanzani”, Università Degli Studi Di Pavia, Pavia, Italy
3
Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
4
Pediatrics, Leiden University Medical Center, 2300 RC Leiden, Netherlands
5
University of Pavia, and Onlus Il Bambino E Il Suo Pediatra, Via XX Settembre 28, Galliate, 28066 Novara, Italy
Human growth and, in particular, adult height are undoubtedly multifactorial processes, involving genetic, hormonal, nutritional and other environmental factors (Waldman and Chia 2013). Regulation of human adult stature has been of particular interest to geneticists, evolutionary and cultural anthropologists, as well as to pediatricians focused on growth disorders (Lettre 2011). Adult height is a prime example of a highly polygenic complex trait with a relatively high heredita
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