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. 2020 Nov;139(11):1471-1483.
doi: 10.1007/s00439-020-02191-x. Epub 2020 Jun 24.

Identification of novel genetic variants associated with short stature in a Baka Pygmies population

Matteo Zoccolillo  1 , Claudia Moia  2 , Sergio Comincini  2 , Davide Cittaro  3 , Dejan Lazarevic  3 , Karen A Pisani  1 , Jan M Wit  4 , Mauro Bozzola  5
Affiliations

Identification of novel genetic variants associated with short stature in a Baka Pygmies population

Matteo Zoccolillo et al. Hum Genet. 2020 Nov.

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.

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Conflict of interest statement

All authors declare absence of interest conflicts.

Figures

Fig. 1
Fig. 1
Boxplots distribution of height (SDS) measurements in Baka Pygmies and Bantu investigated subjects. Red and green circles indicated individuals subjected to WES analysis (Baka Pygmies = 8 and Bantu = 5)
Fig. 2
Fig. 2
Distribution of WES variants in Baka Pygmies and Bantu investigated subjects. The numbers of variants are reported in brackets
Fig. 3
Fig. 3
Manhattan plot Pairwise Fst analysis of 88,830 autosomal SNPs revealed by WES analysis. Thresholds Fst (i.e., 0.30, 0.60 and 0.70) were indicated
Fig. 4
Fig. 4
Heatmap analysis of WES variants frequency differences between Baka Pygmies, Bantu, Africans and Worldwide populations
Fig. 5
Fig. 5
HYAL2 chromosomal localization, gene structure and fine mapping of rs7629425 variant (in bold). ATG start codon is underlined
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