San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Biology and Biotechnology "Lazzaro Spallanzani", Università Degli Studi Di Pavia, Pavia, Italy.
Hum Genet. 2020 Nov;139(11):1471-1483. doi: 10.1007/s00439-020-02191-x. Epub 2020 Jun 24.
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.
人类的生长是一个复杂的特征，由遗传因素与外部刺激（包括环境、营养和激素状态）共同决定。过去，几项全基因组关联研究（GWAS）共同确定了数百个遗传变异体，它们可能对不同世界人群的成年身高有影响。理论上，要更好地理解复杂特征（如成年身高）的机制，一种有价值的方法是研究表现出极端体型表型的人群，如非洲俾格米人。在表型特征描述后，我们对一群俾格米人和他们的非俾格米邻居班图人的外显子组进行了测序，以突出与矮小身材相关的遗传变异体。全外显子组数据分析显示，29 个单核苷酸多态性（SNP）与 Baka 组的身高降低显著相关。在这些变体中，我们重点关注位于透明质酸酶-2（HYAL2）基因 5'-UTR 的 SNP rs7629425。与非洲和非非洲人群相比，替代等位基因的频率显著增加。体外荧光素酶检测显示 rs7629425 C/T 等位基因在转录调节方面存在显著差异。总之，我们的结果表明，HYAL2 基因变异可能在 Baka 俾格米人群矮小身材的病因学中起作用。
