Sequence Characterization of DSG3 Gene to Know Its Role in High-Altitude Hypoxia Adaptation in the Chinese Cashmere Goat.

Xiaohong He,Lin Jiang,Kanwar Kumar Malhi,Yuehui Ma,Chandar Kumar,Yabin Pu,Asghar Ali Kamboh,Qianjun Zhao,Shen Song

doi:10.3389/fgene.2018.00553

Xiaohong He, Lin Jiang + Show 7 more

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https://doi.org/10.3389/fgene.2018.00553

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Abstract

The Tibetan cashmere goat is one of the main goat breeds used by people living in the plateau. It exhibits the distinct phenotypic characteristics observed in lowland goats, allowing them to adapt to the challenging conditions at high altitudes. It provides an ideal model for understanding the genetic mechanisms underlying high-altitude adaptation and hypoxia-related diseases. Our previous exome sequencing of five Chinese cashmere breeds revealed a candidate gene, DSG3 (Desmoglein 3), responsible for the high-altitude adaptation of the Tibetan goat. However, the whole DSG3 gene (44 kbp) consisting of 16 exons in the goat genome was not entirely covered by the exome sequencing. In this study, we resequenced all the 16 exons of the DSG3 gene in ten Chinese native goat populations. Twenty-seven SNP variants were found between the lowland and highland goat populations. The genetic distance (FST) of significant SNPs between the lowland and highland populations ranged from 0.42 to 0.58. By using correlation coefficient analysis, linkage disequilibrium, and haplotype network construction, we found three non-synonymous SNPs (R597E, T595I, and G572S) in exon 5 and two synonymous SNPs in exons 8 and 16 in DSG3. These mutations significantly segregated high- and low-altitude goats in two clusters, indicating the contribution of DSG3 to the high-altitude hypoxia adaptation in the Tibetan goat.

Highlights

Low oxygen or hypoxia is the hardest environmental challenge for humans and animals existing at high altitude
Among the 27 single-nucleotide polymorphism (SNPs) that were identified in desmoglein 3 (DSG3), five SNPs showed the most significant differentiation in the analysis of allele frequency and global FST, including three non-synonymous SNPs, SNP1 (R597E, Chr24: 25794694, exon 5), SNP2 (T595I, Chr24: 25794695, exon 5), and SNP3 (G572S, Chr24: 25794771, exon 5), and two synonymous SNPs, SNPs had a global FST of 0.47 (SNP4) (Chr24: 25799255, exon 8), and SNP5 (Chr24: 25817330, exon 16) (Table 3)
The other four SNPs in DSG3 exhibited a similar pattern of change (Table 1, Supplementary Table S2, and Figures 1, 2)

Summary

Introduction

Low oxygen or hypoxia is the hardest environmental challenge for humans and animals existing at high altitude. Various candidate genes have been identified for high-altitude adaptation, including EPAS1 (endothelial PAS domain protein 1) and HBB (hemoglobin beta) (Gou et al, 2014; Fan et al, 2015; Song et al, 2016) In prior studies, both EPAS1 and HBB revealed six non-synonymous mutations potentially affecting the gene function and influencing high-altitude hypoxic adaptation in dogs (Fan et al, 2015). Both EPAS1 and HBB revealed six non-synonymous mutations potentially affecting the gene function and influencing high-altitude hypoxic adaptation in dogs (Fan et al, 2015) These studies proved that the domestic animals are a useful animal model to explore high-altitude adaptation.

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