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

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.

Comparative genome analyses reveal the unique genetic composition and selection signals underlying the phenotypic characteristics of three Chinese domestic goat breeds

“…Haplo1 (CAAAGGT), which is almost fixed, and Haplo2 (TGTGCAC) for which there were no homozygous individuals. These results are consistent with a previous study [89]. In contrast, these SNP sites continue to segregate in the Bezoar ibex and other domestic goat populations.…”

“…In contrast, these SNP sites continue to segregate in the Bezoar ibex and other domestic goat populations. Notably, the same previous study [89] did not support the assumption that DSG3 was functionally directly related to a cashmere-related trait, because distinct haplotypes were found between TC goats and lowland cashmere goats. In summary, the accumulation of these missense variants in TC is due to their beneficial effects on the function of DSG3 in skin and hair, which further contributed to their adaptation to high-altitude.…”

“…Together with different population statistics, the core selected site seems to encompass the three missense SNPs in exon 12 of DSG3 in TC, which was validated in ten Chinese goat populations by Sanger sequencing [89]. In addition, four other SNPs showed perfect LD with the three missense mutations, and accordingly, only two haplotypes were detected in TC: i.e.…”

Selection Signatures Analysis Reveals Genes Associated with High-Altitude Adaptation in Tibetan Goats from Nagqu, Tibet

“…In Tibetan cashmere goats from the Bange, Ritu, and Cuoqin counties, the EPAS1 (Endothelial PAS domain protein 1) gene was shown to have a strong selection signal and a functional mutation [ 5 ]. The DSG3 (Desmoglein 3) gene was also shown to contribute to high-altitude hypoxia adaptation of Tibetan cashmere goats [ 6 ]. In the Qinghai Tibetan goat, four genes ( CDK2 (Cyclin dependent kinase 2), SOCS2 (Suppressor of cytokine signaling 2), NOXA1 (NADPH oxidase activator 1) and ENPEP (Glutamyl aminopeptidase)) were identified as being important for hypoxia adaptation [ 7 ].…”

Deletion of an Enhancer in FGF5 is Associated With Ectopic Expression in Goat Hair Follicles and the Cashmere Growth Phenotype

“…MC1R and KIT genes have been implicated in human and animal hair pigmentation, re ecting a role in the development and function of melanocytes [44,45]. The DSG3 gene is responsible for the high-altitude adaptation of the Tibetan goat [46,47].…”