Genome-wide scanning reveals genetic diversity and signatures of selection in Chinese indigenous cattle breeds
LIVESTOCK SCIENCE
Authors: Xu, L.; Zhang, W. G.; Shen, H. X.; Zhang, Y.; Zhao, Y. M.; Jia, Y. T.; Gao, X.; Zhu, B.; Xu, L. Y.; Zhang, L. P.; Gao, H. J.; Li, J. Y.; Chen, Y.
Abstract
Chinese indigenous cattle exhibit abundant genetic resources and extensive gene pool, with 53 indigenous breeds generally classified into northern cattle breeds, central cattle breeds, and southern cattle breeds. To determine the population genetic diversity and signatures of selection of Chinese indigenous cattle, we collected 724 cattle from 20 geographically representative Chinese indigenous cattle breeds and genotyped all samples using GeneSeek Genomic Profiler Bovine LD (GGP-LD, n = 30,125). Runs of homozygosity (ROH) and identical by state (IBS) analyses were performed to investigate genetic diversity in Chinese indigenous cattle. Meanwhile, the integrated Haplotype Score (iHS) and F-ST-based d(i) methods were used to reveal candidate selective sweeps. Our results showed that southern cattle breeds have abundant ROH segments and higher IBS values in comparison with northern and central cattle breeds. We also detected many potential selective sweeps in Chinese indigenous cattle. The genes within intervals spanning the candidate regions are associated with growth and development (NCAPG, LAP3, LCORL, IBSP and MEPE), fertility and reproduction (ABCG2, CATSPER4 and H1foo), immune functions (AZU1, PROC and LRP1) and environment adaption (RBFA, BARX2). Overall, these findings provide new insights into the level of genetic diversity of Chinese indigenous cattle, and suggest a role of natural/artificial selection in shaping their genome genetic variability.
BARX2 expression is downregulated by CpG island hypermethylation and is associated with suppressed cell proliferation and invasion of gastric cancer cells
ONCOLOGY REPORTS
Authors: Ma, Juan; Xia, Ling-Ling; Yao, Xue-Qing; Zheng, Shi-Min; Li, Shi; Xu, Li-Shu; Sha, Wei-Hong; Li, Ze-Song
Abstract
BarH-like homeobox 2 (BARX2), a homeobox gene, is associated with several types of cancers. The present study aimed to determine whether DNA methylation downregulates BARX2 expression and whether BARX2 is associated with suppression of gastric carcinogenesis. BARX2 protein expression in normal and cancerous gastric tissues and various gastric cancer (GC) cell lines was detected using immunohistochemical and western blot assays. BARX2 mRNA levels were detected using both reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR). Promoter hypermethylation in GC cells was detected using methylation-specific PCR or bisulfite DNA sequencing PCR. Effects of BARX2 expression on GC cell proliferation, clonal formation, and migration were evaluated after lentivirus-BARX2 transfection. The effect of stable BARX2 transfection on tumor formation was assessed in a nude xenograft mouse model. BARX2 was strongly expressed in the normal gastric mucosa, but weakly or not expressed in GC tissues and most GC cell lines. BARX2 expression was negatively correlated with DNMT (a marker for DNA methylation) expression in the gastric tissues. The BARX2 promoter fragment was hypermethylated in the GC cell lines. Overexpression of BARX2 significantly inhibited GC cell proliferation, clonal formation, and migration. Stable BARX2 transfection inhibited tumor formation in xenograft mice, which was correlated with decreased expression of E-cadherin, proliferation markers, and matrix metalloproteinases. In conclusion, BARX2 expression is aberrantly reduced in GC, which is associated with increased DNA methylation of its promoter. BARX2 inhibits GC cell proliferation, migration, and tumor formation, suggesting that BARX2 acts as a tumor suppressor in gastric carcinogenesis.