Temperature adaptation patterns in Chinese cattle revealed by TRPM2 gene mutation analysis.

Cattle are sensitive to temperature fluctuations but adapt well to inclement weather conditions. When environmental temperatures exceed specific thresholds, heat stress becomes a critical concern for cattle. The TRPM2 gene, which resides on cattle chromosome 1 encodes a TRP channel protein, holding a unique capacity to sense temperature changes and facilitate rapid response to avoid heat stress. Here, we utilized the Bovine Genome Variation Database (BGVD) (http://animal.omics.pro/code/index.php/BosVar), and identified a missense mutation site, c.805A > G: p. Met269Val (rs527146862), within the TRPM2 gene. To elucidate the functional assessment of this mutation in temperature adaptation attributes of Chinese cattle, we genotyped 407 samples from 20 distinct breeds representing diverse climatic zones across China. The association analysis incorporates three temperature parameters and revealed compelling insights in terms of allele frequency. Interestingly, the prevalence of the wild-type allele A was notably higher among northern cattle breeds and this trend diminished gradually as observed in southern cattle populations. Conversely, the mutant-type allele G demonstrated a contrasting trend. Moreover, southern cattle exhibited markedly higher frequencies of GG and GA genotypes (P < 0.01). The presence of heterozygous and homozygous mutations appears to confer an enhanced capacity for adaptation to elevated temperatures. These results provide unequivocal correlation evidence between TRPM2 genotypes (AA, GA, GG) and environmental temperature parameters and comprehend the genetic mechanisms governing temperature adaptation in cattle. This provides valuable insights for strategic breed selection across diverse climatic regions, thereby aiding livestock production amid evolving climate challenges.

The TRPM2 gene encodes TRP channel protein that helps animals in combating heat stress. Twenty Chinese local cattle breeds were genotyped, and association analysis was performed. This investigation encompasses the distribution pattern of the missense mutation locus rs527146862 of the TRPM2 gene in southern, northern, and central cattle populations. The results demonstrated a significant relationship between rs527146862 locus and temperature adaptation attributes in Chinese cattle.

Genome-wide association study reveals that the IBSP locus affects ear size in cattle.

Ear size is a classical model for hot climate adaptation following the evolution, but the genetic basis of the traits associated with ear size remains to be elucidated. Here, we performed a genome-wide association study on 158 cattle to explain the genetic mechanism of ear size. One region on BTA6 between 36.79 and 38.80 Mb included 50 suggestive SNPs and 4 significant SNPs that were significantly associated with ear size. The most significant locus (P = 1.30 × 10-8) was a missense mutation (T250I) on the seventh exon of integrin-binding sialoprotein (IBSP), which had an allele substitution effect of 23.46 cm2 for ear size. Furthermore, this mutation will cause changes in the three-dimensional structure of the protein. To further identify genes underlying this typical feature, we performed a genome scan among nine cattle breeds with different ear sizes by using SweeD. Results suggested that IBSP was under positive selection among four breeds with relatively large ear sizes. The expression levels of IBSP in ear tissues of large- and small-ear cattle were significantly different. A haplotype diversity survey of this missense mutation in worldwide cattle breeds strongly implied that the origin of this missense mutation event was Bos taurus. These findings have important theoretical importance for the exploration of major genes associated with ear size and provide important molecular markers for the identification of cattle germplasm resources.

A whole genome scan reveals distinct features of selection in Zhaotong cattle of Yunnan province.

Over the years, indigenous cattle have not only played an essential role in securing primary food sources but have also been utilized for labor by humans, making them invaluable genetic resources. The Zhaotong cattle, a native Chinese breed from the Yunnan province, possess excellent meat quality and resistance to heat and humidity. Here we used whole genome sequencing data of 104 animals to delve into the population structure, genomic diversity and potential positive selection signals in Zhaotong cattle. The findings of this study demonstrate that the genetic composition of Zhaotong cattle was primarily derived from Chinese indicine cattle and East Asian cattle. The nucleotide diversity of Zhaotong cattle was only lower than that of Chinese indicine cattle, which was much higher than that of other taurine cattle. Genome-wide selection scans detected a series of positive candidate regions containing multiple key genes related to bone development and metabolism (CA10, GABRG3, GLDN and NOTUM), meat quality traits (ALG8, LINGO2, MYO5B, PRKG1 and GABRB1), immune response (ADA2, BMF, LEF1 and PAK6) and heat resistance (EIF2AK4 and LEF1). In summary, this study supplies essential genetic insights into the genome diversity within Zhaotong cattle and provides a foundational framework for comprehending the genetic basis of indigenous cattle breeds.

Genes related to heat tolerance in cattle-a review.

Heat stress is described as the cumulative detrimental effect caused by an imbalance between heat production within the body and heat dissipation. When cattle are exposed to heat stress with skin surface temperatures exceeding 35 °C, gene networks within and across cells respond to environmental heat loads with both intra and extracellular signals that coordinate cellular and whole-animal metabolism changes to store heat and rapidly increase evaporative heat loss. In this study, we examined evidence from genes known to be associated with heat tolerance (Hsp70, HSF1, HspB8, SOD1, PRLH, ATP1A1, MTOR, and EIF2AK4). This information could serve as valuable resource material for breeding programs aimed at increasing the thermotolerance of cattle.

The distribution of a missense mutation in SDK1 gene across native Chinese breeds.

Sidekick cell adhesion molecule 1 (SDK1) gene belonging to the immunoglobulin superfamily (IgSF) is reported to be associated with disease resistance. A novel missense mutation (XM_015469413.1: c.2678 A > G: p. Asp893Gly) in bovine SDK1 gene was observed in the Bovine Genome Variation Database (BGVD). The purpose of the current study was to determine the allelic frequency distribution of XM_015469413.1: c.2678 A > G: p. Asp893Gly and analyze its association with disease resistance in native Chinese cattle. Here, we explored the allele frequency of the missense mutation (M_015469413.1: c.2678 A > G: p. Asp893Gly) in 542 individuals from 27 Chinese indigenous cattle breeds using PCR and DNA sequencing methods. The frequency of the mutant allele (G) gradually decreased from the southern cattle groups to the northern cattle groups, whereas the frequency of the wild-type allele A showed an opposite pattern, consistent with the distribution of indicine and taurine cattle in China. Thus, our results proved that the bovine SDK1 gene might be candidate genes associated with disease resistance in Chinese cattle.

TRPM4 gene variation associated with climatic conditions in Chinese cattle.

The transient receptor potential (TRP) superfamily has been reported to play an important role in heat tolerance pathways. Based on the Bovine Genome Variation Database and Selective Signatures, a missense mutation (NC_037345.1: c.2237A > G: p. His746Arg) (rs209689836) was identified in the transient receptor potential cation channel subfamily M member 4 (TRPM4) gene, a member of the TRP family, corresponding to heat tolerance. Here, we explored the prevalence of this variant in 19 native Chinese cattle (comprised of 404 individuals) to determine its possible association with heat tolerance in Chinese cattle by using PCR and DNA sequencing. The distribution of alleles of NC_037345.1: c.2237A > G: p. His746Arg displays significant geographical differences across native Chinese cattle breeds, consistent with the distribution of indicine and taurine cattle in China. Additionally, the association analysis indicated that the G allele was significantly associated with mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI) (p < .05), suggesting that cattle carrying allele G were distributed in regions with higher T, RH, and THI. In conclusion, our results suggested that the mutation of the TRPM4 gene in Chinese cattle might be a candidate locus associated with heat tolerance.

Assessing genomic diversity and selective pressures in Bashan cattle by whole-genome sequencing data.

Specific ecological environments and domestication have continuously influenced the physiological characteristics of Chinese indigenous cattle. Among them, Bashan cattle belongs to one of the indigenous breeds. However, the genomic diversity of Bashan cattle is still unknown. Published whole-genome sequencing (WGS) data of 13 Bashan cattle and 48 worldwide cattle were used to investigate the genetic composition and selection characteristics of Bashan cattle. The population structure analysis revealed that Bashan cattle harbored ancestries with East Asian taurine and Chinese indicine. Genetic diversity analysis implied the relatively high genomic diversity in Bashan cattle. Through the identification of containing >5 nsSNPs or frameshift mutations genes in Bashan cattle, a large number of pathways related to sensory perception were discovered. CLR, θπ ratio, FST, and XP-EHH methods were used to detect the candidate signatures of positive selection in Bashan cattle. Among the identified genes, most of the enriched signal pathways were related to environmental information processing, biological systems, and metabolism. We mainly reported genes related to the nervous system (HCN1, KATNA1, FSTL1, GRIK2, and CPLX2), immune (CD244, SLAMF1, LY9, and CD48), and reproduction (AKR1C1, AKR1C3, AKR1C4, and TUSC3). Our findings will be significant in understanding the molecular basis underlying phenotypic variation of breed-related traits and improving productivity in Bashan cattle.

A missense mutation (rs209302038) of KRT9 gene associated with heat stress in Chinese cattle.

Type I keratin 9 encoded by the KRT9 gene serves an important special function either in the mature palmar and plantar skin tissue. The changes in skin conditions and thickening of the outer layer of the skin may be affected by environmental variables. A missense mutation rs209302038 (NC_037346.1: g.41782870 G > A) was detected in KRT9, which changing the isoleucine into valine. This study aimed to identify the frequency of allele in this locus in Chinese indigenous cattle, and analyze the connection with heat stress. Our results indicated that the frequency of allele A gradually decreases from south to north, while the frequency of G allele showed the opposite pattern. Further analysis of the association of the different genotypes with three climate factors, which showed that the genotypes (GG, GA, AA) were significantly related to climatic conditions (p < 0.01). Therefore, we speculated that the mutation of the rs209302038 in Chinese indigenous cattle might be a genetic marker to detect heat stress.

Copy number variation of bovine S100A7 as a positional candidate affected body measurements.

Beef production is closely related to the national economy and the attention has been paid to the improvement of beef cattle by molecular markers associated. Copy number variations (CNVs) recently have been gained many researches and recognized as an important source of genetic variation. Extensive studies have indicated that CNVs have effects on a large range of economic traits by a wide range of gene copy number alteration. S100A7 is a member of S100 family which is a famous family of Ca2+-binding proteins. S100A7 plays a crucial role in many important phenotypes (progress) including inflammatory diseases, psoriasis, obesity, etc. The aim of our study was to explore the phenotypic effects of CNV located in the S100A7 gene of bovine chromosome 3. We detected S100A7 CNV by qPCR in different cattle breeds, including Qinchuan cattle, Yunling cattle, Xianan cattle and a crossbred group Pinan. The copy number was identified as gain, normal and loss type, our results showed that the gain type was the main type in three types of S100A7 CNV of the whole tested breeds. After CNV detection, association analysis between S100A7 CNV and growth traits was carried out in four cattle breeds. We found significant effects of the CNV on cattle growth traits with differently preferred CNV types such as gain type with better chest depth (p = 0.043) in QC, loss type with better body length (p = 0.008) and rump width (p = 0.014) in YL, normal with better chest girth (p = 0.001), gain with better waist width (p = 0.001) and rump width (p = 0.044) in PN. These results suggested that the S100A7 CNV could affect the phenotypic traits and be used as a promising genetic marker for cattle molecular breeding.

Muscle transcriptome analysis reveal candidate genes and pathways related to fat and lipid metabolism in Yunling cattle.

Yunling cattle (YL) is a recently developed beef breed harboring a quarter of Yunnan ancestral cattle genome, spanning over past 30 years. Compared with Diqing cattle (DQ), a Yunnan native cattle breed, YL presents various advantages, including rapid growth and exquisite meat quality. However, the molecular mechanisms underlying these phenotypic differences are not clearly understood. To further identify the candidate genes responsible for the quality of the meat in the muscle, longissimus dorsi (LD) muscle was used for RNA-Seq analysis. A total of 508 differentially expressed genes (DEGs) were identified in YL (adjusted p-value <0.01 and log2FoldChange >1), of which 243 were up-regulated and 265 were down-regulated. Functional association analysis showed that the identified DEGs mainly enriched the lipid and fat metabolism pathways. Moreover, it was also observed that several fat-related genes were differentially expressed in both cattle breeds, including three up-regulated genes (MOGAT1, ACSM3, PLPP2) and two down-regulated genes (ADIG, GPAT3). In addition, alternative splice analysis was also performed revealing an important 9-11 exon skipping variation of GPAM gene (crucial for beef marbling) in YL, which is three times higher than that in DQ, suggesting that this variation might have played the central role in the 'snow beef' effect in YL. We believe that our results will help in understanding the mechanism of muscle development and promote the further breeding programs in YL cattle.

A novel SNP of TECPR2 gene associated with heat tolerance in Chinese cattle.

Heat stress affects the animal production and causes serious economic losses to the husbandry. Tectonin beta-propeller repeat containing 2 (TECPR2) gene plays an important role in autophagy which may affect the temperature sensation in animals. A missense mutation (XM_024981840.1:c.3989 G > A p.Arg1330His) of the transcripts X4 in the bovine TECPR2 gene was identified. In this study, the c.3989 G > A variant in TECPR2 gene was genotyped in a total of 25 cattle breeds (520 individuals). Our results indicated that the frequency of A allele showed a decreasing pattern from southern cattle to northern cattle, while the frequency of G allele showed the opposite pattern, which was consistent with the climate distribution of China. Compared with the GG genotype, southern cattle carried more the AA and AG genotypes. Furthermore, the association results carried out that the frequencies of genotypes (GG, AG, AA) and the value of climate parameters (mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI) were significantly correlated (p < 0.01). Hence, we speculated that the c.3989 G > A variant of TECPR2 gene was associated with the heat tolerance trait in Chinese cattle and the locus may be considered as a molecular marker for Chinese cattle breeding.

TAS2R16 introgression from banteng into indigenous Chinese cattle.

Historical hybridization between southern indigenous Chinese cattle and banteng has been well-documented and has resulted in gene introgression. Bitter taste receptors were reported in indigenous cattle as a result of introgression from banteng. To determine the level of introgression of the taste 2 receptor member 16 (TAS2R16) gene from banteng into Chinese cattle, two missense mutations in the bovine TAS2R16 gene were examined. Here, we explored the prevalence of the two variants in 28 indigenous Chinese cattle and banteng breeds (comprising 750 individuals) to determine the influence of banteng introgressions on Chinese cattle based on PCR and DNA sequencing. In our study, the two mutant alleles had a higher frequency distribution in southern China with strong geographic distribution, especially in the south-central and southeast areas. In conclusion, this study examines the impact of introgression on the frequency distributions of mutations in variable regions and the subsequent adaptation of Chinese indigenous cattle to different environmental conditions.

The genetic secrets of adaptation: decoding the significance of the 30-bp insertion in the KRT77 gene for Chinese cattle.

The KRT77 gene is a type II epithelial cell α-keratin gene family member that plays a crucial role in animal epidermal and coat formation. This study aimed to investigate the relationship between the KRT77 gene and the adaptability of Chinese cattle in varying environments by exploring the distribution of an exon insertion of the KRT77 gene in different cattle populations. Our analysis involved amplifying and sequencing DNA samples from 362 individuals from 24 cattle breeds in China. Our findings reveal a gradual increase in the frequency of insertion from the northwest to the southeast population. We conducted an association analysis between the genotypes and climate data, revealing a correlation between the insertion and local annual mean temperature, relative humidity, and temperature humidity index. The study highlights the significance of the newly identified KRT77 gene insertion as a variation associated with environmental adaptation in Chinese cattle.This insertion variation increased insights into the genetic mechanisms that drive adaptation in Chinese cattle, emphasizing the importance of the 30-bp insertion in the KRT77 gene. Our findings facilitate further research to improve cattle breeding strategies for adaptability to changing environments from the northwest to the southeast population. In conclusion, this study provides value.

A missense mutation of the WNK1 gene affects cold tolerance in Chinese domestic cattle.

Inclement weather conditions, especially cold stress, have threatened the cattle industry. Cattle exposed to cold environments for a longer time suffer developmental delay, immunity decline, and eventually death. WNK1 is a member of With-no-lysine kinases (WNKs), widely expressed in animal organs and tissues. WNK1 and WNK4 are expressed in adipose tissue, and WNK4 promotes adipogenesis. WNK1 does not directly affect adipogenesis but has been shown to promote WNK4 expression in several tissues or organs. One missense mutation NC_037346.1:g.107692244, A > G, rs208265410 in the WNK1 gene was detected from the database of bovine genomic variation (BGVD). Here, we collected 328 individuals of 17 breeds representing four groups of Chinese cattle, northern group cattle, southern group cattle, central group cattle, and special group cattle (Tibetan cattle). We also collected the temperature and humidity data records from their relative locations. The frequencies of the G allele in Chinese breeds increased from northern China to southern China, and the frequencies of the A allele showed an opposite trend. Our results indicate that the WNK1 gene might be a candidate gene marker associated with cold tolerance.

Copy number variation of GAL3ST1 gene is associated with growth traits of Chinese cattle.

Copy number variation (CNV) is a type of genomic structural variation, and the research on it has flourished in recent years. According to the high-throughput sequencing data, we found that the copy number variation region of the GAL3ST1 gene was correlated with the growth traits of bovine. It is significant that we study the CNV of GAL3ST1 gene and process the association analysis between results of Q-PCR and growth traits of Chinese cattle. In this research, SPSS software was used to detect the distribution of GAL3ST1 gene copy number in four cattle breeds and the correlation of growth traits was analyzed. Correlation analysis showed that GAL3ST1 CNV had positive effects on some growth traits of bovine (p < 0.05). In addition, the study detects the expression of GAL3ST1 gene in different tissues of Xia'nan cattles on mRNA level. The result showed that GAL3ST1 gene has different expression conditions in different tissues, results showed that the expression level was high in intestine and low in liver tissue. In a word, we speculated that the GAL3ST1 gene can be used as a molecular marker and this study confirmed that the CNV of it can provide theoretical basis for molecular breeding of cattle in China.

Non-Coding RNAs and Adipogenesis.

Adipogenesis is regarded as an intricate network in which multiple transcription factors and signal pathways are involved. Recently, big efforts have focused on understanding the epigenetic mechanisms and their involvement in the regulation of adipocyte development. Multiple studies investigating the regulatory role of non-coding RNAs (ncRNAs) in adipogenesis have been reported so far, especially lncRNA, miRNA, and circRNA. They regulate gene expression at multiple levels through interactions with proteins, DNA, and RNA. Exploring the mechanism of adipogenesis and developments in the field of non-coding RNA may provide a new insight to identify therapeutic targets for obesity and related diseases. Therefore, this article outlines the process of adipogenesis, and discusses updated roles and mechanisms of ncRNAs in the development of adipocytes.

Deletions in GSN gene associated with growth traits of four Chinese cattle breeds.

The aim of this study was to assess the potential of 21 bp mutation in the second intron of the GSN gene as a molecular marker-assisted by exploring the effect of 21 bp mutation on growth traits in four beef cattle breeds. Gelsolin (GSN), a member of the superfamily of gel proteins, is involved in the regulation of a variety of cellular activities in the organism and plays an important function in cell motility, apoptosis, signal transduction and inflammatory responses. Gelatin can not only negatively regulate the pro-apoptotic effect of P53 protein, but also promote apoptosis by blocking the interaction between actin and deoxyribonuclease, so, the GSN gene was selected as a candidate gene in this study. In this study, a 21 bp mutation on the second intron to the GSN gene was verified in 573 individuals of Yunling (YL, n = 220), Jiaxian (JX, n = 140), Xianan (XN, n = 114) and Qinchuan (QC, n = 97) cattle breeds using Once PCR and agarose gel electrophoresis. The association analysis of polymorphisms in the GSN gene with growth traits in four breeds was revealed: in YL cattle, the heart girth and forehead size of heterozygous ID genotype were significantly higher than II genotype (P < 0.05). In JX cattle, the withers height, body length and heart girth of II and ID genotype were significantly highest than DD genotype (P < 0.01); the height at hip cross and height at sacrum of II genotype was significantly highest than DD genotype (P < 0.01), but ID genotype was significantly higher than DD genotype. In XN cattle, the abdominal girth and circumference of the cannon bone of II genotype were significantly higher than ID genotype (P < 0.05). In QC cattle, the hucklebone width of ID genotype was significantly the highest than II genotype (P < 0.01). The results suggest that GSN may be an important candidate gene and that a 21 bp mutation on the second intron to the GSN gene can be used for molecular marker-assisted selection of four beef cattle breeds.

The distribution of four missense mutations in SPTBN5 gene across native Chinese breeds.

Modern cattle belong to two subspecies, Bos taurus and Bos indicus. Since divergence, cattle types have accumulated different genetic variations, which have contributed to highly differentiated phenotypes. The mammalian inner ear possesses functional and morphological innovations that contribute to its unique hearing capacities. The spectrin beta, non-erythrocytic 5 (SPTBN5) gene has been shown to play an important function in the inner ear. Four missense mutations: rs522333459 (c.7232G > C:p.Cys2411Ser), rs718838405 (c.6568A > C:p.Met2190Leu), rs516536785 (c.6283C > T:p.Leu2095Phe) and rs480278206 (c.4201T > C:p.Cys1401Arg) were identified in the bovine SPTBN5 gene by whole genome resequencing (http://animal.nwsuaf.edu.cn/code/index.php/BosVar), which might be candidate mutations related with hearing of both taurine and indicine cattle. In our study, PCR and DNA sequencing were used to explore the allele frequencies of four mutations of 971 individuals belonging to 38 native Chinese cattle breeds. We find that four mutant alleles showing strong geographic distribution, consisting with the ancestry distribution of taurine and indicine in China. In addition, we identified four mutations of SPTBN5 were diverged in taurine and indicine cattle showing signatures of adaptive evolution in two subspecies, which might participate in bovine inner ear development.

A novel SNP of MYO1A gene associated with heat-tolerance in Chinese cattle.

With the advent of global climate change, heat-tolerance is becoming more and more important to the sustainability of animal husbandry production systems. Previous studies have shown that MYO1A gene associated with pigmentation may be closely related to heat-tolerance in cattle. In this study, a novel missense mutation (NC_037332.1 g.56390345 A > G) was first detected in MYO1A in 891 individuals of 35 cattle breeds, which transformed the amino acid isoleucine into valine. The purpose of this study was to determine the allele frequencies distribution of this locus in Chinese indigenous cattle and to analyze the relationship between this locus and heat-tolerance. Further analysis showed that frequency of wild allele A decreased gradually from northern cattle to southern cattle, whereas frequency of mutant type allele G showed the opposite pattern, which was consistent with the distribution of various climatic conditions of China. Additionally, association analysis was carried out between genotypes and four climatic conditions (annual mean temperature (T), relative humidity (H), temperature-humidity index (THI) and average annual sunshine hours (100-cloudiness) (SR)). Analysis results showed that genotypes were significantly correlated with climatic conditions. Therefore, our results suggest that the novel SNP (rs209559414) is related to heat-tolerance trait of Chinese indigenous cattle.

Distribution of the variant at AKIRIN2: c.*188G > A in Chinese cattle.

Marbling score (MS), is an economically important trait in cattle. Previous results showed that a SNP (c.*188G > A) of akirin 2 (AKIRIN2) gene was associated with MS in Japanese Black cattle and Korean cattle. However, the distribution of the genotypic frequency of the single nucleotide polymorphism (SNP) has not been explored in Chinese cattle. In this study, we used polymerase chain reaction (PCR) and DNA sequencing to detect the variation in 1296 individuals from 39 Chinese cattle breeds, one semi-wild bovine species (Dulong) and three introduced breeds (Angus, Holstein and Brahman). Our study found the frequency of the A allele at this locus roughly diminished from north to south in Chinese cattle, and we detected statistically significant differences between Angus and Brahman (p < 0.05), Dulong and another two breeds (Angus and Holstein; p < 0.01) using Chi-Square Independence Test. Our results reflected the variation of AKIRIN2: c.*188G > A in Chinese cattle, which would help us better understand Chinese cattle genetic resources and provide reference for further research.