Genome-wide association study identifies genomic regions associated with key reproductive traits in Korean Hanwoo cows.

BACKGROUND: Conducting genome-wide association studies (GWAS) for reproductive traits in Hanwoo cattle, including age at first calving (AFC), calving interval (CI), gestation length (GL), and number of artificial inseminations per conception (NAIPC), is of paramount significance. These analyses provided a thorough exploration of the genetic basis of these traits, facilitating the identification of key markers for targeted trait improvement. Breeders can optimize their selection strategies, leading to more efficient and sustainable breeding programs, by incorporating genetic insights. This impact extends beyond individual traits and contributes to the overall productivity and profitability of the Hanwoo beef cattle industry. Ultimately, GWAS is essential in ensuring the long-term genetic resilience and adaptability of Hanwoo cattle populations. The primary goal of this study was to identify significant single nucleotide polymorphisms (SNPs) or quantitative trait loci (QTLs) associated with the studied reproductive traits and subsequently map the underlying genes that hold promise for trait improvement. RESULTS: A genome-wide association study of reproductive traits identified 68 significant single nucleotide polymorphisms (SNPs) distributed across 29 Bos taurus autosomes (BTA). Among them, BTA14 exhibited the highest number of identified SNPs (25), whereas BTA6, BTA7, BTA8, BTA10, BTA13, BTA17, and BTA20 exhibited 8, 5, 5, 3, 8, 2, and 12 significant SNPs, respectively. Annotation of candidate genes within a 500 kb region surrounding the significant SNPs led to the identification of ten candidate genes relevant to age at first calving. These genes were: FANCG, UNC13B, TESK1, TLN1, and CREB3 on BTA8; FAM110B, UBXN2B, SDCBP, and TOX on BTA14; and MAP3K1 on BTA20. Additionally, APBA3, TCF12, and ZFR2, located on BTA7 and BTA10, were associated with the calving interval; PAX1, SGCD, and HAND1, located on BTA7 and BTA13, were linked to gestation length; and RBM47, UBE2K, and GPX8, located on BTA6 and BTA20, were linked to the number of artificial inseminations per conception in Hanwoo cows. CONCLUSIONS: The findings of this study enhance our knowledge of the genetic factors that influence reproductive traits in Hanwoo cattle populations and provide a foundation for future breeding strategies focused on improving desirable traits in beef cattle. This research offers new evidence and insights into the genetic variants and genome regions associated with reproductive traits and contributes valuable information to guide future efforts in cattle breeding.

From cancer big data to treatment: Artificial intelligence in cancer research.

In recent years, developing the idea of "cancer big data" has emerged as a result of the significant expansion of various fields such as clinical research, genomics, proteomics and public health records. Advances in omics technologies are making a significant contribution to cancer big data in biomedicine and disease diagnosis. The increasingly availability of extensive cancer big data has set the stage for the development of multimodal artificial intelligence (AI) frameworks. These frameworks aim to analyze high-dimensional multi-omics data, extracting meaningful information that is challenging to obtain manually. Although interpretability and data quality remain critical challenges, these methods hold great promise for advancing our understanding of cancer biology and improving patient care and clinical outcomes. Here, we provide an overview of cancer big data and explore the applications of both traditional machine learning and deep learning approaches in cancer genomic and proteomic studies. We briefly discuss the challenges and potential of AI techniques in the integrated analysis of omics data, as well as the future direction of personalized treatment options in cancer.

Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases.

Tuberculosis (TB) is a major cause of morbidity and mortality and remains an important public health issue in developing countries worldwide. The existing methods and techniques available for the diagnosis of TB are based on combinations of laboratory (chemical and biological), radiological, and clinical tests. These methods are sophisticated and laborious and have limitations in terms of sensitivity, specificity, and accuracy. Clinical settings need improved diagnostic biomarkers to accurately detect biological changes due to pathogen invasion and pharmacological responses. Exosomes are membrane-bound vesicles and mediators of intercellular signaling processes that play a significant role in the pathogenesis of various diseases, such as tuberculosis, and can act as promising biomarkers for the monitoring of TB infection. Compared to conventional biomarkers, exosome-derived biomarkers are advantageous because they are easier to detect in different biofluids, are more sensitive and specific, and may be useful in tracking patients' reactions to therapy. This review provides insights into the types of biomarkers, methods of exosome isolation, and roles of the cargo (proteins) present in exosomes isolated from patients through omics studies, such as proteomics. These findings will aid in developing new prognostic and diagnostic biomarkers and could lead to the identification of new therapeutic targets in the clinical setting.

Assessment of genomic breeding values and their accuracies for carcass traits in Jeju Black cattle using whole-genome SNP chip panels.

The objective of the present study was to evaluate the breeding value and accuracy of genomic estimated breeding values (GEBVs) of carcass traits in Jeju Black cattle (JBC) using Hanwoo steers and JBC as a reference population using the single-trait animal model. Our research included genotype and phenotype information on 19,154 Hanwoo steers with 1097 JBC acting as the reference population. Likewise, the test population consisted of 418 genotyped JBC individuals with no phenotypic records for those carcass traits. For estimating the accuracy of GEBV, we divided the entire population into three groups. Hanwoo and JBC make up the first group; Hanwoo and JBC, who has both the genotype and phenotypic records, are referred to as the reference (training) population, and JBC, who lacks phenotypic information is referred to as the test (validation) population. The second group consists of the JBC (without phenotype) as the test population and Hanwoo as a reference population with phenotype and genotypic data. The only JBCs in the third group are those who have genotypic and phenotypic data on them as a reference population but no phenotypic data on them as a test population. The single-trait animal model was used in all three groups for statistical purposes. The reference populations estimated heritabilities for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) as 0.30, 0.26, 0.26, and 0.34 for the Hanwoo steer and 0.42, 0.27, 0.26, and 0.48 for JBC. The average accuracy for carcass traits in Group 1 was 0.80 for the Hanwoo and JBC reference population compared with 0.73 for the JBC test population. Although the average accuracy for carcass traits in Group 2 was 0.80, it was 0.80 for the Hanwoo reference population and only 0.56 for the JBC test population. The average accuracy for the JBC reference and test populations was 0.68 and 0.50, respectively, when they were included in the accuracy comparison without the Hanwoo reference population. Groups 1 and 2 used Hanwoo as reference population, which led to a better average accuracy; however, Group 3 only used the JBC reference and test population, which led to a lower average accuracy. This might be due to the fact that Group 3 used a smaller reference size than the group that came before it and that the genetic makeup of the Hanwoo and JBC breeds differed. The GEBV accuracy for MS was higher than that of other traits across all three analysis groups, followed by CWT, EMA, and BF, which may be partially explained by the MS traits' higher heritability. This study suggests that in order to achieve more accuracy, a large reference population particular to a breed should be established. Therefore, to increase the accuracy of GEBV prediction and the genetic benefit from genomic selection in JBC, individual reference breeds, and large populations are required.

Neurobiology of zinc and its role in neurogenesis.

BACKGROUND: Zinc (Zn) has a diverse role in many biological processes, such as growth, immunity, anti-oxidation system, homeostatic, and repairing. It acts as a regulatory and structural catalyst ion for activities of various proteins, enzymes, and signal transcription factors, as well as cell proliferation, differentiation, and survival. The Zn ion is essential for neuronal signaling and is mainly distributed within presynaptic vesicles. Zn modulates neuronal plasticity and synaptic activity in both neonatal and adult stages. Alterations in brain Zn status results in a dozen neurological diseases including impaired brain development. Numerous researchers are working on neurogenesis, however, there is a paucity of knowledge about neurogenesis, especially in neurogenesis in adults. Neurogenesis is a multifactorial process and is regulated by many metal ions (e.g. Fe, Cu, Zn, etc.). Among them, Zn has an essential role in neurogenesis. At the molecular level, Zn controls cell cycle, apoptosis, and binding of DNA and several proteins including transcriptional and translational factors. Zn is needed for protein folding and function and Zn acts as an anti-apoptotic agent; organelle stabilizer; and an anti-inflammatory agent. Zn deficiency results in aging, neurodegenerative disease, immune deficiency, abnormal growth, cancer, and other symptoms. Prenatal deficiency of Zn results in developmental disorders in humans and animals. CONCLUSION: Both in vitro and in vivo studies have shown an association between Zn deficiency and increased risk of neurological disorders. This article reviews the existing knowledge on the role of Zn and its importance in neurogenesis.

Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study.

BACKGROUND: Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups. METHODS: The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients' characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years. RESULTS: In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46-0.74), with 0.55 (95% confidence interval 0.41-0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46-0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years. CONCLUSIONS: This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Real-world prescribing and switching patterns of non-calcium containing phosphate binders in dialysis patients in South Korea
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OBJECTIVE: Non-calcium containing phosphate binders (non-CPBs) are useful for the treatment of hyperphosphatemia without a concern of hypercalcemia in patients undergoing dialysis. However, due to their relatively high cost, prescribing non-CPBs is restricted in South Korea. This study was conducted to investigate prescribing patterns, especially switching between CPBs and non-CPBs, in dialysis patients in a real-world setting. MATERIALS AND METHODS: This is an observational study using the National Health Insurance Service claim data. The study population included patients who initiated dialysis between July 2012 and June 2013 and were prescribed phosphate binders at least once during the observation period (2012 - 2016) (n = 10,073). Medication costs and prescribing patterns including switching of phosphate binders were investigated. RESULTS: Compared with the first year of dialysis, the costs of phosphate binders more than doubled during the 4th year of dialysis (from US$ 28.4 to US$ 60.1), largely due to an increase in the cost of non-CPBs (from US$ 117.5 to US$ 237.8). Many patients continued to change drugs between CPBs and non-CPBs. The continuous prescription period of CPBs was shortened each time a drug was changed. A total of 551 patients (13.4%) changed their medication three times between CPBs and non-CPBs. CONCLUSION: Over time on dialysis, use of non-CPB increased and medication costs increased accordingly. Many patients continued to change drugs between CPBs and non-CPBs due to the restricted criteria of the health insurance. Further outcome research is necessary to evaluate the appropriateness of the clinical practice in which CPBs and non-CPBs are alternately used.

Genetic parameters for milk fatty acid composition of Holstein in Korea.

OBJECTIVE: Milk fatty acid (FA) is a main nutritional component that markedly effects human health. Intentional modification of the FA profile has the potential to improve milk quality. This study aimed at the factors affecting elevated FA levels and the estimation of the genetic parameters for milk FAs in the Korean Holstein population. METHODS: Total 885,249 repeated test-day milk records including, milk yield, saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), total unsaturated fatty acids (TUFA), fat and protein percentages were analyzed using CombiFoss FT+ system (Foss Analytical A/S, Denmark). Genetic parameters were estimated by the restricted maximum likelihood procedure based on the repeatability model using the Wombat program. RESULTS: The FA profile varies along with the lactation and the energy balance (EB). With the negative EB in early lactation, mobilization of body fat reserves elevates the desirable FA levels. As a result of that, milk quality is increased by means of nutritionally and usability aspects during the early lactation. Moreover, heritability estimates for SFA, MUFA, PUFA, TUFA were 0.33, 0.42, 0.37, 0.41 respectively. According to the parity wise heritability analysis, first parity cows had relatively lower heritability for SFAs (0.19) than later parities (0.28). CONCLUSION: Genetic parameters indicated that FAs were under stronger genetic control. Therefore, we suggest implementing animal breeding programs towards improving the milk FA profile.

Reduction of slaughter age of Hanwoo steers by early genotyping based on meat yield index.

OBJECTIVE: This study was conducted to determine early hereditary endowment to establish a short-term feeding program. METHODS: Hanwoo steers (n = 140) were equally distributed into four groups (35/group) based on genetic meat yield index (MYI) viz. the greatest, great, low, and the lowest at Jukam Hanwoo farm, Goheung. All animals were fed in group pens (5 animals/pen) with similar feed depending on the growth stage. Rice straw was provided ad libitum, whereas concentrate was fed at 5.71 kg during the growing period (6 to 13 mo) and 9.4 kg during the fattening period (13 to 28 mo). Body weight (BW) was measured at two-month intervals, whereas carcass weight was determined at slaughtering at about 31 months of age. The Affymetrix Bovine Axiom Array 640K single nucleotide polymorphism (SNP) chip was used to determine the meat quantity-related gene in the blood. RESULTS: After 6 months, the highest (p<0.05) BW was observed in the greatest MYI group (190.77 kg) and the lowest (p<0.05) in the lowest MYI group (173.51 kg). The great MYI group also showed significantly (p<0.05) higher BW than the lowest MYI group. After 16 and 24 months, the greatest MYI group had the highest BW gain (p<0.05) and were therefore slaughtered the earliest. Carcass weight was significantly (p<0.05) higher in the greatest and the great MYI groups followed by the low and the lowest MYI groups. Back-fat thickness in the greatest MYI group was highly correlated to carcass weight and marbling score. The SNP array analysis identified the carcass-weight related gene BTB-01280026 with an additive effect. The steers with the allele increasing carcass weight had heavier slaughter weight of about 12 kg. CONCLUSION: Genetic MYI is a potential tool for calf selection, which will reduce the slaughter age while simultaneously increasing carcass weight, back-fat thickness, and marbling score.

The effectiveness of genomic selection for milk production traits of Holstein dairy cattle.

OBJECTIVE: This study was conducted to test the efficiency of genomic selection for milk production traits in a Korean Holstein cattle population. METHODS: A total of 506,481 milk production records from 293,855 animals (2,090 heads with single nucleotide polymorphism information) were used to estimate breeding value by single step best linear unbiased prediction. RESULTS: The heritability estimates for milk, fat, and protein yields in the first parity were 0.28, 0.26, and 0.23, respectively. As the parity increased, the heritability decreased for all milk production traits. The estimated generation intervals of sire for the production of bulls (LSB) and that for the production of cows (LSC) were 7.9 and 8.1 years, respectively, and the estimated generation intervals of dams for the production of bulls (LDB) and cows (LDC) were 4.9 and 4.2 years, respectively. In the overall data set, the reliability of genomic estimated breeding value (GEBV) increased by 9% on average over that of estimated breeding value (EBV), and increased by 7% in cows with test records, about 4% in bulls with progeny records, and 13% in heifers without test records. The difference in the reliability between GEBV and EBV was especially significant for the data from young bulls, i.e. 17% on average for milk (39% vs 22%), fat (39% vs 22%), and protein (37% vs 22%) yields, respectively. When selected for the milk yield using GEBV, the genetic gain increased about 7.1% over the gain with the EBV in the cows with test records, and by 2.9% in bulls with progeny records, while the genetic gain increased by about 24.2% in heifers without test records and by 35% in young bulls without progeny records. CONCLUSION: More genetic gains can be expected through the use of GEBV than EBV, and genomic selection was more effective in the selection of young bulls and heifers without test records.

Genetic diversity and population structure of the Sapsaree, a native Korean dog breed.

BACKGROUND: The Sapsaree is a breed of dog (Canis familiaris) native to Korea, which became perilously close to extinction in the mid-1980s. However, with systematic genetic conservation and restoration efforts, this breed was rescued from extinction and population sizes have been gradually increasing over the past few decades. The aim of this study was to ascertain novel information about the genetic diversity, population structure, and demographic history of the Sapsaree breed using genome-wide single nucleotide polymorphism data. We characterized the genetic profile of the Sapsaree breed by comparison with seven foreign dog breeds with similar morphologies to estimate genetic differentiation within and among these breeds. RESULTS: The results suggest that Sapsarees have higher genetic variance compared with the other breeds analyzed. The majority of the Sapsarees in this study share a discrete genetic pattern, although some individuals were slightly different, possibly as a consequence of the recent restoration process. Concordant results from analyses of linkage disequilibrium, effective population size, genetic diversity, and population structural analyses illustrate a relationship among the Sapsaree and the Tibetan breeds Tibetan terrier and Lhasa Apso, and a small genetic introgression from European breeds. The effective population size of the Sapsaree has contracted dramatically over the past generations, and is currently insufficient to maintain long-term viability of the breed's genetic diversity. CONCLUSIONS: This study provides novel insights regarding the genetic diversity and population structure of the native Korean dog breed Sapsaree. Our results suggest the importance of a strategic and systematic approach to ensure the genetic diversity and the authenticity of the Sapsaree breed.

Comparison of genomic predictions for carcass and reproduction traits in Berkshire, Duroc and Yorkshire populations in Korea.

OBJECTIVE: A genome-based best linear unbiased prediction (GBLUP) method was applied to evaluate accuracies of genomic estimated breeding value (GEBV) of carcass and reproductive traits in Berkshire, Duroc and Yorkshire populations in Korean swine breeding farms. METHODS: The data comprised a total of 1,870, 696, and 1,723 genotyped pigs belonging to Berkshire, Duroc and Yorkshire breeds, respectively. Reference populations for carcass traits consisted of 888 Berkshire, 466 Duroc, and 1,208 Yorkshire pigs, and those for reproductive traits comprised 210, 154, and 890 dams for the respective breeds. The carcass traits analyzed were backfat thickness (BFT) and carcass weight (CWT), and the reproductive traits were total number born (TNB) and number born alive (NBA). For each trait, GEBV accuracies were evaluated with a GEBV BLUP model and realized GEBVs. RESULTS: The accuracies under the GBLUP model for BFT and CWT ranged from 0.33-0.72 and 0.33-0.63, respectively. For NBA and TNB, the model accuracies ranged 0.32 to 0.54 and 0.39 to 0.56, respectively. The realized accuracy estimates for BFT and CWT ranged 0.30 to 0.46 and 0.09 to 0.27, respectively, and 0.50 to 0.70 and 0.70 to 0.87 for NBA and TNB, respectively. For the carcass traits, the GEBV accuracies under the GBLUP model were higher than the realized GEBV accuracies across the breed populations, while for reproductive traits the realized accuracies were higher than the model based GEBV accuracies. CONCLUSION: The genomic prediction accuracy increased with reference population size and heritability of the trait. The GEBV accuracies were also influenced by GEBV estimation method, such that careful selection of animals based on the estimated GEBVs is needed. GEBV accuracy will increase with a larger sized reference population, which would be more beneficial for traits with low heritability such as reproductive traits.

Rearing characteristics of fattening Hanwoo steers managed in different stocking densities.

OBJECTIVE: This study was conducted to analyze the effects of stocking density on growth and carcass quality, and behavior of Hanwoo cattle to conform with global trends, targeting animal welfare production through the practice of environmentally friendly condition. METHODS: Thirty six steers were randomly assigned to three treatment groups (C: 5 heads, T1: 4 heads, T2: 3 heads) and reared in separate pens with a constant stocking density of 50 m2 (C: 10 m2/head, T1: 12.5 m2/head, T2: 16.67 m2/head) per group from 12 to 30 month of age. Growth performance, behavior and carcass quality traits of each steer were recorded and compared between the treatment groups. RESULTS: In general, the average daily gain during the fattening period was lower in group T2 than in T1 and the control groups. However, carcass weight and dressing percentage was lower in the control group than in T1 or T2 groups (p<0.05). Also, marbling score at 30 months of age was the lowest in the control group (p<0.05), while the three heads group (T2) had the greatest longissimus muscle area and marbling score (p<0.05). The behavior of walking time was the greatest in T2 group, while self-grooming and fighting occurred with the most frequency in the control group (p<0.05). CONCLUSION: Our results show that the steers in more spacious stocking density had better carcass quality and wellbeing related behaviors, indicating that a lower density has a positive effect on raising management and carcass quality. Thus it is a need to install appropriate pens fitted to welfare-oriented management practices from growing to fattening period in Hanwoo cattle.

A whole genome association study to detect additive and dominant single nucleotide polymorphisms for growth and carcass traits in Korean native cattle, Hanwoo.

OBJECTIVE: A whole genome association study was conducted to identify single nucleotide polymorphisms (SNPs) with additive and dominant effects for growth and carcass traits in Korean native cattle, Hanwoo. METHODS: The data set comprised 61 sires and their 486 Hanwoo steers that were born between spring of 2005 and fall of 2007. The steers were genotyped with the 35,968 SNPs that were embedded in the Illumina bovine SNP 50K beadchip and six growth and carcass quality traits were measured for the steers. A series of lack-of-fit tests between the models was applied to classify gene expression pattern as additive or dominant. RESULTS: A total of 18 (0), 15 (3), 12 (8), 15 (18), 11 (7), and 21 (1) SNPs were detected at the 5% chromosome (genome) - wise level for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area (LMA) and marbling score, respectively. Among the significant 129 SNPs, 56 SNPs had additive effects, 20 SNPs dominance effects, and 53 SNPs both additive and dominance effects, suggesting that dominance inheritance mode be considered in genetic improvement for growth and carcass quality in Hanwoo. The significant SNPs were located at 33 quantitative trait locus (QTL) regions on 18 Bos Taurus chromosomes (i.e. BTA 3, 4, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 18, 20, 23, 26, 28, and 29) were detected. There is strong evidence that BTA14 is the key chromosome affecting CWT. Also, BTA20 is the key chromosome for almost all traits measured (WWT, YWT, LMA). CONCLUSION: The application of various additive and dominance SNP models enabled better characterization of SNP inheritance mode for growth and carcass quality traits in Hanwoo, and many of the detected SNPs or QTL had dominance effects, suggesting that dominance be considered for the whole-genome SNPs data and implementation of successive molecular breeding schemes in Hanwoo.

Accuracy of genomic breeding value prediction for intramuscular fat using different genomic relationship matrices in Hanwoo (Korean cattle).

OBJECTIVE: Intramuscular fat is one of the meat quality traits that is considered in the selection strategies for Hanwoo (Korean cattle). Different methods are used to estimate the breeding value of selection candidates. In the present work we focused on accuracy of different genotype relationship matrices as described by forni and pedigree based relationship matrix. METHODS: The data set included a total of 778 animals that were genotyped for BovineSNP50 BeadChip. Among these 778 animals, 72 animals were sires for 706 reference animals and were used as a validation dataset. Single trait animal model (best linear unbiased prediction and genomic best linear unbiased prediction) was used to estimate the breeding values from genomic and pedigree information. RESULTS: The diagonal elements for the pedigree based coefficients were slightly higher for the genomic relationship matrices (GRM) based coefficients while off diagonal elements were considerably low for GRM based coefficients. The accuracy of breeding value for the pedigree based relationship matrix (A) was 13% while for GRM (GOF, G05, and Yang) it was 0.37, 0.45, and 0.38, respectively. CONCLUSION: Accuracy of GRM was 1.5 times higher than A in this study. Therefore, genomic information will be more beneficial than pedigree information in the Hanwoo breeding program.

Validation of Single Nucleotide Polymorphisms Associated with Carcass Traits in a Commercial Hanwoo Population.

Four carcass traits, namely carcass weight (CW), eye muscle area (EMA), back fat thickness (BF), and marbling score (MS), are the main price decision parameters used for purchasing Hanwoo beef. The development of DNA markers for these carcass traits for use in a beef management system could result in substantial profit for beef producers in Korea. The objective of this study was to validate the association of highly significant single nucleotide polymorphisms (SNPs) identified in a previous genome-wide association study (GWAS) with the four carcass traits in a commercial Hanwoo population. We genotyped 83 SNPs distributed across all 29 autosomes in 867 steers from a Korean Hanwoo feedlot. Six SNPs, namely ARS-BFGL-NGS-22774 (Chr4, Pos:4889229), ARS-BFGL-NGS-100046 (Chr6, Pos:61917424), ARS-BFGL-NGS-39006 (Chr27, Pos:38059196), ARS-BFGL-NGS-18790 (Chr10, Pos:26489109), ARS-BFGL-NGS-43879 (Chr9, Pos:39964297), and BTB-00775794 (Chr20, Pos:20476265), were found to be associated with CW, EMA, BF, and MS. The ARS-BFGL-NGS-22774, BTB-00775794, and ARS-BFGL-NGS-39006 markers accounted for 1.80%, 1.72%, and 1.35% (p<0.01), respectively, of the phenotypic variance in the commercial Hanwoo population. Many genes located in close proximity to the significant SNPs identified in this study were previously reported to have roles in carcass traits. The results of this study could be useful for marker-assisted selection programs.

Discovery of Gene Sources for Economic Traits in Hanwoo by Whole-genome Resequencing.

Hanwoo, a Korean native cattle (Bos taurus coreana), has great economic value due to high meat quality. Also, the breed has genetic variations that are associated with production traits such as health, disease resistance, reproduction, growth as well as carcass quality. In this study, next generation sequencing technologies and the availability of an appropriate reference genome were applied to discover a large amount of single nucleotide polymorphisms (SNPs) in ten Hanwoo bulls. Analysis of whole-genome resequencing generated a total of 26.5 Gb data, of which 594,716,859 and 592,990,750 reads covered 98.73% and 93.79% of the bovine reference genomes of UMD 3.1 and Btau 4.6.1, respectively. In total, 2,473,884 and 2,402,997 putative SNPs were discovered, of which 1,095,922 (44.3%) and 982,674 (40.9%) novel SNPs were discovered against UMD3.1 and Btau 4.6.1, respectively. Among the SNPs, the 46,301 (UMD 3.1) and 28,613 SNPs (Btau 4.6.1) that were identified as Hanwoo-specific SNPs were included in the functional genes that may be involved in the mechanisms of milk production, tenderness, juiciness, marbling of Hanwoo beef and yellow hair. Most of the Hanwoo-specific SNPs were identified in the promoter region, suggesting that the SNPs influence differential expression of the regulated genes relative to the relevant traits. In particular, the non-synonymous (ns) SNPs found in CORIN, which is a negative regulator of Agouti, might be a causal variant to determine yellow hair of Hanwoo. Our results will provide abundant genetic sources of variation to characterize Hanwoo genetics and for subsequent breeding.

A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.

Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

Multiple Linkage Disequilibrium Mapping Methods to Validate Additive Quantitative Trait Loci in Korean Native Cattle (Hanwoo).

The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a BayesCπ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions.

Genome-wide Association Study to Identify Quantitative Trait Loci for Meat and Carcass Quality Traits in Berkshire.

Meat and carcass quality attributes are of crucial importance influencing consumer preference and profitability in the pork industry. A set of 400 Berkshire pigs were collected from Dasan breeding farm, Namwon, Chonbuk province, Korea that were born between 2012 and 2013. To perform genome wide association studies (GWAS), eleven meat and carcass quality traits were considered, including carcass weight, backfat thickness, pH value after 24 hours (pH24), Commission Internationale de l'Eclairage lightness in meat color (CIE L), redness in meat color (CIE a), yellowness in meat color (CIE b), filtering, drip loss, heat loss, shear force and marbling score. All of the 400 animals were genotyped with the Porcine 62K SNP BeadChips (Illumina Inc., USA). A SAS general linear model procedure (SAS version 9.2) was used to pre-adjust the animal phenotypes before GWAS with sire and sex effects as fixed effects and slaughter age as a covariate. After fitting the fixed and covariate factors in the model, the residuals of the phenotype regressed on additive effects of each single nucleotide polymorphism (SNP) under a linear regression model (PLINK version 1.07). The significant SNPs after permutation testing at a chromosome-wise level were subjected to stepwise regression analysis to determine the best set of SNP markers. A total of 55 significant (p<0.05) SNPs or quantitative trait loci (QTL) were detected on various chromosomes. The QTLs explained from 5.06% to 8.28% of the total phenotypic variation of the traits. Some QTLs with pleiotropic effect were also identified. A pair of significant QTL for pH24 was also found to affect both CIE L and drip loss percentage. The significant QTL after characterization of the functional candidate genes on the QTL or around the QTL region may be effectively and efficiently used in marker assisted selection to achieve enhanced genetic improvement of the trait considered.