ABSTRACT
According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.
Subject(s)
Neoplasms , Humans , Neoplasms/genetics , Neoplasms/drug therapy , Precision Medicine , RNA-Seq , Medicine, Chinese Traditional , Body Constitution/geneticsABSTRACT
Covariance components were estimated for growth traits (BW, birth weight; WW, weaning weight; YW, yearling weight), visual scores (BQ, breed quality; CS, conformation; MS, muscling; NS, navel; PS, finishing precocity), hip height (HH), and carcass traits (BF, backfat thickness; LMA, longissimus muscle area) measured at yearling. Genetic gains were obtained and validation models on direct and maternal effects for BW and WW were fitted. Genetic correlations of growth traits with CS, PS, MS, and HH ranged from 0.20 ± 0.01 to 0.94 ± 0.01 and were positive and low with NS (0.11 ± 0.01 to 0.20 ± 0.01) and favorable with BQ (0.14 ± 0.02 to 0.37 ± 0.02). Null to moderate genetic correlations were obtained between growth and carcass traits. Genetic gains were positive and significant, except for BW. An increase of 0.76 and 0.72 kg is expected for BW and WW, respectively, per unit increase in estimated breeding value (EBV) for direct effect and an additional 0.74 and 1.43, respectively, kg per unit increase in EBV for the maternal effect. Monitoring genetic gains for HH and NS is relevant to maintain an adequate body size and a navel morphological correction, if necessary. Simultaneous selection for growth, morphological, and carcass traits in line with improve maternal performance is a feasible strategy to increase herd productivity.
Subject(s)
Birth Weight/genetics , Body Constitution/genetics , Body Height/genetics , Cattle/growth & development , Cattle/genetics , Genetic Association Studies/veterinary , Quantitative Trait, Heritable , Animals , Breeding , Female , Humans , Male , Maternal Inheritance/genetics , PhenotypeABSTRACT
The goal of this study was to identify potential quantitative trait loci (QTL) for 27 production, fitness, and conformation traits of Guernsey cattle through genome-wide association (GWA) analyses, with extra emphasis on BTA19, where major QTL were observed for several traits. Animals' de-regressed predicted transmitting abilities (PTA) from the December 2018 traditional US evaluation were used as phenotypes. All of the Guernsey cattle included in the QTL analyses were predictor animals in the reference population, ranging from 1,077 to 1,685 animals for different traits. Single-trait GWA analyses were carried out by a mixed-model approach for all 27 traits using imputed high-density genotypes. A major QTL was detected on BTA19, influencing several milk production traits, conformation traits, and livability of Guernsey cattle, and the most significant SNP lie in the region of 26.2 to 28.3 Mb. The myosin heavy chain 10 (MYH10) gene residing within this region was found to be highly associated with milk production and body conformation traits of dairy cattle. After the initial GWA analyses, which suggested that many significant SNP are in linkage with one another, conditional analyses were used for fine mapping. The top significant SNP on BTA19 were fixed as covariables in the model, one at a time, until no more significant SNP were detected on BTA19. After this fine-mapping approach was applied, only 1 significant SNP was detected on BTA19 for most traits, but multiple, independent significant SNP were found for protein yield, dairy form, and stature. In addition, the haplotype that hosts the major QTL on BTA19 was traced to a US Guernsey born in 1954. The haplotype is common in the breed, indicating a long-term influence of this QTL on the US Guernsey population.
Subject(s)
Body Constitution/genetics , Cattle/genetics , Milk , Quantitative Trait Loci , Animals , Cattle/anatomy & histology , Cattle/physiology , Chromosome Mapping , Female , Genetic Linkage , Genome-Wide Association Study/veterinary , Genotype , Haplotypes , PhenotypeABSTRACT
A dopamine type-2 receptor (DRD2) SNP, previously found to be correlated with serum prolactin (PRL) concentrations in cattle, was evaluated for impact on growth traits, serum prolactin concentration, and semen quality. Over a four-year period, yearling beef bulls were allowed diets containing or lacking ergot alkaloids (EA). Every 21 or 28 d semen was collected for semen motility and morphology assessment and blood samples were collected to measure serum PRL concentrations. In addition, body condition score and scrotal circumference were evaluated. Serum PRL concentrations were assessed using a radioimmunoassay. In the first year, all bulls were sacrificed at the end of a 126-day study. Testicles and epididymis were collected at the end of the study or 60 days after removal from treatment. Immunohistochemistry was performed on testis, epididymis, and sperm cells, incubated with or without a primary antibody for DRD2 and counterstained with DAPI. Isolation of DNA was performed on sperm pellets using DNAzol (Thermo Fisher Scientific, Waltham, MA, USA) methods. Polymerase chain reaction was performed to amplify the region of the DRD2 gene containing the SNP of interest. The products were subjected to restriction fragment length polymorphism analysis. Further, all samples were subjected to genotyping using a custom Taqman genotyping assay (Applied Biosystems, Foster city, CA, USA). The presence of DRD2 was detected in the testis, epididymis, and sperm cells. The DRD2 genotype was not associated with semen quality, serum PRL, or growth traits. Consumption of EA resulted in lesser PRL serum concentrations but had no effect on values for other variable examined.
Subject(s)
Cattle , Dopamine Agonists/pharmacology , Growth and Development , Polymorphism, Single Nucleotide , Prolactin/blood , Receptors, Dopamine D2/genetics , Semen/drug effects , Animals , Body Constitution/genetics , Cattle/blood , Cattle/genetics , Cattle/growth & development , Dopamine/blood , Genotype , Growth and Development/drug effects , Growth and Development/genetics , Male , Semen/metabolism , Semen/physiology , Semen Analysis/veterinary , Sperm Motility/drug effects , Sperm Motility/geneticsABSTRACT
The aim of this study was to estimate genetic associations between alternative somatic cell count (SCC) traits and milk yield, composition and udder type traits in Italian Jersey cows. Alternative SCC traits were test-day (TD) somatic cell score (SCS) averaged over early lactation (SCS_150), standard deviation of SCS of the entire lactation (SCS_SD), a binary trait indicating absence or presence of at least one TD SCC >400,000 cells/ml in the lactation (Infection) and the ratio of the number of TD SCC >400,000 cells/ml to total number of TD in the lactation (Severity). Heritabilities of SCC traits, including lactation-mean SCS (SCS_LM), ranged from 0.038 to 0.136. Genetic correlations between SCC traits were moderate to strong, with very few exceptions. Unfavourable genetic associations between milk yield and SCS_SD and Infection indicated that high-producing cows were more susceptible to variation in SCC than low-producing animals. Cows with deep udders, loose attachments, weak ligaments and long teats were more susceptible to an increase of SCC in milk. Overall, results suggest that alternative SCC traits can be exploited to improve cow's resistance to mastitis in Italian Jersey breed.
Subject(s)
Body Composition/genetics , Body Constitution/genetics , Cattle/genetics , Cattle/physiology , Cell Count , Genetic Association Studies , Lactation/genetics , Mammary Glands, Animal/pathology , Milk/cytology , Quantitative Trait, Heritable , Animals , Cattle/anatomy & histology , Female , MastitisABSTRACT
The skin has many important roles in dairy cattle, and skinfold thickness could be used as an indicator of body fat deposition. The objectives of this study were to estimate genetic parameters of skinfold thickness and to explore its association with body condition score (BCS) and milk production traits in a Chinese Holstein population. Skinfold thicknesses over the neck (STN) and the last rib (STR), BCS, and test-day records of milk production traits were available for 6,416 lactating Holstein cows in the summers of 2015 and 2016 in Beijing, China. Multi-trait animal models were used to estimate variance and covariance components using the DMU software. The average STN was 7.15 ± 1.28 mm, and the average STR was 11.76 ± 1.95 mm (mean ± standard deviation). Estimated heritability was 0.13 ± 0.03 for STN and 0.26 ± 0.04 for STR. We detected a high genetic correlation (0.79 ± 0.08; heritability ± standard error) between STN and STR. Genetic correlations between skinfold thickness and BCS were low to moderate: 0.18 between STR and BCS, and 0.33 between STN and BCS. Genetic correlations between skinfold thickness and milk yield, milk fat percentage, and milk protein percentage were negligible, ranging from -0.02 to 0.15. Collectively, skinfold thickness is characterized as a trait with moderate heritability. Skinfold thickness is sensitive to changes in body condition or fat deposition across parities and lactation stages in milking cows, and we confirmed the complementary nature of skinfold thickness and BCS genetically as well as phenotypically by comparing their changing trends throughout lactation and across lactations. The use of skinfold thickness, together with BCS, can assist in the monitoring of changes in body fat deposition to achieve higher management precision.
Subject(s)
Body Constitution/genetics , Cattle/physiology , Milk/chemistry , Skinfold Thickness , Animals , Cattle/genetics , China , Glycolipids/analysis , Glycoproteins/analysis , Lipid Droplets , Milk Proteins/analysisABSTRACT
INTRODUCTION: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly. OBJECTIVE: Considering there has been multiple evidence showing that genetic variation underpins variation of PA-related traits, we aimed to estimate the heritability (h2) of these phenotypes in a sample from the Brazilian population and assess whether males and females differ in relation to those estimates. METHODS: 2,027 participants from a highly admixed population from Baependi, MG, Brazil, had information regarding their PA and sedentary behavior (SB) phenotypes collected through a questionnaire (IPAQ-SF). After data cleaning and transformation procedures, we obtained four variables to be evaluated: total PA (TPA MET), walking time, (WK MET), moderate-vigorous PA (MVPA MET), and SB. A model selection procedure was performed using a single-step covariate inclusion approach. We tested for BMI, waist, hip and neck circumferences, smoking, and depression separately, and performed correlation tests among covariates. Linear mixed models, selection procedure, and the variance components approach to estimate h2 were implemented using SOLAR-Eclipse 8.3.1. RESULTS: We obtained estimates of 0.221, 0.109, 0.226, and 0 for TPA MET, WK MET, MVPA MET, and SB, respectively. We found evidence for gene-sex interactions, with males having higher sex-specific heritabilities than females for TPA MET and MVPA MET. In addition, we found higher estimates of the genetic variance component in males than females for most phenotypes. DISCUSSION/CONCLUSION: The heritability estimates presented in this work show a moderate heritable set of genetic factors affecting PA in a sample from the Brazilian population. The evaluation of the genetic variance component suggests segregating genetic factors in male individuals are more heterogeneous, which can explain why men globally tend to need to practice more intense PA than women to achieve similar health benefits. Hence, these findings have significant implications for the understanding of the genetic architecture of PA and might aid to promote health in the future.
Subject(s)
Exercise , Inheritance Patterns , Models, Genetic , Sedentary Behavior , Sex Characteristics , Body Constitution/genetics , Body Mass Index , Brazil , Depression/genetics , Female , Genetic Association Studies , Genetic Variation , Humans , Male , Phenotype , Population Groups , Self Report , SmokingABSTRACT
According to the Sasang theory, humans can be categorized into one of the four Sasang constitution (SC) types. The four SC types are Tae-Yang (TY), Tae-Eum (TE), So-Yang (SY), and So-Eum (SE), which are determined mainly on the basis of anthropometric characteristics, personality, and the balance of the physiological functions of the major organ systems. There is a growing recognition in the complementary and alternative medicine area that SC types have the potential to be a useful scientific tool for the prevention, diagnosis, and treatment of diseases (Cooper, Evidence Based Complementary and Alternative Medicine, Vol. 6 (Suppl. 1), 2009, pp. 1-3). The main purposes of the present study are to estimate genetic and environmental influences on SC types, and to explore genetic and environmental correlations that affect phenotypic associations among the SC types. In total, 1,742 (365 monozygotic male, 173 dizygotic male, 675 monozygotic female, 271 dizygotic female, and 258 opposite-sex dizygotic) twins (mean age = 19.1 ± 3.1 year) completed a Sasang questionnaire. Univariate and multivariate model-fitting analyses were performed. Total (additive and non-additive) genetic influences were 71% for males and 81% for females in TE, 70% for males and 71% for females in SE, and 47% for both sexes in SY. Non-additive genetic effects were substantial, and shared environmental influences were negligible in most SC types. Multivariate model-fitting analysis revealed that non-additive genetic and individual-specific environmental correlations between TE and SE were -0.92 (95% CI [-0.89, -0.93]) and -0.62 (95% CI [-0.57, -0.68]), respectively. The corresponding estimates were -0.55 (95% CI [-0.48, -0.61]) and -0.44 (95% CI [-0.37, -0.51]) between TE and SY and 0.19 (95% CI [0.09, 0.29]) and -0.40 (95% CI [-0.32, -0.47]) between SE and SY. These results suggest that the phenotypic associations among SC types may be mediated by pleiotropic mechanism of genes.
Subject(s)
Asian People/genetics , Body Constitution/genetics , Environment , Personality/genetics , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Adolescent , Adult , Body Constitution/ethnology , Child , Databases, Factual , Female , Humans , Male , Phenotype , Registries , Republic of Korea , Risk Factors , Young AdultABSTRACT
The objective was to estimate genetic correlations between body weight (BW), scrotal circumference and visual evaluation scores of body conformation measured at standard ages in Guzerat cattle. All measurements were performed at 205 (weaning age), 365, 450 and 550 days of age; for BW, two additional measurements (at birth and 120 days of age) were realized. The data utilized in this study were retrieved from a database of the Brazilian Association of Zebu Breeders that contained information of registered Guzerat animals born between 1970 and 2013. Genetic parameters were estimated in bi-trait analyses by using Bayesian inference. Genetic correlations between BW at 205 and 450 days of age with other traits were high and positive, whereas the correlations between visual evaluation scores with other traits were moderate. Based on correlations herein obtained, we conclude that selection based on BW results in increased visual scores and scrotal circumference, leading to improvements in productive performance and animals with best body conformation.
Subject(s)
Body Constitution/genetics , Body Weight/genetics , Cattle/anatomy & histology , Cattle/genetics , Genetic Association Studies , Scrotum/anatomy & histology , Animals , Bayes Theorem , Cattle/growth & development , Male , Quantitative Trait, HeritableABSTRACT
Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS) and followed replication analysis in Koreans and constitutional subgroups. GWASs in 5,292 individuals of the Korean Genome and Epidemiology Study and replication analyses in 2,567 subjects of the Korea medicine Data Center were performed to identify genetic variants associated with triglyceride (TG) to HDL cholesterol (HDLC), LDL cholesterol (LDLC) to HDLC, and non-HDLC to HDLC ratios. For subgroup analysis, a computer-based constitution analysis tool was used to categorize the constitutional types of the subjects. In the discovery stage, seven variants in four loci, three variants in three loci, and two variants in one locus were associated with the ratios of log-transformed TG:HDLC (log[TG]:HDLC), LDLC:HDLC, and non-HDLC:HDLC, respectively. The associations of the GWAS variants with lipid ratios were replicated in the validation stage: for the log[TG]:HDLC ratio, rs6589566 near APOA5 and rs4244457 and rs6586891 near LPL; for the LDLC:HDLC ratio, rs4420638 near APOC1 and rs17445774 near C2orf47; and for the non-HDLC:HDLC ratio, rs6589566 near APOA5. Five of these six variants are known to be associated with TG, LDLC, and/or HDLC, but rs17445774 was newly identified to be involved in lipid level changes in this study. Constitutional subgroup analysis revealed effects of variants associated with log[TG]:HDLC and non-HDLC:HDLC ratios in both the Tae-Eum and non-Tae-Eum types, whereas the effect of the LDLC:HDLC ratio-associated variants remained only in the Tae-Eum type. In conclusion, we identified three log[TG]:HDLC ratio-associated variants, two LDLC:HDLC ratio-associated variants, and one non-HDLC:HDLC-associated variant in Koreans and the constitutional subgroups.
Subject(s)
Cardiovascular Diseases/genetics , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Genome-Wide Association Study , Metabolic Syndrome/genetics , Triglycerides/blood , Body Constitution/genetics , Cardiovascular Diseases/blood , Cardiovascular Diseases/ethnology , Cholesterol/blood , Cohort Studies , Female , Genetic Variation , Genotype , Humans , Male , Medicine, Korean Traditional , Metabolic Syndrome/blood , Metabolic Syndrome/ethnology , Polymorphism, Single Nucleotide , Regression Analysis , Republic of KoreaABSTRACT
Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics.
Subject(s)
Biological Evolution , Body Constitution/genetics , Human Body , Quantitative Trait, Heritable , Selection, Genetic , Body Constitution/ethnology , Climate , Gene Flow , Genetic Drift , Humans , Male , Phylogeography , Racial GroupsABSTRACT
Facial characteristics, short stature, and skeletal anomalies have been described for the clinical diagnosis of Kabuki Syndrome (KS) in children. However, no studies have investigated body proportions in KS. Knowledge of body proportions in KS may contribute to better insight into the growth pattern and characterization of this genetic disorder. Therefore we compared body proportions of children with KS to normally proportioned controls to investigate if atypical body proportions are part of this genetic disorder. This study was designed and conducted within the setting of the Maastricht University Medical Centre (MUMC+), the official Dutch expert center for Kabuki syndrome. We conducted a cross-sectional study in 32 children (11 children with KS and 21 controls). Body proportions were determined by means of photogrammetric anthropometry, measurements based on digital photography. Body proportions, quantified as body ratios, differ significantly in children with KS from normally proportioned children. Children with KS have larger heads and longer arms proportional to their trunks and have been found to have longer upper arms proportional to their tibia length and feet. Based on deviations in body proportions it was shown possible to discern children with KS from normally proportioned controls.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Body Constitution/genetics , DNA-Binding Proteins/genetics , Face/abnormalities , Hematologic Diseases/diagnosis , Hematologic Diseases/genetics , Neoplasm Proteins/genetics , Vestibular Diseases/diagnosis , Vestibular Diseases/genetics , Abnormalities, Multiple/physiopathology , Anthropometry , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Face/physiopathology , Female , Gene Expression , Hematologic Diseases/physiopathology , Humans , Male , Mutation , Vestibular Diseases/physiopathologyABSTRACT
To include feed-intake-related traits in the breeding goal, accurate estimates of genetic parameters of feed intake, and its correlations with other related traits (i.e., production, conformation) are required to compare different options. However, the correlations between feed intake and conformation traits can vary depending on the population. Therefore, the objective was to estimate genetic correlations between 6 feed-intake-related traits and 7 conformation traits within dairy cattle from 2 countries, the Netherlands (NL) and the United States (US). The feed-intake-related traits were dry matter intake (DMI), residual feed intake (RFI), milk energy output (MilkE), milk yield (MY), body weight (BW), and metabolic body weight (MBW). The conformation traits were stature (ST), chest width (CW), body depth (BD), angularity (ANG), rump angle (RA), rump width (RW), and body condition score (BCS). Feed intake data were available for 1,665 cows in NL and for 1,920 cows in US, from 83 nutritional experiments (48 in NL and 35 in US) conducted between 1991 and 2011 in NL and between 2007 and 2013 in US. Additional conformation records from relatives of the animals with DMI records were added to the database, giving a total of 37,241 cows in NL and 28,809 in US with conformation trait information. Genetic parameters were estimated using bivariate animal model analyses. The model included the following fixed effects for feed-intake-related traits: location by experiment-ration, age of cow at calving modeled with a second order polynomial by parity class, location by year-season, and days in milk, and these fixed effects for the conformation traits: herd by classification date, age of cow at classification, and lactation stage at classification. Both models included additive genetic and residual random effects. The highest estimated genetic correlations involving DMI were with CW in both countries (NL=0.45 and US=0.61), followed by ST (NL=0.33 and US=0.57), BD (NL=0.26 and US=0.49), and BCS (NL=0.24 and US=0.46). The MilkE and MY were moderately correlated with ANG in both countries (0.33 and 0.47 in NL, and 0.36 and 0.48 in US). Finally, BW was highly correlated with CW (0.77 in NL and 0.84 in US) and with BCS (0.83 in NL and 0.85 in US). Feed-intake-related traits were moderately to highly genetically correlated with conformation traits (ST, CW, BD, and BCS) in both countries, making them potentially useful as predictors of DMI.
Subject(s)
Body Constitution/genetics , Cattle/genetics , Eating/genetics , Milk/metabolism , Animal Feed , Animals , Body Weight , Breeding , Cattle/physiology , Feeding Behavior , Female , Lactation , Netherlands , Parity , Phenotype , Pregnancy , United StatesABSTRACT
BACKGROUND: Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types. METHODS: We conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared. RESULTS: We found that the obesity-risk variant in intron 1 of the fat mass and obesity-associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10(-7)), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI. CONCLUSIONS: In summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.
Subject(s)
Body Mass Index , Medicine, Korean Traditional , Obesity/genetics , Phenotype , Somatotypes/genetics , Aged , Body Constitution/genetics , Female , Genome-Wide Association Study/methods , Humans , Male , Middle Aged , Risk FactorsABSTRACT
Despite the economic importance of beef cattle production in Brazil, female reproductive performance, which is strongly associated with production efficiency, is not included in the selection index of most breeding programmes due to low heritability and difficulty in measure. The body condition score (BCS) could be used as an indicator of these traits. However, so far little is known about the feasibility of using BCS as a selection tool for reproductive performance in beef cattle. In this study, we investigated the sources of variation in the BCS of Nellore beef cows, quantified its association with reproductive and maternal traits and estimated its heritability. BCS was analysed using a logistic model that included the following effects: contemporary group at weaning, cow weight and hip height, calving order, reconception together with the weight and scores of conformation and early finishing assigned to calves at weaning. In the genetic analysis, variance components of BCS were estimated through Bayesian inference by fitting an animal model that also included the aforementioned effects. The results showed that BCS was significantly associated with all of the reproductive and maternal variables analysed. The estimated posterior mean of heritability of BCS was 0.24 (highest posterior density interval at 95%: 0.093 to 0.385), indicating an involvement of additive gene action in its determination. The present findings show that BCS can be used as a selection criterion for Nellore females.
Subject(s)
Body Constitution/physiology , Breeding/methods , Cattle/physiology , Meat/standards , Models, Biological , Phenotype , Selection, Genetic , Animals , Bayes Theorem , Body Constitution/genetics , Body Weight/genetics , Brazil , Cattle/genetics , Female , Reproduction/geneticsABSTRACT
Morphological traits often covary within and among species according to simple power laws referred to as allometry. Such allometric relationships may result from common growth regulation, and this has given rise to the hypothesis that allometric exponents may have low evolvability and constrain trait evolution. We formalize hypotheses for how allometry may constrain morphological trait evolution across taxa, and test these using more than 300 empirical estimates of static (within-species) allometric relations of animal morphological traits. Although we find evidence for evolutionary changes in allometric parameters on million-year, cross-species time scales, there is limited evidence for microevolutionary changes in allometric slopes. Accordingly, we find that static allometries often predict evolutionary allometries on the subspecies level, but less so across species. Although there is a large body of work on allometry in a broad sense that includes all kinds of morphological trait-size relationships, we found relatively little information about the evolution of allometry in the narrow sense of a power relationship. Despite the many claims of microevolutionary changes of static allometries in the literature, hardly any of these apply to narrow-sense allometry, and we argue that the hypothesis of strongly constrained static allometric slopes remains viable.
Subject(s)
Evolution, Molecular , Models, Genetic , Animals , Body Constitution/geneticsABSTRACT
UNLABELLED: The concept of Sasang Constitutional Medicine (SCM) has been in existence in Traditional Korean Medicine for more than 100 years. SCM consists of 4 different types; So-Eum (SE), So-Yang (SY), Tae-Eum (TE), and Tae-Yang (TY). In Western medicine, it is more like stratifying individuals according to phenotypic expression. It is of great importance that the Sasang constitution type be evaluated accurately and recognized by the medical communities for prevention, early diagnosis and treatment of cardiovascular diseases (CVD). SUBJECTS AND METHODS: From the Ansung-Ansan prospective cohort study, 10,038 participants were recruited from years 2001-2002. Of 10,038 original participants, 3022 subjects underwent Sasang Constitutional Type (SCT) evaluation. The Cox proportional hazard model was used to predict CVD during the ten year follow-up period. RESULTS: Of 3022 participants, SCT classified into 364 (12%) SE, 1053 (34.8%) SY, 1605 (53.1%) TE, and no TY. Three hundred seventy nine (16%) newly developed CVD during the following period, yielding 10-year cumulative incidence of 160/1000 person. The frequency of CVD within three SCT without metabolic syndrome (MetS) shows 13.4% in SE, 13.6% in SY, and 14.3% in TE, respectively (p=NS). The CVD events were significantly different among the types when MetS was present. The demographic and clinical characteristics revealed the TE group was significantly older, more obese, higher blood pressure, glucose values, and lipid profiles levels. The frequency of MetS and type 2 diabetes mellitus (T2DM) was also higher in TE type than either SE and SY types (all p<0.001). The Cox proportional hazard analysis revealed age, female gender, rural residence, higher ALT level, and lower beta-cell function remain as an independent risk factor, as well as SY with MetS (RR=1.838 (95% CI 1.23-2.74), p=0.003). Furthermore, 10 year CVD survival rate was 86.4% in no MetS group, 83.4% in TE, 79.6% in SE, and 76.4% in SY all with MetS (p<0.001). CONCLUSIONS: The findings from this study suggest MetS increases risk for CVD in certain physical conditions like SY type. Therefore, we would like to suggest that SCT is a strong indicator for CVD.
Subject(s)
Asian People , Body Constitution , Cardiovascular Diseases/diagnosis , Medicine, Korean Traditional , Metabolic Syndrome/diagnosis , Somatotypes , Adult , Asian People/genetics , Body Constitution/genetics , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Cohort Studies , Early Diagnosis , Female , Humans , Incidence , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Middle Aged , Phenotype , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Reproducibility of Results , Republic of Korea/epidemiology , Risk Factors , Somatotypes/geneticsABSTRACT
The first objective of this study was to compare the productive and reproductive performance of Holstein-Friesian (CH HF), Fleckvieh (CH FV), and Brown Swiss (CH BS) cows of Swiss origin with New Zealand Holstein-Friesian (NZ HF) cows in pasture-based compact-calving systems; NZ HF cows were chosen as the reference population for such grazing systems. The second objective was to analyze the relationships within and between breeds regarding reproductive performance, milk yield, and body condition score (BCS) dynamics. On 15 commercial Swiss farms, NZ HF cows were paired with Swiss cows over 3 yr. Overall, the study involved 259 complete lactations from 134 cows: 131 from 58 NZ HF, 40 from 24 CH HF, 43 from 27 CH FV, and 45 from 25 CH BS cows. All production parameters were affected by cow breed. Milk and energy-corrected milk yield over 270 d of lactation differed by 1,000 kg between the 2 extreme groups; CH HF having the highest yield and CH BS the lowest. The NZ HF cows had the greatest milk fat and protein concentrations over the lactation and exhibited the highest lactation persistency. Body weight differed by 90 kg between extreme groups; NZ HF and CH BS being the lightest and CH HF and CH FV the heaviest. As a result, the 2 HF strains achieved the highest milk production efficiency (270-d energy-corrected milk/body weight(0.75)). Although less efficient at milk production, CH FV had a high 21-d submission rate (86%) and a high conception rate within 2 inseminations (89%), achieving high pregnancy rates within the first 3 and 6 wk of the breeding period (65 and 81%, respectively). Conversely, poorer reproductive performance was recorded for CH HF cows, with NZ HF and CH BS being intermediate. Both BCS at nadir and at 100 d postpartum had a positive effect on the 6-wk pregnancy rate, even when breed was included in the model. The BCS at 100 d of lactation also positively affected first service conception rate. In conclusion, despite their high milk production efficiency, even in low-input systems, CH HF were not suited to pasture-based seasonal-calving production systems due to poor reproductive performance. On the contrary, CH FV fulfilled the compact-calving reproduction objectives and deserve further consideration in seasonal calving systems, despite their lower milk production potential.
Subject(s)
Body Constitution/physiology , Cattle/physiology , Dairying/methods , Lactation/physiology , Animals , Body Constitution/genetics , Body Weight , Cattle/genetics , Fats/analysis , Female , Lactation/genetics , Milk/chemistry , Milk Proteins/analysis , Pregnancy , Species SpecificityABSTRACT
The objectives of this research were to estimate genetic parameters for body condition score (BCS) and locomotion (LOC), and to assess their relationships with angularity (ANG), milk yield, fat and protein content, and fat to protein content ratio (F:P) in the Italian Holstein Friesian breed. The Italian Holstein Friesian Cattle Breeders Association collects type trait data once on all registered first lactation cows. Body condition score and LOC were introduced in the conformation scoring system in 2007 and 2009, respectively. Variance (and covariance) components among traits were estimated with a Bayesian approach via a Gibbs sampling algorithm and an animal model. Heritability estimates were 0.114 and 0.049 for BCS and LOC, respectively. The genetic correlation between BCS and LOC was weak (-0.084) and not different from zero; therefore, the traits seem to be genetically independent, but further investigation on possible departures from linearity of this relationship is needed. Angularity was strongly negatively correlated with BCS (-0.612), and strongly positively correlated with LOC (0.650). The genetic relationship of milk yield with BCS was moderately negative (-0.386), and was moderately positive (0.238) with LOC. These results indicate that high-producing cows tend to be thinner and tend to have better locomotion than low-producing cows. The genetic correlation of BCS with fat content (0.094) and F:P (-0.014) was very weak and not different from zero, and with protein content (0.173) was weak but different from zero. Locomotion was weakly correlated with fat content (0.071), protein content (0.028), and F:P (0.074), and correlations were not different from zero. Phenotypic correlations were generally weaker than their genetic counterparts, ranging from -0.241 (BCS with ANG) to 0.245 (LOC with ANG). Before including BCS and LOC in the selection index of the Italian Holstein breed, the correlations with other traits currently used to improve type and functionality of animals need to be investigated.
Subject(s)
Body Constitution/genetics , Cattle/genetics , Lactation/genetics , Locomotion/genetics , Quantitative Trait, Heritable , Animals , Cattle/anatomy & histology , Fats/analysis , Female , Italy , Milk/chemistry , Milk Proteins/analysis , PhenotypeABSTRACT
Understanding how fitness is related to genetic variation is of crucial importance in both evolutionary ecology and conservation biology. We report a study of heterozygosity-fitness correlations in a wild, noninbred population of Zenaida Doves, Zenaida aurita, based on a sample comprising 489 individuals (382 adults and 107 juveniles) typed at 13 microsatellite loci, resulting in a data set comprising 5793 genotypes. In both adults and juveniles, and irrespective of sex, no evidence was found for an effect of either multilocus or single-locus heterozygosity on traits potentially related to fitness such as foraging tactic, competitive ability, and fluctuating asymmetry. In contrast, a significant negative correlation between body condition and multilocus heterozygosity, indicative of outbreeding depression, was found in juveniles, whereas no such trend was observed in adults. However, the frequency distribution of heterozygosity did not differ between the two age classes, suggesting compensatory growth by heterozygous juveniles. We discuss our results in relation to some practical limitations associated with studies of heterozygosity-fitness correlations, and suggest that tropical bird species with allopatric divergence between island populations may provide a good biological model for the detection of outbreeding depression.