Physiological genomics最新文献

{"title":"Association of SNP-SNP interactions of surfactant protein genes with severity of respiratory syncytial virus infection in children.","authors":"Chintan K Gandhi, Lynnlee C Depicolzuane, Chixiang Chen, Catherine M Roberts, Natalie Sicher, Katelyn Johnson Wegerson, Neal J Thomas, Rongling Wu, Joanna Floros","doi":"10.1152/physiolgenomics.00045.2024","DOIUrl":"10.1152/physiolgenomics.00045.2024","url":null,"abstract":"<p><p>The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of <i>SFTP</i> genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of <i>SFTPA2</i>, and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either <i>SFTPA1</i> or <i>SFTPA2</i>. All interactions were intergenic except one, among SNPs of <i>SFTPA1</i>. The remaining interactions were either among SNPs of hydrophilic SPs alone (<i>n</i> = 8) or among SNPs of both hydrophilic or hydrophobic SPs (<i>n</i> = 11). Our findings indicate that SNPs of all <i>SFTP</i>s may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of <i>SFTPA1</i> and/or <i>SFTPA2</i> SNPs in these interactions underscores their significance in RSV severity.<b>NEW & NOTEWORTHY</b> Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of <i>SFTPA1</i> and <i>SFTPA2</i> SNPs. This highlights the comprehensive role of all SPs in genetic susceptibility to RSV severity, shedding light on potential avenues for targeted interventions.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Podocyte cell-specific <i>Npr1</i> is required for blood pressure and renal homeostasis in male and female mice: role of sex-specific differences.","authors":"Chandramohan Ramasamy, Kandasamy Neelamegam, Samivel Ramachandran, Huijing Xia, Daniel R Kapusta, Farhad R Danesh, Kailash N Pandey","doi":"10.1152/physiolgenomics.00137.2023","DOIUrl":"10.1152/physiolgenomics.00137.2023","url":null,"abstract":"<p><p>Atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase A/natriuretic peptide receptor A (GC-A/NPRA), stimulating natriuresis and diuresis and reducing blood pressure (BP), but the role of ANP/NPRA signaling in podocytes (highly specialized epithelial cells covering the outer surfaces of renal glomerular capillaries) remains unclear. This study aimed to determine the effect of conditional deletion of podocyte-specific <i>Npr1</i> (encoding NPRA) gene knockout (KO) in male and female mice. Tamoxifen-treated wild-type control (PD <i>Npr1</i> f/f; WT), heterozygous (PD-Cre-<i>Npr1</i> f/+; HT), and KO (PD-Cre-<i>Npr1</i> f/-) mice were fed a normal-, low-, or high-salt diet for 4 wk. Podocytes isolated from HT and KO male and female mice showed complete absence of <i>Npr1</i> mRNA and NPRA protein compared with WT mice. BP, plasma creatinine, plasma sodium, urinary protein, and albumin/creatinine ratio were significantly increased, whereas plasma total protein, albumin, creatinine clearance, and urinary sodium levels were significantly reduced in the HT and KO male and female mice compared with WT mice. These changes were significantly greater in males than in females. On a normal-salt diet, glomerular filtration rate was significantly decreased in PD <i>Npr1</i> HT and KO male and female mice compared with WT mice. Immunofluorescence of podocin and synaptopodin was also significantly reduced in HT and KO mice compared with WT mice. These observations suggest that in podocytes, ANP/NPRA signaling may be crucial in the maintenance and regulation of glomerular filtration and BP and serve as a biomarker of renal function in a sex-dependent manner.<b>NEW & NOTEWORTHY</b> Our results demonstrate that the podocyte-specific deletion of <i>Npr1</i> showed increased blood pressure (BP) and altered biomarkers of renal functions, with greater magnitudes in animals fed a high-salt diet in a sex-dependent manner. The results suggest a direct and sex-dependent effect of <i>Npr1</i> ablation in podocytes on the regulation of BP and renal function and reveal that podocytes may be considered an important target for the ANP-BNP/NPRA/cGMP signaling cascade.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gill ionocyte remodeling mediates blood pH regulation in rockfish (<i>Sebastes diploproa</i>) exposed to environmentally relevant hypercapnia.","authors":"Garfield T Kwan, Alexander M Clifford, Kaelan J Prime, Till S Harter, Martin Tresguerres","doi":"10.1152/physiolgenomics.00057.2024","DOIUrl":"10.1152/physiolgenomics.00057.2024","url":null,"abstract":"<p><p>Marine fishes excrete excess H⁺ using basolateral Na⁺-K⁺-ATPase (NKA) and apical Na⁺/H⁺ exchanger 3 (NHE3) in gill ionocytes. However, the mechanisms that regulate H⁺ excretion during exposure to environmentally relevant hypercapnia (ERH) remain poorly understood. Here, we explored transcriptomic, proteomic, and cellular responses in gills of juvenile splitnose rockfish (<i>Sebastes diploproa</i>) exposed to 3 days of ERH conditions (pH ∼7.5, ∼1,600 μatm Pco₂). Blood pH was fully regulated at ∼7.75 despite a lack of significant changes in gill <i>1</i>) mRNAs coding for proteins involved in blood acid-base regulation, <i>2</i>) total NKA and NHE3 protein abundance, and <i>3</i>) ionocyte density. However, ERH-exposed rockfish demonstrated increased NKA and NHE3 abundance on the ionocyte plasma membrane coupled with wider apical membranes and greater extension of apical microvilli. The observed gill ionocyte remodeling is consistent with enhanced H⁺ excretion that maintains blood pH homeostasis during exposure to ERH and does not necessitate changes at the expression or translation levels. These mechanisms of phenotypic plasticity may allow fishes to regulate blood pH during environmentally relevant acid-base challenges and thus have important implications for both understanding how organisms respond to climate change and for selecting appropriate metrics to evaluate its impact on marine ecosystems.<b>NEW & NOTEWORTHY</b> Splitnose rockfish exposed to environmentally relevant hypercapnia utilize existing proteins (rather than generate additional machinery) to maintain homeostasis.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A matter of food and substrain: obesogenic diets induce differential severity of cardiac remodeling in C57Bl/6J and C57Bl/6N substrains.","authors":"Lorena Cascarano, Hrag Esfahani, Pierre Michel, Caroline Bouzin, Chantal Dessy, Jean-Luc Balligand, Lauriane Y M Michel","doi":"10.1152/physiolgenomics.00044.2024","DOIUrl":"10.1152/physiolgenomics.00044.2024","url":null,"abstract":"<p><p>The prevalence of metabolic syndrome in cardiac diseases such as heart failure with preserved ejection fraction (HFpEF) prompts the scientific community to investigate its adverse effects on cardiac function and remodeling. However, the selection of a preclinical model of obesity-induced cardiac remodeling has proven more challenging with inconsistencies often found in very similar mouse models. Here, we investigated the implication of genetic background as well as diet composition to identify a suitable model of diet-induced cardiac alterations. C57Bl/6J and C57Bl/6N male mice were subjected to distinct obesogenic diets consisting of high-fat and moderate sucrose content (HF-S) or high-sucrose and moderate lipid content (F-HS) versus matching control diets. Five-month dietary intervention with obesogenic diets induced weight gain, adipocyte hypertrophy, and increased visceral and subcutaneous fat mass in both substrains. Obese mice showed similar impairment of glucose disposition and insulin tolerance, with both strains developing insulin resistance within 2 mo. However, echocardiographic follow-up and histological analysis confirmed that the HF-S diet increased cardiac hypertrophy, interstitial fibrosis, and left atrial area in the C57Bl/6J strain only. In contrast, the C57Bl/6N strain exhibited cardiac eccentric remodeling under control diets, possibly owing to a genetic mutation in the myosin light chain kinase 3 (<i>Mylk3</i>) gene, specific to this substrain, which was not further enhanced under obesogenic diets. Altogether, the present results highlight the importance of carefully selecting the suitable mouse strain and diets to model diet-induced cardiac remodeling. In this regard, C57Bl/6J mice develop significant cardiac remodeling in response to HF-S and seem to be a suitable model for cardiometabolic disease.<b>NEW & NOTEWORTHY</b> Metabolic syndrome is highly prevalent in cardiac pathologies. Underlying mechanisms have not been thoroughly investigated, owing to the lack of reliable preclinical model of diet-induced cardiac remodeling. Our work demonstrates that genetic variants in inbred strains influence the response to metabolic stress and identifies C57Bl/6J mice as a suitable model for cardiometabolic disease in response to high-fat diet. These findings reinforce the need to carefully select the mouse strain in relation to the imposed pathophysiologic stress.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redistribution of SOD3 expression due to R213G polymorphism affects pulmonary interstitial macrophage reprogramming in response to hypoxia.","authors":"Caitlin V Lewis, Anastacia M Garcia, Samuel D Burciaga, Janelle N Posey, Mariah Jordan, Thi-Tina N Nguyen, Kurt R Stenmark, Claudia Mickael, Christina Sul, Cassidy Delaney, Eva S Nozik","doi":"10.1152/physiolgenomics.00078.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00078.2024","url":null,"abstract":"<p><p>The extracellular isoform of superoxide dismutase (SOD3) is decreased in patients and animals with pulmonary hypertension (PH). The human R213G single nucleotide polymorphism (SNP) in SOD3 causes its release from tissue extracellular matrix (ECM) into extracellular fluids, without modulating enzyme activity, increasing cardiovascular disease risk in humans and exacerbating chronic hypoxic PH in mice. Given the importance of interstitial macrophages (IM) to PH pathogenesis, this study aimed to determine whether R213G SOD3 increases IM accumulation and alters IM reprogramming in response to hypoxia. R213G mice and wild-type (WT) controls were exposed to hypobaric hypoxia for 4 or 14 days compared to normoxia. Flow cytometry demonstrated a transient increase in IMs at day 4 in both strains. Contrary to our hypothesis, the R213G SNP did not augment IM accumulation. To determine strain differences in the IM reprogramming response to hypoxia, we performed RNAsequencing on IMs isolated at each time point. We found that IMs from R213G mice exposed to hypoxia activated ECM-related pathways and a combination of alternative macrophage and proinflammatory signaling. Furthermore, when compared to WT responses, IMs from R213G mice lacked metabolic remodeling and demonstrated a blunted anti-inflammatory response between the early (day 4) and later (day 14) time points. We confirmed metabolic responses using Agilent Seahorse assays whereby WT, but not R213G, IMs upregulated glycolysis at day 4 that returned to baseline at day 14. Finally, we identify differential regulation of several redox-sensitive upstream regulators that could be investigated in future studies.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise and tumor proteome: Insights from a neuroblastoma model.","authors":"Abel Plaza-Florido, Beatriz G Gálvez, Juan A López, Alejandro Santos-Lozano, Sandra Zazo, Cecilia Rincón-Castanedo, Asunción Martín-Ruiz, Jorge Lumbreras, Laura C Terron-Camero, Alejandro López-Soto, Eduardo Andrés-León, África González-Murillo, Federico Rojo, Manuel Ramírez, Alejandro Lucia, Carmen Fiuza-Luces","doi":"10.1152/physiolgenomics.00064.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00064.2024","url":null,"abstract":"<p><strong>Background/aim: </strong>The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB).</p><p><strong>Methods: </strong>Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level.</p><p><strong>Results: </strong>Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression.</p><p><strong>Conclusion: </strong>Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes in gene expression of growing nonhuman primate antral follicles.","authors":"Catherine A VandeVoort, Charles L Chaffin, Peter Z Schall, Keith E Latham","doi":"10.1152/physiolgenomics.00023.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00023.2024","url":null,"abstract":"<p><p>The growth of the ovarian antral follicle is a complex process that is difficult to study, especially in human and nonhuman primates. Understanding the antral stage of development is key to new approaches to regulating reproduction. This study analyzed cohorts of three sizes of developing antral follicles obtained from adult rhesus macaque females using RNA sequencing of oocytes and cumulus and granulosa cells. The overall objective of this study was to identify key developmental changes in gene expression in oocytes, granulosa, and cumulus cells, as nonhuman primate antral stage follicles transition through progressively larger sizes in the absence of exogenous hormonal stimulation. Only a relatively small number of genes displayed altered mRNA expression levels in any of the three cell types during this period. Most of the identified differentially expressed genes (DEGs) decreased in the granulosa cells or increased in the cumulus cells. Although the number of DEGs observed was small, these DEGs indicate predicted effects on distinct upstream regulators in the cumulus and granulosa cells. This study is particularly important because it shows for the first time the gene expression changes during antral follicle growth in a medically relevant model.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of shared and disease-specific intratumoral microbiome-host gene associations in gastrointestinal tumors.","authors":"Jing Liu, Hongyan Wang, Shuai Zhang, Jinyang Liu","doi":"10.1152/physiolgenomics.00036.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00036.2024","url":null,"abstract":"<p><p>Intratumoral microbiota and host genes interact to promote gastrointestinal disorders, but how the two interact to influence host tumorigenesis remains unclear. Here, we utilized a machine learning-based framework to jointly dissect the paired intratumoral microbiome and host transcriptome profiles in patients with colon adenocarcinoma, hepatocellular carcinoma, and gastric cancer. We identified associations between intratumoral microbes and host genes that depict shared as well as cancer type-specific patterns. We found that a common set of host gene and pathways implicated in cell proliferation and energy metabolism are associated with cancer type-specific intratumoral microbes. Additionally, we also found that intratumoral microbes that have been implicated in three gastrointestinal tumors, such as <i>Lachnoclostridium</i>, are correlated with different host pathways in each tumor, indicating that similar microbes can influence host tumorigenesis in a cancer type-specific manner by regulation of different host genes. Our study reveals patterns of association between intratumoral microbiota and host genes in gastrointestinal tumors, providing new insights into the biology of gastrointestinal tumors.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the anti-inflammatory drug budesonide on the gut microbiota and cytokine production of 13-lined ground squirrels during pre-hibernation fattening","authors":"Kirsten Grond, Jewel Zur Tulod, Courtney C. Kurtz, Khrystyne N Duddleston","doi":"10.1152/physiolgenomics.00034.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00034.2024","url":null,"abstract":"Physiological Genomics, Ahead of Print. <br/>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping.","authors":"Panagiota Kyratzi, Oswald Matika, Amey H Brassington, Connie E Clare, Juan Xu, David A Barrett, Richard D Emes, Alan L Archibald, Andras Paldi, Kevin D Sinclair, Jonathan Wattis, Cyril Rauch","doi":"10.1152/physiolgenomics.00049.2024","DOIUrl":"10.1152/physiolgenomics.00049.2024","url":null,"abstract":"<p><p>Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic Informational Field Theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Whilst GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in <i>ovis aries</i> related to bone growth (Dataset-1) and to a series of linked metabolic and epigenetic pathways (Dataset-2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}