Quantitative translation of dog-to-human aging by conserved remodeling of the DNA methylome
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE146920 | GEO | 2020/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
2022-08-12 | PXD034449 | Pride
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
2022-08-12 | PXD033420 | Pride
Project description:Diverse dataset of 1247 dogs from many breeds and wolves used to investigate the origins of dog domestication
2014-11-20 | GSE63439 | GEO
Project description:Through thousands of years of breeding and strong human selection, the dog (Canis lupus familiaris) exists today within hundreds of closed populations throughout the world, each with defined phenotypes. A singular geographic region with broad diversity in dog breeds presents an interesting opportunity to observe potential mechanisms of breed formation. Italy claims 14 internationally recognized dog breeds, with numerous additional local varieties. To determine the relationship among Italian dog populations, we integrated genetic data from 263 dogs representing 23 closed dog populations from Italy, seven Apennine gray wolves. Using 142,840 genome-wide SNPs, this dataset was used in the identification of breed development routes for the Italian breeds that included divergence from common populations for a specific purpose, admixture of regional stock with that from other regions, and isolated selection of local stock with specific attributes.
2018-10-10 | GSE121027 | GEO
Project description:We used buccal samples from two different dog breeds with well established differences in average lifespan to perform genome-scale identification of ageing-associated differentially methylated positions (aDMPs) in a total of 48 different dogs. A significant proportion of aDMPs that gained methylation with age replicated in an independent cohort. Furthermore, we also show that human aDMPs show similar ageing-associated dynamics at the homologous genomic regions in the dog. The replicated aDMPs show a faster rate of change with age in the shorter lived dog species. Strikingly, these aDMPs also show a faster rate of change with age in dogs overall compared with humans.
2018-01-17 | GSE86058 | GEO
Project description:Dogs are commonly used models of human inherited retinal disorders. Because the dog retina contains a macula-like region, dogs are susceptible to maculopathies with many shared genetic etiologies with humans. Human macular gene expression has been characterized and provides insight into the underlying basis of macular disease. We sought to compare macular gene expression profiles in dogs and humans and interrogate macular disease-associated genes for differential expression between macula and periphery. RNA sequencing was performed on 8mm samples of the dog macular region and superior peripheral region, sampling retina and retinal pigmented epithelium/choroid separately. Read sequences were mapped to CanFam3.1 and raw read counts were analyzed to determine significantly differentially expressed genes between macula and periphery within each tissue. A similar analytic pipeline was used with a published dataset of human samples to allow direct dog/human comparisons. Pathways and processes involved in significantly DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery. Dogs and humans shared the extent and direction of macular retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. There were fewer similarities between dog and human in the supporting tissues of the retina (the RPE, choroid, sclera). Many genes implicated in heritable retinal and macular disorders in both dogs and humans were differentially expressed between macula and periphery. Approximately 2/3 of genes associated with human age-related macular degeneration were differentially expressed in at least one human tissue, whereas approximately half were differentially expressed in at least one dog tissue. This work underpins the dog macular retinal region as analogous to the human macula in terms of differential gene expression. Whilst age-related maculopathy has not been described in dogs, evidence supports the study of aging of the macula and susceptibility to age-associated pathology in dogs.
2024-07-25 | GSE227619 | GEO
Project description:Dog platelets were isolated and stimulated from 10 different dogs and protein quantiattaion was done based on LFQ.
2021-09-08 | PXD015935 | Pride
Project description:Diverse dataset of 1247 dogs from many breeds and wolves used to investigate the origins of dog domestication DNA for 1228 dogs from 35 breeds and 19 wolves was extracted from whole blood samples and genotyped on the Affymetrix Canine v2 Arrays. Genotypes were called using Affymetrix's snp5-probeset-genotype software and the BRLMM-P calling algorithm. The included breed designations are owner reported.
2014-11-20 | E-GEOD-63439 | biostudies-arrayexpress
Project description:Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1-3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. We use genome wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). Two different case-only variants targeted the same approximately 500-bp highly conserved regulatory element between the cadherin genes CDH2 and DSC3. We functionally test these variants in a human neuroblastoma cell line and show that they cause significant changes in gene expression, likely due to disrupted transcription factor binding. This work demonstrates how we can use the unique genetics of dog breeds, and mechanistic similarities between human and dog diseases, to find genes and regulatory pathways underlying complex psychiatric disorders.
2013-12-20 | GSE53488 | GEO
Project description:Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1-3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. We use genome wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). Two different case-only variants targeted the same approximately 500-bp highly conserved regulatory element between the cadherin genes CDH2 and DSC3. We functionally test these variants in a human neuroblastoma cell line and show that they cause significant changes in gene expression, likely due to disrupted transcription factor binding. This work demonstrates how we can use the unique genetics of dog breeds, and mechanistic similarities between human and dog diseases, to find genes and regulatory pathways underlying complex psychiatric disorders. Affymetrix SNP arrays were performed according to the manufacturer's directions. Genome wide association analysis was performed for 87 doberman pinshcers OCD cases and 63 breed-matched controls.
2013-12-20 | E-GEOD-53488 | biostudies-arrayexpress