RESUMEN
During the second part of the twentieth century, Belyaev selected tame and aggressive foxes (Vulpes vulpes), in an effort known as the "farm-fox experiment", to recapitulate the process of animal domestication. Using these tame and aggressive foxes as founders of segregant backcross and intercross populations we have employed interval mapping to identify a locus for tame behavior on fox chromosome VVU12. This locus is orthologous to, and therefore validates, a genomic region recently implicated in canine domestication. The tame versus aggressive behavioral phenotype was characterized as the first principal component (PC) of a PC matrix made up of many distinct behavioral traits (e.g. wags tail; comes to the front of the cage; allows head to be touched; holds observer's hand with its mouth; etc.). Mean values of this PC for F1, backcross and intercross populations defined a linear gradient of heritable behavior ranging from tame to aggressive. The second PC did not follow such a gradient, but also mapped to VVU12, and distinguished between active and passive behaviors. These data suggest that (1) there are at least two VVU12 loci associated with behavior; (2) expression of these loci is dependent on interactions with other parts of the genome (the genome context) and therefore varies from one crossbred population to another depending on the individual parents that participated in the cross.
Asunto(s)
Conducta Animal , Mapeo Cromosómico/métodos , Zorros/genética , Genética Conductual , Animales , Animales Domésticos , Cruzamientos Genéticos , Predisposición Genética a la Enfermedad , Escala de Lod , Modelos Genéticos , Linaje , Fenotipo , Análisis de Componente Principal , Especificidad de la EspecieRESUMEN
Purebred dogs are a valuable resource for genetic analysis of quantitative traits. Quantitative traits are complex, controlled by many genes that are contained within regions of the genome known as quantitative trait loci (QTL). The genetic architecture of quantitative traits is defined by the characteristics of these genes: their number, the magnitude of their effects, their positions in the genome and their interactions with each other. QTL analysis is a valuable tool for exploring genetic architecture, and highlighting regions of the genome that contribute to the variation of a trait within a population.
Asunto(s)
Perros/genética , Sitios de Carácter Cuantitativo , Caracteres Sexuales , Animales , Cruzamiento , Mapeo Cromosómico , Perros/anatomía & histología , Femenino , Variación Genética , Desequilibrio de Ligamiento , Masculino , FenotipoRESUMEN
Phenotypic stereotypes are traits, often polygenic, that have been stringently selected to conform to specific criteria. In dogs, Canis familiaris, stereotypes result from breed standards set for conformation, performance (behaviors), etc. As a consequence, phenotypic values measured on a few individuals are representative of the breed stereotype. We used DNA samples isolated from 148 dog breeds to associate SNP markers with breed stereotypes. Using size as a trait to test the method, we identified six significant quantitative trait loci (QTL) on five chromosomes that include candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Less well-documented data for behavioral stereotypes tentatively identified loci for herding, pointing, boldness, and trainability. Four significant loci were identified for longevity, a breed characteristic not under direct selection, but inversely correlated with breed size. The strengths and limitations of the approach are discussed as well as its potential to identify loci regulating the within-breed incidence of specific polygenic diseases.
Asunto(s)
Mapeo Cromosómico/veterinaria , Perros/genética , Polimorfismo de Nucleótido Simple , Animales , Conducta Animal , Tamaño Corporal/genética , Cruzamiento , Mapeo Cromosómico/métodos , Perros/anatomía & histología , Perros/clasificación , Perros/psicología , Femenino , Genotipo , Longevidad/genética , Masculino , Sitios de Carácter Cuantitativo , Especificidad de la EspecieRESUMEN
Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pancreatitis.
Asunto(s)
Cruzamiento , Mapeo Cromosómico/veterinaria , Perros/genética , Predisposición Genética a la Enfermedad , Animales , Tamaño Corporal , Perros/crecimiento & desarrollo , Frecuencia de los Genes , Displasia Pélvica Canina/genética , Longevidad/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter CuantitativoRESUMEN
Necropsies and extensive histological evaluation for clinical and sub-clinical disease of approximately three hundred Portuguese Water dogs are available as part of an ongoing study to assess their state of health at end of life. Throughout life these dogs enjoyed a variety of lifestyles and environments. Here we carry out retrospective quantitative assessments of life-time dietary input and physical activity for each dog. To do this, collagens from skull vault bone and from dentine have been analyzed for ratios of stable isotopes to determine differences in diet that individual dogs experienced during late or early life respectively. Robustness of skull bone (weight/unit of skull size) was used as a relative indicator of the amount of physical activity experienced during a dog's lifetime. These environmental parameters were correlated with the frequency and severity of specific disease processes determined at necropsy. Both measures were shown to exert significant low-level (r < 25%) differential effects on specific diseases. The value of retrospective analysis of environmental influences is discussed.
RESUMEN
The discovery of non-random chromosome segregation (Figure 1) is discussed from the perspective of what was known in 1965 and 1966. The distinction between daughter, parent, or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel's laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grandparent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established tissue culture lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al., 1966, 1967; Lark, 1967, 1969a,b,c) the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972) of this discovery.
RESUMEN
A dog model has been used to evaluate histological changes arising from senescence. Autopsies of 145 Portuguese Water Dogs have been used to evaluate the individual and group "state of health" at time of death. For each dog, weights or dimensions of organs or tissues were obtained, together with histological evaluation of tissues. Twenty-three morphological metrics correlated significantly to age at death. Many of these involved muscles; others were associated with derivatives of embryonic foregut. The latter included lengths of the small intestine and trachea as well as weights of the stomach and some lung lobes. Nearly all of the dogs examined had histological changes in multiple tissues, ranging from two to 12 per dog. Associations among pathologies included inflammatory bowel disease with osteoporosis and dental calculus/periodontitis with atherosclerosis and amyloidosis. In addition, two clusters of histological changes were correlated to aging: hyperplasia, frequency of adenomas, and hemosiderosis constituted one group; inflammation, plasmacytic and lymphocytic infiltration, fibrosis, and atrophy, another. Heritability analysis indicated that many of the changes in tissue/organ morphology or histology could be heritable and possibly associated with IGF1, but more autopsies will be required to substantiate these genetic relationships.
Asunto(s)
Envejecimiento/genética , Envejecimiento/patología , Estructuras Animales/patología , Longevidad/genética , Neoplasias/patología , Animales , Autopsia , PerrosRESUMEN
Directional asymmetry (DA) is a characteristic of most vertebrates, most strikingly exhibited by the placement of various organs (heart, lungs, liver, etc.) but also noted in small differences in the metrics of skeletal structures such as the pelvis of certain fish or sauropsids. We have analyzed DA in the skeleton of the fox (V. vulpes), using â¼1,000 radiographs of foxes from populations used in the genetic analysis of behavior and morphology. Careful measurements from this robust data base demonstrate that: 1) DA occurs in the limb bones, the ileum, and ischium and in the mandible; 2) regardless of the direction of the length asymmetry vector of a particular skeletal unit, the vectorial direction of length is always opposite to that of width; 3) with the exception of the humerus and radius, there is no correlation or inverse correlation between vectorial amplitudes or magnitudes of bone asymmetries. 4) Postnatal measurements on foxes demonstrate that the asymmetry increases after birth and continues to change (increasing or decreasing) during postnatal growth. 5) A behavior test for preferential use of a specific forelimb exhibited fluctuating asymmetry but not DA. None of the skeletal asymmetries were significantly correlated with a preferential use of a specific forelimb. We suggest that for the majority of fox skeletal parameters, growth on the right and left side of the fox are differentially biased resulting in fixed differences between the two sides in either the rate of growth or the length of the period during which growth occurs. Random effects around these fixed differences perturb the magnitude of the effects such that the magnitudes of length and width asymmetries are not inversely correlated at the level of individual animals.
Asunto(s)
Huesos/diagnóstico por imagen , Zorros/anatomía & histología , Animales , Huesos de la Extremidad Superior/diagnóstico por imagen , Extremidades/diagnóstico por imagen , Miembro Anterior/diagnóstico por imagen , Zorros/crecimiento & desarrollo , Húmero/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Huesos Pélvicos/diagnóstico por imagen , Pelvis , Radiografía , Radio (Anatomía)/diagnóstico por imagen , Cráneo/diagnóstico por imagenRESUMEN
Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, approximately 30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2-2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in other tetrapod taxa.
RESUMEN
Four erythrocyte variables (erythrocyte count, hemoglobin, mean cell volume, packed cell volume), 14 serum variables (alanine transferase, albumin, alkaline phosphatase, calcium, chloride, cholesterol, creatinine, glucose, phosphorus, potassium, sodium, total protein, triglycerides, urea nitrogen), and 7 venous acid-base variables (base excess, bicarbonate, carbon dioxide partial pressure, oxygen partial pressure, oxygen saturation, pH, and total carbon dioxide) were evaluated for heritability in domestic cats (Felis catus). Values used for individual cats were expressed as the mean over all lifetime measurements, using 444-530 animals for clinical chemistry, 629 animals for acid-base, and 564 animals for erythrocyte metrics. Gender and age at death (where applicable) also were evaluated for correlation with variables. Heritabilities for clinical chemistry, acid-base, and erythrocyte variables ranged, respectively, from 0.13 to 0.78, from 0.23 to 0.59, and from 0.41 to 0.69 (P < 0.05). This result indicates that serum variability has a genetic basis and is segregating in this feline population. These findings may have important implications in both research and clinical medicine.
Asunto(s)
Gatos/sangre , Gatos/genética , Equilibrio Ácido-Base/genética , Factores de Edad , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/genética , Animales , Análisis Químico de la Sangre/veterinaria , Glucemia/genética , Glucemia/metabolismo , Colesterol/sangre , Colesterol/genética , Creatinina/sangre , Índices de Eritrocitos/genética , Índices de Eritrocitos/veterinaria , Femenino , Pruebas Hematológicas/veterinaria , Masculino , Triglicéridos/sangre , Triglicéridos/genéticaRESUMEN
Soybean is trifoliolate, but 4-, 5-, or 6-foliolate leaves have been reported and expression of such multi-foliolate (MF) leaf forms has been shown to be heritable. Here we analyze the genetic complexity of the MF phenotype and the dependence of its expression on the environment. Recombinant inbred (RI) segregants of soybean were grown in different environments. The frequency of plants expressing the MF phenotype as well as the frequency of nodes exhibiting MF leaves varied with both the environment and the RI segregant genotype. Growth chamber experiments supported field observations suggesting that environment (day length, temperature, etc.) at emergence influenced expression of MF during subsequent growth. Marker facilitated analyses of three RI segregant populations identified quantitative trait loci (QTLs) in 17 regions of the soybean genome. These either directly regulated MF phenotype expression, or were involved in interactions with such loci. Loci, identified in one RI population also were identifiable in another, different, RI population. Most of the loci affected both the frequency of plants expressing MF, and the number of nodes on MF plants that expressed the phenotype. However, a few loci differentiated between these two effects. Many loci affected plants in both field experiments, however, a few differentiated between the two environments. Similar patterns were observed for interactions between loci. QTLs regulating the MF phenotype were located in genome regions that also contained QTLs regulating major agronomic traits-e.g. yield, lodging, etc. This suggests that the loci involved regulate plant growth at some over-arching level, controlling multiple phenotypes or traits.
Asunto(s)
Glycine max/crecimiento & desarrollo , Glycine max/genética , Ambiente , Genes Homeobox , Genes de Plantas , Genotipo , Endogamia , Fenotipo , Hojas de la Planta/crecimiento & desarrollo , Sitios de Carácter CuantitativoRESUMEN
The mammalian skeleton presents an ideal system in which to study the genetic architecture of a set of related polygenic traits and the skeleton of the domestic dog (Canis familiaris) is arguably the best system in which to address the relationship between genes and anatomy. We have analyzed the genetic basis for skeletal variation in a population of >450 Portuguese Water Dogs. At this stage of this ongoing project, we have identified >40 putative quantitative trait loci (QTLs) for heritable skeletal phenotypes located on 22 different chromosomes, including the "X." A striking aspect of these is the regulation of suites of traits representing bones located in different parts of the skeleton but related by function. Here we illustrate this by describing genetic variation in postcranial morphology. Two suites of traits are involved. One regulates the size of the pelvis relative to dimensions of the limb bones. The other regulates the shape of the pelvis. Both are examples of trade-offs that may be prototypical of different breeds. For the size of the pelvis relative to limb bones, we describe four QTLs located on autosome CFA 12, 30, 31, and X. For pelvic shape we describe QTLs on autosome CFA 2, 3, 22, and 36. The relation of these polygenic systems to musculoskeletal function is discussed.
Asunto(s)
Huesos/metabolismo , Perros/genética , Variación Genética/genética , Animales , Huesos/anatomía & histología , Mapeo Cromosómico , Cromosomas de los Mamíferos/genética , Perros/anatomía & histología , Genotipo , Ilion/anatomía & histología , Ilion/metabolismo , Isquion/anatomía & histología , Isquion/metabolismo , Pelvis/anatomía & histología , Fenotipo , Sitios de Carácter Cuantitativo/genéticaRESUMEN
Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In females, the haplotype of CFA 15 resulting in small size is dominant. In males, the haplotype for large size is dominant. Females, homozygous at the CHM marker on the X chromosome and homozygous for the large size CFA 15 haplotype are, on average, as large as large males. However, all females that are heterozygous at the CHM marker are small, regardless of their CFA 15 genotype. This interaction suggests a genetic mechanism that in turn leads to a scenario for the evolution of size sexual dimorphism consistent with a proposal of Lande that sexual dimorphism can evolve because females secondarily become smaller than males as a consequence of natural selection for optimal size. Our results also can explain Rensch's Rule, which states that size is often positively correlated with the level of size sexual dimorphism.
Asunto(s)
Tamaño Corporal/genética , Cromosomas de los Mamíferos/genética , Perros/genética , Cromosoma X/genética , Animales , Femenino , Genotipo , Haplotipos , Factor I del Crecimiento Similar a la Insulina/genética , Masculino , Fenotipo , Sitios de Carácter Cuantitativo/genética , Factores SexualesRESUMEN
In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint. A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxity. A significant directed asymmetry was observed, such that greater laxity was observed in the left than the right hip. This asymmetry was not heritable. However, the average Norberg angle was highly heritable as were the Norberg angles of either the right or left hips. After correction for pedigree effects, two QTLs were identified using the metrics of the left and right hips as separate data sets. Both are on canine chromosome 1 (CFA1), separated by about 95 Mb. One QTL, associated with the SSR marker FH2524 was significant for the left, but not the right hip. The other, associated with FH2598, was significant for the right but not the left hip. For both QTLs, some extreme phenotypes were best explained by specific interactions between haplotypes.
Asunto(s)
Displasia Pélvica Canina/genética , Sitios de Carácter Cuantitativo/genética , Algoritmos , Animales , Cromosomas de los Mamíferos/genética , Perros , Marcadores Genéticos , Genotipo , Displasia Pélvica Canina/patología , Articulación de la Cadera/patología , Modelos Genéticos , Linaje , Fenotipo , Mapeo de Híbrido por RadiaciónRESUMEN
Evolution of mammalian skeletal structure can be rapid and the changes profound, as illustrated by the morphological diversity of the domestic dog. Here we use principal component analysis of skeletal variation in a population of Portuguese Water Dogs to reveal systems of traits defining skeletal structures. This analysis classifies phenotypic variation into independent components that can be used to dissect genetic networks regulating complex biological systems. We show that unlinked quantitative trait loci associated with these principal components individually promote both correlations within structures (e.g., within the skull or among the limb bones) and inverse correlations between structures (e.g., skull vs. limb bones). These quantitative trait loci are consistent with regulatory genes that inhibit growth of some bones while enhancing growth of others. These systems of traits could explain the skeletal differences between divergent breeds such as Greyhounds and Pit Bulls, and even some of the skeletal transformations that characterize the evolution of hominids.