Biomedical subjects

T R Famula

Publications and source records attributed to T R Famula.

At least 19 recordsLinked to original sources

PubMed2006

Genetic evaluation of Addison's disease in the Portuguese Water Dog.

BACKGROUND: Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. RESULTS: The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (+/- 0.16); there were no differences in risk for disease across sexes (p > 0.49). Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. CONCLUSION: The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

Addison Disease↗

PubMed2006

Meta-analysis of factors affecting carcass characteristics of feedlot steers.

A meta-analysis was conducted to assess the effects of biological type (early-moderate or late maturity) and implant status (estrogenic, combination, or nonimplanted; repeats included) on HCW (kg); LM area (cm2); 12th-rib fat thickness (fat thickness, cm); KPH (%), and intramuscular fat (%) at harvest, to provide inputs to an ongoing program for modeling beef cattle growth and carcass quality. Forty-three publications from 1982 to 2004 with consistent intramuscular fat data were evaluated. Two studies were undertaken: 1) with fat thickness as a covariate and 2) with BW as a covariate. The intercept-slope covariance estimate was not statistically different from 0 for LM area (P = 0.11), KPH (P = 0.19), and intramuscular fat (P = 0.74) in study 1, and for LM area (P = 0.44), fat thickness (P = 0.11), KPH (P = 0.19), and intramuscular fat (P = 0.74) in study 2; therefore, a reduced model without a covariance component was fitted for these carcass characteristics. A covariance component was fitted for HCW (P = 0.01, study 1 and P = 0.05, study 2) and for intramuscular fat (P = 0.05, study 2). In study 1, the results for maturity indicated differences between early-moderate and late maturity for HCW (P < 0.01) and LM area (P < 0.01) but no differences for KPH (P = 0.26) and intramuscular fat (P = 0.50); for implant status, an estrogenic or combination implant increased HCW by 2.9% (P = 0.27) or 4.8% (P < 0.01), increased LM area by 3.2% (P = 0.23) or 6.3% (P < 0.01), decreased intramuscular fat by 8.1% (P < 0.01) or 5.4% (P < 0.01), respectively, and decreased KPH by 7.6% (P = 0.34) for estrogenic implants but increased KPH by 1.1% (P = 0.36) for combination implants, compared with nonimplanted steers. In study 2, the results at 600 kg of BW for implant status (implant or nonimplant) indicated no differences for HCW (P = 0.63) and LM area (P = 0.73), but there were differences for fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular fat (P < 0.01); the results for maturity (early-moderate or late maturity) indicated no differences for HCW (P = 0.94), but there were differences for LM area (P < 0.01), fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular fat (P < 0.01). The difference between early-moderate and late maturity (studies 1 and 2) confirmed that frame size accounts for a substantial portion of the variation in carcass composition. Studies 1 and 2 also indicate that implant status had significant effects on carcass quality.

Animals↗

PubMed2005

Meiotic instability of chicken ultra-long telomeres and mapping of a 2.8 megabase array to the W-sex chromosome.

The objective of this research was to study the meiotic stability of a subset of chicken telomere arrays, which are the largest reported for any vertebrate species. Inheritance of these ultra-long telomere arrays (200 kb to 3 mb) was studied in a highly homozygous inbred line, UCD 003 (F >or= 99.9). Analysis of array transmission in four families indicated unexpected heterogeneity and non-Mendelian segregation including high-frequency-generation of novel arrays. Additionally, the largest array detected (2.8 Mb) was female-specific and correlated to the most intense telomeric DNA signal on the W-sex chromosome by fluorescence in situ hybridization (FISH). These results are discussed in regard to the potential functions of the ultra-long telomere arrays in the chicken genome including generation of genetic variation through enhanced recombination, protection against erosion by providing a buffer for gene-dense regions, and sex-chromosome organization.

Animals↗

PubMed2005

Inheritance of resistance to Xylella fastidiosa within a Vitis rupestris x Vitis arizonica hybrid population.

The inheritance of resistance to Xylella fastidiosa (Xf), the bacterium which causes Pierce's disease (PD) in grapevines, was evaluated within a factorial mating design consisting of 16 full-sib families with resistance derived from Vitis arizonica interspecific hybrids. Measurements of disease progression under greenhouse conditions were based on quantitative assessment of Xf populations in stem tissues and on three phenotypic scores: leaf scorch, a cane maturation index (CMI) and an index that incorporated shoot stunting into the cane maturation index (CMSSI). Measurement of bacterial populations yielded the highest broad-sense heritability for resistance on a genotype mean basis (0.97), indicating that this measure of resistance was the least effected by environmental variation. Narrow-sense heritability of PD resistance was moderately high and measured 0.52, 0.60, 0.63 and 0.37 for Xf populations, CMI scores, CMSSI scores and leaf scorch values, respectively. Complex segregation analysis using the computer program Statistical Analysis for Genetic Epidemiology (SAGE: ) strongly indicated the existence of a major gene for PD resistance, which accounted for 91% of the total genetic variance. Conversion of the quantitative data into qualitative resistance levels and evaluation via a chi-square analysis showed that 15 of the 16 families segregated in accordance with a single gene hypothesis with a dominant allele controlling PD resistance. These data indicate that the trait should be relatively easy to pass on from parents to progeny in a breeding program for the development of PD-resistant grape cultivars, particularly when selection is based on cane maturation scores or stem Xf populations.

Breeding↗

PubMed2005

Uveodermatologic (VKH-like) syndrome in American Akita dogs is associated with an increased frequency of DQA1*00201.

The Akita breed of dog is affected by a number of distinct immune-mediated diseases, including thyroiditis, sebaceous adenitis, pemphigus foliaceus, uveitis, polyarthritis, myasthenia gravis, and uveodermatologic (UV) syndrome. UV syndrome is manifested by progressive uveitis and depigmenting dermatitis that closely resembles the human Vogt - Koyanagi - Harada syndrome. This study examined the allelic diversity of the three DLA class II loci (DRB1, DQA1, and DQB1) in the American Akita dog, and the relationship of specific DLA class II alleles to the UV. Low allelic variation was demonstrated within genes of DLA class II. American Akita dogs possessed six of the reported 16 DQA1 alleles, but only eight of 61 reported alleles in DRB1 and nine of 47 reported alleles in DQB1. Almost one-half of American Akita dogs were homozygous for a single allele at DQA1 and up to a quarter at DRB1 and DQB1. DLA-DQA1*00201 was associated with a significantly higher relative risk (RR = 15.3) or odds ratio (OR = 15.99) for UV syndrome than other DLA class II alleles. No significant association was noted with haplotypes of DRB1, DQB1, and DQA1 alleles; DRB1*03201-DQA1*00201 trended toward significance. This study confirmed loss of DLA genetic diversity in the American Akita dog in common with other pure breeds of dog and suggested a role for certain DLA class II gene alleles in the pathogenesis of UV.

Alleles↗

PubMed2005

Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development.

Linear bone growth depends upon proliferation, maturation, and apoptosis of growth plate chondrocytes, processes regulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I). To investigate the contribution of GH, IGF-I and apoptosis to growth plate function, the expression of GH receptor (GHR) and IGF-I receptor (IGF-IR) mRNA were evaluated by in situ hybridization in fractionated costochondral growth plates of growing rats (at 2, 4, and 7 weeks). Apoptosis was determined by TUNEL assay and morphology in histological sections. GHR mRNA was greatest in resting cells with hypertropic cells increasing GHR expression with increasing age. Hypertropic and resting cell IGF-IR mRNA declined over the ages studied. Receptor mRNA expression was altered by exposing cells to GH or IGF-I. GH and IGF significantly decreased GHR mRNA in proliferative cells. GH and IGF also decreased IGF-IR mRNA in resting cells and the 2- and 4-week-old proliferative and hypertropic cells. Treating cells in culture with GH increased the number of apoptotic cells across all ages and zones. Histologically, apoptotic cells were observed at the chondro-osseous junction and within actively proliferating chondrocytes but not in resting cells. Apoptosis was highest at 4 weeks of age with lateral regions displaying the greatest number of cells undergoing apoptosis. These data indicate that apoptosis plays a role in growth plate function, particularly spatial configuration as indicated by the preferential lateral cell apoptosis. The susceptibility of proliferative cells to GHR and IGF-IR down regulation during the period of greatest apoptosis supports a role for the GH-IGF axis in both proliferation and apoptosis during growth plate development.

Animals↗

PubMed2004

Evidence of increased substrate availability to in vitro-derived bovine foetuses and association with accelerated conceptus growth.

Changes in placental development have been associated with foetal abnormalities after in vitro embryo manipulations. This study was designed to investigate bovine conceptus development and substrate levels in plasma and fluids in in vivo- and in vitro-produced (IVP) concepti and neonates. In vivo-produced and IVP embryos were derived by established embryo production procedures. Pregnant animals from both groups were slaughtered on days 90 or 180 of gestation, or allowed to go to term. Conceptus and neonatal physical traits were recorded; foetal, maternal and neonatal blood, and foetal fluids were collected for the determination of blood and fluid chemistry, and glucose, fructose and lactate concentrations. Placental transcripts for specific glucose transporters were determined by quantitative RT-PCR. No significant differences in uterine and conceptus traits were observed between groups on day 90. On day 180, larger uterine, placental and foetal weights, and an increase in placental gross surface area (SA) in IVP pregnancies were associated with increased glucose and fructose accumulation in foetal plasma and associated fluids, with no differences in the expression of components of the glucose transporter system. Therefore, the enlarged placental SA in IVP pregnancies suggests an increase in substrate uptake and transport capacity. Newborn IVP calves displayed higher birth weights and plasma fructose concentrations soon after birth, findings which appeared to be associated with clinical and metabolic distress. Our results indicated larger concepti and increased placental fructogenic capacity in mid- to late IVP pregnancies, features which appeared to be associated with an enhanced substrate supply, potentially glucose, to the conceptus.

Animals↗

PubMed2004

Heritability and segregation analysis of deafness in U.S. Dalmatians.

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Animals↗

PubMed2003

Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle.

The heritability of hypoadrenocorticism (Addison's disease) was evaluated in 778 standard poodles with known Addisonian phenotypes. Addisonian status was confirmed clinically by adrenocorticotropic hormone (ACTH) challenge and 8.6 per cent of the poodles enrolled in the study were classified as being Addisonian. Hypoadrenocorticism affected both sexes with equal probability (P > 0.1). The most common coat colours had a negligible effect on the incidence of hypoadrenocorticism (P > 0.09), although red coat colour had a significant impact on the disease, probably due to the relatively small numbers of dogs with that coat colour. The heritability of hypoadrenocorticism in the standard poodle was estimated to be 0.75. Complex segregation analyses suggested that hypoadrenocorticism in the breed is influenced by an autosomal recessive locus. Clarification of both the heritability and mode of inheritance of hypoadrenocorticism in the standard poodle allows for better-informed breeding decisions.

Adrenal Insufficiency↗

PubMed2002

Growth of Holstein calves from birth to 90 days: the influence of dietary zinc and BLAD status.

The main objective of this study was to describe Holstein neonatal growth and development as influenced by dietary zinc supplementation and the CD18 genotype, both of which may affect immune competence. Holstein calves (n = 421), after being fed colostrum, were brought to a calf facility, randomly assigned to one of four zinc supplementation groups (control at 40 mg Zn/kg DM or the control diet supplemented with an additional 60 mg Zn/kg DM provided as either zinc sulfate, zinc lysine, or zinc methionine), weighed, and measured for morphometric growth parameters. Measurements were repeated at 30, 60, and 90 d. Calves were also genotyped for the presence of the mutant D128G CD18 allele, which, if present in two copies, causes bovine leukocyte adhesion deficiency. Zinc supplementation above 40 mg Zn/kg DM, regardless of the chemical form, did not accelerate growth (P > 0.25). Further, overall calf growth performance was not suppressed or improved (P > 0.4) in calves heterozygous at the CD18 locus relative to calves homozygous for the normal CD18 allele, although genotype negatively affected some morphometric measurements (P < 0.05). Using these data, quadratic models of early growth were generated as a preliminary step to develop growth criteria that will allow producers, veterinarians, and animal scientists to identify poor growth performance early in neonatal life. Such criteria provide the basis for tools to improve economic performance.

Animals↗

PubMed2001

Gender effects in hearing loss in Dalmatians.

Brainstem auditory-evoked-response data were collected from 3101 Dalmatian dogs from 1984 to 1998 at the Veterinary Medicine Teaching Hospital at the University of California, Davis. Also collected were data on eye color and the presence or absence of a color-patch at birth. Our objective was to evaluate the role of gender in hearing loss, including the possibility that the probability of suffering unilateral or bilateral deafness was greater if the dam was hearing impaired than if the sire was hearing impaired. Results of a multiple-trait threshold-model analysis support the commonly held observation that females were more likely to be deaf than males. In addition, females were also more likely to have two blue eyes (a condition associated with an increased prevalence of deafness). However, gender differences in hearing loss were limited to these direct observations. There was no detectable difference in the prevalence of hearing loss between offspring of deaf mothers and the offspring of deaf fathers. Finally, there was no detectable decrease in the prevalence of hearing loss over the years covered in the data set - suggesting that Dalmatian breeders are not yet selecting against hearing problems.

Animals↗

PubMed2001

Posthatch oral estrogen exposure impairs adult reproductive performance of zebra finch in a sex-specific manner.

We determined whether short-term, posthatch oral exposure to estradiol benzoate (EB) or the industrial surfactant octylphenol (OP) could impair the reproductive performance of zebra finches. If so, naturally occurring phytoestrogens and xenoestrogens might influence reproduction in wild populations. Chicks were given oral administration of 10 or 100 nmol EB per gram of body mass (earlier work showed the latter to be the minimum oral dose required to maximally masculinize female song nuclei) or an equimolar amount of OP daily from 5 through 11 days of age. Canola oil was used as a vehicle and control. Reproductive testing was done either in individual pair cages or in communal cages that permitted self-selection of mates, N = 10 pairs per group. Pairs consisted of EB-treated males and females, EB-treated males paired with canola-treated females, vice versa, and canola-treated males and females. Posthatch EB treatment produced sex-specific impairments in reproduction that, in some instances, were additive when both sexes were treated. Egg production was reduced and egg breakage was increased in 100 nmol/g EB-treated male and female pairs. The incidence of missing eggs was increased in 10 nmol/g EB-treated male and female pairs. Candled fertility was reduced in both groups containing 100 nmol/g EB-treated males. The number of hatched chicks was severely reduced in all EB-treated groups. No adverse effects of OP treatment were detected. These significant treatment effects (all P < 0.05) show that posthatch EB treatment profoundly disrupts the reproductive performance of zebra finches, suggesting that exposure to estrogens in the wild could impair the reproductive performance of wild populations.

Age Factors↗

PubMed2001

Growth hormone and fertility in oMt1a-oGH transgenic mice.

Female mice carrying a regulatable growth hormone transgene (oMt1a-oGH) are subfertile when the transgene is actively expressed. This study was designed to characterize subfertility caused by increased concentrations of growth hormone. In particular, this study aimed to: (i) determine the effects of transgene activation and inactivation on mating, conception, maintenance of pregnancy, ovulation rate, litter characteristics and embryonic survival at day 17 of pregnancy, (ii) characterize oestrous cyclicity in transgenic versus wild-type female mice, and (iii) correlate corticosterone concentrations with transgene expression and reproductive performance. Transgenic and wild-type female mice were allocated randomly to one of four treatment groups at weaning: (i) transgenic female mice that always express the transgene, (ii) transgenic female mice that never express the transgene, (iii) transgenic female mice that express the transgene for up to 8 weeks of age and (iv) non-transgenic wild-type female mice receiving the transgene stimulus until 8 weeks of age. Activation followed by inactivation of the transgene resulted in an increased incidence of remating, resulting in an extended interval to establish pregnancy in comparison with all other treatment groups. Transgenic mice that always expressed the transgene and those that expressed the transgene for up to 8 weeks of age had lower pregnancy rates and higher ovulation rates compared with mice from other treatment groups. Both embryonic survival and the duration of the oestrous cycle did not differ among treatment groups. Active expression of the transgene resulted in an increase in the plasma concentration of corticosterone, which was associated with reduced fertility. These data indicate that the presence of a high growth hormone concentration impedes the establishment and maintenance of pregnancy. Increased plasma corticosterone concentrations may interfere with implantation as well as potentiate leptin resistance, which has been reported previously in studies with these mice.

Analysis of Variance↗

PubMed2001

Contributions of tissues to expression of a major gene for growth in chimeric mice.

The objective of this research was to determine the effect of genotype of particular tissues and organs on the growth of a chimera produced by aggregating an embryo homozygous for the high-growth (hg) allele with an embryo from a control line of wild-type mice lacking the deletion responsible for the high-growth phenotype. A total of 107 chimeric mice were produced, 81 males and 26 females. The preponderance of male chimeras closely fit the expected 3:1 ratio of males to females in balanced chimeric populations, suggesting that neither of the two genetic lines appeared to have a selective advantage for contributions to chimeric tissues. No single correlation between individual tissue chimerism and mouse growth was remarkable relative to correlations of chimerism of other tissues to growth. Other statistical models, including multiple regression techniques, did nothing to identify particular organs, tissues or various combinations that improved the explanation of expression of the high-growth phenotype by percentage of high-growth cells in that organ. These observations suggest that the chromosomal deletion thought to cause the high-growth phenotype has a systemic effect, without dominant effects of or on individual organs or tissues; the precise mechanism has yet to be determined.

Animals↗

PubMed2001

Genetic architecture of adaptive differentiation in evolving host races of the soapberry bug, Jadera haematoloma.

To explore genetic architecture and adaptive evolution, we conducted environmental and genetic experiments with two recently (ca. 100 generations) diverged, geographically adjacent races of the soapberry bug. One race occurs on a native host plant species, the other on an introduced host. We focused on three traits: length of the mouthparts, body size and development time. The first experiment was an environmental manipulation, comparing individuals of each population reared on one or the other host species ('cross-rearing') and estimating three evolutionary rates for each trait. The first rate, 'evolutionary path' compares ancestral-derived populations when both were reared on the introduced host. The second, 'current ecological contrast' compares populations with each reared on its natal host. The third, 'evolved tradeoff' compares the two races when reared on the native host. Differences among these rates are striking and informative. For example, development time, which appears to be relatively undifferentiated phenotypically, has actually evolved very rapidly via countergradient selection. The pattern differs for each trait, and clear developmental tradeoffs have evolved as quickly as adaptation to the new host in each. The second experiment was a two-generation 'line cross' study. With joint-scaling analyses, we compared purebred, hybrid and backcrossed individuals to describe genetic architecture. Additive genetic variance for mouthpart length was consistently large (ca. 60%), but the interaction of dominance, maternal effects and epistasis was important in the other traits. Rearing host strongly affected genetic architecture. There was no clear relationship between genetic architecture and rate of evolution. Selection has produced both additive and nonadditive differentiation between the host races with surprising speed, consistent with theoretical predictions about evolution in fitness-associated traits.

Adaptation, Biological↗

PubMed2000

Segregation analysis of epilepsy in the Belgian tervueren dog.

In 1986, a survey of the incidence of epileptic seizures among dogs in the American Belgian Tervuren Club was undertaken. By 1989, 557 of the 607 members had returned completed surveys, providing seizure information about 938 dogs. The survey classified the dogs into one of four categories: 1) no seizures observed (738 dogs); 2) one seizure observed (26 dogs); 3) two to five seizures observed (82 dogs); and 4) more than five seizures observed (92 dogs). To evaluate the plausibility of a major gene model, a regressive logistic model was applied to these data. The results suggest that a single locus with a large effect on the incidence of seizures may be segregating in this population.

Alleles↗

PubMed2000

Complex segregation analysis of deafness in Dalmatians.

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.

Alleles↗

PubMed1998

Reducing the incidence of epileptic seizures in the Belgian Tervuren through selection.

There is growing evidence that idiopathic epilepsy in the Belgium Tervuren has a genetic foundation. Reducing the incidence of this disorder, which may afflict as much as 17% of the breed, will rely upon the wise selection of parents. Seizure data on 997 dogs from the American Belgian Tervuren Club were collected through questionnaires in which animals were classified into one of four mutually exclusive categories: 1) no seizures observed, 2) one seizure observed, 3) two to five seizures, and 4) more than five seizures. The analysis of this ordered data made use of a threshold model of Bayesian inference. Integration of posterior densities was accomplished through Gibbs sampling. Through this analysis we are able to predict that the offspring of the mating of two non-epileptic dogs has a probability of 0.99 of never suffering from a seizure. The offspring of the mating of two dogs who have each had 1 seizure has a predicted probability 0.58 of never suffering from a seizure. Prevention of this disease is best prescribed through the selection of non-epileptic dogs as parents of future generations.

Animals↗