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PubMedDate not supplied

Complex segregation analysis in a sample of consecutive newborns with cleft lip with or without cleft palate in Italy.

The mode of inheritance of cleft lip with or without cleft palate (CL/P) has been extensively investigated, but the results are controversial. We report results of complex segregation analysis performed in the families of 636 consecutive newborns with CL/P registered in the northeast Italy and Emilia Romagna congenital malformation registries to test hypotheses regarding CL/P inheritance. The programs POINTER and COMDS have been used. POINTER could not distinguish between alternative genetic models, and only the hypothesis of no familial transmission could be rejected. COMDS results, after inclusion of the severity parameter, rejected the hypotheses of a single major locus and were consistent with the two-locus model with a major dominant locus and at least one modifier locus.

Cleft Lip↗

PubMed1987

Genetic studies of cation tests and hypertension.

Several tests of cation concentration and transport are being studied among members of large Utah pedigrees as part of a study of the genetic and environmental determinants of essential hypertension. Corrected urinary sodium excretion and plasma sodium concentration correlated well in spouses and siblings (r = 0.21-0.54, p less than 0.001), suggesting the effects of shared family environment (e.g., sodium intake). Intraerythrocytic sodium concentration and sodium-lithium countertransport showed no significant correlation in spouses and very significant correlations between siblings and between parents and offspring (r = 0.34-0.58, p less than 0.001), suggesting mostly genetic determination. Using maximum likelihood tests of different genetic models, both sodium-lithium countertransport and intraerythrocytic sodium showed predominantly polygenic determination (H2 = 70%) and some possible major gene determinants (H2 = 18-25%) for a total heritability of 89 to 95% for these characteristics. These data suggest both genes and shared family environment contribute to the familiality of cation tests. They also illustrate the need and utility of quantitative methods for objective analysis of pedigree data.

Adult↗

PubMed1987

Cataracts and hypertension in salt-sensitive rats. A possible ion transport defect.

In previous unrelated studies, we observed a 35 to 50% incidence of cataract formation in several groups of Dahl salt-sensitive hypertensive rats (DS) over a 4-year period. In the present study we evaluated longitudinal changes in blood pressure in DS in which cataracts eventually developed and those in which cataracts did not develop when all animals were maintained on a high sodium diet. Lenses were evaluated by slit-lamp microscopy to determine if cataractous lesions were similar among rats, to classify lesion types, and to define the age at which cataracts were detectable in DS. The possible participation of several cataractogenic risk factors as major influences on cataract formation also was evaluated. Finally, aqueous humor concentrations and lenticular content of sodium and potassium were determined to evaluate the possibility that a defect in ion transport at the lens epithelium and ciliary body might play a role in cataractogenesis in DS, since ion transport defects have been shown to lead to lens opacification in other models of genetic and experimental cataracts. Parallel studies were performed in Dahl salt-resistant control rats (DR). A high incidence of cataract formation was found in DS. Although systolic blood pressure was not consistently greater in adult DS with cataracts compared with values in age-matched DS without cataracts, the initial pressor response to a high salt diet was greatest in weanling DS in which cataractous lesions later developed. Slit-lamp analysis revealed that cataracts in this genetic model were cortical, with one mixed cortical, nuclear lesion. Posterior subcapsular lesions were not observed, suggesting that lesions were not steroid-induced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Ca(2+)-dependent mitogen-activated protein kinase activation in spontaneously hypertensive rat vascular smooth muscle defines a hypertensive signal transduction phenotype.

The mechanisms responsible for altered vascular smooth muscle cell (VSMC) function in hypertension remain unknown. In the spontaneously hypertensive rat (SHR) model of genetic hypertension, there are multiple abnormalities in VSMC function, including increased growth, Na(+)-H+ exchange, and increased signal transduction by protein kinase C. The family of kinases termed mitogen-activated protein (MAP) kinases has recently been shown to be essential mediators of growth factor signal transduction. In the present study, alterations in MAP kinase function in the hypertensive phenotype were investigated using early-passage SHR and Wistar-Kyoto (WKY) VSMCs stimulated with angiotensin II (Ang II, 100 nmol/L) or platelet-derived growth factor-BB (PDGF-BB, 10 ng/mL). MAP kinase activity was measured by in-gel kinase assays and Western blot analysis. Two differences between SHR and WKY rats were observed for Ang II-mediated MAP kinase activation: (1) Inactivation after Ang II stimulation was more rapid in SHR than WKY VSMCs. (2) Activity in SHR VSMCs showed a greater dependence on Ca2+ mobilization, since chelation of intracellular Ca2+ with BAPTA inhibited maximal activity by 95% in SHR VSMCs but by only 50% in WKY VSMCs. In contrast to the results with Ang II, no differences in PDGF-stimulated MAP kinase activity were observed. These findings establish activation of MAP kinase by Ang II as a feature that distinguishes SHR VSMCs from WKY VSMCs and suggest that differences in regulation of MAP kinase signaling may alter cellular events that are increased in the SHR genetic model of hypertension.

Angiotensin II↗

PubMed2001

Evidence of a cohort effect for age at onset of schizophrenia.

OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may have introduced a bias into anticipation studies of schizophrenia. METHOD: A retrospective review of the medical records of all admissions for psychotic disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis of schizophrenia and age-at-onset data were included (N=419). For analyses, subjects were placed into one of three successive birth cohorts: 1905-1944 (N=96), 1945-1964 (N=200), and 1965-1984 (N=123). RESULTS: The mean age at first appearance of psychotic symptoms and, similarly, the mean age at first hospitalization significantly decreased over time in successive birth cohorts (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at onset of schizophrenia needs to be incorporated into genetic models.

Adult↗

PubMed2002

Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction.

Recent progress in the understanding of autoimmune adrenal disease, including a detailed analysis of a group of patients with Addison's disease (AD), has been reviewed. Criteria for defining an autoimmune disease and the main features of autoimmune AD (history, prevalence, etiology, histopathology, clinical and laboratory findings, cell-mediated andhumoral immunity, autoantigens and their autoepitopes, genetics, animal models, associated autoimmune diseases, pathogenesis, natural history, therapy) have been described. Furthermore, the autoimmune polyglandular syndromes (APS) associated with AD (revised classification, animal models, genetics, natural history) have been discussed. Of Italian patients with primary AD (n = 317), 83% had autoimmune AD. At the onset, all patients with autoimmune AD (100%) had detectable adrenal cortex and/or steroid 21-hydroxylase autoantibodies. In the course of natural history of autoimmune AD, the presence of adrenal cortex and/or steroid 21-hydroxylase autoantibodies identified patients at risk to develop AD. Different risks of progression to clinical AD were found in children and adults, and three stages of subclinical hypoadrenalism have been defined. Normal or atrophic adrenal glands have been demonstrated by imaging in patients with clinical or subclinical AD. Autoimmune AD presented in four forms: as APS type 1 (13% of the patients), APS type 2 (41%), APS type 4 (5%), and isolated AD (41%). There were differences in genetics, age at onset, prevalence of adrenal cortex/21-hydroxylase autoantibodies, and associated autoimmune diseases in these groups. "Incomplete" forms of APS have been identified demonstrating that APS are more prevalent than previously reported. A varied prevalence of hypergonadotropic hypogonadism in patients with AD and value of steroid-producing cells autoantibodies reactive with steroid 17alpha-hydroxylase or P450 side-chain cleavage enzyme as markers of this disease has been discussed. In addition, the prevalence, characteristic autoantigens, and autoantibodies of minor autoimmune diseases associated with AD have been described. Imaging of adrenal glands, genetic tests, and biochemical analysis have been shown to contribute to early and correct diagnosis of primary non-autoimmune AD in the cases of hypoadrenalism with undetectable adrenal autoantibodies. An original flow chart for the diagnosis of AD has been proposed.

Adrenal Insufficiency↗

PubMed1996

SHORT INTEGUMENT (SIN1), a gene required for ovule development in Arabidopsis, also controls flowering time.

The short integument (sin1) mutation causes a female-specific infertility, and a defect in the control of time to flowering in Arabidopsis. Female sterility of Sin- plants is due to abnormal ovule integument development and aberrant differentiation of the megagametophyte in a subset of ovules. An additional defect of sin1 mutants is the production of an increased number of vegetative leaf and inflorescence primordia leading to delayed flowering. The delayed flowering phenotype of sin1-1 is not due to a defect in the perception of day length periodicity or in gibberellic acid metabolism. Phenotypes of double mutant combinations of sin1 with terminalflower (tfl1) indicate that SIN1 activity is required for precocious floral induction typical in a tfl1 mutant. Unexpectedly, sin1-1 tfl1-1 plants do not make pollen, thus revealing a novel role for TFL1 in the anther. Early flowers of sin1-1 ap1-1 double mutants are transformed to long inflorescence-like shoots. A genetic model for the role of SIN1 in flowering time control is proposed.

Adaptor Protein Complex 1↗

PubMed1998

Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes.

Inhibition of fibroblast growth factor (FGF) signaling prevents trunk and tail formation in Xenopus and zebrafish embryos. While the T-box transcription factor Brachyury (called No Tail in zebrafish) is a key mediator of FGF signaling in the notochord and tail, the pathways activated by FGF in non-notochordal trunk mesoderm have been uncertain. Previous studies have shown that the spadetail gene is required for non-notochordal trunk mesoderm formation; spadetail mutant embryos have major trunk mesoderm deficiencies, but relatively normal tail and notochord development. We demonstrate here that spadetail encodes a T-box transcription factor with homologues in Xenopus and chick. Spadetail is likely to be a key mediator of FGF signaling in trunk non-notochordal mesoderm, since spadetail expression is regulated by FGF signaling. Trunk and tail development are therefore dependent upon the complementary actions of two T-box genes, spadetail and no tail. We show that the regulatory hierarchy among spadetail, no tail and a third T-box gene, tbx6, are substantially different during trunk and tail mesoderm formation, and propose a genetic model that accounts for the regional phenotypes of spadetail and no tail mutants.

Amino Acid Sequence↗

PubMed2004

A behavior genetic investigation of the relationship between leadership and personality.

Phenotypic research on leadership style has long considered the importance of individual differences in personality when identifying the behaviors associated with good leaders. Although leadership and many personality traits have been separately shown to be heritable, these constructs have not been examined with genetically informative data to identify common sources of heritability in the two domains. A logical extension to current research, therefore, is to examine the extent to which factors of personality are predictive of leadership dimensions and the extent to which unique genetic contributions to the relationship between personality and leadership style may be identified. Adult twin pairs (183 MZ and 64 same-sex DZ) completed the Multifactor Leadership Questionnaire (MLQ) and the Personality Research Form (PRF). Univariate analyses indicated that both leadership factors (transformational and transactional leadership) and all five of the "Big Five" factors (openness, conscientiousness, extraversion, disagreeableness, and neuroticism) were best fit by genetic models. Multivariate genetic analyses suggest that transformational leadership shows a statistically significant positive genetic correlation with conscientiousness, extraversion, and openness to experience. Transactional leadership shows a significant negative genetic correlation with conscientiousness and extraversion, and a significant positive genetic correlation with disagreeableness. These results underscore the importance of conscientiousness and extraversion in predicting leadership style, and illustrate important differences between transformational and transactional leaders.

Adult↗

PubMed2005

Incorporation of competitive effects in forest tree or animal breeding programs.

Competition among domesticated plants or animals can have a dramatic negative impact on yield of a stand or farm. The usual quantitative genetic model ignores these competitive interactions and could result in seriously incorrect breeding decisions and acerbate animal well-being. A general solution to this problem is given, for either forest tree breeding or penned animals, with mixed-model methodology (BLUP) utilized to separate effects on the phenotype due to the individuals' own genes (direct effects) and those from competing individuals (associative effects) and thereby to allow an optimum index selection on those effects. Biological verification was based on two lines of Japanese quail selected for 6-week weight; one line was selected only for direct effects (D-BLUP) while the other was selected on an optimal index for both direct and associative effects (C-BLUP). Results over 23 cycles of selection showed that C-BLUP produced a significant positive response to selection (b=0.52+/-0.25 g/hatch) whereas D-BLUP resulted in a nonsignificant negative response (b=-0.10+/-0.25 g/hatch). The regression of percentage of mortality on hatch number was significantly different between methods, decreasing with C-BLUP (b=-0.06+/-0.15 deaths/hatch) and increasing with D-BLUP (b=0.32+/-0.15 deaths/hatch). These results demonstrate that the traditional D-BLUP approach without associative effects not only is detrimental to response to selection but also compromises the well-being of animals. The differences in response show that competitive effects can be included in breeding programs, without measuring new traits, so that costs of the breeding program need not increase.

Animals↗

PubMed2005

Accumulation of nonfunctional S-haplotypes results in the breakdown of gametophytic self-incompatibility in tetraploid Prunus.

The transition from self-incompatibility (SI) to self-compatibility (SC) is regarded as one of the most prevalent transitions in Angiosperm evolution, having profound impacts on the genetic structure of populations. Yet, the identity and function of mutations that result in the breakdown of SI in nature are not well understood. This work provides the first detailed genetic description of the breakdown of S-RNase-mediated gametophytic self-incompatibility (GSI) in a polyploid species that exhibits genotype-dependent loss of SI. Genetic analyses of six natural sour cherry (Rosaceae, Prunus cerasus) selections identified seven independent, nonfunctional S-haplotypes with disrupted pistil component (stylar-S) and/or pollen component (pollen-S) function. A genetic model demonstrating that the breakdown of SI in sour cherry is due to the accumulation of a minimum of two nonfunctional S-haplotypes within a single individual is developed and validated. Our finding that sour cherry is SI when only one nonfunctional S-haplotype is present has significant evolutionary implications since nonfunctional S-haplotypes would be maintained in the population without causing an abrupt shift to SC. Furthermore, we demonstrate that heteroallelic sour cherry pollen is self-incompatible, which is counter to the well-documented phenomenon in the Solanaceae where SC accompanying polyploidization is frequently due to the SC of heteroallelic pollen.

Alleles↗

PubMed2000

Roles of selection intensity, major genes, and minor genes in evolution of insecticide resistance.

A prominent hypothesis about insecticide resistance is that genes of major effect play a key role in field-evolved resistance because the intensity of selection is extremely high in the field. A corollary hypothesis is that the lower intensity of selection in laboratory selection experiments favors polygenic control of insecticide resistance. Contrary to these hypotheses, a literature review revealed that the intensity of selection for insecticide resistance in the field varies widely and overlaps broadly with selection intensities in the laboratory. Also contrary to these hypotheses, results from simulations of population genetic models suggest that selection intensities typical of laboratory selection experiments favor resistance that is conferred by major genes. Major genes dominated responses to selection for resistance across a wide range of simulated selection intensities, with and without fitness costs and refuges. The simulation results also suggest that the intensity of selection, rather than the number of loci conferring resistance, is central in determining rates of resistance evolution and effectiveness of refuges.

Animals↗

PubMed2002

Visualization of whole-mount skeletal expression patterns of LacZ reporters using a tissue clearing protocol.

Gene targeting or trapping constructs that utilize the lacZ gene encoding beta-galactosidase activity to trap promoter expression have become an increasingly important way to disrupt gene function and monitor gene expression. A number of genes targeted in this way have revealed both expected and unexpected developmental abnormalities of the skeleton. The use of X-gal staining to monitor gene expression in developing skeletal structures is hampered in these mutants because, during the critical latter stages of mouse embryonic development, visualization is hindered by the opacity of overlying soft tissue. Here, we report the development of a reliable method to clear exogenous tissue in late-stage embryos and neonates that still preserves skeletal X-gal staining patterns. This protocol reveals (i) specific cell staining in localized regions of developing bone and cartilage in two different genetic models and (ii) that the intensity of X-gal staining is consistent with the level of expression of lacZ. We conclude that this protocol accurately reflects both the specificity and intensity of expression and will facilitate the analysis of mouse skeletal development.

Animals↗

PubMed1995

Comparison of evaluation-selection systems for maximizing genetic response at the same level of inbreeding.

Use of improved methods of genetic evaluation and intense selection lead to higher rates of genetic change but also lead to higher rates of inbreeding. A number of methods have been proposed to attain high rates of genetic response with moderate or low inbreeding (i.e., restrict the number of close relatives selected, use false high heritability in the genetic evaluation, use assortative mating, adjust estimated breeding values for the relationship with those already selected, avoid matings of related individuals, and increase the number of parents selected). These various methods were compared here using stochastic simulation of an infinitesimal genetic model. The results were studied graphically plotting response against inbreeding, so allowing comparison of the methods at each of a range of inbreeding levels. None of the methods was best over all conditions. At high rates of inbreeding and with a fixed number of sires, several of the methods gave large decreases in inbreeding for small losses in response. However, these were matched by simply increasing the number of sires selected. There is an optimum response-inbreeding "front" attained by several methods, and this front seems hard to breach. Characterization of the front would be useful in designing selection programs.

Algorithms↗

PubMed2004

Maximizing genetic gain over multiple generations with quantitative trait locus selection and control of inbreeding.

Stochastic computer simulation was used to investigate the potential extra genetic gains obtained from gene-assisted selection (GAS) by combining 1) optimization of genetic contributions for maximizing gain, while restricting the rate of inbreeding with 2) optimization of the relative emphasis given to the QTL over generations. The genetic model assumed implied a mixed inheritance model in which a single quantitative trait locus (i.e., QTL) is segregating together with polygenes. When compared with standard GAS (i.e., fixed contributions and equal emphasis on the QTL and polygenic EBV), combined optimization of contributions of selection candidates and weights on the QTL across generations allowed substantial increases in gain at a fixed rate of inbreeding and avoided the conflict between short- and long-term responses in GAS schemes. Most of the increase of gain was produced by optimization of selection candidates' contributions. Optimization of the relative emphasis given to the QTL over generations had, however, a greater effect on avoiding the long-term loss usually observed in GAS schemes. Optimized contribution schemes led to lower gametic phase disequilibrium between the QTL and polygenes and to higher selection intensities both on the QTL and polygenes than with standard truncation selection with fixed contributions of selection candidates.

Alleles↗

PubMed1990

Rectovaginal constriction in Jersey cattle: genetics and breed dynamics.

Data from farmer-owned herds and from experimental matings supported monofactorial recessive inheritance of rectovaginal constriction in US Jersey cattle. Kempthorne's population genetics model of a recessive trait involving only male selection was extended to include mutation and converted to selection of females only. Computer analyses with that model estimate slow decline in the frequency of the gene for rectovaginal constriction. Practical dynamics of the disorder in a breed registering 50,000 females and 2,000 males annually are given for current conditions and after 500 generations of selection.

Alleles↗

PubMed2006

DNA damage signaling and repair in Dictyostelium discoideum.

Repair of DNA double strand breaks (DSBs) is critical for the maintenance of genome integrity. DNA DSBs can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). Whilst HR requires sequences homologous to the damaged DNA template in order to facilitate repair, NHEJ occurs through recognition of DNA DSBs by a variety of proteins that process and rejoin DNA termini by direct ligation. Here we review two recent reports that NHEJ is conserved in the social amoeba Dictyostelium discoideum. Certain components of the mammalian NHEJ pathway that are absent in genetically tractable organisms such as yeast are present in Dictyostelium and we discuss potential directions for future research, in addition to considering this organism as a genetic model system for the study of NHEJ in vivo.

Animals↗

PubMed1999

[Hand clasping--an overview].

The literature concerning the asymmetry clasping hands is reviewed based on 192 studies. This paper describes the incidence, sex differences, age differences and genetical problems including twinning. The incidence of left hand clasping ranges from 30% to 75% (mean 43%). The review confirms the so-called east-west-gradient and there is a predominance of the left type in Europe. Age and sex differences are only small. There is only a small relationship between hand clasping and handedness. 18 authors examined hand clasping in families and 4 in twins. The family data suggest that hand clasping may be under genetic control, yet it is clear that no simple genetic model for the inheritance can be applied. Both monozygotic and dizygotic twins show a low concordance and the R-R, R-L and L-L pairs in monozygotic and dizygotic twins are in binomial distribution.

Functional Laterality↗