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PubMed2005

Human umbilical cord blood progenitors: the potential of these hematopoietic cells to become neural.

The mononuclear fraction from human umbilical cord blood (HUCB) contains a significant number of stem/progenitor cells that in theory could be come any cell in the body, including neurons. Taking into consideration that transdifferentiation would be a very rare event and also knowing that overlapping genetic programs for hematopoiesis and neuropoiesis exist, we undertook a characterization of the HUCB mononuclear fraction, including analysis of cellular subpopulations and their morphology, cell viability, proliferation, and expression of neural and hematopoietic antigens. Two cell populations were apparent-adherent and floating fractions. The adherent fraction was mainly lymphocytes (~53%) expressing hematopoietic antigens. Upon replate, the floating population had many cells that expressed stem cell antigens. More of the cells in this subfraction expressed neural proteins. Neurotrophin receptors trkB and trkC were present in both cell fractions, although expression was higher in the floating fraction. Our initial characterization suggests that a subpopulation of cells exists within the HUCB mononuclear fraction that seems to have the potential to become neural cells, which could then be used in the development of cell-based therapies for brain injuries and diseases.

Antigens, CD↗
PubMed2002

Personality and the genetic risk for alcohol dependence.

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest, whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol, account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women.

Adult↗
PubMed1992

Genes for directing vacuolar morphogenesis in Saccharomyces cerevisiae. I. Isolation and characterization of two classes of vam mutants.

We identified nine VAM genes (for vacuolar morphology) by genetic analyses on mutants with defective vacuolar morphologies and assembly in the yeast Saccharomyces cerevisiae. The nine VAM genes were classified into two classes according to the mutant phenotypes. The class I vam mutants (vam1, vam5, vam8, and vam9) show a few small vesicles that are stained with histochemical markers for the vacuolar compartment. They also have defects in the maturation of vacuolar marker proteins, and their growth is hypersensitive to high concentrations of CaCl2 or a temperature of 37 degrees C. There are apparent genetic overlaps among the class I vam mutations and other mutations including cls, end, pep, and vps, which have been shown to be involved in the expression of the vacuolar functions. The class II vam mutants (vam2, vam3, vam4, vam6, and vam7) contain numerous small vesicles stained with the vacuolar histochemical markers and mature forms of the vacuolar proteins and do not show any apparent growth defects in the presence of CaCl2 or at 37 degrees C.

Blotting, Western↗
PubMed1990

Metabolic considerations in hypertension.

The frequent concurrence of other cardiovascular risk factors in hypertensive patients, such as obesity and diabetes mellitus, suggests that overlapping genetic and environmental factors may contribute to the common metabolic and cardiovascular derangements observed in these populations. Hypertension and hyperglycemia accelerate atherosclerosis in diabetics, and play an important role in associated morbidity and mortality. Several abnormalities in blood pressure regulatory systems such as the renin-angiotensin system, the sympathetic nervous system, and sodium/volume control have been described in diabetes mellitus. Sodium retention and cardiovascular hyperreactivity appear to occur early in the course of diabetes mellitus, even at normal blood pressure levels and before onset of renal failure, and could set the stage for the development of hypertension. The relationship between obesity and hypertension is also well-established, and may reflect metabolic and cardiovascular adaptations in obese subjects which predispose to blood pressure elevations. Obese subjects display changes in sympathetic nervous system activity, sodium metabolism, and vascular hemodynamics. Sodium-sensitive blood pressure responses in the obese may be secondary to increased cardiac output or fluid volume, and are directly related to circulating insulin levels. Certain metabolic and vascular characteristics of obesity and diabetes mellitus are found in patients with essential hypertension. It has been suggested that insulin and insulin resistance may be the common link between these risk factors. Improved understanding of metabolic considerations in the treatment of obese and diabetic hypertensives should lead to more careful selection of medications that avoid metabolic complications. Although diuretics and beta-blockers may be useful in some patients, there are several reasons not to recommend their use as initial therapy in obese and diabetic hypertensives. On the other hand, calcium channel blockers and angiotensin converting enzyme inhibitors are highly effective, with minimal effects on metabolic parameters, and are well-suited as first-line therapy in the treatment of obese and diabetic hypertensives.

Antihypertensive Agents↗
PubMed1994

[Alcohol dependence and affective disorders].

The complex relationship between alcohol dependence and affective disorder has long been noted. Alcohol is capable of producing sadness in both alcoholics and nonalcoholics, but this sadness is time-limited and should not be confused with an affective disorder. Secondary alcohol dependence can occur in the midst of almost any psychiatric disorder. However, primary alcohol dependence with secondary affective disorder is not seen so often in inpatient alcoholics. There have been a large number of genetic-marker studies in the attempt to detect association and linkage with alcohol dependence, but there is no consistent evidence of genetic overlap between alcohol dependence and affective disorders. The administration of lithium may be useful in the treatment of alcohol dependence, but further research is required to determine whether lithium is useful in the treatment of depressive state of alcohol dependence.

Alcoholism↗
PubMed1993

Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression.

Meningioma is a common tumor of the central nervous system which displays morphological heterogeneity. In order to determine whether this phenotypic variability is associated with distinct or overlapping genetic lesions, we compared genotypes at several loci defined by allele length polymorphism in tumor and normal tissues from patients with meningioma. In particular, we concentrated on loci on chromosomes 22 and 10 because these genomic regions have previously been shown to be altered in the former in sporadic and familial meningiomas and in the latter as a late stage event in progression of another common brain tumor, astrocytoma. We examined 38 tumors which were classified as benign, atypical, or malignant by morphological criteria, invasive characteristics, or both. We found that loss of heterozygosity (LOH) for loci on chromosome 22 occurred in 5 of 15 benign, 2 of 2 atypical, and 5 of 10 malignant meningiomas. Similar alterations of chromosome 10 were found in 0 of 20 benign, 1 of 2 atypical, and 4 of 13 malignant meningiomas. Among the malignant tumors, LOH for loci on chromosome 10 occurred in 2 of 4 morphologically malignant tumors and in 2 of 4 morphologically and invasively malignant tumors. In contrast, LOH was not observed for any of the 5 informative tumors classified as malignant by invasive characteristics only. LOH for loci on chromosome 22 accompanied (but was not restricted to) allelic loss of loci on chromosome 10. These data suggest that the progression of meningiomas from arachnoidal cells to the morphologically malignant phenotype may, in part, entail the loss of a tumor suppressor gene(s) on chromosome 22 early in the process and that this may be compounded by alterations of chromosome 10, the LOH of which is associated with morphological signs of malignancy.

Adult↗
PubMed2005

Is there overlap between the genetic determinants of mammographic density and bone mineral density?

Mammographic density and bone mineral density, risk factors for breast cancer and osteoporotic fractures, respectively, are both thought to reflect cumulative exposure to estrogen and are highly heritable. We asked if there was overlap between the genes that explain their variances. We studied 63 monozygous and 71 dizygous female twin pairs ages 38 to 71 years (mean, 50 years). Absolute and percent mammographic densities were measured by a computer-assisted method, and bone mineral density was measured at the lumbar spine, femoral neck, and forearm by dual energy X-ray absorptiometry. After adjusting for age, height, and weight, the within-person and cross-trait cross-twin correlations between the mammographic density and bone mineral density measures were between -0.09 and 0.16 (SEs, 0.07-0.09) and independent of zygosity (all P > 0.05). We conclude that there is little, if any, overlap between the genetic or environmental determinants of disease risk associated with these traits.

Adult↗
PubMed1984

Beta-adrenergic and muscarinic cholinergic receptors: overlap in their genetic determination.

Significant positive correlation between the ligand binding values for beta-adrenergic receptors and those for muscarinic cholinergic receptors was found in five inbred strains of mice (r = 0.84) and in different vertebrate species (r = 0.99). Comparative analysis of analogous receptor studies done on various brain regions in other laboratories revealed high positive correlation between regional binding values for these two receptors. In conjunction with the work presented here, an overlap in the genetic determination of beta-adrenergic and muscarinic cholinergic receptors is suggested.

Animals↗
PubMed2002

The structure of language abilities at 4 years: a twin study.

Normal language development was studied in 310 pairs of 4-year-old twins born in the United Kingdom in 1994. Twins were assessed individually in their homes on a diverse battery of language and nonverbal measures. Rotated factor analyses indicated the presence of a general Language factor (L) as well as a general Nonverbal (NV) factor. Moderate genetic influence was found for both L and NV abilities. Bivariate genetic analysis estimated a genetic correlation of .63 between L and NV abilities, implying that over half of the genetic influence on L overlaps with genetic influence on NV. These results suggest that at age 4, genetic influences on individual differences in language overlap substantially with genetic influences on individual differences in other cognitive abilities, although perhaps less so than later in development.

Child Language↗
PubMed2006

Genetic and environmental influences on stages of alcohol use across adolescence and into young adulthood.

The progression to alcohol dependence unfolds across multiple stages, including the decision to initiate use, the development of regular patterns of use, and (for some individuals) the subsequent development of problems associated with alcohol use. Using data from two population-based, longitudinal twin studies, FinnTwin16 (FT16) and FinnTwin12 (FT12), we applied multiple stage genetic models (Heath et al., Twin Res. 5 (2002) 113) to better understand the extent to which genetic and environmental influences impact the initiation of alcohol use, frequency of use in adolescence and young adulthood, and alcohol problems in young adulthood. Shared environmental factors played a large role in initiation, and a more moderate role on frequency of use, and it was largely the same influences acting across these stages of use. However, there was no significant evidence of shared environmental influences on alcohol problems in early adulthood. Problems were largely influenced by genetic factors that overlapped with genetic influences on frequency of use. Unique environmental factors were largely specific to each stage, with some overlap between alcohol problems and frequency of use at age 25.

Adolescent↗
PubMed2004

Forms of cannabis and cocaine: a twin study.

Cannabis and cocaine are illicit psychoactive substances that have fallen under intense scrutiny by epidemiologists and behavioral geneticists. However, most analyses have used a composite variable to represent the use of these two drugs. For example, the composite variable of cannabis use often includes use of marijuana or hashish. Similarly, cocaine use involves different preparations (crack vs. cocaine hydrochloride) and varying routes of administration (intranasal insufflation vs. smoking). While there is some epidemiological evidence for the difference in addictive potentials between crack and intranasal cocaine, genetically informative studies have not examined the relationship between the forms of cannabis or cocaine. We used data from male and female same-sex twin pairs to examine the extent of genetic, shared environmental, and unique environmental overlap between (i) marijuana and hashish for cannabis use and (ii) intranasal and crack cocaine for cocaine use. Bivariate Cholesky models were fit using the structural equation modeling software Mx. Our results indicate that for both drugs, the individual drug forms show a complete overlap of genetic factors and a substantial overlap of shared environmental influences. While marijuana and hashish share a moderate proportion of their unique environment, crack and intranasal cocaine only show a modest overlap of unique environmental factors, adding some evidence for form-specific environmental factors. In conclusion, there is substantial overlap of familial factors between forms of a single drug and preference is primarily determined by unique environmental influences. These findings also reinforce the validity of composite variables in epidemiological and genetic research.

Adult↗
PubMed1983

The genetic analysis of recombination using adenovirus overlapping terminal DNA fragments.

We have studied the consequences of genetic recombination between overlapping terminal fragments of adenovirus genomes with respect to markers in the overlapping sequence. The findings are consistent with general recombination occurring approximately isotonically within the interval. In particular, single markers within the overlap, scored nonselectively, showed frequencies of recovery dependent on the position of their locus in relation to the ends of the overlap. Pairs of ts markers recombined to form ts+ progeny in proportion to their distance apart, provided the markers were oriented so that a single crossover between them would produce a full-length genome bearing both ts+ alleles. In the opposite orientation, where such a single crossover would be expected to produce ts/ts recombinants, the ts+ frequency was much lower, indicating that multiple recombination events are rare in this system. These findings rule out site-specific recombination, recombination occurring exclusively at the cleaved ends of the overlap, and recombination by means of mismatch repair of a heteroduplex the length of the overlap. They also indicate either that any heteroduplex junction region formed in the course of this reaction is quite short or that it is not subject to heteroduplex repair. Finally, our results demonstrate the efficacy of overlap recombination as a genetic and physical mapping tool and as a method of strain construction, and they suggest other applications, such as using overlap recombination to demonstrate that closely spaced pairs of markers (e.g., putative second-site reversions and their accompanying ts lesions) can be segregated.

Adenoviridae↗
PubMed2004

A twin study of personality and illicit drug use and abuse/dependence.

Although personality measures such as neuroticism (N), extraversion (E) and novelty-seeking (NS) are associated with the use and abuse/dependence of illicit drugs, little is known about the degree to which these associations are due to genetic or environmental factors. The goal of this analysis was to estimate the extent of genetic and environmental overlap between three dimensions of personality (N, E and NS) and illicit psychoactive substance use and abuse/dependence. Using data from adult male and female twins from the Mid-Atlantic Twin Registry, we used the structural equation modeling package Mx to perform bivariate Cholesky decompositions for personality measures of N, E and NS, individually with cannabis, cocaine, sedatives, stimulants and hallucinogens. This was done separately for use and for a polychotomous diagnosis of abuse and/or dependence. Sex differences were tested. The phenotypic relationship between personality and use and abuse/dependence of illicit drugs were moderate and most of the covariance was explained by genetic factors. Sexes could be equated for N and E but not for NS. For NS, use and abuse/dependence of illicit drugs showed greater phenotypic and genetic overlap in males than females. Of the personality measures, NS and illicit drug use and abuse/dependence were most closely related. NS was most closely related to cannabis use while N showed significant genetic overlap with sedative use. NS in males appears to be a good indicator of risk for cannabis use. This result may be useful for candidate gene studies.

Adult↗
PubMed2003

A behavioral genetic study of the overlap between personality and parenting.

The current study had three aims. The first was to examine the covariation between personality of parents and parenting behaviors. The second aim was to examine the genetic and environmental influences on parenting behaviors. The third aim was to examine the extent to which the association between personality and parenting was mediated by genetic and environmental factors. Personality (Five Factor Model, NEO-FFI) and parenting data were collected as part of a larger German study of 300 adult twin pairs (GOSAT). The current paper analyzes data on a subset of the 300 twin pairs from the GOSAT sample who were concordant for having children (n=98 pairs or 196 individuals). Results indicated modest overlap between personality and parenting. In addition, univariate behavioral genetic analyses indicated moderate genetic influence on select parenting dimensions. Results also indicated that the moderate phenotypic covariation between personality and parenting was attributed largely to nongenetic factors. Implications of the findings for research on parenting and personality are considered.

Adolescent↗
PubMed2006

Genetic influences on the overlap between low IQ and antisocial behavior in young children.

The well-documented relation between the phenotypes of low IQ and childhood antisocial behavior could be explained by either common genetic influences or environmental influences. These competing explanations were examined through use of the Environmental Risk Longitudinal Twin Study 1994-1995 cohort (Moffitt & the E-Risk Study Team, 2002) of 1,116 twin pairs and their families. Children's IQ was assessed via individual testing at age 5 years. Mothers and teachers reported on children's antisocial behavior at ages 5 and 7 years. Low IQ was related to antisocial behavior at age 5 years and predicted relatively higher antisocial behavior scores at age 7 years when antisocial behavior at age 5 years was controlled. This association was significantly stronger among boys than among girls. Genetic influences common to both phenotypes explained 100% of the low IQ-antisocial behavior relation in boys. Findings suggest that specific candidate genes and neurobiological processes should be tested in relation to both phenotypes.

Adolescent↗
PubMed1993

Genetics and high cognitive ability.

More is known about the genetics of general cognitive ability (g) than any other trait in psychology. Recent findings on the genetics of g include the following three examples: (1) heritability increases throughout the lifespan; (2) heritabilities of performance in cognitive tests are strongly correlated with the tests' loadings on a g factor; and (3) genetic effects on scholastic achievement largely overlap with genetic effects on cognitive ability. This body of genetic research addresses the aetiology of individual differences in the normal range. Much less is known about the genetics of the high end of the distribution. Finding heritability in the normal range of cognitive ability does not imply that high ability is also genetic in origin. However, the first twin study of high IQ children, which uses a new technique that analyses the average difference between extreme groups and the rest of the population, suggests that high IQ is as heritable as individual differences in the normal range. We are currently engaged in a molecular genetic study that attempts to identify specific genes that contribute to high ability.

Adolescent↗
PubMed2006

Recurrent otitis media and tonsillitis: common disease predisposition.

OBJECTIVE: To estimate the relative contribution of genetic and environmental effects to the association between recurrent otitis media and recurrent tonsillitis. METHODS: Self-report questionnaire data from a population-based cohort of 9479 Norwegian twins born from 1967 to 1979. Recurrent otitis media and recurrent tonsillitis were main outcome measures. Structural equation modelling was used to fit alternative biometric models to the twin data and to estimate the relative contribution of genetic and environmental effects to the association between otitis media and tonsillitis. RESULTS: The lifetime prevalence was 11.7% (95% CI: 11.0-12.3) for recurrent tonsillitis and 11.2% (95% CI 10.5-11.9) for recurrent otitis media. Tetrachoric correlations were greater in monozygotic than in dizygotic twins in both males and females. A model specifying additive genetic effects and individual environmental effects for otitis media and tonsillitis and non-additive genetic effects for tonsillitis yielded the best fit. There was no evidence for sex differences in the genetic source or magnitude of the genetic effects. There was a substantial overlap in genetic factors influencing variation in liability to otitis media and tonsillitis. CONCLUSION: Common genetic factors contribute substantially to comorbidity between recurrent otitis media and recurrent tonsillitis.

Environment↗