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PubMedDate not supplied

Effects of data structure on the estimation of covariance functions to describe genotype by environment interactions in a reaction norm model.

Covariance functions have been proposed to predict breeding values and genetic (co)variances as a function of phenotypic within herd-year averages (environmental parameters) to include genotype by environment interaction. The objective of this paper was to investigate the influence of definition of environmental parameters and non-random use of sires on expected breeding values and estimated genetic variances across environments. Breeding values were simulated as a linear function of simulated herd effects. The definition of environmental parameters hardly influenced the results. In situations with random use of sires, estimated genetic correlations between the trait expressed in different environments were 0.93, 0.93 and 0.97 while simulated at 0.89 and estimated genetic variances deviated up to 30% from the simulated values. Non random use of sires, poor genetic connectedness and small herd size had a large impact on the estimated covariance functions, expected breeding values and calculated environmental parameters. Estimated genetic correlations between a trait expressed in different environments were biased upwards and breeding values were more biased when genetic connectedness became poorer and herd composition more diverse. The best possible solution at this stage is to use environmental parameters combining large numbers of animals per herd, while losing some information on genotype by environment interaction in the data.

Analysis of Variance↗

PubMed2002

Effect of forward and reverse selection for ethanol-induced locomotor response on other measures of ethanol sensitivity.

BACKGROUND: Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST-1 and -2) and low (SLOW-1 and -2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse-selected lines, named r-FAST and r-SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection. METHODS: These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling-induced convulsions during chronic ethanol withdrawal, and ethanol-induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined. RESULTS: Handling-induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol-induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r-SLOW mice only. Ethanol clearance rates were similar among all lines and replicates. CONCLUSIONS: These data demonstrate the usefulness of reverse-selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait-relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait-relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.

Animals↗

PubMed1994

Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains.

Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.

Alcohol Drinking↗

PubMed1986

[Genetic analysis of the structure of predisposition to diabetes mellitus. III. Genetic heterogeneity of diabetes mellitus with different ages of onset].

The results of genetical-epidemiological analysis of the three conventional forms of diabetes mellitus (DM) differentiated for age-at-onset are presented (the form I - from 0 to 29 y. the form II - from 30 to 59 y. the form III - 60 y. and older). The estimates of heritability of liability to the forms I, II and III of DM were 0.57, 0.70 and 0.65, respectively. It was shown that genetic components of the forms I and II are virtually different: genetic correlation between these forms was rA = 0.216 +/- 0.203, which is statistically insignificant. These data support the hypothesis assuming genetic independence of juvenile and adult forms of DM. On the other hand, the forms II and III were found to have an essential number of genes in common: genetic correlation was rA = 0.495 +/- 0.134, being significant at the 5% level. Thus, the forms II and III of DM are not to be considered as two genetically distinct diseases. The low recurrence risks of the form I for siblings (not more than 3.6%) allow to reject the hypothesis of simple monogenic inheritance of juvenile DM and to propose multifactorial nature of the disease.

Adolescent↗

PubMed1999

Neuroticism and self-esteem as indices of the vulnerability to major depression in women.

BACKGROUND: Neuroticism and self-esteem, two commonly used personality constructs, are thought to reflect a person's underlying vulnerability to major depression. The relative strength of these predictors is not known. METHOD: Information was gathered on 2163 individual women from an epidemiological sample of female female twin pairs. Neuroticism was assessed by the Eysenck Personality Questionnaire and global self-esteem by the Rosenberg Self-Esteem Scale. Major depression (DSM-III-R criteria) and stressful life events were also assessed. The personality constructs were studied in relation to major depression by logistic regression and structural equation modelling. RESULTS: Both cross-sectionally and prospectively, examined individually, neuroticism was a stronger predictor of risk for major depression than was self-esteem. When examined together, the predictive power of neuroticism remained substantial, while that of self-esteem largely disappeared. The same pattern of findings was obtained when a subset of subjects who had recently experienced stressful life events was analysed. By trivariate twin modelling, we found that the covariation of self-esteem, neuroticism and major depression was due largely to genetic factors. When self-esteem was the 'upstream' variable, a substantial genetic correlation remained between neuroticism and major depression. By contrast, when neuroticism was the 'upstream' variable, the genetic correlation between self-esteem and major depression disappeared. CONCLUSIONS: The personality construct of neuroticism is a substantially better index of a woman's underlying vulnerability to major depression than is self-esteem. These findings suggest that overall emotionality or emotional reactivity to the environment reflects risk for depression better than does global self-concept.

Adult↗

PubMed2000

Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.

BACKGROUND: Respiratory syncytial virus (RSV) infects nearly all children by the end of their second winter. Why some develop bronchiolitis is poorly understood; it is not known whether there is a genetic component. The pathological features include neutrophil infiltration and high levels of interleukin 8 (IL-8), a potent neutrophil chemoattractant. METHODS: Common genetic variants of the promoter region of the IL-8 gene were identified by sequencing DNA from 36 healthy individuals. Genetic correlates of IL-8 production were assessed using whole blood from 50 healthy subjects. To investigate genetic correlates of disease severity 117 nuclear families were recruited in which a child had required hospital admission for RSV bronchiolitis. RESULTS: A common single nucleotide polymorphism (allele frequency 0.44) was identified 251 bp upstream of the IL-8 transcription start site. The IL8-251A allele tended to be associated with increased IL-8 production by lipopolysaccharide stimulated whole blood (p=0.07). Using the transmission disequilibrium test, the frequency of this allele was significantly increased in infants with bronchiolitis (transmission = 62% (95% confidence interval (CI) 53 to 71), p=0.014) and particularly in those without known risk factors (transmission = 78% (95% CI 62 to 93), p=0.004). CONCLUSION: Disease severity following RSV infection appears to be determined by a genetic factor close to the IL-8 gene. Further analysis of this effect may elucidate causal processes in the pathogenesis of RSV bronchiolitis.

Alleles↗

PubMed1997

Genetic analysis of somatic cell score and female fertility of Israeli Holsteins with an individual animal model.

The individual animal model was used to analyze the conception index, defined as the inverse of the number of inseminations to conception, and mean lactation somatic cell scores (SCS) of Israeli Holsteins. In addition, multitrait variance components were estimated for these traits and for milk production traits. The animal model analyses included 440,558 lactation records for conception index and 224,869 SCS records collected over 10 yr. First parity heritabilities were 0.035 for conception index and 0.158 for SCS. Genetic correlations were negative between conception index and milk production traits and positive between SCS and milk production traits. Genetic correlations between first and second lactations were 0.9 for conception index and 0.7 for SCS. Phenotypic correlations were 0.08 and 0.3, respectively. Despite the low heritability for conception index, the standard deviation of the sire evaluations was 2%, and the range of evaluations was 10%. Predicted genetic trends for conception index and SCS were computed based on the current selection index of Israel. The realized genetic trend for the conception index was slightly positive, despite the predicted negative trend, and the realized genetic trend for SCS, although positive as predicted, was fourfold the predicted value. The reasons for these discrepancies are not known.

Animals↗

PubMedDate not supplied

Restricted maximum likelihood estimation of genetic principal components and smoothed covariance matrices.

Principal component analysis is a widely used 'dimension reduction' technique, albeit generally at a phenotypic level. It is shown that we can estimate genetic principal components directly through a simple reparameterisation of the usual linear, mixed model. This is applicable to any analysis fitting multiple, correlated genetic effects, whether effects for individual traits or sets of random regression coefficients to model trajectories. Depending on the magnitude of genetic correlation, a subset of the principal component generally suffices to capture the bulk of genetic variation. Corresponding estimates of genetic covariance matrices are more parsimonious, have reduced rank and are smoothed, with the number of parameters required to model the dispersion structure reduced from k(k+1)/2 to m(2k-m+1)/2 for k effects and m principal components. Estimation of these parameters, the largest eigenvalues and pertaining eigenvectors of the genetic covariance matrix, via restricted maximum likelihood using derivatives of the likelihood, is described. It is shown that reduced rank estimation can reduce computational requirements of multivariate analyses substantially. An application to the analysis of eight traits recorded via live ultrasound scanning of beef cattle is given.

Analysis of Variance↗

PubMed1984

Genetic variation of abdominal fat, body weight, and carcass weight in a female broiler line.

Pedigreed matings in a commercial purebred female broiler selection line produced 311 males and 341 females, which were slaughtered at 50 days of age. Coefficients of variation of abdominal fat weights were higher than live and carcass weights. The coefficient of variation was reduced when abdominal fat was regressed on live weight or when percentage of live or carcass weight was used. Leaf fat was approximately two-thirds and gizzard fat was approximately one-third of the total abdominal fat. Heritabilities for abdominal fat were high, and the genetic correlations between the fat and live or carcass weights ranged from .43 to .50 in males and .32 to .40 in females. The phenotypic correlations between fat and live weight were reduced when abdominal fat weight was subtracted from live weight, showing that the part-whole relationship between abdominal fat included in live body weight increased the correlations. The heritabilities indicate that it should be possible to reduce abdominal fat by selection, and the genetic correlations signify that a method has to be devised to increase body weight while simultaneously reducing abdominal fat weight.

Abdomen↗

PubMed1989

Genetic parameters of egg characteristics in Japanese quail.

Heritability, phenotypic and genetic correlations of egg characteristics of Japanese quail were investigated to obtain basal information on breeding, strain identification and genetic monitoring. For this study, 3230 eggs produced from 323 female were used. Measurement were taken on egg weight, yolk weight, albumen weight, shell weight, egg shape index, albumen height, specific gravity, shell thickness, shell strength and yolk color. Heritability estimates of egg characteristics were high and ranged from 0.62 to 0.84. Diverse phenotypic and genetic correlations were observed among egg characteristics. These results indicate that individual selection should be the most efficient method of improving egg characteristics and that consideration should be given to the interrelationship of characteristics to accomplish genetic improvement. The possibility exists these assays of egg characteristics can be used for strain identification and genetic monitoring without killing an individual of quail.

Animals↗

PubMed1996

Triiodothyronine exerts a major pleiotropic effect on reverse cholesterol transport phenotypes.

The thyroid hormone triiodothyronine (T3) is known to be a potent mediator of APOA1 gene expression. With the use of multivariate quantitative genetic analysis, we have assessed the magnitude of shared effects of T3 on plasma concentrations of apolipoprotein AI (apo AI) and three related phenotypes: HDL-C, apo AII, and LpAI (which is a concentration of apo AI that contains HDL particles). Maximum likelihood techniques were used to simultaneously estimate mean effects and variance components in large, extended Mexican American families living in San Antonio, Tex. We found that T3 accounted for 16%, 23%, 21%, and 37% of the additive genetic variance in HDL-C, apo AI, apo AII, and LpAI, respectively, while explaining virtually none of the random environmental variance in these phenotypes. T3 also has a pronounced effect on the pairwise genetic correlations among the four phenotypes: After the pleiotropic effects of T3 concentrations are controlled for, the genetic correlations are reduced by 6% in the case of HDL-C and apo AI and 97% for apo AII and LpAI. Thus, genes that influence T3 have a significant effect on HDL-C, apo AI, apo AII, and LpAI and also on the correlations among these phenotypes.

Adolescent↗

PubMed1991

Assessment of ethanol's hedonic effects in mice selectively bred for sensitivity to ethanol-induced hypothermia.

Mice selectively bred for sensitivity (COLD) or insensitivity (HOT) to the hypothermic effect of ethanol were tested in three tasks purported to assess ethanol's hedonic properties: place conditioning, taste conditioning, and ethanol drinking. In the place conditioning task, distinctive tactile (floor) stimuli were differentially paired with injection of ethanol (2.25 g/kg) or saline, and preference for the tactile stimuli was assessed during a choice test without ethanol. In the taste conditioning task, fluid-deprived mice were given repeated access to saccharin followed by injection of ethanol (2.25 g/kg). In the drinking task, mice were given access on alternate days to a single drinking tube containing water or ethanol in a concentration that gradually increased from 1 to 12% (v/v) over days. HOT mice showed greater conditioned preference for ethanol-paired flavor cues, and greater aversion for ethanol-paired flavor cues, and drank less ethanol at concentrations above 5% than COLD mice. HOT mice also showed higher levels of ethanol-stimulated activity than COLD mice. Control experiments indicated that the lines did not differ in initial preference for the tactile and flavor stimuli used in the conditioning tasks. Because the same line differences were seen in mice selected from two genetically independent populations, these studies offer strong evidence of genetic correlations between ethanol's thermal effect and its effect on activity, place conditioning and taste conditioning. Evidence of a genetic correlation between ethanol's thermal effect and ethanol drinking, however, is weaker since it is based on a line difference observed in only one of the genetic replicates. (ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1984

Genetics of growth and reproduction in the turkey. 9. Long-term selection for increased 16-week body weight.

Sixteen generations of selection of turkeys for increased 16-week body weight alone resulted in a large increase in body weight at 8, 16, 20, and 24 weeks of age of both males and females and at sexual maturity for females. The realized heritability for 16-week body weight was .29 +/- .02 for males and .24 +/- .01 for females. There was no significant effect on egg production during the first three generations of selection. However, egg production of the growth strain relative to the corresponding randombred control declined greatly during the next two generations. Eleven further generations of selection did not result in additional declines in egg production. These results suggest that the genetic correlation between 16-week body weight and egg production was zero initially, became strongly negative for Generations 4 and 5, and then ultimately returned to zero. Genetic increases in body weight were associated with decreases in intensity of lay with no effect on broodiness. Based on a subjective rating of deviation of legs and ability to walk, the legs of the growth strain were poorer than those of its corresponding randombred control in the last four generations of selection. This indicates that there is a positive genetic correlation between 16-week body weight and frequency of leg problems. Genetic increases in 16-week body weight were accompanied by increases in egg weight and a decrease in rate of response to stimulatory lighting. The effect on fertility was inconsistent. There was no effect on hatch of fertile eggs.

Animals↗

PubMed1996

Realized sampling variances of estimates of genetic parameters and the difference between genetic and phenotypic correlations.

A data set of 1572 heritability estimates and 1015 pairs of genetic and phenotypic correlation estimates, constructed from a survey of published beef cattle genetic parameter estimates, provided a rare opportunity to study realized sampling variances of genetic parameter estimates. The distribution of both heritability estimates and genetic correlation estimates, when plotted against estimated accuracy, was consistent with random error variance being some three times the sampling variance predicted from standard formulae. This result was consistent with the observation that the variance of estimates of heritabilities and genetic correlations between populations were about four times the predicted sampling variance, suggesting few real differences in genetic parameters between populations. Except where there was a strong biological or statistical expectation of a difference, there was little evidence for differences between genetic and phenotypic correlations for most trait combinations or for differences in genetic correlations between populations. These results suggest that, even for controlled populations, estimating genetic parameters specific to a given population is less useful than commonly believed. A serendipitous discovery was that, in the standard formula for theoretical standard error of a genetic correlation estimate, the heritabilities refer to the estimated values and not, as seems generally assumed, the true population values.

Analysis of Variance↗

PubMed2022

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Africa, Southern↗

PubMed1990

Clinical correlation and genetic polymorphism of the human immunodeficiency virus proviral DNA obtained after polymerase chain reaction amplification.

Polymerase chain reaction (PCR) was used to amplify a long sequence of human immunodeficiency virus (HIV) DNA, to assess the correlation between PCR signal and clinical stage of disease, and to demonstrate the genotypic variability of different HIV isolates. Twenty-four (96%) of 25 anti-HIV-reactive patients and none of 12 controls were positive for HIV proviral DNA by PCR. After quantification of the PCR signal, a significant difference in the relative amount of HIV proviral DNA per 10(5) peripheral blood mononuclear cells between symptomatic patients (Centers for Disease Control [CDC] class IV) (32,284 +/- 5225 cpm [mean +/- SE], equivalent to 802 HIV plasmid DNA copies) and patients without symptoms (CDC class II/III) (5484 +/- 1469 cpm [mean +/- SE], equivalent to 67 HIV plasmid DNA copies) was observed (P less than .01). Restriction analysis of PCR products in selected samples showed extensive genetic polymorphism between different isolates and more than one viral genotype per isolate. There was a clear correlation between the appearance of clinical symptoms in HIV infection and high levels of viral replication.

Blotting, Southern↗

PubMed1998

Twin study of dissociative experience.

The relative influence of genetic and environmental influences on measures of pathological and nonpathological dissociative experience was estimated using a classic twin-study design. Subjects were 177 monozygotic and 152 dizygotic volunteer general population twin pairs who completed two measures of dissociative capacity identified from the items comprising the Dissociative Experiences Scale (DES). Additive genetic influences accounted for 48% and 55% of the variance in scales measuring pathological and nonpathological dissociative experience, respectively. Heritability estimates did not differ by gender. The genetic correlation between these measures was estimated at .91, suggesting common genetic factors underlying pathological and nonpathological dissociative capacity. Genetic and environmental correlations between the DES scales and measures of personality disorder traits (Dimensional Assessment of Personality Pathology-Basic Questionnaire; DAPP-BQ) were also estimated. Significant genetic correlations (median = .38) were found between the DES scales and DAPP-BQ cognitive dysregulation, affective lability, and suspiciousness, suggesting that the genetic factors underlying particular aspects of personality disorder also influence dissociative capacity.

Adolescent↗

PubMed2001

Genetic parameter estimates for pre-weaning weight traits in Dorper sheep.

Genetic parameters were estimated for birth-, 42-day, and 100-day (weaning) weight in the Dorper flock of the Glen Agricultural Institute in South Africa. Direct heritability estimates of 0.11, 0.28 and 0.20 and maternal heritability estimates of 0.10, 0.10 and 0.10 were obtained for body weights at birth, 42 and 100 days, respectively. The corresponding genetic correlation estimates between direct and maternal effects were 0.35, -0.63 and -0.58, respectively. Both direct and maternal genetic correlation estimates among the traits were of moderate to high magnitude and positive. It is concluded that the traits can be improved by selection with no serious antagonisms among traits studied.

Journal Article↗