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PubMed2000

Genetics of risk factors for melanoma: an adult twin study of nevi and freckles.

BACKGROUND: We sought by use of an adult twin study to investigate the relative contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to determine if age and sun exposure influence the heritability of nevi. DESIGN AND METHODS: Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calculated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for nevus and freckle counts. RESULTS: The intraclass correlation for total nevus counts was.83 in monozygotic pairs compared with.51 in dizygotic pairs. Quantitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years old, the additive genetic variance on total nevus count was 36% (95% confidence interval [CI] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and unique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%). Body site was also found to affect the heritability estimates for nevus counts, with a statistically significant difference between sun-exposed and sun-protected sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was.91 in monozygotic twin pairs compared with.54 in dizygotic twin pairs. Additive genetic effects explained 91% (95% CI = 86%-94%) of the variance in freckle counts. CONCLUSION: The contribution of genetic factors on the variance for total nevus counts increased with age, and sun exposure appears to influence the expression of nevi. The results of this study highlight the need to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes.

Adult↗
PubMed2005

Modeling the adaptive potential of isolated populations: experimental simulations using Drosophila.

The genetic variability underlying many morphological and stress resistance traits may largely depend on the effects of genetic drift balanced by polygenic mutation. This model of adaptive potential has played a central role in the minimum viable population size concept and has been used to predict the effective population size necessary to prevent extinction within changing environments. However, there have been few long-term experimental studies of adaptive potential within isolated populations, and no study has thus far provided an experimental test of the drift-mutation model of quantitative genetic variation. Using the sternopleural bristle number of Drosophila melanogaster as a model quantitative trait, we performed repeated measurements of adaptive potential on 15 replicate populations of two and 10 male-female pairs over 30 and 77 generations, respectively. Declines in adaptive potential were analyzed by comparing observed and expected changes in realized heritability over time. The only significant model deviation occurred immediately after bottlenecks of two pairs, in which greater than expected declines in realized heritability were observed. This result suggests that changes in allelic diversity during bottleneck events may be as important as changes in heterozygosity in determining adaptive potential. Drift-mutation model expectations were otherwise realized over all generations. Our results validate the use of the drift-mutation model as a tool for understanding the dynamics of adaptive potential for peripheral fitness characters, but suggest caution in applying this model to recently bottlenecked populations.

Animals↗
PubMed2002

Genetics and caging type affect birth weight in captive pigtailed macaques (Macaca nemestrina).

The heritability of birth weight was estimated in 3,562 captive pigtailed macaques using 30 years of breeding and pedigree records. Based on a pedigree of over 12,000 animals, quantitative genetic analyses were performed using statistical variance decomposition methods. The model included additive genetic effects, cytoplasmic genetic effects, birth environment, shared maternal environment, and unmeasured environmental effects. The results demonstrated a strong (h(2) = 0.51) heritable component of birth weight overall, and included significant additive genetic heritability (h(2) = 0.23), and cytoplasmic heritability (h(2) = 0.09). In addition, a significant effect of birth location and cage type was identified, explaining an additional 6% of birth weight variance. The use of a nonhuman primate model for studying the effects of genes on birth weight eliminated many of the problems associated with confounding variables in human studies, and allowed for the quantification of a heritable component of birth weight.

Animals↗
PubMed1976

The genetics of shovel shape in maxillary central incisors in man.

From dental casts of 94 parent-offspring and 127 full-sib pairs, sampled from two Chilean populations, shovelling indices are computed to measure the degree of shovelling of maxillary central incisors quantitatively. Genetic correlations are computed to determine the role of genetic factors in explaining the variation in this trait. Assuming only hereditary factors to be responsible for the transmission of shovel shape, 68% of total variability is ascribed to the additive effect of genes.

Anthropology, Physical↗
PubMed1987

Genetic determination of hypothalamic tyrosine hydroxylase activity in mice.

Tyrosine hydroxylase (TH) activity data obtained from hypothalamic tissue samples of highly inbred mouse strains with known differences in their mesencephalic TH activity (BALB/cJ, C57BL/6ByJ, CXBI/ByJ), F1 hybrids and F2 generations were subjected to quantitative genetic analysis. No differences were observed between C57BL/6ByJ and CXBI/ByJ strains, but highly significant differences were found in hypothalamic TH activity between BALB/cJ and C57BL/6ByJ strains. Segregating genetic factors could not be detected in the replicate (C57BL/6ByJ X CXBI/ByJ) F2 generations, while the presence of segregating genetic units was indicated in the (C57BL/6ByJ X BALB/cJ)F2 population. Estimation of minimum number of genes and Elston's non-parametric one-locus test reveal that more genes are responsible for strain differences of TH activity in the hypothalamus compared to the dopaminergic areas of the mesotelencephalon. The results indicate that the heterogeneity of the catecholamine neuronal populations and terminal fields in the hypothalamus is reflected by the complex nature of the genetic control of TH activity in this brain region.

Animals↗
PubMed2003

Genetic contributions to expression of the baboon cingular remnant.

Primitive mammalian molar morphology is characterised in part by a ridge of enamel that encircles the entire base of the molar crown, the cingulum. Many higher primates have reduced the cingulum, but often retain remnant features on the lingual surface of maxillary molars and the labial surface of mandibular molars. Two of these remnants in cercopithecoid primates, the interconulus and interconulid, are morphologically similar though the interconulus is found on maxillary molars and the interconulid is located on mandibular molars. Here we present results from a quantitative genetic analysis of expression of these two traits in a sample of 479 modern savannah baboons from the Southwest Foundation for Biomedical Research (SFBR). We found that both traits are significantly heritable with little variance attributable to other factors, such as sex, age, and molar crown size. Bivariate analyses yielded point estimates for genetic correlations between left and right side expression that are either equal to or not significantly different from 1.0; meaning that 100% of their additive genetic variance is due to the effects of the same gene or suite of genes. By contrast, our estimates of the genetic correlations between maxillary and mandibular expression of this trait range from 0.52 to 0.72, suggesting that 28-52% of the additive genetic variance in the interconulus and interconulid is due to the effects of shared genes. These results demonstrate that intra-arch expression is characterised by complete pleiotropy whereas inter-arch expression is caused by incomplete pleiotropy. These results are relevant to dental developmental studies as well as paleontological analyses of the evolution of the primate dentition.

Animals↗
PubMed2001

From chicken coops to genome maps: generating phenotype from the molecular blueprint.

The tools of molecular and cellular biology can be used to precisely describe traits in terms of a sequence of nucleic acids when their molecular and cellular bases are well understood. The entire genome of elite production birds, however, cannot be written as a series of A's, T's, C's, and G's because the interaction between alleles at the same and different loci is too large and there is likely to be many genotypes that encode the same production trait phenotype. A first draft of the genetic map of the chicken is anticipated within the next few years, but a complete molecular description of the genome of birds with elite production characteristics is not anticipated in the near future. Quantitative genetics will remain the cornerstone of breeding programs for production traits. Novel sequences encoding traits such as enhanced nutritional capability (e.g., expression of phytase) and resistance to specific diseases could be introduced into lines of chickens using the tools of molecular and cellular biology. Cloning could be used by the poultry industry to disperse highly desirable genotypes without the need for grandparent and parent flocks for multiplication.

Animals↗
PubMed1984

Genetic variation and craniofacial growth in inbred rats.

There has been no experimental study clarifying the contribution of genetic variation to craniofacial growth on a longitudinal basis, although its importance is generally accepted. Utilizing diallel crosses of five strains of inbred rats, the present study concerns an estimation of the contribution genetic variation makes to the longitudinal change of craniofacial size. The overall sizes of craniofacial complex components of F1-offspring rats were investigated postnatally by means of roentgenographic cephalometry, and quantitative genetic analysis was performed by the method of Wearden [1964]. It was revealed that the relative contributions of the genetic and environmental components to total variance in craniofacial size varied with age and that the genetic component of variance significantly increased until the 80th day. On the other hand, the maternal component of variance showed the maximum value during the early periods of postnatal growth (ie, the 10th to 25th day), gradually declining thereafter to a very small amount by the 80th day. The environmental component of variance increased slightly and gradually with age through the experimental period. In conclusion it appeared that genetic variation became more significant during longitudinal growth of the craniofacial complex as the maternal effects diminished.

Age Factors↗
PubMed1999

Genetic and environmental influences on individual differences in masculinity, femininity, and gender diagnosticity: analyzing data from a classic twin study.

Analyzing data from Loehlin and Nichols's (1976) classic twin study, we computed measures of Masculine Instrumentality (M), Feminine Expressiveness (F), and Gender Diagnosticity (GD). Quantitative genetic modeling analyses of within-sex individual differences in M, F, and GD indicated that: (1) Additive genetic factors contribute significantly to individual differences in M, F, and GD. (2) The environmental effects on M, F, and GD tend to be nonshared. (3) The genetic and environmental components of individual differences in M, F, and GD tend not to show gender differences. Finally, (4) the estimated within-sex heritability of GD (.53) is significantly greater than the estimated within-sex heritabilities of either M (.36) or F (.38).

Adult↗
PubMed1996

Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.

Animals↗
PubMed2003

Physical aggression and expressive vocabulary in 19-month-old twins.

In the prevention of physical aggression, possible etiological links with language development are rarely taken into account. Indeed, little is known about when language and aggressive behavior become linked during development and which mechanisms are responsible for this association. This study investigated the association between physical aggression and language in late infancy with a genetic design that involved 562 19-month-old twins. A modest but significant correlation (r = -.20) was found between physical aggression and expressive vocabulary. Substantial heritability was found for physical aggression. Quantitative genetic modeling suggests that the correlation between expressive vocabulary and physical aggression cannot be explained by shared etiologies. However, phenotype-to-phenotype models indicate that the covariation can be entirely accounted for by a significant phenotypic path from expressive vocabulary to physical aggression. The implications of these results for early prevention of chronic physical aggression are discussed.

Aggression↗
PubMed2005

Paternal inheritance of the primary sex ratio in a copepod.

Uniparentally inherited genetic elements are under strong selection to manipulate sex determination in their host and shift the host sex ratio towards the transmitting sex. For any sex-ratio trait, lineage analysis and quantitative genetics are important tools for characterizing the mode of inheritance (biparental vs. maternal vs. paternal) thereby narrowing the field of possible sex-determining mechanisms (e.g. polygenic, sex chromosomes with meiotic drive, cytoplasmic microorganisms). The primary sex ratio of the harpacticoid copepod, Tigriopus californicus is often male-biased and is highly variable among full sib families. We found that this extra-binomial variation for the primary sex ratio is paternally but not maternally transmitted in T. californicus. Paternal transmission of the primary sex ratio has been well documented in the haplo-diploid hymenoptera but is relatively rare in diplo-diploid organisms. If the sex-ratio trait is paternally transmitted in other closely related harpacticoid copepods it would explain why male biased primary sex ratios are so common in this group.

Animals↗
PubMed2001

Global analysis of regional differences in craniometric diversity and population substructure.

Estimates of genetic diversity in major geographic regions are frequently made by pooling all individuals into regional aggregates. This method can potentially bias results if there are differences in population substructure within regions, since increased variation among local populations could inflate regional diversity. A preferred method of estimating regional diversity is to compute the mean diversity within local populations. Both methods are applied to a global sample of craniometric data consisting of 57 measurements taken on 1734 crania from 18 local populations in six geographic regions: sub-Saharan Africa, Europe, East Asia, Australasia, Polynesia, and the Americas. Each region is represented by three local populations. Both methods for estimating regional diversity show sub-Saharan Africa to have the highest levels of phenotypic variation, consistent with many genetic studies. Polynesia and the Americas both show high levels of regional diversity when regional aggregates are used, but the lowest mean local population diversity. Regional estimates of F(ST) made using quantitative genetic methods show that both Polynesia and the Americas also have the highest levels of differentiation among local populations, which inflates regional diversity. Regional differences in F(ST) are directly related to the geographic dispersion of samples within each region; higher F(ST) values occur when the local populations are geographically dispersed. These results show that geographic sampling can affect results, and suggest caution in making inferences regarding regional diversity when population substructure is ignored.

Africa South of the Sahara↗
PubMed2005

Genetic constraints and sexual dimorphism in immune defense.

The absence of continued evolutionary change despite the presence of genetic variation and directional selection is very common. Genetic correlations between traits can reduce the evolvability of traits. One intriguing example might be found in a sexual conflict over sexually dimorphic traits: a common genetic architecture constrains the response to selection on a trait subjected to sexually asymmetric selection pressures. Here we show that males and females of the mealworm beetle Tenebrio molitor differ in the quantitative genetic architecture of four traits related to immune defense and condition. Moreover, high genetic correlations between the sexes constitute a genetic constraint to the evolution of sexual dimorphism in immune defense. Our results suggest a general mechanism by which sexual conflict can promote evolutionary stasis. We furthermore show negative genetic correlations, strong indications of trade-offs, between immune traits for two pairs of traits in females.

Analysis of Variance↗
PubMed2005

Hybridization and invasiveness in the freshwater snail Melanoides tuberculata: hybrid vigour is more important than increase in genetic variance.

Many invasive taxa are hybrids, but how hybridization boosts the invasive process remains poorly known. We address this question in the clonal freshwater snail Melanoides tuberculata from Martinique, using three parental and two hybrid lines. We combine an extensive field survey (1990-2003) and a quantitative genetic experiment to show that hybrid lines have outcompeted their parents in natural habitats, and that this increased invasiveness co-occurred with pronounced shifts in life-history traits, such as growth, fecundity and juvenile size. Given the little time between hybrid creation and sampling, and the moderate standing genetic variance for life-history traits in hybrids, we show that some of the observed trait changes between parents and hybrids were unlikely to arise only by continuous selection. We therefore suggest that a large part of hybrid advantage stems from immediate heterosis upon hybridization.

Analysis of Variance↗
PubMed2000

Familial association between allergic disorders and depression in adult Finnish twins.

Clinical studies have shown a relationship between allergic disorders and depression, panic disorder, attention deficit/hyperactivity disorder, and social anxiety for a significant subset of patients with these disorders. The nature of the relationship, whether due to shared environmental or biologic vulnerabilities or as a result of the stress of chronic illness, has been less clear. By examining the covariance of atopic disorders and depressive symptoms in a community sample of monozygotic (MZ) and dizygotic (DZ) twins, the contribution of genetic and/or shared environmental etiological factors can be established. A Finnish sample of 1337 MZ and 2506 DZ twin pairs, ages 33-60 years, was sent questionnaires inquiring about history of asthma, eczema, and atopic rhinitis, as well as the Beck Depression Inventory (BDI). The nature of the covariation between twins of these symptoms was investigated by fitting competing genetic and environmental models. Within-person correlation between atopic symptoms and BDI was 0.103 (P < 0.001) for the total sample. Using the Mx statistical modeling program to fit the data to competing quantitative genetic models, the best fitting model estimated that 64% of the association between atopy and BDI was due to shared familial vulnerability, primarily additive genetic influences. Although the measures for allergic disorders and depression are crude, this study supports the hypothesis that there is a small shared genetic risk for atopic and depressive symptoms, and if replicated, may open research for common mechanisms between allergic and depressive disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:146-153, 2000.

Adult↗
PubMed2005

Direct and indirect assortative mating: a multivariate approach to plant flowering schedules.

This paper develops methods to partition the phenotypic correlation between mates for a focal trait--the standard measure for assortative mating--into a direct component and additional indirect components. Indirect assortative mating occurs when a nonassorting trait is correlated within individuals to a directly assorting trait. Direct and indirect assortative mating is assessed for flowering phenology in Brassica rapa. The flowering time of pollen recipients (mothers) was strongly correlated (rho=0.67) to that of potential pollen donors (fathers). Similarly, recipients and donors were correlated for duration of their flowering periods (rho=0.32) and stem diameters (rho=0.52). A partitioning of between-mate correlations revealed direct assortative mating for flowering time and period duration. However, assortment for stem diameter is explained solely through its correlation to flowering time. Examination of standard quantitative genetic theory shows that indirect assortative mating inflates genetic variance in a focal trait and the genetic covariance between focal and phenotypically correlated traits.

Algorithms↗
PubMedDate not supplied

Aging: the fitness-stress continuum and genetic variability.

Assuming the stress theory of aging, longevity depends upon primary selection for stress resistance and metabolic efficiency. Predominantly based upon experimental studies in the insect Drosophila melanogaster, high genetic variability for fitness, especially mortality, occurs under extreme stress. Isofemale strains derived from the progeny of recently collected single inseminated Drosophila females from the wild should provide useful biological material for extrapolating to quantitative genetic studies in man. Furthermore, environments from the benign (hormetic) to the extreme can be incorporated. Survival to old age may depend upon genes for metabolic efficiency that respond to the environmental challenges of living as limits to adaptation are approached. Under this scenario the survival of longevity mutants in man to ages analogous to the extreme life spans found in some experimental organisms under benign or protected laboratory conditions is unlikely. More future emphasis is needed on genetic variation of longevity in natural populations of experimental organisms under an array of realistically stressful environments to act as an evolutionary model for longevity in our own species.

Adaptation, Physiological↗