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At least 19 recordsLinked to original sources

The evolution of gene number: are heritable and non-heritable errors equally important?

Is there a limit to the number of genes carried by an organism? Two reasons have been. First, as most mutations are deleterious, for a given per locus mutation rate there must exist an upper limit to the number of genes that is consistent with individual survival. Second, the imprecision of the mechanisms governing gene expression might also restrict genomic complexity. As gene expression errors are probably much more common than mutations, it is the latter that are more likely to impose a limit. However, these errors are not heritable and therefore cannot accumulate in populations. Which of the two sorts of effect are more likely to impose a limit? We address this issue in two ways. First, we ask about the load imposed by each sort of error. We show that the harmful effect of non-heritable failures is higher than that of heritable mutations, if (p) x (delta) > mu, where p is the rate of non-heritable failures, delta measures the harmful effect of these failures and mu is the rate of heritable mutations. Therefore, although the rate of non-heritable errors might be very high, this does not demonstrate that they are more important than mutations as their impact must be discounted by the strength of their effects. Further, we note that both theory and evidence suggest that the most common errors are of the least importance. Second, we discuss the population genetics of a new gene duplication. Previous attempts to make a connection between error rates and limits on gene number are based on group selection arguments. These fail to show a direct limitation on the spread of gene duplications. We note that empirical evidence indicates that duplication per se tends to result in expression errors that may be heritable. We therefore argue that a hybrid model, one evoking heritable expression errors, is likely to be the most realistic.

Animals↗

Heritability of growth curve parameters and heritability of final size: a simulation study.

Simulations of nestling growth in Great Tits (Parus major) were used to show the consequences genetic variation in the parameters of growth curves could have on the amount of genetic variation in final body weight. This was done for the case of good environmental conditions (i.e. adequate food supply), and for poor environmental conditions (food limitation). A three-parameter process-error growth model based on the Richards curve (Brisbin et al., 1986) was used. The three parameters were the asymptote, the shape, and the time to complete approximately 95% of growth. In simulations, where only the asymptotic value was heritable, genetic variation in final weight was larger under good conditions than under poor conditions. Food limitations decreased the amount of genetic variation and the heritability estimate of final size. Similarly, sib competition, (based on body size differences of nestlings within broods) combined with food limitations lowered heritabilities. Sib competition under good conditions had no effect on heritabilities. In contrast, when the time to complete approximately 95% of growth was heritable, heritabilities for final size were not lower under poor conditions either without or in the presence of sib competition. This model suggests that different amounts of genetic variation in final size under good and poor conditions could be linked to the amount of genetic variation present in the growth curve parameters. The results agreed with an empirical study on body weight in a passerine bird, the Great Tit, where only the asymptote displayed heritable variation and more genetic variance was expressed under good conditions.

Animals↗

Species-level heritability reaffirmed: a comment on "on the heritability of geographic range sizes".

For many current issues in macroevolution and macroecology, it is important to know to what degree the attributes of species are shared among closely related lineages, a concept sometimes referred to as species-level heritability. Recently, Webb and Gaston proposed a new method for analyzing the heritability of geographic range size and concluded that range size is not heritable in Cretaceous gastropods (data from Jablonski) and modern birds (their data). Here we show that Webb and Gaston's method is flawed in that it implicitly assumes that range sizes are uniformly distributed. When range size distributions show their characteristic strong right skew, Webb and Gaston's method spuriously tends to find that range sizes of closely related pairs of species are more dissimilar than the random expectation. A reanalysis of Jablonski's data finds range size to be robustly and strongly heritable in Cretaceous gastropods and less strongly but still significantly heritable in present-day birds.

Animals↗

Heritability of pre-adult viability differences can explain apparent heritability of sperm displacement ability in Drosophila melanogaster.

Sperm displacement has been the subject of a large number of evolutionary studies because of its effects on relative male reproductive success. To understand better the evolutionary role of variation in sperm displacement ability (SDA), an obvious aim is to measure its heritability. In this paper, we show that a standard method used to measure the heritability of SDA can be misleading. First, we show that using conventional methods (based on counts of adult offspring of multiply mated females), SDA appears to be heritable. However, an examination of potentially confounding variables strongly suggests that this result is misleading, and that the heritable component is more likely to be pre-adult viability. Consequently, it is likely that there is little measurable heritable genetic variation for SDA in D. melanogaster. We conclude that, although conventional methods of measuring sperm displacement will usually be adequate for phenotypic measurements, greater care must be taken when measuring genetic variances.

Animals↗

The extended genotype: the heritability of personality accounts for the heritability of recalled family environments in twins reared apart.

How are retrospective accounts of family rearing environments linked to adult personality? We addressed this question by measuring both domains in a sample of 180 reared-apart twins. Twins completed extensive measures of rearing environments (the Minnesota-Briggs History Record, the Block Environmental Questionnaire, the Family Environment Scale, and the Physical Facilities Questionnaire) and an omnibus measure of adult personality (the Multidimensional Personality Questionnaire). Retrospective accounts of family environments were partially heritable and all the heritable variance in environmental measures could be accounted for by heritable variance in personality. In addition, differences between twins in their accounts of their rearing environments (nonshared environmental factors) were not significantly linked to differences between twins in their personalities. Hence, family environmental measures appear to be heritable because personality genes influence the way people shape and recall their rearing environments. In addition, differences in reared-apart twins' retrospectively recalled rearing environments appear to have little impact on differences in their personalities in adulthood.

Adult↗

A detailed analysis of chromosomal changes in heritable and non-heritable retinoblastoma.

Full cytogenetic analysis of 27 different retinoblastoma tumors is presented. Gross aneuploidy of chromosome arms 6p and 1q were very common, being observed in 15/27 and 21/27 tumors, respectively. However, we found that chromosome 13 was rarely missing: only 3/27 had a detectable monosomy affecting 13q14. Monosomy of chromosome 13 by small deletion or rearrangement was also not observed in any of 12 retinoblastoma tumor lines analyzed detail at the 300-400 chromosome band level. A novel observation in retinoblastoma was the discovery of non-random translocations at three specific breakpoints, 14q32 (4/12), 17p12 (5/12), and 10q25 (3/12). Genomic rearrangements similar to those described involving C-myc in Burkitt lymphoma 14q+ cells could not be demonstrated in the four 14q+ retinoblastoma lines using molecular techniques, and a probe mapping to the site implicated to have an activating role in lymphoma. These data suggest that there is a target for rearrangement at 14q32 but it is not the same sequence used in some Burkitt lymphomas. Two other breakpoints (2p24 and 8q24) coincided with the mapped position of cellular oncogenes, but also failed to show a molecular rearrangement with the oncogene probes. The breakpoints, 10q25 and 17p12, are constitutional fragile sites which may predispose these regions to act as acceptors of translocations in malignant cells. One line had double minute chromosomes, and was the only one of 16 (6%) tested with the N-myc probe which had an amplification. Different tumors from single patients with multifocal heritable retinoblastoma showed independent karyotype evolution. Unilateral non-heritable tumors exhibited a high level of karyotype stability throughout both in vivo and in vitro growth. The various common patterns of aneuploidy and translocations probably confer an early selective advantage to malignant cells, rather than induce malignant transformation.

Aneuploidy↗

Heritable protein variants induced by exposure to ethylnitrosourea: heritability, subcellular location, and tissue distribution.

The heritability, subcellular location, and tissue distribution of liver protein alterations found in the two-dimensional electrophoresis patterns of 4 offspring from male mice treated with N-ethyl-N-nitrosourea (ENU) were studied. Mice homozygous for each of the 4 ENU-induced protein variants were found to be viable and fertile, although the number of homozygous offspring from crosses between heterozygous carriers of one variant (ENU 2) was less than that expected for a nondetrimental trait. Two of the proteins altered by ENU-induced mutations were associated with the crude mitochondrial fraction, another was found predominantly in the microsomal fraction, and the fourth was associated with the mitochondrial, microsomal, and cytosol fractions. All of the ENU-induced mutations affected proteins that were not liver-specific; i.e., the proteins were found in other tissues in addition to the liver.

Animals↗

Proportion of heritable paraganglioma cases and associated clinical characteristics.

OBJECTIVE/HYPOTHESIS: To determine the heritable proportion of paraganglioma (PGL) and identify clinical features associated with heritable PGL. STUDY DESIGN: Patients diagnosed with head and neck PGLs, identified retrospectively through clinical otolaryngology practices and/or participation in previous PGL research studies, were given a medical and family history questionnaire. METHODS: Questionnaire information was used to classify participants as having "heritable" or "non-heritable" cases of PGL. Classification of the participants identified through otolaryngology clinics was used to estimate the heritable proportion of PGL. Statistical analysis was performed to identify significant differences in the clinical characteristics of the heritable versus non-heritable groups. RESULTS: Among the otolaryngology clinic population, 35% were classified as having heritable PGL. Individuals with heritable PGL were younger on average than those with non-heritable PGL. The majority of non-heritable participants were female, but there was an equal gender ratio among the heritable participants. Individuals diagnosed with a carotid body tumor (CBT) were 5.8 times more likely to be classified as heritable than those diagnosed with PGL at other anatomic locations. CONCLUSIONS: Approximately 35% of individuals who present to an otolaryngologist with a head and neck PGL have inherited a predisposition for this growth. Among individuals diagnosed with head and neck PGL, those diagnosed with CBT are 5.8 times more likely to have an inherited predisposition than those diagnosed with PGL at other anatomic locations.

Adult↗

The impact of pedigree structure on heritability estimates for pulse pressure in three studies.

OBJECTIVES: Pulse pressure (PP) is a measure of large artery stiffness and has been shown to be an important predictor of cardiovascular morbidity and mortality. The aims of the present study were to investigate the heritability of PP in three studies, the Diabetes Heart Study (DHS), the Insulin Resistance Atherosclerosis Family Study (IRAS FS), and the NHLBI Family Heart Study (FHS), to estimate the residual heritability after inclusion of a common set of covariates, and to investigate the impact of pedigree structure on estimating heritability. METHODS AND RESULTS: DHS is primarily a sibling pair nuclear family study design, while both IRAS FS and FHS have large pedigrees. Heritability estimates of log-transformed PP were obtained using variance component models. After adjusting for age, gender, ethnicity/center, height, diabetes status, and mean arterial pressure (MAP), heritability estimates of PP were 0.40 +/- 0.08 , 0.22 +/- 0.05, and 0.19 +/- 0.03 in DHS, IRAS FS, and FHS, respectively. The heritability estimate from DHS was significantly different from both IRAS FS and FHS (both p values <0.05). A random re-sampling technique (modified bootstrap) was used to explore the heritability in the IRAS FS and FHS data when these pedigrees were trimmed to mimic the DHS pedigree structure. The re-sampling method (mimicking a sibling pair nuclear family design in all studies) yielded PP heritability estimates of 0.37, 0.34, and 0.27 in DHS, IRAS FS, and FHS, respectively. There was no significant difference among the heritability estimates from the three studies based on the re-sampling method. CONCLUSION: We have shown that PP has a moderately heritable component in three different studies. These data illustrate the influence of pedigree structure can have on estimating heritability. Thoughtful comparisons of heritability estimates must consider study design factors such as pedigree structure.

Adolescent↗

Heritability analyses of IQ scores: science or numerology?

Estimates of IQ heritability are subject to a variety of systematic errors. The IQ scores themselves contain uncontrollable, systematic errors of unknown magnitude. These arise because IQ scores, unlike conventional physical and biological measurements, have a purely instrumental definition. The effects of these errors are apparent in the very large discrepancies among IQ correlations measured by different investigators. Genotype-environment correlations, whose effects can sometimes be minimized, if not wholly eliminated, in experiments with plants and animals, are nearly always important in human populations. The absence of significant effects arising from genotype-environment correlations is a necessary condition for the applicability of conventional heritability analysis to phenotypically plastic traits. When this condition fails, no quantitative inferences about heritability can be drawn from measured phenotypic variances and covariances, except under special conditions that are unlikely to be satisfied by phenotypically plastic traits in human populations. Inadequate understanding of the precise environmental factors relevant to the development of specific behavioral traits is an important source of systematic errors, as is the inability to allow adequately for the effects of assortative mating and gene-gene interaction. Systematic cultural differences and differences in psychological environment among races and among sociocco-nomic groups vitiate any attempt to draw from IQ data meaningful inferences about genetic differences. Estimates based on phenotypic correlations between separated monozygotic twins-usually considered to be the most reliable kind of estimates-are vitiated by systematic errors inherent in IQ tests, by the presence of genotype-environment correlation, and by the lack of detailed understanding of environmental factors relevant to the development of behavioral traits. Other kinds of estimates are beset, in addition, by systematic errors arising from incomplete allowance for the effects of assortative mating and from gene-gene interactions. The only potentially useful data are phenotypic correlations between unrelated foster children reared together, which could, in principle, yield lower limits for e(2). Available data indicate that, for unrelated foster children reared together, the broad heritability (h(2)) may lie between 0.0 and 0.5. This estimate does not apply to populations composed of children reared by their biological parents or by near relatives. For such populations the heritability of IQ remains undefined. The only data that might yield meaningful estimates ot narrow heritability are phenotypic correlations between half-sibs reared in statistically independent environments. No useful data of this kind are available. Intervention studies like Heber's Milwaukee Project afford an alternative and comparatively direct way of studying the plasticity of cognitive and other behavioral traits in human populations. Results obtained so far strongly suggest that the development of cognitive skills is highly sensitive to variations in environmental factors. These conclusions have three obvious implications for the broader issues mentioned at the beginning of this article. 1) Published analyses of IQ data provide no support whatever for Jensen's thesis that inequalities in cognitive performance are due largely to genetic differences. As Lewontin (8) has clearly shown, the value of the broad heritability of IQ is in any case only marginally relevant to this question. I have argued that conventional estimates of the broad heritability of IQ are invalid and that the only data on which potentially valid estimates might be based are consistent with a broad heritability of less than 0.5. On the other hand, intervention studies, if their findings prove to be replicable, would directly establish that, under suitable conditions, the offspring of parents whose cognitive skills are so poorly developed as to exclude them from all but the most menial occupations can achieve what are regarded as distinctly high levels of cognitive performance. Thus, despite the fact that children differ suibstantially in cognitive aptitudes and appetites, and despite the very high probability that these differences have a substantial genetic component, available scientific evidence strongly suggests that environmental factors are responsible for the failure of children not suffering from specific neurological disorders to achieve adequate levels of cognitive performance. 2) Under prevailing social conditions, no valid inferences can be drawn from IQ data concerning systematic genetic differences among races or socioeconomic groups. Research along present lines directed toward this end-whatever its ethical status-is scientifically worthless. 3) Since there are no suitable data for estimating the narrow heritability of IQ, it seems pointless to speculate about the prospects for a hereditary meritocracy based on IQ.

Black People↗

Heritability of event-related brain potentials in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Estimates of heritability are presented for amplitude and latency of the N1 and P3 components of the ERP measured at 19 scalp locations in response to visual and auditory stimuli for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. Significant heritabilities were found for visual P3 amplitude in response to all stimuli and for visual P3 latency in response to target and novel, but not non-target, stimuli. Heritability of visual N1 latencies was uniformly low, whereas heritability of visual N1 amplitude was significant for all electrodes in response to the non-target stimuli but only for posterior electrodes in the other two stimulus conditions. Heritabilities for auditory target P3 were similar to those of the visual stimuli, with auditory target P3 amplitudes and latencies both demonstrating significant heritability. For auditory P2 in response to non-target stimuli, peak amplitude was heritable, but latency was not. Auditory N1 amplitude and latency were significantly heritable for both target and non-target conditions and did not demonstrate the anterior/posterior patterning obtained for visual N1 amplitude. This study represents the first systematic assessment of heritability of these potential neurophysiological markers in families with a history of alcoholism and suggests that many of these ERP phenotypes have heritabilities strong enough to justify genomic screening for loci jointly influencing ERP abnormalities and liability to alcoholism.

Adolescent↗

Broad and narrow heritabilities of quantitative traits in a founder population.

Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.

Blood Pressure↗