Changes In Heritability Research Articles

Longitudinal changes in telomere length and associated genetic parameters in dairy cattle analysed using random regression models.

Telomeres cap the ends of linear chromosomes and shorten with age in many organisms. In humans short telomeres have been linked to morbidity and mortality. With the accumulation of longitudinal datasets the focus shifts from investigating telomere length (TL) to exploring TL change within individuals over time. Some studies indicate that the speed of telomere attrition is predictive of future disease. The objectives of the present study were to 1) characterize the change in bovine relative leukocyte TL (RLTL) across the lifetime in Holstein Friesian dairy cattle, 2) estimate genetic parameters of RLTL over time and 3) investigate the association of differences in individual RLTL profiles with productive lifespan. RLTL measurements were analysed using Legendre polynomials in a random regression model to describe TL profiles and genetic variance over age. The analyses were based on 1,328 repeated RLTL measurements of 308 female Holstein Friesian dairy cattle. A quadratic Legendre polynomial was fitted to the fixed effect of age in months and to the random effect of the animal identity. Changes in RLTL, heritability and within-trait genetic correlation along the age trajectory were calculated and illustrated. At a population level, the relationship between RLTL and age was described by a positive quadratic function. Individuals varied significantly regarding the direction and amount of RLTL change over life. The heritability of RLTL ranged from 0.36 to 0.47 (SE = 0.05–0.08) and remained statistically unchanged over time. The genetic correlation of RLTL at birth with measurements later in life decreased with the time interval between samplings from near unity to 0.69, indicating that TL later in life might be regulated by different genes than TL early in life. Even though animals differed in their RLTL profiles significantly, those differences were not correlated with productive lifespan (p = 0.954).

Reaction norm for yearling weight in beef cattle using single-step genomic evaluation.

When the environment on which the animals are raised is very diverse, selecting the best sires for different environments may require the use of models that account for genotype by environment interaction (G × E). The main objective of this study was to evaluate the existence of G × E for yearling weight (YW) in Nellore cattle using reaction norm models with only pedigree and pedigree combined with genomic relationships. Additionally, genomic regions associated with each environment gradient were identified. A total of 67,996 YW records were used in reaction norm models to calculate EBV and genomic EBV. The method of choice for genomic evaluations was single-step genomic BLUP (ssGBLUP). Traditional and genomic models were tested on the ability to predict future animal performance. Genetic parameters for YW were obtained with the average information restricted maximum likelihood method, with and without adding genomic information for 5,091 animals. Additive genetic variances explained by windows of 200 adjacent SNP were used to identify genomic regions associated with the environmental gradient. Estimated variance components for the intercept and the slope in traditional and genomic models were similar. In both models, the observed changes in heritabilities and genetic correlations for YW across environments indicate the occurrence of genotype by environment interactions. Both traditional and genomic models were capable of identifying the genotype by environment interaction; however, the inclusion of genomic information in reaction norm models improved the ability to predict animals' future performance by 7.9% on average. The proportion of genetic variance explained by the top SNP window was 0.77% for the regression intercept (BTA5) and 0.82% for the slope (BTA14). Single-step GBLUP seems to be a suitable model to predict genetic values for YW in different production environments.

The paradox of intelligence: Heritability and malleability coexist in hidden gene-environment interplay.

Intelligence can have an extremely high heritability, but also be malleable; a paradox that has been the source of continuous controversy. Here we attempt to clarify the issue, and advance a frequently overlooked solution to the paradox: Intelligence is a trait with unusual properties that create a large reservoir of hidden gene-environment (GE) networks, allowing for the contribution of high genetic and environmental influences on individual differences in IQ. GE interplay is difficult to specify with current methods, and is underestimated in standard metrics of heritability (thus inflating estimates of "genetic" effects). We describe empirical evidence for GE interplay in intelligence, with malleability existing on top of heritability. The evidence covers cognitive gains consequent to adoption/immigration, changes in IQ's heritability across life span and socioeconomic status, gains in IQ over time consequent to societal development (the Flynn effect), the slowdown of age-related cognitive decline, and the gains in intelligence from early education. The GE solution has novel implications for enduring problems, including our inability to identify intelligence-related genes (also known as IQ's "missing heritability"), and the loss of initial benefits from early intervention programs (such as "Head Start"). The GE solution can be a powerful guide to future research, and may also aid policies to overcome barriers to the development of intelligence, particularly in impoverished and underprivileged populations. (PsycINFO Database Record

Environmental stress correlates with increases in both genetic and residual variances: A meta-analysis of animal studies.

Adaptive evolutionary responses are determined by the strength of selection and amount of genetic variation within traits, however, both are known to vary across environmental conditions. As selection is generally expected to be strongest under stressful conditions, understanding how the expression of genetic variation changes across stressful and benign environmental conditions is crucial for predicting the rate of adaptive change. Although theory generally predicts increased genetic variation under stress, previous syntheses of the field have found limited support for this notion. These studies have focused on heritability, which is dependent on other environmentally sensitive, but nongenetic, sources of variation. Here, we aim to complement these studies with a meta-analysis in which we examine changes in coefficient of variation (CV) in maternal, genetic, and residual variances across stressful and benign conditions. Confirming previous analyses, we did not find any clear direction in how heritability changes across stressful and benign conditions. However, when analyzing CV, we found higher genetic and residual variance under highly stressful conditions in life-history traits but not in morphological traits. Our findings are of broad significance to contemporary evolution suggesting that rapid evolutionary adaptive response may be mediated by increased evolutionary potential in stressed populations.

Changes in genetic variances and heritabilities in an early white maize population following S1 selection for grain yield, Striga resistance and drought tolerance

SUMMARYDrought is a major constraint to maize production in West and Central Africa (WCA). Assessment of genetic gain from S1 recurrent selection under drought is crucial for the development of drought tolerance breeding strategies. In an early white population, 60 S1 families each derived from the base population and three cycles of selection were evaluated under drought and well-watered conditions at two locations in Nigeria for 2 years to determine genetic variability, gains from selection and predict response to selection for grain yield and other traits. Genetic variances generally decreased for yield and other traits in advanced cycles under drought and well-watered conditions except yield and ear height under well-watered conditions. Similarly, heritabilities for yield and other traits decreased in advanced cycles under drought but increased in advanced cycles under well-watered conditions. Realized gain for yield was 0·291 t/ha, corresponding to 30·5% per cycle under drought and 0·352 kg/ha with a corresponding gain of 16·7% per cycle under well-watered conditions. Predicted gain based on C3 was 0·282 and 0·583 t/ha under drought and well-watered conditions. Low genetic variances, heritabilities and predicted gain for yield and other traits suggested a need to introgress drought tolerance genes into the population.

Applying Biometric Growth Curve Models to Developmental Synchronies in Cognitive Development: The Louisville Twin Study.

Biometric latent growth curve models were applied to data from the LTS in order to replicate and extend Wilson's (Child Dev 54:298-316, 1983) findings. Assessments of cognitive development were available from 8 measurement occasions covering the period 4-15years for 1032 individuals. Latent growth curve models were fit to percent correct for 7 subscales: information, similarities, arithmetic, vocabulary, comprehension, picture completion, and block design. Models were fit separately to WPPSI (ages 4-6years) and WISC-R (ages 7-15). Results indicated the expected increases in heritability in younger childhood, and plateaus in heritability as children reached age 10years. Heritability of change, per se (slope estimates), varied dramatically across domains. Significant genetic influences on slope parameters that were independent of initial levels of performance were found for only information and picture completion subscales. Thus evidence for both genetic continuity and genetic innovation in the development of cognitive abilities in childhood were found.

A Bayesian generalized random regression model for estimating heritability using overdispersed count data

BackgroundFaecal egg counts are a common indicator of nematode infection and since it is a heritable trait, it provides a marker for selective breeding. However, since resistance to disease changes as the adaptive immune system develops, quantifying temporal changes in heritability could help improve selective breeding programs. Faecal egg counts can be extremely skewed and difficult to handle statistically. Therefore, previous heritability analyses have log transformed faecal egg counts to estimate heritability on a latent scale. However, such transformations may not always be appropriate. In addition, analyses of faecal egg counts have typically used univariate rather than multivariate analyses such as random regression that are appropriate when traits are correlated. We present a method for estimating the heritability of untransformed faecal egg counts over the grazing season using random regression.ResultsReplicating standard univariate analyses, we showed the dependence of heritability estimates on choice of transformation. Then, using a multitrait model, we exposed temporal correlations, highlighting the need for a random regression approach. Since random regression can sometimes involve the estimation of more parameters than observations or result in computationally intractable problems, we chose to investigate reduced rank random regression. Using standard software (WOMBAT), we discuss the estimation of variance components for log transformed data using both full and reduced rank analyses. Then, we modelled the untransformed data assuming it to be negative binomially distributed and used Metropolis Hastings to fit a generalized reduced rank random regression model with an additive genetic, permanent environmental and maternal effect. These three variance components explained more than 80 % of the total phenotypic variation, whereas the variance components for the log transformed data accounted for considerably less. The heritability, on a link scale, increased from around 0.25 at the beginning of the grazing season to around 0.4 at the end.ConclusionsRandom regressions are a useful tool for quantifying sources of variation across time. Our MCMC (Markov chain Monte Carlo) algorithm provides a flexible approach to fitting random regression models to non-normal data. Here we applied the algorithm to negative binomially distributed faecal egg count data, but this method is readily applicable to other types of overdispersed data.

Epigenetics and poetry: challenges to genetic determinism in Michael Byers’ Long for This World, and Mei-mei Berssenbrugge's ‘The Four Year Old Girl’

The essay explores how a poem, Mei-Mei Berssenbrugge's poem ‘The Four Year Old Girl’ (1998), and a novel, Michael Byers's Long for This World (2003), draw on the resources of the aesthetic to reflect on epistemological, ethical, and affective consequences of genetic variation that generates perceived disability. Although neither text explicitly addresses epigenetics, the same drive to understand genetic information in terms of development and environment which drives biological and medical research in epigenetics is very much present. The essay discusses the semantic space occupied by the concept of epigenetics, and then asks how, if at all, poetry might contribute to the intense debates opened up by challenges to genetic determinism by transgenerational heritability of changes to DNA. The essay contrasts avant-garde poetry with both amateur poetry about genetic disability and with a realist novel depicting a doctor and his family trying to help a child with a severe genetic condition. I suggest that we can think of Long for This World as an epigenetic novel, and ‘The Four Year Old Girl’ as an investigation of the semantic space now being opened up by epigenetics.

Genetic modeling of feed intake.

With the development of automatic self-feeders and electronic identification, automated, repeated measurements of individual feed intake (FI) and BW are becoming available in more species. Consequently, genetic models for longitudinal data need to be applied to study FI or related traits. To handle this type of data, several flexible mixed-model approaches exist such as character process (CPr), structured antedependence (SAD), or random regression (RR) models. The objective of this study was to compare how these different approaches estimate both the covariance structure between successive measurements of FI and genetic parameters and their ability to predict future performances in 3 species (rabbits, ducks, and pigs). Results were consistent between species. It was found that the SAD and CPr models fit the data better than the RR models. Estimations of genetic and phenotypic correlation matrices were quite consistent between SAD and CPr models, whereas correlations estimated with the RR model were not. Structured antedependence and CPr models provided, as expected and in accordance with previous studies, a decrease of the correlations with the time interval between measurements. The changes in heritability with time showed the same trend for the SAD and RR models but not for the CPr model. Our results show that, in comparison with the CPr model, the SAD and RR models have the advantage of providing stable predictions of future phenotypes 1 wk forward whatever the number of observations used to estimate the parameters. Therefore, to study repeated measurements of FI, the SAD approach seems to be very appropriate in terms of genetic selection and real-time managements of animals.

What twin studies tell us about the heritability of brain development, morphology, and function: a review.

The development of brain structure and function shows large inter-individual variation. The extent to which this variation is due to genetic or environmental influences has been investigated in twin studies using structural and functional Magnetic Resonance Imaging (MRI). The current review presents an overview of twin studies using MRI in children, adults and elderly, and focuses on cross-sectional and longitudinal designs. The majority of the investigated brain measures are heritable to a large extent (60–80 %), although spatial differences in heritability are observed as well. Cross-sectional studies suggest that heritability estimates slightly increase from childhood to adulthood. Long-term longitudinal studies are better suited to study developmental changes in heritability, but these studies are limited. Results so far suggest that the heritability of change over time is relatively low or absent, but more studies are needed to confirm these findings. Compared to brain structure, twin studies of brain function are scarce, and show much lower heritability estimates (~40 %). The insights from heritability studies aid our understanding of individual differences in brain structure and function. With the recent start of large genetic MRI consortia, the chance of finding genes that explain the heritability of brain morphology increases. Gene identification may provide insight in biological mechanisms involved in brain processes, which in turn will learn us more about healthy and disturbed brain functioning.

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence.

The onset of psychosis is usually preceded by psychotic experiences (PE). Little is known about the etiology of PE and whether the degree of genetic and environmental influences varies across different levels of severity. A recognized challenge is to identify individuals at high risk of developing psychotic disorders prior to disease onset. To investigate the degree of genetic and environmental influences on specific PE, assessed dimensionally, in adolescents in the community and in those who have many, frequent experiences (defined using quantitative cutoffs). We also assessed the degree of overlap in etiological influences between specific PE. Structural equation model-fitting, including univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis, and the Cherny method, was used to analyze a representative community sample of 5059 adolescent twin pairs (mean [SD] age, 16.31 [0.68] years) from England and Wales. Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia, as well as parent-rated negative symptoms). Genetic influences were apparent for all PE (15%-59%), with modest shared environment for hallucinations and negative symptoms (17%-24%) and significant nonshared environment (49%-64%) for the self-rated scales and 17% for parent-rated negative symptoms. Three empirical approaches converged to suggest that the etiology in extreme-scoring groups (most extreme scoring: 5%, 10%, and 15%) did not differ significantly from that of the whole distribution. There was no linear change in heritability across the distribution of PE, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the PE that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities, 0.54-0.71). These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent PE and milder, less frequent manifestations in adolescents. Individual PE in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of PE, being highest for paranoia and parent-rated negative symptoms and lowest for hallucinations.

Heritable changes in regional cortical thickness with age.

It is now well established that regional indices of brain structure such as cortical thickness, surface area or grey matter volume exhibit spatially variable patterns of heritability. However, a recent study found these patterns to change with age during development, a result supported by gene expression studies. Changes in heritability have not been investigated in adulthood so far and could have important implications in the study of heritability and genetic correlations in the brain as well as in the discovery of specific genes explaining them. Herein, we tested for genotype by age (G ×A) interactions, an extension of genotype by environment interactions, through adulthood and healthy aging in 902 subjects from the Genetics of Brain Structure (GOBS) study. A "jackknife" based method for the analysis of stable cortical thickness clusters (JASC) and scale selection is also introduced. Although additive genetic variance remained constant throughout adulthood, we found evidence for incomplete pleiotropy across age in the cortical thickness of paralimbic and parieto-temporal areas. This suggests that different genetic factors account for cortical thickness heritability at different ages in these regions.

Assessment of age-related changes in heritability and IGF-1 gene effect on circulating IGF-1 levels

It is well established that insulin-like growth factor 1 (IGF-1) circulating levels correlate with age and that heritability and influence of IGF-1 gene variation on IGF-1 levels also well-known. However, the influence of age on the genetic factors determining IGF-1 levels is not clear. In this study, we compared heritability estimates between younger (<52 years) and older (>52 years) twins and tested: (a) whether single nucleotide polymorphisms (SNPs) lying within 100 kbp of the IGF-1 gene are also associated with IGF-1 variation and (b) whether associated SNPs show interaction with age on IGF-1 levels. To achieve these aims, we measured plasma levels of IGF-1 and genotyped 18 SNPs with minor allele frequency >0.1 in a large sample, 4,471 UK female twins. Heritability explained 42 % of IGF-1 variation adjusted for age and in unadjusted sample was independent of age. Ten SNPs in four haploblocks showed significant association with IGF-1 levels, with p = 0.01-0.0005. The most distal SNP was located up to 90 kbp from the IGF-1 gene. When their age-dependent effects were examined, one SNP, rs855203, showed significant (p = 0.0009) age-dependent interaction effect on IGF-1 levels variation. This is the first study to test the age × genotype interaction in IGF-1 levels. The genomic region marked by rs855203 may consequently be of significance for further molecular and pharmacogenetic research, in particular in advanced age.

Changes of heritability and genetic correlations in production traits over time in red abalone (Haliotis rufescens) under culture

Red abalone Haliotis rufescens is one of the most valuable mollusks in the international market, but it has a low growth rate. A breeding program is being developed to increase its growth rate in Chile. We estimated the changes in direct heritability (h2), maternal/common environments heritability (m2) and genetic correlations (rG) of growth traits (shell length and width, total mass, flesh mass and foot protein as an indicator of meat quality) measured during 2 years (every 4 months) from the juvenile stage (27 months) to the adult harvesting age (51 months), in 60 full-sib red abalone families. Heritabilities for growth traits measured in juveniles and young adults (27–35 months of age), were low (0.07–0.17) and not significant. Initial low h2 were associated with significant amounts of maternal/common environmental effects (m2 = 0.4). In young adults and abalone near the harvest age (39–51 months of age) h2 were much higher (0.32–0.75). These results emphasize the importance of multiple estimations of h2 over time. Among meat quality traits, only the h2 for the flesh mass for adults at harvesting age was significant (0.15). We observed strong positive rG (>0.9) between shell sizes (easy to measure) and total and flesh masses (trait more related to market value than shell sizes but harder to measure) for adults at harvesting age. Thus, if the 5% largest 51 month old abalone were selected from the population as broodstock we expect a positively correlated response on flesh mass of 23.4%.

English

Thirty diverse genotypes of fenugreek were grown in six (E1 to E6) environments during the winter seasons at the Agriculture Farm of Visva-Bharati University, India. The estimates of genotypic and phenotypic coefficients (GCV and PCV) variation in all the environments were moderate for plant height and test weight, and high for branch number, pod number, husk weight, stem weight and seed yield indicating little influence of the environments on the estimates of these two genetic parameters. On the other hand, days to flowering, pod length, seeds per pod and harvest index showed changes in GCV and PCV values with the changes in environments. Pattern of consistency in heritability estimates over six environments revealed that days to flowering and test weight with high heritability were less influenced by environment; pod length and seed yield with moderate heritability were moderately influenced by environment; and harvest index with low heritability was highly influenced by environment. Estimates of heritability were more or less same in E1 and E2 while it changed from high to moderate for plant height, branch number, pod number and seeds per pod and from moderate to low for pod length, husk weight, stem weight and harvest index in other environments. This indicated that E1 and E2 exerted almost similar environmental effect on the genetic expression of the characters, which was supported by almost similar environmental indexes of E1 and E2 for different characters. Changes in heritability in the rest environments might be due to variable environmental effects on the expression of characters. Key words: Environments, morphological characters fenugreek, heritability, Trigonella foenum-graecum, variability.

Genetic analysis of milk yield, fat and protein content in Holstein dairy cows in Iran: Legendre

Abstract. Data including 219 105 test day records of 22 569 first parity Holstein cows in 56 herds were analysed for milk yield, fat content and protein content. Legendre polynomials were used in a random regression model to explain traits curves, additive genetic and permanent environmental effects along days in milk (DIM). Legendre polynomials of order 3 were used to describe additive genetic effects on the traits. For permanent environmental effects, for milk the order of 6 and for fat and protein content the order of 4 were used. Heterogeneity of residual variance was considered. Restricted maximum likelihood (REML) methodology was used to estimate the required parameters. Variations in genetic, permanent environment and residual effects and heritability changes along DIM were computed and illustrated. Daily heritability estimates averaged as 0.22, 0.14 and 0.23 for milk, fat and protein contents, respectively. Minimum correlations between DIM for additive genetic effects were as 0.49, −0.01 and 0.34 for milk, fat and protein contents. There were higher genetic correlations between test day milk yield and protein content compared to fat content. The genetic trend of milk yield has increased over the years from 1971 to 2005, while the genetic trend for fat and protein content declined.

Alcohol consumption in men is influenced by qualitatively different genetic factors in adolescence and adulthood

Alcohol consumption is influenced by genetic factors. Previous studies have examined the heritability of alcohol consumption, or related phenotypes, from adolescence into adulthood, frequently finding that total heritability changes over time. However, it remains unclear whether the same genes underlie liability to alcohol consumption across development versus whether novel risk genes become important over time. Method A population-based study of adult male twins (n=1790) born in Virginia, USA, retrospectively reported on their average monthly alcohol consumption from early adolescence through adulthood. We used twin modeling methods to explore genetic and environmental influences on alcohol consumption over time. One latent genetic factor accounted for the majority of the heritability in alcohol consumption during mid- to late adolescence, but its influence declined thereafter; from young adulthood forward, heritability was largely attributable to a second genetic factor. The total heritability of alcohol consumption increased from 0 at ages 12-14 years to 0.40 by ages 18-21 years. Shared environmental factors declined in influence over time. The heritability of alcohol consumption over time is dynamic both quantitatively and qualitatively. These results have important implications for gene identification endeavors. Furthermore, these findings could inform efforts to elucidate developmentally dynamic behaviors, such as antisocial behavior.

Common genetic variants, acting additively, are a major source of risk for autism

BackgroundAutism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals.MethodsBy using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status.ResultsBy analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating.ConclusionsOur results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability.

The fate of heritability in the postgenomic era

This commentary argues that age changes in heritability are incompatible with Charney's theory. The new genetics must be tempered by the findings that many epigenetic phenomena are random and are linked to pathology, thus making them peripheral to the design of complex adaptations. Behavior-genetic findings are compatible with strong maternal effects; G × E correlations likely underestimate environmental effects; and G × E interactions are unlikely to be an important aspect of normal development.

Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines

BackgroundImatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.MethodsWe conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.ResultsCytotoxicity within cell lines was highly heritable following imatinib treatment (h2 = 0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly >10).ConclusionsInduction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.