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Results for “Genetic correlation”

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PubMed2006

Genetic variation of ecophysiological traits in two gynodioecious species of Schiedea (Caryophyllaceae).

Evolution of dimorphic breeding systems may involve changes in ecophysiological traits as well as floral morphology because of greater resource demands on females. Differences between related species suggest that ecophysiological traits should be heritable, and species with higher female frequencies should show greater sexual differentiation. We used modified partial diallel crossing designs to estimate narrow-sense heritabilities and genetic correlations of sex-specific ecophysiological and morphological traits in closely related gynodioecious Schiedea salicaria (13% females) and Schiedea adamantis (39% females). In S. salicaria, hermaphrodites and females differed in photosynthetic rate and specific leaf area (SLA). Narrow-sense heritabilities were significant for stomatal conductance, SLA and inflorescence number in hermaphrodites, and for SLA and inflorescence number in females. Schiedea adamantis had no sexual dimorphism in measured traits; stomatal conductance, stem number and inflorescence number were heritable in females, and stem number was heritable in hermaphrodites. In both species, significant genetic correlations of traits between sexes were rare, indicating that traits can evolve independently in response to sex-differential selection. Significant genetic correlations were detected between certain traits within sexes of both species. Low heritability of some ecophysiological traits may reflect low additive genetic variability or high phenotypic plasticity in these traits.

Carbon↗

PubMed1989

Estimates of genetic and environmental (co)variances for first lactation on milk yield, survival, and calving interval.

Variance and covariance components for milk yield, survival to second freshening, calving interval in first lactation were estimated by REML with the expectation and maximization algorithm for an animal model which included herd-year-season effects. Cows without calving interval but with milk yield were included. Each of the four data sets of 15 herds included about 3000 Holstein cows. Relationships across herds were ignored to enable inversion of the coefficient matrix of mixed model equations. Quadratics and their expectations were accumulated herd by herd. Heritability of milk yield (.32) agrees with reports by same methods. Heritabilities of survival (.11) and calving interval(.15) are slightly larger and genetic correlations smaller than results from different methods of estimation. Genetic correlation between milk yield and calving interval (.09) indicates genetic ability to produce more milk is lightly associated with decreased fertility.

Analysis of Variance↗

PubMed2005

Genetic parameters for female fertility traits and a fertility index in Spanish dairy cattle.

Genetic correlations among female fertility traits (linear and binary) were estimated using 225,085 artificial insemination records from 120,713 lactations on 63,160 Holstein cows. Fertility traits were: calving interval, days open, a linear transformation of days open, days to first insemination, interval between first and last insemination, number of inseminations per service period, pregnancy within 56 and 90 d after first insemination, and success in first insemination. A bivariate animal model was implemented using Bayesian methods in the case of binary traits. Low heritabilities (0.02 to 0.06) were estimated for these fertility traits. Strong genetic correlations (0.89 to 0.99) were found among traits, except for days to first service, where the genetic correlation with other fertility traits ranged from -0.52 to -0.18 for binary traits, and from 0.50 to 0.82 for days to first service, calving interval, and days open. Four fertility indices were proposed utilizing information from insemination records; these indices combined one indicator of the beginning of the service period and one indicator of conception rate. Two additional indices used information from the milk-recording scheme, including calving interval and a linear transformation of days open. The fertility index composed of days to first service and pregnancy within 56 d achieved the highest genetic gain for reducing fertility cost, reducing days to first service, and reducing the number of inseminations per lactation ($8.60, -1.31 d, and -0.03 AI, respectively). This index achieved at least 15% higher genetic gain than obtained from indices with information from the milk recording scheme only (calving interval and days open).

Analysis of Variance↗

PubMed2006

Genetics of litter size in three maternal lines of rabbits: repeatability versus multiple-trait models.

Variance components were estimated in 3 lines of rabbits selected for litter size at weaning (A, Prat, and V) to test one of the assumptions of the models used for selection: that litter size data at different parities are repeated measurements of the same trait. Multiple-trait analyses were performed for the total number of kits born (TB), the number of kits born alive (BA), and the number of kits weaned (NW) per litter. Estimates were obtained by REML in multivariate analyses, including all of the information of the selection criteria, under a repeatability model or a multiple-trait model, considering litter size at the first, second, and subsequent parities as different traits. Models included the fixed effects of the physiological status of the female and the year-season of mating day, buck and doe random permanent environmental effects, and doe additive genetic effects. Results indicated that prolificacy was determined mainly by doe components and that the service sire had a very small effect. Heritabilities for the first and second parities were greater than the estimates obtained under the repeatability model (0.04 to 0.14 for the repeatability model). In the A and V lines, similar values of heritability were found at the first and second parities, but in the Prat line heritability at the second parity was always greater than at the first and greater parities (values of 0.21, 0.17, and 0.15 for TB, BA, and NW, respectively, in second parities of the Prat line). Genetic correlations between the same traits at different parities were approximately 0.8 for all traits in line A, but much lower in the other 2 lines. On average, the values were 0.64 for TB, 0.48 for BA, and 0.39 for NW between the first and second parities, and 0.65 for TB, 0.56 for BA, and 0.45 for NW between the first and third and greater parities. Genetic correlations between the second and greater parities showed the greatest values (approximately 0.8) in lines A and Prat for all traits, but they were lower in line V (0.63 for BA and 0.37 for NW). The heterogeneity of heritabilities and genetic correlations between parities lower than 0.9 suggests that litter size at different parities could be considered as different traits when genetic evaluations are performed. However, when the accuracies of predicted breeding values under a multiple-trait and a repeatability model were calculated, assuming the first to be the true model, the values obtained were nearly the same for all traits in all lines.

Animals↗

PubMed2004

Estimation of genetic parameters based on individual and group mean records in laying hens.

(1) The study was conducted to estimate the heritability, genetic correlations and breeding values of laying hens based on individual records and group mean records. (2) Records of two pure lines from a commercial breeding programme of White Leghorns from three generations housed in single cages and in group cages were used. A total of 8483 and 8817 individual records of lines A and D, respectively, and a total of 1358 (line A) and 1161 (line D) group mean records were analysed. (3) An animal model using Restricted Maximum Likelihood (REML) was used to estimate variance components of individual records. Group mean records were analysed using the sire model, taking heterogeneity of error variance and correlated residual effects into account. Breeding values of sires were estimated based on the BLUP method using a multivariate sire model. Spearman Rank correlations were used to compare sire breeding values estimated from individual records and from group mean records. The traits studied were monthly egg production, cumulative production and egg weight. (4) Heritability estimates based on individual records were higher than from group mean records. Heritabilities for cumulative production records were higher than for monthly production, based on individual as well as group mean records. The estimates of genetic correlations between monthly egg production and cumulative production were moderate to high. Egg production and egg weight recorded individually were highly genetically correlated with those recorded on group means. Sire breeding values estimated from individual records showed high correlations with those from group mean records. (5) Differences in the ranking of sire breeding values estimated from individual vs group mean records were negligible, indicating that no genotype x environment interaction exists. Selection based on individual performance records of laying hens housed in single cages could give a good response on performance of laying hens housed in group cages. Cumulative egg production over periods 1 to 6 is the best trait for the selection programme.

Animals↗

PubMedDate not supplied

A comparison of bivariate and univariate QTL mapping in livestock populations.

This study presents a multivariate, variance component-based QTL mapping model implemented via restricted maximum likelihood (REML). The method was applied to investigate bivariate and univariate QTL mapping analyses, using simulated data. Specifically, we report results on the statistical power to detect a QTL and on the precision of parameter estimates using univariate and bivariate approaches. The model and methodology were also applied to study the effectiveness of partitioning the overall genetic correlation between two traits into a component due to many genes of small effect, and one due to the QTL. It is shown that when the QTL has a pleiotropic effect on two traits, a bivariate analysis leads to a higher statistical power of detecting the QTL and to a more precise estimate of the QTL's map position, in particular in the case when the QTL has a small effect on the trait. The increase in power is most marked in cases where the contributions of the QTL and of the polygenic components to the genetic correlation have opposite signs. The bivariate REML analysis can successfully partition the two components contributing to the genetic correlation between traits.

Animals↗

PubMed2005

Quantitative genetics of bioenergetics and growth-related traits in the wild mammal, Phyllotis darwini.

We studied the potential for response to selection in typical physiological-thermoregulatory traits of mammals such as maximum metabolic rate (MMR), nonshivering thermogenesis (NST) and basal metabolic rate (BMR) on cold-acclimated animals. We used an animal model approach to estimate both narrow-sense heritabilities (h2) and genetic correlations between physiological and growth-related traits. Univariate analyses showed that MMR presented high, significant heritability (h2 = 0.69 +/- 0.35, asymptotic standard error), suggesting the potential for microevolution in this variable. However, NST and BMR presented low, nonsignificant h2, and NST showed large maternal/common environmental/nonadditive effects (c2 = 0.34 +/- 0.17). Heritabilities were large and significant (h2 > 0.5) for all growth-related traits (birth mass, growth rate, weaning mass). The only significant genetic correlations we found between a physiological trait and a growth-related trait was between NST and birth mass (r = -0.74; P < 0.05). Overall, these results suggest that additive genetic variance is present in several bioenergetic traits, and that genetic correlations could be present between those different kinds of traits.

Acclimatization↗

PubMed2004

Genotype x environment interaction for grazing versus confinement. I. Production traits.

The objective of this study was to investigate the possible existence of a genotype x environment interaction (GxE) for production traits of US Holsteins in grazing versus confinement herds. Grazing herds were defined as those that utilized grazing for at least 6 mo and were enrolled in dairy herd improvement (DHI). Control herds were confinement DHI herds of comparable size in similar regions. The performance of daughters in grazing herds and control herds was examined using linear regression of mature equivalent milk, fat, and protein yield on the November 2000 USDA-DHI predicted transmitting abilities (PTA) of their sires for those traits. Heritabilities and genetic correlations were estimated using restricted maximum likelihood in a bivariate animal model that considered the same trait in different environments as different traits. Product-moment and rank correlations were calculated between sires' estimated breeding values, estimated separately in both environments. For grazing herds, the coefficient of regression of milk, fat and protein on PTA were 0.78, 0.76, and 0.78, respectively. Corresponding coefficients in the control herds were 0.99, 0.96, and 0.98. Estimates of heritability for the traits ranged from 0.2 to 0.25, and differences between grazing and control environments were small. Estimates of the genetic correlations for the traits in both environments were 0.89, 0.88, and 0.91 for milk, fat, and protein, respectively. Within-quartile analyses revealed a lower correlation for milk and protein between the upper and lower grazing quartiles, while the same quartiles for the control herds did not differ from unity. Rank correlation coefficients between sire estimated breeding values from the 2 environments were 0.59, 0.63, and 0.66 for milk, fat, and protein, respectively. The mean rank change for the top 100 sires between the two environments was 27. The regression coefficients indicate that expected daughter differences may be overstated by current sire PTA in grazing herds. Genetic correlations less than unity suggests that there is, at least, some reranking among sires in both environments, while the rank correlations indicate the possibility of sire reranking when evaluations were performed within management system. However, differences are not so large as to justify separate genetic evaluations for each system.

Animals↗

PubMed2004

Genetic parameters for indicators of host resistance to parasites from weaning to hogget age in Merino sheep.

Fecal egg count (FEC) has been widely used as an indicator of host resistance to gastrointestinal parasites in sheep and has been shown to be a heritable trait. Two other possible indicators of parasites, dag score (DS; accumulated fecal material) and fecal consistency score (FCS), were investigated in this study, along with BW. All four traits were studied to see how heritability and genetic correlations varied with age from weaning (4 mo) to hogget age (approximately 400 d). More than 1,100 lambs, the offspring of 37 rams, were recorded eight times between weaning (3 to 5 mo of age) and hogget age (13 to 18 mo of age) on two farms. Sire models were fitted to the data from each trait at each recording and in a repeatability model involving the whole data set. Overall, the heritabilities were 0.28+/-0.072 (FEC), 0.11+/-0.036 (DS), 0.12+/-0.036 (FCS), and 0.23+/-0.070 (BW). By fitting random regression models to the time-series data, it was possible to see how these heritability values varied as the lambs aged, from weaning to hogget age. The heritability of FEC rose from 0.2 at weaning to 0.65 at 400 d. Dag score had a higher heritability (0.25) in the middle of the age range and a low value at weaning (<0.1) and hogget age (0.16). The heritability of FCS was low, with a value of 0.2 at weaning reducing to 0.05 as the animals aged. Body weight had zero heritability at weaning, which rose to greater than 0.6 at hogget age. Most traits had low genetic correlations between them, the only exception being that between FCS and DS (0.63). Most genetic correlations varied little over the age range with the exception of FEC and BW, which fell from 0 at weaning to -0.63 at hogget age. Whereas FCS and DS may be good indicators of scouring, they are very different from FEC as an indicator of host resistance to gastrointestinal parasites.

Aging↗

PubMed2004

Genetics of length of productive life and lifetime prolificacy in the Finnish Landrace and Large White pig populations.

The objective of this study was to estimate direct and indirect selection potential for length of productive life and lifetime prolificacy in Finnish Large White and Landrace swine populations. To study the direct selection potential, the heritabilities of these traits were estimated. The genetic correlations of length of productive life and lifetime prolificacy with prolificacy traits and overall leg conformation were estimated to evaluate whether selection for these traits could indirectly improve measures of sow longevity. In addition, correlations between length of productive life, lifetime prolificacy, ADG, and backfat thickness were estimated. Records were used from Finnish purebred Landrace (n = 26,744) and Large White (n = 24,007) sows born on operations that perform on-farm production tests on all females. Heritabilities were estimated using both a survival analysis procedure and a linear model. Due to computational limitations, correlations were estimated with the linear model only. Estimated length of productive life heritabilities obtained from linear model analyses were less (0.05 to 0.10) than those obtained from survival analyses (0.16 to 0.19). This may be indicative of the superiority of survival analysis compared with linear model analysis methods when evaluating longevity or similar types of data. All the prolificacy traits were genetically correlated with length of productive life and lifetime prolificacy, and the correlations were greater than 0.13. These results indicate that selection for increased number of piglets weaned in the first litter and for short first farrowing interval is beneficial for sow longevity and also for sow's lifetime prolificacy. The genetic correlations between length of productive life and leg conformation score also were favorable (0.32 in Landrace and 0.17 in Large White). The heritability estimates indicate that survival analysis is likely the most appropriate method of evaluating longevity traits in swine. Because of computational problems, simultaneous analysis of linear traits and longevity is not currently possible. More research is needed to develop methods for multiple linear and survival trait analyses.

Animals↗

PubMed2005

Genetic evaluation of elbow angles as predictors of elbow dysplasia in German shepherd dogs.

Elbow angles were measured in X-rays of both elbows to elucidate the usefulness of such data for selecting against elbow dysplasia (ED) in German shepherd dogs. These measurements record the size, proportions and alignments of the anconeal process (PA), the radius (RA), the olecranon (OL), and the ulnar trochlear notch (UL). The reference system for evaluating the information content of the measurements was the score for ED (ED-SV) as recommended by the International Elbow Working Group. Data from 2645 X-rayed dogs born from 1998 to 2001 in 1331 kennels were analysed by using residual maximum likelihood procedures to estimate heritabilities, additive genetic correlations and residual correlations. The pedigree file included 11,426 dogs and contained ancestors for up to six generations. ED-SV was significantly influenced by sex, by age within sex and by month of birth. The elbow angles were significantly influenced by the month and year of birth, X-ray positioning of the dog's forelimbs, angle of elbow flection, litter size and number of dogs X-rayed by the veterinary practitioners. The following heritability estimates were found: h2=0.18+/-0.04 for ED; h2=0.76+/-0.04 for OL; h2=0.52+/-0.05 for PA; h2=0.50+/-0.04 for UL; and h2=0.39+/-0.04 for RA. The additive genetic correlations of ED-SV with three elbow angles (OL, UL and RA) were close to zero. A higher additive genetic correlation to ED-SV was found only for PA, for which r(g)=0.31. The distributions of predicted breeding values for susceptibility to ED were not affected by regarding the elbow angles as additional traits in the multivariate prediction procedure. Measurements of elbow angles were thus shown to be unsuitable for use in selection programmes against ED in German shepherd dogs.

Animals↗

PubMedDate not supplied

Genetic variance and covariance patterns for body weight and energy balance characters in an advanced intercross population of mice.

We estimated heritabilities and genetic correlations for a suite of 15 characters in five functional groups in an advanced intercross population of over 2000 mice derived from a cross of inbred lines selected for high and low heat loss. Heritabilities averaged 0.56 for three body weights, 0.23 for two energy balance characters, 0.48 for three bone characters, 0.35 for four measures of adiposity, and 0.27 for three organ weights, all of which were generally consistent in magnitude with estimates derived in previous studies. Genetic correlations varied from -0.65 to +0.98, and were higher within these functional groups than between groups. These correlations generally conformed to a priori expectations, being positive in sign for energy expenditure and consumption (+0.24) and negative in sign for energy expenditure and adiposity (-0.17). The genetic correlations of adiposity with body weight at 3, 6, and 12 weeks of age (-0.29, -0.22, -0.26) all were negative in sign but not statistically significant. The independence of body weight and adiposity suggests that this advanced intercross population is ideal for a comprehensive discovery of genes controlling regulation of mammalian adiposity that are distinct from those for body weight.

Age Factors↗

PubMed2003

Genotype x environment interaction for milk production of daughters of Australian dairy sires from test-day records.

In Australia, dairy farming is carried out in environments that vary in many ways, including level of feeding and climate variables such as temperature and humidity. The aim of this study was to assess the magnitude of genotype x environment interactions (GxE) on milk production traits (milk yield, protein yield, and fat yield) for a range of environmental descriptors. The environment on individual test days was described by herd size (HS), average herd protein yield (AHTDP), herd test-day coefficient of variation for protein yield (HTDCV), and temperature humidity index (THI). A sire random regression model was used to model the response of a sire's daughters to variation in the environment and to calculate the genetic correlation between the same traits measured in two widely different environments. Using test-day records, rather than average lactation yields, allowed exploitation of within-cow variation as well as between-cow variation at different levels of AHTDP, and led to more accurate estimates of sire breeding values for "response to environment." The greatest GxE observed was due to variation in AHTDP, with a genetic correlation of 0.78 between protein yield when AHTDP = 0.54 kg and protein yield when AHTDP = 1.1 kg (the 5th and 95th percentile of the distribution of AHTDP). The GxE was also observed for THI, with a genetic correlation of 0.90 between protein yield at the 5th and 95th percentile of THI. The use of response to environment estimated breeding values to improve the accuracy of international sire evaluations is discussed.

Animals↗

PubMed1994

Evolutionary pattern of human respiratory syncytial virus (subgroup A): cocirculating lineages and correlation of genetic and antigenic changes in the G glycoprotein.

The genetic and antigenic variability of the G glycoproteins from 76 human respiratory syncytial (RS) viruses (subgroup A) isolated during six consecutive epidemics in either Montevideo, Uruguay, or Madrid, Spain, have been analyzed. Genetic diversity was evaluated for all viruses by the RNase A mismatch cleavage method and for selected strains by dideoxy sequencing. The sequences reported here were added to those published for six isolates from Birmingham, United Kingdom, and for two reference strains (A2 and Long), to derive a phylogenetic tree of subgroup A viruses that contained two main branches and several subbranches. During the same epidemic, viruses from different branches were isolated. In addition, closely related viruses were isolated in distant places and in different years. These results illustrate the capacity of the virus to spread worldwide, influencing its mode of evolution. The antigenic analysis of all isolates was carried out with a panel of anti-G monoclonal antibodies that recognized strain-specific (or variable) epitopes. A close correlation between genetic relatedness and antigenic relatedness in the G protein was observed. These results, together with an accumulation of amino acid changes in a major antigenic area of the G glycoprotein, suggest that immune selection may be a factor influencing the generation of RS virus diversity. The pattern of RS virus evolution is thus similar to that described for influenza type B viruses, expect that the level of genetic divergence among the G glycoproteins of RS virus isolates is the highest reported for an RNA virus gene product.

Amino Acid Sequence↗

PubMed1989

Biochemical correlates of genetic variation in marine lower invertebrates.

In this paper extensive data on enzyme variation in 23 species of coelenterates and sponges were used to investigate the possible correlation of levels of genetic variation with various parameters of enzyme molecular structure and function. The data provide an opportunity not only to look for such correlations for the first time in lower invertebrates, but also to study organisms with far higher average levels of genetic variability than those used in any previous work. A clear inverse relationship was found between enzyme subunit number and levels of polymorphism, with monomers being more variable than dimers or tetramers. No significant difference in polymorphism could be found in enzymes of the functional groups I and II of Gillespie and Langley (1974). Regulatory enzymes appeared to be significant relationship was observed between regulatory power and subunit structure which could bias this result. The results suggest that both neutralist and selectionist ideas may have a useful role to play in the understanding of the factors which can influence or limit levels of genetic variation.

Animals↗

PubMed2006

Ornament evolution in dragon lizards: multiple gains and widespread losses reveal a complex history of evolutionary change.

The expression in females of ornaments thought to be the target of sexual selection in males is a long-standing puzzle. Two main hypotheses are proposed to account for the existence of conspicuous ornaments in both sexes (mutual ornamentation): genetic correlation between the sexes and sexual selection on females as well as males. We examined the pattern of ornament gains and losses in 240 species of dragon lizards (Agamidae) in order to elucidate the relative contribution of these two factors in the evolution of mutual ornamentation. In addition, we tested whether the type of shelter used by lizards to avoid predators predicts the evolutionary loss or constraint of ornament expression. We found evidence that the origin of female ornaments is broadly consistent with the predictions of the genetic correlation hypothesis. Ornaments appear congruently in both sexes with some lineages subsequently evolving male biased sexual dimorphism, apparently through the process of natural selection for reduced ornamentation in females. Nevertheless, ornaments have also frequently evolved in both sexes independently. This suggests that genetic correlations are potentially weak for several lineages and sexual selection on females is responsible for at least some evolutionary change in this group. Unexpectedly, we found that the evolutionary loss of some ornaments is concentrated more in males than females and this trend cannot be fully explained by our measures of natural selection.

Animals↗

PubMed2025

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links.

OBJECTIVE: To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. METHODS: We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status-a marker of neurodegeneration-in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). RESULTS: Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). INTERPRETATION: Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.

Journal Article↗

PubMed2003

Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status.

We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence in situ hybridization (FISH), or both. Follow-up marrow biopsies, interphase FISH for bcr-abl, and conventional cytogenetics were performed at 3-month intervals (up to 24 months) after therapy initiation. All patients exhibited a reduction in bone marrow cellularity with decreases in myeloid/erythroid ratios at 3 to 6 months after therapy. The percentage of bcr-abl-positive cells by FISH decreased in all patients (pretherapy median, 73%; 3 months median, 47%). Cytogenetic and FISH data defined 2 groups after 6 months of follow-up: 5 patients became negative for bcr-abl by FISH; 8 remained positive, 4 of whom developed signs of clonal cytogenetic evolution. Patients who became negative for bcr-abl had no morphologic evidence of CML at 15 to 24 months of follow-up, whereas patients who remained positive redeveloped morphologic features of CML as cellularity increased. Some bcr-abl-positive patients showed signs of progression, including 2 patients who developed myeloid blast phase. Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response.

Antineoplastic Agents↗