Prognostic correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities in chronic lymphocytic leukemia patients.

BACKGROUND AND AIM: Chronic lymphocytic leukemia (CLL) is a monoclonal malignancy of B lymphocytes. Since common mutations in NOTCH1 and SF3B1, along with other possible chromosomal alterations, change disease severity and survival of patients with CLL, we aimed to evaluate the correlation of common mutations in NOTCH1 and SF3B1 as the poor prognostic markers with chromosomal abnormalities and clinical hematology. METHOD: This retrospective study was performed on the peripheral blood of 51 patients diagnosed before chemotherapy with CLL. G-banding karyotype and FISH were performed. For NOTCH1, exon 34 and for SF3B1, exons 14,15,16 were assessed using Sanger sequencing. RESULTS: The mutation frequency of NOTCH1 and SF3B1 with the pathogenic clinical status was 6:51 (11.76%), and variants obtained from both genes were 9:51 (17.64%). The frequency of SF3B1 mutation (K666E) was higher than in previous studies (p-value <.05). There was a significant correlation between NOTCH1 mutations and del17p13 (p-value = .068), also SF3B1 mutations with del11q22 (p-value = .095) and del13q14 (p-value = .066). Up to 90% of the specific stimuli used for the G-banding karyotype successfully identified the malignant clone. There was a significant relationship between the cluster of differentiation 38 (CD38) expression level and NOTCH1 mutations (p-value = .019) and a significant correlation between Binet classification and the SF3B1 (p-value = .096). CONCLUSION: The correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities and CD38 expression may reveal the overall patient's survival rate. The mutations may be effective in the clonal expansion and progression of CLL, particularly in the diagnosis stage, as well as the control and management of the treatment.

Genomic comparisons of Persian Kurdish, Persian Arabian and American Thoroughbred horse populations.

The present research aimed to characterize the Persian Kurdish horse population relative to the Persian Arabian and American Thoroughbred populations using genome-wide SNP data. Fifty-eight Kurdish, 38 Persian Arabian and 83 Thoroughbred horses were genotyped across 670,796 markers. After quality control and pruning to eliminate linkage disequilibrium between loci which resulted in 13,554 SNPs in 52 Kurdish, 24 Persian Arabian and 58 Thoroughbred horses, the Kurdish horses were generally distinguished from the Persian Arabian samples by Principal Component Analyses, cluster analyses and calculation of pairwise FST. Both Persian breeds were discriminated from the Thoroughbred. Pairwise FST between the two Persian samples (0.013) was significantly greater than zero and several fold less than those found between the Thoroughbred and Kurdish (0.052) or Thoroughbred and Persian Arabian (0.057). Cluster analysis assuming three genetic clusters assigned the Kurdish horse and Thoroughbred to distinct clusters (0.942 in cluster 2 and 0.953 in cluster 3 respectively); the Persian Arabian was not in a distinct cluster (0.519 in cluster 1), demonstrating shared ancestry or recent admixture with the Kurdish breed. Diversity as quantified by expected heterozygosity was the highest in the Kurdish horse (0.342), followed by the Persian Arabian (0.328) and the Thoroughbred (0.326). Analysis of Molecular Variance showed that 4.47% of the genetic variation was present among populations (P<0.001). Population-specific inbreeding indices (FIS) were not significantly different from zero in any of the populations. Analysis of individual inbreeding based on runs of homozygosity using a larger SNP set suggested greater diversity in both the Kurdish and Persian Arabian than in the Thoroughbred. These results have implications for developing conservation strategies to achieve sound breeding goals while maintaining genetic diversity.

The effect of dietary organic selenium on reproductive performance of broiler breeder roosters under dexamethasone induced stress.

Stress has deleterious impact on semen quality and fertility of roosters. This study was investigated to know whether dietary supplementation of organic selenium (oSe) could improve semen quality and fertility of male broiler breeder under dexamethasone (Dexa) induced stress. Forty broiler breeder roosters (64 week of age) were randomly allotted to four groups (10 roosters/group) and fed a standard diet supplemented with different levels of oSe during 10 successive weeks of the experimental period. To induce stress, the birds received injections of 2 mg/kg BW of Dexa during weeks 5 and 6 of the experiment, in one-day-intervals manner. The roosters were not treated with Dexa and oSe (negative control; NC), or treated with Dexa and different levels of oSe including 0 (positive control; PC), 0.30 (Se30+Dexa) or 0.45 (Se45+Dexa) mg/kg diet. Body weight was measured weekly and semen quality parameters and fertility were evaluated every two weeks. Except for seminal volume and total sperm production which was not affected by the treatment, body weight, semen quality parameters, total antioxidant capacity (TAC) and malondialdehyde (MDA) in seminal plasma were influenced by interactive effect of treatment and time (P < 0.05). Dexamethasone injection adversely affected semen quality parameters (semen concentration, motility and plasma membrane integrity) in PC group compared to NC group (P < 0.05); however, dietary supplementation of oSe ameliorated these negative impacts in Dexa-treated roosters (P < 0.05). Fertility was also improved by dietary supplementation of oSe compared to control groups (P < 0.05). These results indicate that although induction of stress have negative effects on rooster semen quality parameters, dietary inclusion of oSe may exert beneficial impact on mitigating the harmful effects of stress on semen quality and fertility rate of broiler breeder roosters.

Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat.

The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS). This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair) traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY, and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic causality and potential epistatic relationships.

Comparative evaluation of Nabi and Beltsville extenders for cryopreservation of rooster semen.

Two experiments were conducted to evaluate the new rooster semen freezing extender which is containing a low level of glycerol and soybean lecithin as an alternative protective agent in the extender. The aim of the first experiment was to evaluate a new extender for freeze-thawing rooster semen known as "Nabi" extender compared to Beltsville. Second experiment was also performed to determine whether the Nabi extender has negative reactions on fertilization after artificial insemination (AI) or no. In the first experiment, post-thaw motion parameters, mitochondrial function and sperm apoptosis were analyzed using Sperm Class Analyzer (SCA), rhodamine-123 and Annexin-V, respectively for frozen-thawed semen in Nabi and Beltsville extender. Results showed that total motility, progressive motility, velocity parameters (VCL, VSL, VAP, LIN and STR) and live spermatozoa with active mitochondria were significantly higher in Nabi compare to Beltsville extender (P < 0.01). Also, the percentages of post-thawed live and early apoptotic spermatozoa were significantly higher in Nabi compared to Beltsville extender (14.46 ± 0.95 vs. 19.27 ± 0.95 and 14.83 ± 4.51 vs. 39.27 ± 4.51, respectively). For apoptotic spermatozoa, the percentages of post-thawed late apoptotic spermatozoa were significantly lower in Nabi (29.66 ± 3.11) compared to Beltsville extender (69.07 ± 3.11), but the type of extender had no effect on the percentages of post-thawed necrotic spermatozoa. In the second experiment, 20 broiler breeder hens (Ross 308) were inseminated with thawed semen using the new freezing diluents or fresh semen for determination of fertility rate. Fertility rate with thawed semen (with Nabi extender) was lower compared to fresh semen (by approximately 8% points). It can be concluded that Nabi extender would improve post-thawed rooster sperm in vitro quality compared to Beltsville extender. The fertility rates of insemination in hens with freeze-thaw sperm were comparable with fresh sperm.

The influence of genetic background versus commercial breeding programs on chicken immunocompetence.

Immunocompetence of livestock plays an important role in farm profitability because it directly affects health maintenance. Genetics significantly influences the immune system, and the genotypic structure of modern fast-growing chickens has been changed, particularly after decades of breeding for higher production. Therefore, this study was designed to help determine if intensive breeding programs have adversely affected immunocompetence or whether the immune response profiles are controlled to greater extent by genetic background. Thus, 3 indigenous chicken populations from different genetic backgrounds and 2 globally available modern broiler strains, Ross 308 and Cobb 500, were evaluated for various aspects of immune response. These included antibody responses against sheep red blood cells and Brucella abortus antigen, as well as some aspects of cell-mediated immunocompetence by toe web swelling test and in vitro blood mononuclear cell proliferation. Significant differences (P < 0.05) in antibody responses to both antigens and cellular proliferation were observed among populations but not consistently between modern commercial strains versus the indigenous populations. In fact, the immune response profiles of Cobb 500 were similar to the indigenous populations, but varied compared with the other commercial strain. In addition, considerable variation was recorded between indigenous populations for all responses measured in this study. The results of this study suggest that the variation observed in immune responses between these strains of chickens is most likely due to differences in the genetic background between each strain of chicken rather than by commercial selection programs for high production.

Prediction of breeding values for dairy cattle using artificial neural networks and neuro-fuzzy systems.

Developing machine learning and soft computing techniques has provided many opportunities for researchers to establish new analytical methods in different areas of science. The objective of this study is to investigate the potential of two types of intelligent learning methods, artificial neural networks and neuro-fuzzy systems, in order to estimate breeding values (EBV) of Iranian dairy cattle. Initially, the breeding values of lactating Holstein cows for milk and fat yield were estimated using conventional best linear unbiased prediction (BLUP) with an animal model. Once that was established, a multilayer perceptron was used to build ANN to predict breeding values from the performance data of selection candidates. Subsequently, fuzzy logic was used to form an NFS, a hybrid intelligent system that was implemented via a local linear model tree algorithm. For milk yield the correlations between EBV and EBV predicted by the ANN and NFS were 0.92 and 0.93, respectively. Corresponding correlations for fat yield were 0.93 and 0.93, respectively. Correlations between multitrait predictions of EBVs for milk and fat yield when predicted simultaneously by ANN were 0.93 and 0.93, respectively, whereas corresponding correlations with reference EBV for multitrait NFS were 0.94 and 0.95, respectively, for milk and fat production.

Estimation of genetic parameters for body weight and egg production traits in Mazandaran native chicken.

Native chicken breeding station of Mazandaran was established in 1988 with two main objectives: genetic improvement through selection programs and dissemination of indigenous Mazandarani birds. (Co)variance components and genetic parameters for economically important traits were estimated using (bi) univariate animal models with ASREML procedure in Mazandarani native chicken. The data were from 18 generations of selection (1988-2009). Heritability estimates for body weight at different ages [at hatch (bw1), 8 (bw8), 12 (bw12) weeks of ages and sex maturation (wsm)] ranged from 0.24 ± 0.00 to 0.47 ± 0.01. Heritability for reproductive traits including age at sex maturation (asm); egg number (en); weight of first egg (ew1); average egg weight at 28 (ew28), 30 (ew30), and 32 (ew32) weeks of age; their averages (av); average egg weight for the first 12 weeks of production (ew12); egg mass (em); and egg intensity (eint) varied from 0.16 ± 0.01 to 0.43 ± 0.01. Generally, the magnitudes of heritability for the investigated traits were moderate. However, egg production traits showed smaller heritability compared with growth traits. Genetic correlations among egg weight at different ages were mostly higher than 0.8. On the one hand, body weight at different ages showed positive and relatively moderate genetic correlations with egg weight traits (ew1, ew28, ew30, ew32, ew12, and av) and varied from 0.30 ± 0.03 to 0.59 ± 0.02. On the other hand, low negative genetic correlations were obtained between body weight traits (bw1, bw8, bw12, and wsm) and egg number (en). Also, there is low negative genetic correlation (-24 ± 0.04 to -29 ± 0.05) between egg number and egg weight. Therefore, during simultaneous selection process for both growth and egg production traits, probable reduction in egg production due to low reduction in egg number may be compensated by increases in egg weight.

Risk factors for abortion in dairy cows from commercial Holstein dairy herds in the Tehran region.

In last decade, pregnancy loss in dairy cattle has had an upward trend bringing difficulties for breeders: the annual cost is estimated around 396 billion Rials (i.e. around 40 million US$) for the Iranian dairy industry. The present study was conducted to determine the influence of maternal factors on abortion and to predict the probability of abortion as well as the effect of these factors on the fetal lifetime in Holstein dairy cattle. Data from 44,629 established pregnancies that included 14,226 heifers and 30,403 pregnancies from 12,265 parous cows in nine industrial dairy herds around Tehran were used. Overall, 4871 pregnancies of parous cows resulted in abortion. Prediction of the probability of abortion (PPA) was estimated by a logistic regression model. Survival analysis was performed using an accelerated failure time (AFT) model assuming a multi-modal hazard function. Effective factors included age of dam at conception, gravidity, open days, number of previous abortion(s), abortion before/after 60 days of gestation in previous conception, herd and season of insemination. The PPA decreased with increasing open days, increasing gravidity and no previous abortion. In addition, the PPA was greater for cows which had been inseminated during summer versus winter. However, the difference between autumn and spring was not significant. Overall, 25 sires out of 695 from which sperm was collected for artificial insemination (AI) had significantly higher risk of abortion, with odds ratios ranging between 1.44 and 4.73 compared to the average. The survival probability increased slightly during gestation as gravidity increased for cows that had a previous abortion. Cows that had aborted before 60 days of gestation in previous conception tended to abort later in their next conceptions.

Heterogeneity of variance for milk traits at climitical regions in Holstein dairy cattle in Iran and the best method(s) for data transformation.

In this research, heterogeneity of variance components in cattle populations at climatical regions in the first three lactations was studied. The data set included the following: 161328 records of first, 123369 records of second and 81013 records of third lactations, which was collected by Animal Breeding Center of Iran from 1983 to 2004. Records of three lactations were divided in the base of Domarten method. Bartlett test for heterogeneity of variance components was significant among all subgroups. In order to decrease the heterogeneity of variance components, we used several data transformation methods including Logarithmic, Square root and Arc sin transformations. Logarithmic transformation decreased the heterogeneity of variance components in the three lactations and other methods had not effect for removing the heterogeneity in any group. Genetic parameters and heritability were estimated for three lactations by MATVEC program, using animal model. Results showed that the heritability estimates of milk yield were decreased from the first lactation to the third; also the heritability estimates of transformed data were slightly higher than the original data. Comparison between estimated parameters in single trait and two traits analysis, before and after data transformation, showed that there were not significant differences between derived results.

Effect of the threshold nature of traits on heritability estimates obtained by linear model.

In this research we used stochastic method to simulate litter size data under assumption that the phenotype of the trait of interest is categorically distributed with a liability of normally distributed background effect. For the phenotypic categorical measurements, normal distribution of liability was assumed. Analysis was conducted by DFREML for phenotypic categorical data set. In the simulation process, we applied different true background heritabilities in combination with different threshold points. The points with the lowest heritability had the lowest variation in estimated heritability and those with the highest heritability had the highest variation. Results clearly show that by moving threshold points from the population mean towards the two tails of the distribution and also by increasing the true heritability, the differences between estimated heritability and true heritability increases. The linear model has always underestimated true heritabilities. It is possible to use our estimates to obtain a confidence range for true heritability when we have information about approximate location of threshold and estimates of heritability obtained by linear model.