Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
Data from an F 2 cross between breeds of livestock are typically analysed by least squares line-cross or half-sib models to detect quantitative trait loci (QTL) that differ between or segregate within breeds. These models can also be combined to increase power to detect QTL, while maintaining the computational efficiency of least squares. Tests between models allow QTL to be characterized into those that are fixed (LC QTL), or segregating at similar (HS QTL) or different (CB QTL) frequencies in parental breeds. To evaluate power of the combined model, data wih various differences in QTL allele frequencies (FD) between parental breeds were simulated. Use of all models increased power to detect QTL. The line-cross model was the most powerful model to detect QTL for FD>0.6. The combined and half-sib models had similar power for FD<0.4. The proportion of detected QTL declared as LC QTL decreased with FD. The opposite was observed for HS QTL. The proportion of CB QTL decreased as FD deviated from 0.5. Accuracy of map position tended to be greatest for CB QTL. Models were applied to a cross of Berkshire and Yorkshire pig breeds and revealed 160 (40) QTL at the 5% chromosome (genome)-wise level for the 39 growth, carcass composition and quality traits, of which 72, 54, and 34 were declared as LC, HS and CB QTL. Fourteen CB QTL were detected only by the combined model. Thus, the combined model can increase power to detect QTL and mapping accuracy and enable characterization of QTL that segregate within breeds.
A Duroc-Pietrain resource population was built to detect quantitative trait loci (QTL) that affect growth, carcass composition, and pork quality. The data were analyzed by applying three least-squares Mendelian models: a line-cross (LC) model, a half-sib (HS) model, and a combined LC and HS model (CB), which enabled the detection of QTL that had fixed, equal, and different allele frequencies for alternate breed alleles, respectively. Permutation tests were performed to determine 5% chromosome-wide and 5% genome-wide threshold values. A total of 40 (137) QTL were detected at the 5% genome-wide (chromosome-wide) level for the 35 traits analyzed. Of the 137 QTL detected, 62 were classified as the LC type (LC-QTL), 47 as the HS type (HS-QTL), and 28 as the CB type (CB-QTL). The results indicate that implementation of a series of model-based framework is not only beneficial to detect QTL, but also provides us with a new and more robust interpretation from which further methodology could be developed.
Porcine chromosome 6 (SSC6) has been reported to have QTL affecting intramuscular fat content (IMF) in multiple populations. The objective of this study was to investigate the effect of FABP3 and LEPR genetic variations as well as their mRNA expression on the IMF trait in a three-generation of Korean native pig and Yorkshire crossed animals. Several polymorphisms of the FABP3 (HinfI, HaeIII and HinfI*) were significantly associated with moisture, tenderness and flavor score (P < 0.05), and were used to construct haplotypes: haplotype 1 (-TCT-) increased the marbling and intramuscular fat content, however, haplotype 2 (-CCT-) decreased tenderness. The LEPR AvaII polymorphism showed significant association with moisture, intramuscular fat, cholesterol and flavor score (P < 0.05). The linkage analyses with six microsatellites mapped FABP3 gene in the interval between the markers Sw1129 and S0228 (Sw1129--11.7 cM--FABP3-9.1 cM--S0228), and the LEPR gene between the markers S0121 and Sw322 (S0121--7.5 cM--LEPR--28.5 cM--Sw322). QTL mapping suggested a significant QTL affecting Moisture (83 cM) and IMF (84 cM) located close to marker S0228. The gene expression results showed that in the loin muscle, both of the FABP3 and LEPR genes showed significantly higher expression in pigs with higher IMF%, however, in the backfat, only FABP3 showed differential expression between these two groups of pigs (significantly higher expression in pigs with lower IMF%) (P < 0.05). In the liver, both of these two genes did not show any difference between the high and low IMF% groups.
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