Polymorphism and association of progesterone receptor gene with milk production and reproductive traits of rabbits

Using the PCR RFLP method polymorphism and three different genotypes (AA, AG and GG) were detected in the progesterone receptor gene (PGR) promoter in a local Slovak crossbred rabbit line. We have noted a slightly majority frequency of allele A (0.53) over allele G (0.47). Comparing the observed and expected genotype frequencies with the χ² test the results were statistically significant, which means the tested rabbit population was non-equilibrium. The best results and significantly highest milk production (P < 0.001) were recorded in the does of GG genotype compared to AA genotype. Other association studies aimed at the effect of genotypes on litter size showed the highest litter size and number of weaned rabbits per litter in GG genotype. A significantly higher (P < 0.05) average number of stillborn kits per litter was in the group of does with AA genotype (0.62) compared with GG genotype (0.34).

Exploring the Genetic Background of the Differences in Nest-Building Behavior in European Rabbit

Once a day, nursing and absentee mothering make the wild rabbit (Oryctolagus cuniculus) an ideal model animal for measuring differences in maternal behavior. Behavioral events and their hormonal regulation leading to parturition are well documented; however, the genetic background behind individual differences in this complex process is unknown. Decreased progesterone hormone level and the reduction of progesterone receptor activity are crucial to initiating the collection of nest material. The progesterone receptor gene is a likely candidate affecting nest-building behavior. In addition to several known point mutations in the progesterone receptor gene of the European wild rabbit, we have found a new mutation in the promoter region of the gene at 2682 T > C. Although this new single nucleotide polymorphism (SNP) was not involved in the formation of the nest-building behavior, an SNP (2464G > A) already described in the promoter region showed an association with individual differences in the initiation of hay carrying. The distribution of this SNP delivered an opposite result compared to domestic rabbits. Genotype (GG) with high uterine capacity was most frequent; the hereditary value of the trait was h2 = 0.10. Thus, progesterone receptor gene polymorphism may manifest in individual differences affecting breeding success in this species.

Molecular Evaluation of PROGINS Mutation in Progesterone Receptor Gene and Determination of its Frequency, Distribution Pattern and Association with Breast Cancer Susceptibility in Saudi Arabia

Aims: Experimental and clinical evidence demonstrate that progesterone hormone and its nuclear receptor, the Progesterone Receptor (PR), play critical role in controlling mammary gland tumorigenesis and breast cancer development. Hormonal therapy (Tomaxifen) is the frontline treatment for hormone-dependent breast cancers. Progesterone hormone induces its action on the target cells by binding with its Progesterone receptor (PgR) therefore any genetic variations, which might induce alienation in the progesterone receptor, can result in an increased susceptibility of gynecological cancers. Alu insertion (PROGINS) mutation in PgR gene is reported to be associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. However, its association with breast cancer risk remains inconclusive. Therefore, we investigated the association of PROGINS allele and its link with breast cancer risk. Methods: This case control study was performed on 200 subjects in which 100 were breast cancer cases and 100 gender matched healthy controls.The mutation was detected by using mutation specific PCR and results were confirmed by direct Sanger sequencing. Results: A clinically significant difference was reported in genotype distribution of PROGINs allele among the cases and gender-matched healthy controls (P<0. 032). Genotype frequencies of A1/A1, A1/A2, A2/A2 reported in cases was 81%, 19% (18% & 1%) and in matched healthy controls were 93%, 7% (6% & 1%). The higher frequency of PROGINs allele (19%) was observed in cases than the healthy controls (7%). The findings indicated that PgR variants (CC vs CT) increased the risk of Breast cancer in codominant inheritance model with OR= 3.44, 95% CI =1. 30-9.09, P<0.021) whereas nonsignificant association was found for CC vs TT genotypes with OR=1.14, 95% CI=0.07-18.658, P=0. 92. However, subgroup analysis revealed that CT + TT vs CC genotype increased the risk of breast cancer in dominant inheritance model tested OR = 3. 11, 95% CI = (1.24-7.79), P = 0.015). A nonsignificant association for PgR (CC+CT) vs TT) genotypes were reported in breast cancer OR = 1. 0, 95% CI= (0. 061-16.21), P=1) in recessive inheritance model tested. However, analysis with clinicalpathological variables revealed that the PROGINs allele is significantly associated with the distant metastasis and advanced stage of the disease. Conclusion: The mutation specific PCR was successfully developed as an alternative to Sanger sequencing for the cost-effective detection for PROGINS allele of progesterone receptor gene. A clinically significant correlation of PROGINs allele was reported with the distant metastasis and advanced stage of the disease. Taken together, these results demonstrated that PROGINS variant is associated with an increased susceptibility to Breast cancer, providing novel insights into the genetic etiology and underlying biology of Breast carcinogenesis. Further studies with large sample sizes are required to validate our findings.

SELECTION-GENETIC CHARACTERISTICS OF RABBITS POLTAVSKA SILVER BREED BY POLYMORPHISM OF PROGESTERONE RECEPTOR GENE

Genetic certification of the Poltavska silver rabbits by the progesterone receptor gene was carried out by amplification of the corresponding sections of genomic DNA in the Polymerase Chain Reaction (PCR). As a result of PCR analysis it was found that the discrete DNA bands of rabbits were intensive hybridization spectra and characterized by different numbers, locations, and intensities of detected fragments. Based on the results of genotyping of Poltavska silver rabbits the following data on their genetic structure were obtained for gene polymorphism G2464A. In actual distribution of genotypes number of homozygous animals with the G gene was 18.3% (11 animals), number of homozygotes for A allele was almost twice as large (31.7%). The Wright fixation index for both polymorphic variants was negative which demonstrates the advantage of heterozygotes in population for tested genes. It was established that high values of multiple fertility rate in three aprons were found in rabbits with the GG genotype, and the lowest - with the AA genotype. In general there was a tendency to increase fertility by an average of 12% in three spouts for the “desired genotype” GG compared to animals that had genotypes AA and AG (p<0.05). Analysis of variation in milk yield of rabbits genotypes by polymorphic variants of progesterone receptor showed that this indicator was higher in homozygous animals AA, and the lowest - in heterozygotes AG. Moreover, rabbits with GG genotype were 3% inferior to them (the difference is not significant). According to the results of one-way analysis of variance, the influence of the rabbit genotype on the progesterone receptor gene on their milk production was found but no statistically significant difference between groups of animals with different genotypes. According to the data obtained it can be argued that the genotype of Poltavska Silver female rabbits in progesterone receptor gene has statistically significant effect on the manifestation of multiple pregnancy which can also be used in breeding.