Relationship between MTNR1A melatonin receptor gene polymorphism and seasonal reproduction in different goat breeds

The reproductive activity of goats bred in temperate latitude follows a seasonal pattern, influenced by annual variation in day length. Daily variation in pineal melatonin secretion is the neuroendocrine signal recognized by animals through the link between this hormone and melatonin receptor 1a (MTNR1A). A total of 345 goats of different breeds (225 Sarda, 30 Saanen, 30 Chamois Coloured, 30 Maltese and 30 Nubian) with a kidding period in October-December or January-March were analysed to verify if a link exists between the structure of the receptor gene and reproductive activity. The main part of exon II of MTNR1A gene was amplified by PCR and then digested with MnlI and RsaI to prove the presence of restriction sites. Sequencing of 20 cloned samples and 20 purified samples permitted comparison with previously published sequences. No polymorphism was found using MnlI enzyme, as all 345 samples showed the cleavage site in position 605 and all the goats were MM genotype. However, using RsaI enzyme, some Sarda goats, showed a polymorphic site in position 53. Nine Sarda goats were R/r genotype, lacking this cleavage site only in one allele, while the other animals, both Sarda and the other breeds, presented the cleavage site in both the alleles and were thus R/R genotype. No r/r genotype was found in any of the breeds. In Sarda goats the allelic frequency was 0.98 for R allele and 0.02 for r allele; genotypic frequency was 96.00% for R/R genotype and 4.00% for R/r genotype. A strong link emerged from statistical analysis (P<0.001) between R/r genotype and reproductive activity, which was strongly influenced by photoperiod. Sequencing indicated six nucleotide changes that did not induce any amino acid change. Data showed that polymorphism was present and that it influences reproductive activity only in the Sarda breed.     

Interferon-gamma and interleukin-4 single nucleotide gene polymorphisms in Paracoccidioidomycosis

The gene polymorphisms interferon-gamma (IFN-γ) +874 T/A and interleukin (IL)-4 −590 C/T have been associated with the altered production of cytokines. Therefore, they might be indicative of the occurrence of Paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis. The analysis of single nucleotide polymorphism (SNP) at position +874 IFN-γ showed an increase occurrence of A/T genotype in both PCM patients and healthy individuals as control (HIC) (56% and 45%, respectively), while the allelic distribution showed 82% of A allele in the patients and 80% in the controls. The SNP of −590 IL-4 showed that C/T genotype was significantly (p < 0.05) more prevalent (39%) in PCM group compared to the HIC group (19%), while IL-4 C/C genotype was significantly less frequent (59%) in the patient group compared to the control group (81%). Otherwise, 41% of PCM patients and 19% of HIC individuals carried the IL-4 T allele. Stimulation of peripheral blood mononuclear cells (PBMC) from PCM patients with cell extract antigenic preparations (PbAg) as well as secreted and surface antigens (MEXO) of P. brasiliensis evidenced that there is no difference in the IFN-γ production related to A and T alleles between PCM and HIC individuals. However, with IL-4 production, PCM patients classified as C phenotype showed two times more IL-4 production than PCM patients classified as T phenotype and HIC controls. In conclusion, our results suggest that functional genetic variants in the IL-4 promoter could influence the production of IL-4 in PCM.     

G to C transition at position −173 of MIF gene of the recipient is associated with reduced relapse rates after allogeneic stem cell transplantation

Pro-inflammatory and dendritic cell-activating properties of macrophage migration inhibitory factor (MIF) suggest a potentially important role for MIF in alloantigen-specific immune responses after allogeneic stem cell transplantation (allo-SCT). We tested whether MIF −173 G/C gene polymorphism of donor or patient had impacts on the outcomes after allo-SCT. Four hundred and fifty-four donor–patient pairs were genotyped and mortality, relapse, and development of complications were analyzed. Patient but not donor MIF −173*C allele was associated with improved overall survival (OS) (5 years: 60.8% versus 46.3%, p = 0.042) and disease free survival (DFS) (5 years: 55.4% versus 39.5%; p = 0.014) due to a reduction in relapse (day 2000: 22.8% versus 42.0% p = 0.006) but not due to decreased transplantation-related mortality (TRM) (p = 0.44). Multivariate analysis proved patient −173*C allele as an independent factor for reducing relapse after allo-SCT (p = 0.023). Subgroup analysis showed a clear MIF −173*C allele-related reduction in relapse for those patients who did not receive T cell depleted (TCD) SCT (p = 0.01) in contrast to patients receiving TCD SCT (p = 0.20). In summary, patient MIF −173*C allele may be linked to specific, yet unrevealed functions in tumor biology and graft versus leukemia and lymphoma effects and potentially presents a novel prognostic marker for patient-tailored counseling and therapy in allo-SCT.     

A potential role for the endothelin ET A receptor in salt-sensitive hypertension of the proANP gene-disrupted mouse

We have previously shown that the partial disruption of the gene for atrial natriuretic peptide (ANP) results in a salt-sensitive phenotype. The present study examined the possibility that alterations in either the ANP natriuretic pathway or endothelin (ET) system in the kidney of the salt-challenged ANP +/− mouse was responsible for its salt-sensitive phenotype. Plasma ANP levels and renal cGMP activity were increased in response to a salt load in both ANP +/+ and +/− mice. However, the mRNA expression of proANP was found to be increased only in the ANP +/− kidney along with its guanylyl cyclase-linked receptor, NPRA; the upregulation of NPRA mRNA was limited to the renal medulla. This suggests that the renal ANP pathway remains capable of responding to a salt load in the ANP +/− animal, but may be compensating for other dysfunctional pathways. We also report a significant increase in renal ET-1 mRNA and ET_A receptor protein expression in medulla and cortex of the salt-treated, ANP +/− mouse, but not its wild-type counterpart. In fact, ET_A expression decreased in the renal cortex of the ANP +/+ salt-treated animal. The ET_B receptor expression was not affected by diet in either genotype. We hypothesize that the salt-sensitive hypertension in the ANP +/− mouse is exacerbated, and possibly driven by the vasoconstrictive effects resulting from an upregulated ET-1/ET_A pathway.     

Association of Polymorphic Markers of the Antioxidant Enzyme Genes with Diabetic Polyneuropathy in Type 1 Diabetes Mellitus

The allele and genotype frequency distributions of polymorphic markers of genes coding for antioxidant enzymes were compared for type 1 diabetes mellitus patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients) had nonoverlapping (polar) phenotypes. Group DPN+ included 86 patients with DPN and diabetic record no more than 5 years. Control group DPN– included patients without DPN and diabetic record of at least 10 years. Comparative analysis with Fisher's exact test revealed a significant difference in allele and genotype frequency distributions of the (–262) polymorphic marker of the CAT gene. Polymorphic markers C1167T of the CAT gene, Pro/Leu of the GPX1 gene, 0/+ of the GSTT1 gene, and 0/+ of the GSTM1 gene showed no significant difference in allele or genotype frequency distribution. On this evidence, these markers were not associated with DPN in the sample examined.     

Association of tumor necrosis factor alpha, interferon gamma and interleukin 10 gene polymorphisms with peripheral neuropathy in South Indian patients with type 2 diabetes

Diabetic peripheral neuropathy (DPN) is a major global health threat and a common complication of diabetes. Peripheral nerve complications due to irregular cytokine production are eminent factors in many inflammatory diseases. The present study focused on gene polymorphisms of pro and anti-inflammatory cytokines that may be responsible for nerve damage in diabetic neuropathy. We examined three common functional SNPs primarily at the positions on genes of tumor necrosis alpha (TNFα) −308G/A, interferon gamma (IFNγ) +874A/T and interleukin (IL) 10 −1082G/A in order to establish their association with peripheral neuropathy in type 2 diabetes. Results: Genotypic frequencies obtained from TNFα −308G/A gene analysis in DPN group comprised 86.4% of G/A, 10.6% of G/G and 3% of A/A genotype, where as the control group had 94% of G/A, 2% of G/G and 4% of A/A which could not reach the statistical significance with the disease after Bonferroni correction. The IFNγ +874 A/T polymorphism in patient group revealed 33.3% of A/A, 47.5% of A/T and 19.2% of T/T genotype. The A/A genotype had attained statistical significance of P = 0.04 (P corrected); OR 2; 95% CI 1.14–3.64 when compared to controls. The IL10 −1082 G/A polymorphism in the patient group has showed 62.6% of A/A, 21.2% of G/A, 16.2% of G/G genotype, revealing significant association with G/G genotype (P < 0.01, OR 2.9; 95% CI 1.47–5.84) when compared to controls. Conclusion: Our findings indicate that the tested markers within the IFNγ and IL-10 genes, but not the TNFα gene, are significantly associated with peripheral neuropathy in South Indian type 2 diabetic patients. The study shows that the ‘high-producer’ IL-10 −1082 G/G genotype and the ‘low-producer’ IFNγ +874 A/A genotype may be responsible for the down regulation of immune response leading to inflammation in this setting.     

Association between expression of reproductive seasonality and alleles of the gene for Mel(1a) receptor in the ewe

To determine whether a link exists between reproductive seasonality and the structure of the gene for melatonin receptor Mel(1a), the latter was studied in two groups of Mérinos d'Arles (MA) ewes previously chosen for their genetic value, which took into account their own out-of-season ovulatory activity adjusted by environmental parameters and that of their relatives. The genomic DNA of 36 ewes found regularly cycling in spring (group H) and that of 35 ewes never cycling in spring (group L) during the 2-3 yr before the present study was prepared, and the cDNA corresponding to almost all exon II was amplified and checked for the presence of MnlI restriction sites. The presence (+) or absence (-) of an MnlI site at position 605 led to genotypes "++", "+-", and "--", whose frequencies differed significantly (P < 0.001) between the H and L groups: 52.8%, 47.2%, and 0% vs. 28.5%, 42.9%, and 28.5%, respectively. Sequencing of exon II cDNA in group L ewes with genotype -- showed the presence of only one allele - with 4 mutations, while that in ewes with genotype ++ showed different types of alleles unrelated to the H or L groups. These + alleles exhibited a combination of 1 to 7 of the 8 mutations recorded in the part of exon II studied. The genotyping of 29 ewes from the more seasonal Ile-de-France breed indicated that 38% of animals had a -- genotype and exhibited the same mutations as in the MA ewes. Finally, a comparison of (125)I-melatonin binding to membrane preparations of pars tuberalis showed a lower number of binding sites (P < 0. 0005) in MA ewes with genotype ++ than in those with genotype -- (43. 2 +/- 4.4 vs. 75.4 +/- 8.4 fmol/mg protein in genotype ++ and genotype --, respectively). In conclusion, the data show an association between genotype -- for site MnlI at position 605 and seasonal anovulatory activity in MA ewes.     

Pig melatonin receptor 1a (MTNR1A) genotype is associated with seasonal variation of sow litter size

The duration of nocturnal melatonin secretion reaches its minimum in summer, a physiological event that is likely related with the diminished sow fertility and delayed puberty typically observed in this season. Melatonin exerts its function by binding two different receptors named as MTNR1A and MTNR1B. Interestingly, the MTNR1A gene is located on a chromosome SSC17 region where QTL for prolificacy traits have been detected in previous studies. In this work, we have found a synonymous T162C polymorphism at exon 2 of the pig MTNR1A gene. An association analysis between this polymorphism and sow prolificacy in an Iberian ×  Meishan intercross was performed. The utilization of four statistical models of increasing complexity demonstrated that the MTNR1A gene has both additive and dominant effects on total number of born piglets (TNB) and number of piglets born alive (NBA). Additive effects were significant in summer (TNB, P < 0.01; NBA, P < 0.001), whereas dominant effects reached significance both in fall (TNB, P < 0.01; NBA, P < 0.05) and in winter (TNB, P < 0.001; NBA, P < 0.05). The seasonal variation observed for MTNR1A additive and dominant effects might be produced by the influence of photoperiod on the pattern and duration of melatonin secretion. These results illustrate that the complex interaction between genotype and environment can be an important source of phenotypic variation of reproductive traits.     

Genetic diversity of prion protein gene in Asian native goat

This study seeks to investigate the genetic variability of PRNP in Asian goats. We sequenced the PRNP coding region using a total of 193 samples from seven Asian countries (Japan, Laos, Vietnam, Bhutan, Mongolia, Myanmar and Cambodia). Sequence comparison revealed five previously reported polymorphisms in the PRNP coding region. Two of those polymorphisms (G126A and C414T) were silent mutations, and the other three (T304G, A428G and T718C) caused amino acid changes (W102G, H143R and S240P). In the total of 193 animals, one amino acid mutation (T304G) exhibited low variability (minor allele frequency = 0.04), but the other four were high (0.31–0.36). In addition, allele frequencies of C414T and T718C exhibited remarkable differences among countries (p-values of 6.50E−17 and 5.49E−18). These results suggest high genetic variability of PRNP among these countries and are useful information for estimating genetic diversity in Asian goats.     

Effect of genotype at the MTNR1A locus and melatonin treatment on first conception in Sarda ewe lambs

A sample of 423 Sarda ewe lambs from three different farms was used to evaluate the effect of one or two melatonin implants on the time of first conception. On each farm, 141 animals were divided into three groups. On June 30 these animals received either no treatment (Group C), 18 mg melatonin (Group M1, one implant), or 18 + 18 mg melatonin (Group M2, two implants). Thirty-five days after treatment, rams were introduced in the ewe lambs flock and subsequently removed after 40 days. Lambing dates were recorded between 150 and 190 days from the first day of male introduction. Genotyping and sequencing of the MT1 exon 2 were carried out to analyze the structure and the possible influence of the MT1 receptor gene on reproductive response to melatonin treatment. Melatonin-treated animals had a higher rate of pregnancy (P < 0.05) and lambed earlier (P < 0.05) compared with untreated animals. Single nucleotide polymorphisms were found in exon II of MT1 gene at positions C606T and G612A leading to genotypes C/C, C/T or T/T and +/+, +/− and −/−, respectively. Melatonin-treated animals of +/+ genotype showed a higher number of pregnancies (P < 0.05) and lambed earlier (P < 0.05) compared to untreated animals of the same genotype. Melatonin treatment did not affect reproductive activity in any other genotype analyzed. No correlation between genotype and the time of first conception was found in untreated animals. Concluding data revealed the positive effect of melatonin treatment on the time of first conception in ewe lambs and highlighted that +/+ genotype is able to influence reproductive response to melatonin treatment.     

Ala45Thr polymorphism of the NEUROD1 gene and diabetes susceptibility: a meta-analysis

A meta-analysis assessed whether the Ala45Thr polymorphism of the neurogenic differentiation 1 (NEUROD1) gene is associated with increased risk of diabetes mellitus type 1 (T1D) or type 2 (T2D). Fourteen case-control studies were analyzed, including genotype data on 3,057 patients with diabetes (T1D n=1,213, T2D n=1,844) and 2,446 controls. Overall and race-specific summary odds ratios (ORs) were obtained with fixed and random effects models. The Thr allele did not significantly increase the overall risk for T1D (OR 1.27 [0.94–1.71], P=0.12) or T2D (OR 1.07 [0.90–1.28], P=0.46). The Thr allele conferred increased susceptibility in subjects of Asian racial descent to T1D (OR 1.88 [1.10–3.21], P=0.020), but not to T2D (OR 1.08 [0.74–1.56], P=0.70). There was no association in subjects of European descent (OR 0.97 [0.76–1.23], P=0.80 for T1D; OR 1.03 [0.88–1.21], P=0.68 for T2D). Larger studies seemed to show more conservative estimates for the association with T1D (P=0.083). The Ala45Thr polymorphism of the NEUROD1 gene has no effect on susceptibility to T2D. It may however be a risk factor for susceptibility to T1D, in particular for subjects of Asian descent, although bias cannot be totally excluded.     

Polymorphisms of Alcohol Dehydrogenase Genes ADH1Band ADH7 in Russian Populations of Siberia

Three Russian populations of Siberia were examined for allele and genotype frequency distributions of two alcohol dehydrogenase genes, ADH1B (exon 3 polymorphism A/G detectable with MslI) and ADH7 (intron 5 polymorphism G/C detectable with StyI). No interpopulation or sex difference in allele frequencies was revealed. Allele ADH1B*G (+ MslI, A2) was rare (3.6–7.5%); the frequency of the mutant ADH7 allele (–StyI, B2) was 46.02% in the total sample (N = 339). The genotype frequencies obeyed the Hardy–Weinberg equilibrium and the alleles were in linkage equilibrium in each population. Frequency of ADH7 allele B2 increased beyond 40 years of age in the total sample (by 11%, P = 0.001) and in the Tomsk population (by 9%, P= 0.017). The ADH1B and ADH7 polymorphisms had no effect on the antioxidant activity (AOA), which was inferred from the ability of serum to reduce the yield of thiobarbituric acid-reactive species in the Fe²⁺–lecithin system. In the Tomsk population, carriers of AHD1B allele A2 showed a significant increase in very low density lipoproteins (by 9.95%, P = 0.045) and a near significant increase in systolic pressure (by 6.8%, P = 0.068) and serum triglycerides (by 6.16%, P = 0.058).     

Applying polynomial standard curve method to correct bias encountered in estimating allele frequencies using DNA pooling strategy

DNA pooling approach is a cost-saving strategy which is crucial for multiple-SNP association study and particularly for laboratories with limited budget. However, the biased allele frequency estimates cannot be completely abolished by κ correction. Using the SNaPshot™, we systematically examined the relations between actual minor allele frequencies (AMiAFs) levels and estimates obtained from the pooling process for all six types of SNPs. We applied principle of polynomial standard curves method (PSCM) to produce allele frequency estimates in pooled DNA samples and compared it with the κ method. The results showed that estimates derived from the PSCM were in general closer to AMiAFs than those from the κ method, particularly for C/G and G/T polymorphisms at the range of AMiAF between 20–40%. We demonstrated that applying PSCM in the SNaPshot™ platform is suitable for multiple-SNP association study using pooling strategy, due to its cost effectiveness and estimation accuracy.     

Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men

Background: Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: −33T > C IL4, −174 G > C IL6, −251 T > A IL8 and 1188 A > C IL12B. Methods: 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation–maximization algorithm and haplotype frequencies were compared. Results: We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Conclusions: Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.     

Polymorphisms of CYP1B1 and COMT in Breast and Endometrial Cancer

CYP1B1 and COMT code for the key enzymes of catecholestrogen biosynthesis and metabolism, and their polymorphisms determine the variation of enzyme activities. RFLP analysis was used to study the allele and genotype frequency distributions of CYP1B1 polymorphisms Arg48Gly, Ala119Ser, and Val432Leu, and COMT polymorphism Val158Met among 210 breast cancer patients, 138 endometrial cancer patients, and 152 healthy women. The COMT polymorphism showed no significant association with breast or endometrial cancer. For the first time, such association was observed for the CYP1B1 polymorphisms. CYP1B1 allele C (Arg48), which codes for the enzyme more active in estradiol 4-hydroxylation, was associated with higher risk of breast (OR = 3.22, CI 2.34–4.43, P = 0.000) and endometrial (OR = 2.43, CI 1.72–3.44, P = 0.000) cancer. Similar data were obtained for CYP1B1 allele G (Ala119): OR = 2.18, CI 1.58–3.01, P = 0.000 in breast cancer and OR = 2.52, CI 1.78–3.56, P = 0.000 in endometrial cancer. Risk of endometrial but not breast cancer was significantly higher in carriers of CYP1B1 genotype Val432/Val. This was explained by stronger estrogen dependence and, consequently, higher estrogen responsiveness of the endometrium as compared with the mammary gland.     

ICChI, a glycosylated chitinase from the latex of Ipomoea carnea

A multi-functional enzyme ICChI with chitinase/lysozyme/exochitinase activity from the latex of Ipomoea carnea subsp. fistulosa was purified to homogeneity using ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography. The enzyme is glycosylated (14–15%), has a molecular mass of 34.94 kDa (MALDI–TOF) and an isoelectric point of pH 5.3. The enzyme is stable in pH range 5.0–9.0, 80 °C and the optimal activity is observed at pH 6.0 and 60 °C. Using p-nitrophenyl-N-acetyl-β-d-glucosaminide, the kinetic parameters K_m, V_max, K_cat and specificity constant of the enzyme were calculated as 0.5 mM, 2.5 × 10⁻⁸ mol min⁻¹ μg enzyme⁻¹, 29.0 s⁻¹ and 58.0 mM⁻¹ s⁻¹ respectively. The extinction coefficient was estimated as 20.56 M⁻¹ cm⁻¹. The protein contains eight tryptophan, 20 tyrosine and six cysteine residues forming three disulfide bridges. The polyclonal antibodies raised and immunodiffusion suggests that the antigenic determinants of ICChI are unique. The first fifteen N-terminal residues G–E–I–A–I–Y–W–G–Q–N–G–G–E–G–S exhibited considerable similarity to other known chitinases. Owing to these unique properties the reported enzyme would find applications in agricultural, pharmaceutical, biomedical and biotechnological fields.     

Polymorphic markers of the NO synthase genes and genetic predisposition to diabetic polyneuropathy in type 1 diabetes mellitus

The allele and genotype frequency distributions of polymorphic markers of the NOS1, NOS2, and NOS3 genes coding for three different NO synthases were compared for type 1 diabetes mellitus (T1DM) patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients, ethnic Russians or East Slavs from Moscow) had nonoverlapping (polar) phenotypes. Group DPN+ included patients with DPN and T1DM duration of no more than 5 years. Control group DPN- included patients without DPN and with T1DM duration of at least 10 years. No significant differences in allele and genotype frequency distributions were revealed for the polymorphic markers (CA) _n of gene NOS1 (CCTTT) _n of gene NOS2, and ecNOS4a/4b and Glu298Asp of gene NOS3, suggesting a lack of association between the polymorphic markers and DPN. In the case of the (CCTTT) _n polymorphic marker of the NOS2 gene, a tendency toward an association with DPN was observed for allele 14. Carriers of this allele have a lower risk of DPN in T1DM.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 224–229.Original Russian Text Copyright © 2005 by Zotova, Voronko, Bursa, Galeev, Strokov, Nosikov.     

Association between expression of reproductive seasonality and alleles of melatonin receptor 1A in goats

To determine whether a link exists between reproductive seasonality and the structure of the melatonin receptor 1A (MTNR1A) gene, the latter was studied in year-round estrous breeds (Jining Grey and Boer goats) and seasonal estrous breeds (Liaoning Cashmere, Inner Mongolia Cashmere, Wendeng milk and Beijing native goats). A large fragment of exon 2 of MTNR1A gene was amplified by PCR using sheep sense and antisense primers in 260 does of six breeds. The uniform 824 bp PCR product was digested with restriction endonucleases MnII and RsaI, and checked for the presence of restriction sites. No polymorphism at the MnII cleavage sites was detected in all six goat breeds and no relationship could be established between the MnII cleavage sites of MTNR1A gene and reproductive seasonality in goats. For polymorphic RsaI cleavage site at base position 53, only genotype RR (267 bp/267 bp) was detected in Jining Grey goats, both genotype RR and genotype Rr (267 bp/320 bp) were found in all other goat breeds, no genotype rr (320 bp/320 bp) was detected in all six goat breeds. Frequency of genotype RR was obviously higher, and frequency of genotype Rr was obviously lower in year-round estrous goat breeds than in seasonal estrous goat breeds. Sequencing revealed one mutation (G52A) in genotype Rr compared with genotype RR. For polymorphic RsaI cleavage site, the differences of genotype distributions were significant (P<0.05) between year-round estrous goat breeds and seasonal estrous goat breeds. These results preliminarily showed an association between genotype RR and year-round estrus in goats, and an association between genotype Rr and seasonal estrus in goats.