A1 Allele Research Articles

STUDY OF BETA-CASEIN GENE POLYMORPHISM IN DOMESTIC BREED DAIRY COWS

Studies have been conducted on the study of beta-casein gene polymorphism in Sumy inbred cattle populations of the Ukrainian black-spotted dairy and Ukrainian brown dairy breeds. The research was carried out in the breeding plants of the State Enterprise "Experimental Farm of the Institute of Agriculture of the North East of the National Academy of Sciences". Determination of polymorphism of the beta-casein gene was carried out in the genetic laboratory of the Bogomolets Institute of Physiology of the National Academy of Sciences using a molecular biological analysis of allele recognition, using the polymerase chain reaction (PCR) method in real time. It was established that cows of the studied breeds are characterized by polymorphism at the CSN2 locus. Allele A2 prevailed in frequency in animals of both groups. A difference in the frequency of this allele was established between them, to the advantage of animals of the Ukrainian brown dairy breed (by 1.4 times). No difference was found between actual and expected frequencies of genotypes in cows of both breeds. The results of the molecular genetic analysis of the cattle of the two breeds reflect the genetic structure at the studied locus, which corresponds to the breed characteristics of the Swiss and Holstein.

Genotypic profiling of A1 and A2 β-casein alleles in Punganur cattle using PCR-RFLP

Milk is regarded as nature’s perfect food due to the presence of essential nutrients required for the growth and development of mammals. The consumption of milk with a specific β casein variant either A1 or A2 had a relationship with the risk of diseases has been identified. Considering the importance of β casein variants with the health significance, the present study was undertaken in Punganur cattle (N=175) by using PCR-RFLP with Dde I restriction enzyme that showed the distribution of A1A2 (121 bp, 86 bp, and 35 bp) in 5 animals, A2A2 (86 bp and 35 bp) in 170 animals with no evidence of A1A1 genotype. The genotypic frequency of the A1A2 heterozygous β-casein variant of exon7 of the CSN2 gene was 0.029, whereas, for the A2A2 homozygous β-casein variant was 0.971 and the A1A1 homozygous β-casein variant is absent in Punganur cattle. The A1 allelic frequency of exon7 of the CSN2 gene was 0.014, whereas, the A2 gene frequency is 0.986 in Punganur cattle. The study indicates that there is a minimum genetic variability in the tested population of the Punganur cattle breed suggesting less or lower level of crossbreeding activities with exotic animals.

ABO Blood Type and Urinary Bladder Cancer: Phenotype, Genotype, Allelic Association with a Clinical or Histological Stage and Recurrence Rate.

Background Previous research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. Aim To investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. Materials and Methods In the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence-specific primers. We compared ABO phenotypes, genotypes, and alleles between patients and the healthy controls and investigated their distribution according to the clinical and histological stage and recurrence rate. Results No statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 ( p < 0.001), A1 ( p < 0.001), and B ( p = 0.013), and a lower proportion of metastatic disease in A2 (0%, p = 0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, p < 0.001), A1 (70.1%, p = 0.019), of nonmuscle invasive tumors in patients with O1 (55.1%, p < 0.001), O2 (100%, p = 0.045), and recurrent tumors in patients with O1 (70.2%, p < 0.001) and A1 (74.2%, p = 0.007) alleles. Conclusion We did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage, and recurrence rate, respectively.

Occurrence of beta-casein allele A1 in Bovidae species

In the last two decades bovine beta-casein variant A1 has attracted attention in the dairy industry as a source of beta-casomorphin-7 opioid-like peptide with potentially harmful effects on human health. Because the origin of this variant is unknown, the aim of the study was to investigate its occurrence in different species of the Bovidae family. Blood samples were taken from 137 animals belonging to 17 Bovidae species. All animals were genotyped in beta-casein locus by Illumina Bovine MDv2 Chip. The results shown that allele A1 was present in Bos taurus cattle, including primitive cattle (Watusi and Ukraine) and in a modern dairy breed (Holstein). In Dahomey cattle, two heterozygous A1A2 individuals were found. In all remaining species, no animal carrying allele A1 of beta-casein was identified. It may be concluded that allele A2 is ancestral to allele A1 and was spread especially within modern dairy cattle

POLYMORPHISM OF THE BETA-CASEIN GENE IN HOLSTEIN-ZEBU COWS IN THE NORTH OF MINAS GERAIS, BRAZIL

This study aimed to investigate A1 and A2 polymorphisms of the beta-casein gene in crossbred Holstein-Zebu (HZ) cows from four herds in Northern Minas Gerais, Brazil. Blood samples were collected from 112 randomly selected cows, of wich 66 were at ½ HZ, and 46 were at ¾ HZ. DNA extraction was conducted using the phenol-chloroform method, and polymorphisms were evaluated using the amplification refractory mutation system - polymerase chain reaction technique. The results demonstrated that 72/112 (64.3%) cows were heterozygous (A1A2), 33/112 (29.5%) were homozygous for A2A2, and 7/112 (6.2%) were A1A1 homozygous. The percentage of A2A2 cows ranged from 10.7 to 41.4% among the evaluated herds. The frequencies of the A1 and A2 alleles were 38.4 and 61.6%, respectively. The A2 allele was the most frequent in both breeds. The ½ HZ cows were 1.8 times more likely (Odds Ratio) to belong to the A1A1 genotype. The distribution of genotypes was in Hardy-Weinberg equilibrium in three of the herds; however, the total of samples and the stratified samples according to breeds were not in equilibrium considering α = 0.05.

Milk protein polymorphisms and casein haplotypes in Blanco Orejinegro cattle of Colombia

The aim was to determine the genetic variation in the CSN1S1, CSN2, CSN1S2, CSN3 and LGB genes in Blanco Orejinegro cattle. 419 animals from 15 herds were genotyped with GGP Bovine 150 K (n= 70) and 50 K (n= 349) chips. Information was obtained from 43 SNPs in the mentioned genes and protein variants *B, *C and *D of αS1-CN; *A1, *A2, *B, *H2 and *F of β-CN; *A and *D of αS2-CN, *A, *A1, *B, *I and *H of κ-CN and *A, *B, *C, *D, *E, *F and *H of β-LG were reconstructed. Allele and genotypic frequencies were estimated for SNPs and for protein variants; Hardy-Weinberg equilibrium and FST values were evaluated for each of the SNPs under different structuring criteria. LD values and haplotypic frequencies were estimated for caseins. The most frequent variants were CSN1S1*B (0.804), CSN2*A2 (0.509), CSN1S2*A (0.997), CSN3*A (0.679) and β-LG*B (0.657). None of the variants showed deviations from HWE, but the CSN2*A2 allele showed a slight increasing trend over time. The FST values were low (0.035) regardless of the structuring criteria. Twenty-eight CSN1S1-CSN2-CSN1S2-CSN3 haplotypes were found, 22 of them with frequencies &lt;5%; the three most frequent were BB-A1A2-AA-AA-AA-AA (16.6%), BB-A1A2-AA-AA-AA-AB (14.1%) and BB-A2A2-AA-AA-AA (10.1%). A good potential of BON cattle to produce high quality milk with functional value was reported.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

Association between dopamine receptor D2 Taq IA gene polymorphism (rs1800497) and personality traits.

This study aimed to find a potential association between the DRD2 Taq1A gene polymorphism (rs1800497 C32806T) and personality traits. In all, 249 youths were recruited for this study. The Short-form Revised Eysenck Personality Questionnaire was administered to assess personality traits. The participants were genotyped for the DRD2 Taq1A polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis was carried out to find a possible association between the genotypes and aspects of personality traits assessed. The frequencies of the A1 and A2 alleles in our sampled population were 215 (43.2%) and 283 (56.8%), while the frequencies of A1A1, A1A2, and A2A2 were 67 (26.9%), 81 (32.5%), and 101 (40.6%), respectively. The study population was not in Hardy-Weinberg equilibrium (χ2 = 17.64, p < 0.001). The A2 allele was significantly associated with extraversion. Although this allele was also associated with neuroticism, psychoticism, and lie, the association was not significant. The A2 allele of the DRD2 Taq1A polymorphism was found to be more associated with extraversion, as measured by the Short-form Revised Eysenck Personality Questionnaire.

Analysis of β-casein gene for A1 and A2 allelic variants in Holstein-Local crossbred cattle of Bangladesh using allele-specific PCR

Beta-casein (CSN2) is one of the important bovine milk proteins synthesized by β-casein gene. The aim of this study was to investigate the A1 and A2 allelic variants of CSN2 gene in Holstein-Friesian and Local (HF×L) crossbred cattle of Bangladesh. Allele specific polymerase chain reaction (AS-PCR) was carried out for genotyping of allelic variants. A total of 390 blood samples of HF×L crossbred cattle was included from govt., military and private dairy farms. Six different crossbred genotypes were identified in the studied population as 50%HF×50%L, 62.5%HF×37.5%L, 68.75%HF×31.25%L, 75%HF×25%L, 81.25%HF×18.75%L and 87.5%HF×12.5%L. The mean frequencies of the A1A1, A1A2, and A2A2 genotypes were 0.11, 0.48, and 0.41, respectively, while the corresponding frequencies of the A1 and A2 alleles were 0.34 and 0.66, respectively. The frequency of desirable A2A2 genotype reduced from 0.60 (50%HF×50%L) to 0.38 (87.5%HF×12.5%L) with the advancement of exotic HF inheritance from 50 to 87.5%. In contrast, the frequency of A1A1 and A1A2 genotypes increased proportionately with the progression of HF inheritance level. The undesirable A1A1 genotype frequency was found highest in the HF crossbreds of private dairy farms (0.13) compared to government (0.08) and military dairy farm (0.07) that signifies the availability of upper graded cows in the private dairy farms. Altogether, this study provides current scenario of A1 and A2 allelic variants of HF×L crossbreds of Bangladesh that could be utilized to design suitable breeding plans in crossbreeding programs for production of premium quality milk.

MMP-3 gene regulates the carcinogenesis and metabolic process of ovarian cancer, evidence from a Chinese population: Observational study and meta-analysis.

The current investigation aims to explore the relationship between matrix metalloproteinase-3 (MMP-3) gene polymorphism and ovarian cancer (OC) risk. Two hundred forty pathologically confirmed OC patients and 390 healthy controls participated in the present investigation. Polymerase chain reaction-restriction fragment length polymorphism was applied to investigate the present polymorphism. At the same time, the meta-analysis was also performed to comprehensively explore the relationship. Three genotypes (5A/5A, 5A/6A, and 6A/6A) were observed for MMP-3 gene polymorphism. 6A/6A genotype and 6A allele displayed significant increase in OC patients (all P < .05). Meta-analysis found that no significant results (all P > .05). In conclusion, our results indicate that MMP-3 gene polymorphism contributes increased risk to OC for southern Chinese population. And meta-analysis indicates that MMP-3 gene polymorphism contributes no risk to OC in other populations.

Analysis of Genetic Variation of MatK Gene Sequences in Ammothamnus lehmannii NCBI Popset 2440747918 Using In Silico RFLP

Genetic diversity or genetic variation is variation that occurs in an organism due to differences in the sequence of nucleotide bases (adenine, thymine, guanine and cytosine) that form DNA in cells. Variation genetics can be studied in silico using available gene sequences in the NCBI genbank database. This study used the MatK (Maturase-K) gene sequence with the identity number Popset 2440747918 which was downloaded in fasta format from NCBI . Then screening of restriction enzyme candidates was carried out to determine the restriction enzymes prior to in silico RFLP. The restriction enzyme selected from the screening was the restriction enzyme HindIII which has the recognition site A'AGC_T. The results obtained from 79 samples of DNA sequences, 76 samples were cut and 3 samples were not. And found three allele variations with the percentage of the presence of fragments A1 (86.07%), A2 (10.12%) and A3 (3.79%). The percentage values and frequencies of these A1, A2 and A3 alleles indicate a low level of genetic variation.

Prevalence of 4a/4b polymorphic variants of the eNOS gene introne in patients with different types of encephalopathies

Questions related to the disruption of vasoregulatory processes as essential factor in neurological pathology require further study. The leading role in the vasoregulatory mechanisms is played by endothelial NO synthase which gene has 15 allelic variants. Recent data indicated a probable association between eNOS gene polymorphism and cerebrovascular diseases. The aim of the present work was to study the prevalence of the 4a/4b introne polymorphism of the eNOS gene in patients with various types of encephalopathies and to evaluate the influence of a particular genotype of the studied gene on the occurrence and/or progression of encephalopathy. A total of 96 patients with encephalopathies of various genesis: chronic traumatic encephalopathy, chronic alcohol-induced encephalopathy, chronic vascular encephalopathy, post-infectious encephalopathy were involved in the study. The patients received inpatient treatment in the neurological department of “Ternopil Regional Clinical Psychoneurological Hospital”. Molecular and genetic differentiation of the studied gene variants was carried out by allele-specific PCR or PCR-restriction fragment length polymorphism analysis by standard operational protocols. Analysis of the frequency distribution of eNOS gene 4a/4b polymorphic variant showed that 4b allele prevailed among patients with all types of encephalopathies carriers­. Relative to practically healthy individuals the difference was found only in patients with chronic vascular encephalopathy (CVE), among whom about 39% were carriers of the 4a allele. The presence of the 4a allele was shown to increased the risk of CVE occurrence and/or progression by 4.5 times. The results obtained suggest the reasonability to include the 4a/b intron polymorphism of the eNOS gene in a genetic panel to monitor patients CVE. Keywords: 4a/4b introne, encephalopathies, endothelial NO-synthase, eNOS gene polymorphism

Population-Specific Distribution of TPMT Deficiency Variants and Ancestry Proportions in Ecuadorian Ethnic Groups: Towards Personalized Medicine.

Thiopurine S-methyltransferase (TPMT) is an enzyme that metabolizes purine analogs, agents used in the treatment of acute lymphoblastic leukemia. Improper drug metabolism leads to toxicity in chemotherapy patients and reduces treatment effectiveness. TPMT variants associated with reduced enzymatic activity vary across populations. Therefore, studying these variants in heterogeneous populations, such as Ecuadorians, can help identify molecular causes of deficiency for this enzyme. We sequenced the entire TPMT coding region in 550 Ecuadorian individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnicities. Moreover, we conducted an ancestry analysis using 46 informative ancestry markers. We identified 8 single nucleotide variants in the coding region of TPMT. The most prevalent alleles were TPMT*3A, TPMT*3B, and TPMT*3C, with frequencies of 0.055, 0.012, and 0.015, respectively. Additionally, we found rare alleles TPMT*4 and TPMT*8 with frequencies of 0.005 and 0.003. Correlating the ancestry proportions with TPMT-deficient genotypes, we observed that the Native American ancestry proportion influenced the distribution of the TPMT*1/TPMT*3A genotype (OR = 5.977, p = 0.002), while the contribution of African ancestral populations was associated with the TPMT*1/TPMT*3C genotype (OR = 9.769, p = 0.003). The rates of TPMT-deficient genotypes observed in Mestizo (f = 0.121) and Indigenous (f = 0.273) groups provide evidence for the influence of Native American ancestry and the prevalence of the TPMT*3A allele. In contrast, although Afro-Ecuadorian groups demonstrate similar deficiency rates (f = 0.160), the genetic factors involved are associated with contributions from African ancestral populations, specifically the prevalent TPMT*3C allele. The distribution of TPMT-deficient variants offers valuable insights into the populations under study, underscoring the necessity for genetic screening strategies to prevent thiopurine toxicity events among Latin American minority groups.

Distribution of beta-casein genotype in two generations in cows of the Kholmogory breed

One of the most effective ways to produce A2 milk is marker selection using the results of animal genotyping according to beta-casein genotypes, since A2 milk is produced only by cows with the A2A2 genotype. In this study, the inheritance of the beta-casein gene genotype in two generations of cows of the Kholmogory breed in "Agrofirma "Kholmogorskaya" and "Kholmogorskiy plemzavod", Arkhangelsk region was studied. The A1 and A2 alleles of the beta-casein gene were determined by an allele-specific PCR method. As a result of the study, it was found out that the frequency of the A1 and A2 alleles of the beta-casein gene in daughter offspring and mother cows practically did not change in one generation (A1 allele from 53 to 54 % and A2 allele from 46 % to 47 %; A1 allele from 68 to 61 % and A2 allele from 32 to 39 %). This fact indicates the absence of breeding pressure. Since the task of modern animal husbandry is to create herds of the Kholmogory breed with the A2A2 genotype for the production of high-quality milk, then for further breeding, attention should be paid to animals with the A1A2 and A2A2 genotypes. Having modeled the selection in herds, that is, excluding mothers with the A1A1 genotype from reproduction, and calculating the distribution of genotypes of descendants in the remaining part of the maternal stock of both herds, it was found that the proportion of descendants with the A1A1 genotype decreases in farms, the relative number of heterozygous daughters in the breeding farm increased by 5.0 %, and in the agrofirm decreased by 6.3 %, but at the same time, the number of A2A2 daughters increased by 6.7 and 4.0 %, respectively.

Association of variants in the ABCB1, CYP2C19 and CYP2C9 genes for Juvenile Myoclonic Epilepsy.

Juvenile myoclonic epilepsy (JME) is the most common of the generalized genetic epilepsies, with multiple causal and susceptibility genes; however, its etiopathogenesis is mainly unknown. The toxic effects caused by xenobiotics in cells occur during their metabolic transformation, mainly by enzymes belonging to cytochrome P450. The elimination of these compounds by transporters of the ABC type protects the central nervous system, but their accumulation causes neuronal damage, resulting in neurological diseases. The present study has sought the association between single nucleotide genetic variants of the CYP2C9, CYP2C19, and ABCB1 genes and the development of JME in patients compared to healthy controls. The CC1236 and GG2677 genotypes of ABCB1 in women; allele G 2677, genotypes GG 2677 and CC 3435 in men; the CYP2C19*2A allele, and the CYP2C19*3G/A genotype in both sexes were found to be risk factors for JME. Furthermore, carriers of the TTGGCC genotype combination of the ABCB1 gene (1236/2677/3435) have a 10.5 times higher risk of developing JME than non-carriers. Using the STRING database, we found an interaction between the proteins encoded by these genes and other possible proteins. These findings indicate that the CYP450 system and ABC transporters could interact with other genes in the JME.

Evaluation of matrix metalloproteinase-1, -2, -3, -7, and -13 gene polymorphisms in patients with chronic periodontitis and healthy controls.

The current study aimed to investigate the association of matrix metalloproteinase- (MMP-) 1, -2, -3, -7, and -13 gene polymorphisms with chronic periodontitis (CP) in an Iranian population. In this case-control study, 87 subjects with CP and 89 periodontally healthy subjects were allocated to case and control groups, respectively. Subjects' venous blood samples (5cc) were collected, and DNA extraction was performed. A spectrophotometer was utilized to assess the concentration of extracted DNAs. The desired gene polymorphisms were examined using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) followed by electrophoresis. Statistical analyses were done using the Pearson Chi-Square test, odds ratio, and t-Test using SPSS Version 28. The MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 gene polymorphisms significantly differed between case and control groups (PV = 0.019, 0.007, and 0.028, respectively). In contrast, the gene polymorphisms of MMP-2 (-1306 C/T) rs243865 and MMP-13 (-77 A/G) rs2252070 did not make a significant difference. Regarding allele frequencies, the presence of the 2G allele in the MMP-1 (-1607) rs1799750 genotype increased the CP susceptibility significantly, while subjects with the 6A allele in their MMP-3 (-1171) rs3025058 genotype showed significantly lower susceptibility to CP (PV = 0.008 and < 0.001, respectively). In the studied population, gene polymorphisms in the DNA sequences of MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 may have impacts on CP incidence. Clinicians should be cautious about the association between MMP-1, MMP-3, and MMP-7 gene polymorphisms and the incidence of chronic periodontitis during periodontal treatment planning.

The variation in the beta-casein genotypes and its effect on milk yield and genomic values in Holstein-Friesian cows

The A2 milk marker is gaining popularity worldwide; thus, many farms plan to convert their dairy cattle herds to the A2A2 genotype. Variation in beta-casein genotypes needs to be monitored in large dairy cattle populations. Therefore we aimed to evaluate the genotypic distributions, population genetics, and diversity parameters in Holstein-Friesian cows. A total of 1200 cattle were genotyped using the Affymetrix® Axiom® array system. We performed an association analysis regarding the CSN2 genotypes and phenotypic traits, including lactation and test-day milk yield. We next evaluated the effects of the genotypes considering the genetic merit of the animals. Animals were grouped based on their PTAs for milk production, fat, protein, and daughter pregnancy rate. Thus, we tested the genotype × genetic merit interaction for significance. The A2 allele frequency is remarkably high (0.68), and the heterozygous genotype is predominant (46.25%). The marker showed intermediate variability and diversity levels, indicating a considerable frequency of the A1A1 genotype (9.33%) remains in the population. ANOVA results showed no significant association between the CSN2 genotypes and milk yield traits. A similar finding is valid for the genotype × genetic merit regarding the genomic test results. The data presented here may be helpful for further investigations and applications on A2 milk production.

"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS).

Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al 1990; a significant association between the minor DRD2 allele, Taq A1 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CβS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Relationships of beta-casein genetics with production, fertility, and survival of purebred organic Holstein dairy cows

The objective of this study was to compare β-casein genotype of purebred certified-organic Holstein cows, and their effect on production, fertility, and survival. Holstein cows (n = 1,982) from 13 certified-organic dairy herds from the western, midwestern, and northeastern United States were genomically tested with CLARIFIDE Plus (Zoetis) for β-casein genotype. Two hundred fourteen cows were A1A1 (11%), 848 cows were A1A2 (43%), and 920 cows were A2A2 (46%). In total, 2,249 lactation records, 1,025 from the first parity and 1,224 records during second and greater parities were used. Test-day milk, fat, and protein production (305-d) and somatic cell score were obtained from the Dairy Herd Improvement Association. A lower limit of 50 d for days open was applied, and cows with more than 250 d open had days open set to 250 d. Independent variables for statistical analysis were the fixed effects of herd, parity, β-casein genotype (A1A1, A1A2, A2A2), and β-casein genotype by parity interaction. Cow nested within parity was the random effect in the statistical models for fertility and production traits. Herd had a significant effect on all fertility, production, and survival variables. Parity affected the number of times bred per pregnancy and days open, milk, fat, and protein production, and somatic cell score. Beta-casein genotype and herd influenced the percentage of cows surviving to first and second lactation. Results indicate no difference in production and fertility regarding β-casein genotype for organic dairy herds. Survival was biased against the A1 allele, which is indicated by lower survival rates during first lactation. These results may offer organic producers more flexibility in breeding and culling decisions to produce A2A2 milk.