Polymorphism In Exon Research Articles

Study the C/T Single Nucleotide Polymorphism at Tyrosine Kinase Domain of Insulin Receptor Gene in Patients with Polycystic Ovary Syndrome in Babylon Province

Polycystic ovary syndrome (PCOS) is the commonest gynecological endocrinopathy, is characterizedby chronic anovulation and hyperandrogenism and is also associated with increase insulin secretion andmetabolic disease and insulin resistance. Present study aims to examine the association between the singlenucleotide polymorphism (rs1799817) of exon 17 of the insulin receptor (INSR) gene and polycystic ovarysyndrome (PCOS) in a Babylon women. Fifty women with PCOS and fifty healthy Iraqi women, age andBMI matching were achieved between study groups. Biochemical parameters that estimated were fastingglucose, fasting insulin, luteinizing hormone, testosterone. His 1058 C/T polymorphism at the tyrosinekinase domain in the INSR gene was analyzed by restriction fragment length polymorphism (RFLPPCR). Significant increase in the levels of fasting glucose fasting insulin, HOMA-IR, LH, testosteronewere noticed in patient when compared with control. TT genotype frequency was higher in PCOS patientswhereas CC genotype was higher in control women. All parameters that estimate in this study were higherin TT genotype of patient group. In conclusion there are an association of C/T polymorphism at His1058 ofINSR in patients women with PCOS in Babylon Province. Insulin resistance in PCOS patients might differfrom these that result from obesity.

Allelic polymorphism in exon 1 of GDF9 and exon 2 of BMP15 genes and its impact on litter size at lambing in Iran-Black sheep

The main purpose of this study was to assess the presence of the previously reported single nucleotide polymorphisms (SNPs) in the sheep growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes and their association with litter size at lambing in Iran-Black sheep breed. Blood samples were taken from 120 Iran-Black ewes. DNA extraction was conducted using a modified salting-out method. DNA fragments with sizes of 462bp and 141bp for the GDF9 and BMP15 genes were amplified using PCR with specific primers, respectively. The PCR-RFLP approach was adopted for detecting the genotypes. The results indicated that the SNP in the exon 2 of BMP15 is a monomorphic locus in Iran-Black sheep. However, the substitution of G to A nucleotide was determined in the GDF9 locus. Digestion of the 462bp PCR product from exon 1 of theGDF9 using the HhaI restriction enzyme produced fragments of 52, 156, and 254bp. However, DNA fragments containing the A nucleotide yielded only two fragments (52 and 410bp). The heterozygous animals for this mutation in GDF9 locus had fragments of all four sizes (52, 156, 254, and 410bp). The frequency (0.75) of the wild type allele (+) in GDF9 locus was higher than the frequency (0.25) of mutant allele (G). The observed frequencies for the GG, G+ and ++ genotypes were 0.05, 0.40 and 0.55, respectively. The association results indicated that the mutation of GDF9 gene has a substantial impact on lambing rate and the Iran-Black ewes with the GG and G+ genotypes had higher lambing rate than those with the ++ genotype. Thus, a gene assisted selection program to improve lambing rate in this breed can be designed based on the GDF9 gene mutation. Key words: BMP15, GDF9, Litter Size, Iran-Black Sheep

Latitudinal gradients in genetic diversity and natural selection at a highly adaptive gene in terrestrial mammals

Identifying where high genetic diversity is located across our planet and what factors affect the geographical patterns of genetic variation not only provides important insights into distributions of biodiversity but is also crucial for human health, animal and plant breeding and biodiversity conservation. Recent studies show that genetic diversity at nearly neutral genes decreases from the tropics to the poles in different taxa, mirroring the oldest recognized latitudinal gradient of species richness, yet functional genetic diversity has received little attention at such broad spatial or taxonomic scales. Here, we investigated latitudinal gradients in genetic diversity at a polymorphic exon 2 (MHC II DRB gene, 1515 sequences) of the major histocompatibility complex that confers resistance to parasites in 93 terrestrial mammal species at the global scale. We also estimated the effects of species traits, positive selection and anthropogenic biomes on genetic diversity. We found clear latitudinal gradients in genetic diversity and the presence of positive selection at exon 2. Absolute latitude, the presence of positive selection and body mass are important predictors of within‐species genetic diversity. A higher occurrence of positive selection, faster evolutionary speed or slower drift at low latitudes may shape the latitudinal gradient in the within‐species genetic diversity of the gene. Our results contribute to a greater understanding of how species traits, selection and drift geographically shape functional genetic diversity, broadening the generality of latitudinal biodiversity gradient. The results highlight the importance of conservation at low latitudes.

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer

The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127C/T) in subjects with type 2 diabetes and diabetic foot ulcers. This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n=150), group II: type 2 diabetes mellitus subjects (T2DM, n=150) and group III: infected diabetic foot ulcer subjects (DFU, n=100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP. NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR=1.95 (1.02-3.72), p=0.04) and DFU (OR=5.66 (2.98-10.76), p=0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with "TT" genotype compared to the "CC" and "CT" genotypes. NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU.

Characteristics of Grain Physicochemical Properties and the Starch Structure in Rice Carrying a Mutated ALK/SSIIa Gene.

The gelatinization temperature (GT) of endosperm starch influences rice eating and the cooking quality (ECQ). ALK encoding soluble starch synthase IIa (SSIIa) is the major gene determining grain GT in rice. Herein, we identified a spontaneous ALK mutant named ALKd, which resulted from a G/T single-nucleotide polymorphism (SNP) in exon 1 of the ALKc allele from the high-GT indica rice cultivar. Compared with grains from the ALKc near-isogenic line (NIL), NIL(ALKd) grains exhibited a high GT (2.3 °C) and improved retrogradation properties. The NIL(ALKd) grain starch contained an increased proportion of amylopectin intermediate chains (DP 13-24) at the expense of short chains (DP < 12), resulting in enhancements in both the crystallinity and the lamellar peak intensity compared with low-GT rice grains. Moreover, both NIL(ALKd) and NIL(ALKc) grains also featured a significantly lower apparent amylose content (AAC), harder gel consistency (GC), higher pasting curve, and poorer taste values in comparison to Nip(ALKa) grains. Taken together, this work provides novel insights underlying the allelic variation of the ALK gene in rice.

Anthracycline-induced cardiotoxicity: molecular and genetic predictors for risk assessment

Abstract Objective The objective of this study was to evaluate the role of molecular and genetic biomarkers in the development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy. Methods A total of 176 women, median age of 45,0 [42,0; 50,0] years with breast cancer without cardiovascular diseases who received anthracycline antibiotics as part of polychemotherapeutic treatment were enrolled in the study. Two-dimensional transthoracic echocardiography and 6-minute walk test were performed at baseline and at the 12 months after polychemotherapy. Serum levels of NT-proBNP, sFas-L were measured using an enzyme immunoassay after polychemotherapeutic treatment. Evaluation of gene polymorphisms of p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522) and nitric oxide synthase (NOS3, Glu298Asp, rs1799983) were carried out by polymerase chain reaction at baseline. Results After the 12 months of polychemotherapy all patients had breast cancer remission and were divided into 2 groups: group 1 (n=52) comprised patients with anthracycline-induced cardiotoxicity, group 2 (n=124) comprised those without it. After polychemotherapeutic treatment the median value of NT-proBNP in group 1 was higher (p&amp;lt;0,00001) by 52,4% than in group 2 (113 [101,8; 126,15] pg/mL and 53,8 [43,4; 63,0] pg/mL, respectively). The median value of sFas-L in group 1 was higher (p&amp;lt;0,00001) by 44,3% than in group 2 (125,3 [111,85; 133,95] pg/mL and 69,8 [59,8; 77,6] pg/mL, respectively). Based on ROC-analysis, sFas-L concentration of 95.8 pg/mL (sensitivity of 92.2%, specificity of 92.1%, and AUC=0,951; p=0,0001) and NT-proBNP concentration of 71.5 pg/mL (sensitivity of 99.9%, specificity of 91.9%, and AUC=0,951; p=0,0001) were identified as a cut-off values predicting the development of anthracycline-induced cardiotoxicity. The development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy significantly was related to the presence of T/T genotype of NOS3 gene (OR = 3,059; p=0,018) and with Arg/Arg genotype of p53 protein gene (OR = 2,972; p=0,001). While, the presence of Pro/Pro the Pro53 gene genotype of p53 protein gene was related to the absence of anthracycline-induced cardiotoxicity. Conclusion Our data suggest that evaluation of polymorphisms gene of p53 (rs1042522) and NOS3 (rs1799983) can be recommended before polychemotherapy in women with breast cancer for the risk assessment of anthracycline-induced cardiotoxicity. The serum levels of NT-proBNP and sFas-L after polychemotherapy may be considered as non-invasive biomarkers for prediction of the development of anthracycline-induced cardiotoxicity in women with breast cancer during the 12 months after polychemotherapy. Funding Acknowledgement Type of funding source: None

Mutation Spectrum of the Phenylalanine Hydroxylase Gene in Phenylketonuria Patients in Golestan Province, Iran

Background. As an autosomal recessive disease, phenylketonuria (PKU) is caused by deficiency in phenylalanine hydroxylase (PAH) gene. The incidence of different mutations in phenylalanine hydroxylase is associated with differences in race and ethnicity. The aim of this study is to investigate the mutation spectrum in hotspot region of PAH gene in PKU patients. Materials and Method. For this purpose, we studied exons 6, 7, 10–11 and 12 and adjacent flanking regions of PAH gene from a total of 26 unrelated hyperphenylalaninemia patients (13 males and 13 females) in Golestan province using PCR-sequencing method. Results. Among 26 analyzed patients, 11 distinct mutations were found in combinations of 18 genotypes. A mutation detection rate of 64% was achieved. The high heterogeneity of PKU was reported in this study. The most prevalent mutations were IVS10-11G>A (19.23%), followed by IVS11+1G>C, p.P416HfsX36 and p.R261Q which accounted for 66.67% of mutant alleles. IVS9-1G>T and p.P416HfsX36 are novel mutations. Exonic polymorphisms L385L and Q232Q and intronic polymorphisms IVS10+155T>C, IVS10+156T>G, and IVS10-193G>C were found to have high frequency. Conclusion. A mutation spectrum with high frequency was predicted in Northern region of Iran due to its ethnic heterogeneity. Furthermore, it seems that the presence of some mutations in Golestan province indicates gene flow between Iran and the neighboring countries.

Single nucleotide polymorphism at cluster of differentiation 14 (CD14) gene and its association with fertility traits in crossbred cattle of Kerala

Cluster of differentiation 14 (CD14) gene is an important molecule for innate unity and found to be significantly associated with fertility traits in cattle. The objectives of present study were to detect the single nucleotide polymorphisms (SNPs) in exon 1 region of CD14 gene and to evaluate the association of genetic variants with fertility traits viz. Service period and Age at First Calving in crossbred cattle of Kerala. The study was conducted on two hundred and sixteen crossbred cattle maintained at various farms of Kerala Veterinary and Animal Sciences University. Genomic DNA was isolated and polymorphisms of gene were detected by Single Strand Confirmation Polymorphism. Two SNPs, c.445T>G and c.432C>T were detected in exon 1 coding region of CD14 gene. The frequencies of CC and CT genotypes were 0.82 and 0.18 in the population. In addition, a significant association between SNPs and service period was observed in crossbred cattle population under study. Crossbred cattle with CT diplo types showed lower values for service period than those with CC diplo types. The association of CD14 gene with these traits emphasizes the importance of bovine CD14 as a candidate gene for marker assisted selection for fertility traits in crossbred cattle

Identification of Polymorphisms of Gene CSN2 of B Casein in Greek Cow Breeds (Holstein) by Restriction Fragment Length Polymorphism

The research focused to detect and identify genetic polymorphisms in exon 7 of the &amp;beta;-casein CSN2 gene in blood samples from Greek Holstein cows. For this purpose, DNA was extracted from 120 blood samples of cows. The desired region of exon 7 was amplified by PCR, resulting in a 121 bp product. The PCR product was digested by restriction fragment length polymorphism (RFLP) method. The results suggest that the A1A2 genotype prevails over the others. Specifically, of the 120 cattle, 72 showed triple bands of 121 bp, 86 bp, and 35 bp indicating the A1A2 genotype. The 42 cattle showed a single band at 121 bp, indicating that they carried the A1A1 genotype. The remaining 6 showed only two bands of 86 and 35 bps, indicating that they carried the A2A2 genotype. In the total population of heterozygotes A1A2-0.60 were the most frequent, while homozygotes A2A2-0.06 were the least frequent ones. This suggests a slight superiority of allele A-0.65.

A Novel Missense Single Nucleotide Polymorphism in the GREM1 Gene is Highly Associated with Higher Reproductive Traits in Awassi Sheep.

GREM1 (gremlin1) is a known inhibitor for BMP15 (bone morphogenetic protein 15) family, but its genetic diversity in sheep is unknown. The present study was conducted to analyze the polymorphism of GREM1 gene using PCR- single-strand conformation polymorphism (SSCP) and DNA sequencing methods and to assess the possible association of GREM1 gene polymorphism with reproductive traits in Awassi ewes. A total of 224 ewes, 124 producing singles and 100 producing twins, were included in the study. Two SSCP patterns were detected in two amplified loci within the exon 2. Two exonic novel single nucleotide polymorphism (SNP)s were identified, c.74T > G (the silent SNP p.Met123 =) and c.30T > A with (the missense SNP p.Ile237Phe). Statistical analyses indicated a non-significant (P > 0.05) association of p.Met123 = with the analyzed reproductive traits of fecundity, prolificacy, litter size, and twinning rate. Meanwhile, p.Ile237Phe SNP exhibited a highly significant (P < 0.01) association with the measured reproductive traits, in which ewes with TA genotype (with p.Ile237Phe SNP) exhibited higher litter size, twinning ratio, fecundity, and prolificacy than those with TT genotype (without p.Ile237Phe SNP). The deleterious impact of p.Ile237Phe SNP was observed by the means of ten different state-of-the-art in silico tools that predicted a highly damaging effect of p.Ile237Phe SNP on the structure, function, and stability of gremlin1. In conclusion, the results of our study suggest that p.Ile237Phe SNP has a remarkable negative impact on the gremlin1 structure, function, and stability. Since gremlin1 is a known inhibitor of reproductive performance, a consequent higher reproductive performance was observed in ewes with damaged gremlin1 (with p.Ile237Phe SNP) than those with non-damaged gremlin1 (without p.Ile237Phe SNP). Therefore, it can be stated that the implementation of the novel p.Ile237Phe SNP in the GREM1 gene could be a useful marker in marker-assisted selection. This manuscript is the first one to describe GREM1 gene variations in sheep.

Prevalence and significance of M541L single nucleotide polymorphism in the central European cohort of gastrointestinal stromal tumor patients

Single nucleotide polymorphisms can create a genetic microenvironment in some tumors that affects the course of treatment, resistance, etc. Whether single nucleotide polymorphisms have an impact on gastrointestinal stromal tumor (GIST) development and disease progression is not yet accurately verified. KIT SNPM541L in exon 10 correlates with a worse prognosis of many cancers. The impact of KIT SNPM541L in GISTs is relatively unknown and, therefore, its analyses could have potential in patient therapy and could provide more detailed information on tumor character, clinical presentation, or tumor behavior in treatment. The aim of the study was the analysis of the biological and clinical significance of the KIT SNPM541L polymorphism in exon 10. Paraffin sample tissues were obtained from the National GIST Register in Martin. Retrospective samples from 177 GIST patients were divided into several groups. Detection of SNPM541L was performed by Sanger sequencing. Statisitical analyses were performed to determine the prevalence of KIT SNPM541L in the Slovak GIST cohort, to search for correlation between c-KIT status and clinicopathological, molecular and biological data. Overall, 29 samples out of 177 showed KIT SNPM541L polymorphism. Our results do not support the association between KIT SNPM541L and increased risk of relapse in localized primary GISTs. Additionally, we found a positive correlation between KIT SNPM541L occurrence and earlier onset of relapse in PDGFRa and WT subgroup of GISTs.

DNA polymorphism of FSHR gene and its association with infertility traits in Egyptian buffaloes

The objectives of this study were to detect genetic polymorphism in exon 10 of Follicle Stimulating Hormone Receptor gene (FSHR) by using RFLP and direct sequence methods, also to investigate their possible association with infertility traits in Egyptian buffaloes. A total number of 50 female Egyptian buffaloes at Mahallet Mousa experimental farms in Kafr El-sheikh province were investigated. Animals were divided into three groups: normal fertile (20 animals), infertile due to anestrum (15 animals) and infertile due to repeat breeding (15 animals). Genomic DNA was extracted from blood samples, then PCR was performed with annealing temperatures of 57oC to amplify 231 bp of FSHR exon 10 gene. The amplicons were digested with Hin1II (NlaIII) restriction enzyme. The results showed that all the investigated buffaloes were monomorphic and genotyped as A/A genotype. Moreover, the monomorphism of buffaloes FSHR exon 10 gene was confirmed by sequencing three samples from each buffaloes’ group. It seems that FSHR gene are highly conserved in the investigated buffalo’s population.

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism: Association with Risk and Severity of Premature Coronary Artery Disease

Background: Many different genetic associations with premature coronary artery disease (PCAD) have been identified. One exonic single nucleotide polymorphism (SNP) rs5888 of Scavenger receptor class B type1 (SCARB 1) gene has been linked to lipid traits as well as subclinical atherosclerosis. Objective: To investigate the association between SNP rs5888 of SCARB 1 gene and PCAD risk and severity. Patients and Methods: This study was conducted on 50 Egyptian patients diagnosed as PCAD by coronary angiograph (PCAD group) and (50) age- and sex-matched non-CAD subjects who showed no luminal stenosis in coronary angiographic served as a control group (non-CAD group). Gensini score was calculated as an indication for atherosclerosis severity for patients only. Detection of rs5888 polymorphism of SCARB 1 gene was done by realtime polymerase chain reaction (PCR) and high resolution melting analysis (HRM). Results: The mutant TT and CT genotypes were more frequently distributed in PCAD group compared to nonPCAD group (34 % and 48 % vs. 26 % and 18 %, respectively). The (CT) genotype conferred a positive risk for PCAD in males (OR: 6.117, 95% CI (1.744-21.452); p < 0.01). T allele conferred a positive risk for PCAD (OR: 2.564, 95% CI (1.440-4.543); p < 0.05). Highest Gensini score was found in PCAD patients with (TT) genotype (p < 0.01). Conclusion: The mutant (CT) genotype and the T allele of SCARB 1 SNP rs5888 were associated with increased risk of PCAD and the mutant (TT) genotype was associated with disease severity calculated by Gensini score.

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism: Association with Risk and Severity of Premature Coronary Artery Disease

Background: Many different genetic associations with premature coronary artery disease (PCAD) have been identified. One exonic single nucleotide polymorphism (SNP) rs5888 of Scavenger receptor class B type1 (SCARB 1) gene has been linked to lipid traits as well as subclinical atherosclerosis. Objective: To investigate the association between SNP rs5888 of SCARB 1 gene and PCAD risk and severity. Patients and Methods: This study was conducted on 50 Egyptian patients diagnosed as PCAD by coronary angiograph (PCAD group) and (50) age- and sex-matched non-CAD subjects who showed no luminal stenosis in coronary angiographic served as a control group (non-CAD group). Gensini score was calculated as an indication for atherosclerosis severity for patients only. Detection of rs5888 polymorphism of SCARB 1 gene was done by realtime polymerase chain reaction (PCR) and high resolution melting analysis (HRM). Results: The mutant TT and CT genotypes were more frequently distributed in PCAD group compared to nonPCAD group (34 % and 48 % vs. 26 % and 18 %, respectively). The (CT) genotype conferred a positive risk for PCAD in males (OR: 6.117, 95% CI (1.744-21.452); p < 0.01). T allele conferred a positive risk for PCAD (OR: 2.564, 95% CI (1.440-4.543); p < 0.05). Highest Gensini score was found in PCAD patients with (TT) genotype (p < 0.01). Conclusion: The mutant (CT) genotype and the T allele of SCARB 1 SNP rs5888 were associated with increased risk of PCAD and the mutant (TT) genotype was associated with disease severity calculated by Gensini score.

NT5C2 methylation regulatory interplay between DNMT1 and insulin receptor in type 2 diabetes

Epigenetics alternation of non-genetic variation and genome-wide association study proven allelic variants may associate with insulin secretion in type 2 diabetes (T2D) development. We analyzed promoter DNA methylation array to evaluate the associated with increased susceptibility to T2D (30 cases, 10 controls) and found 1,091 gene hypermethylated in promoter regions. We performed the association study of T2D and found 698 single nucleotide polymorphisms in exon and promoter sites by using 2,270 subjects (560 cases, 1,710 controls). A comparison of DNA hypermethylation and gene silencing of mouse T2D results in our T2D patients’ results showed that the 5′-nucleotidase, cytosolic II (NT5C2) and fucosyltransferase 8 (FUT8) genes were strongly associated with increased susceptibility to T2D. DNA hypermethylation in promoter regions reduced NT5C2 gene expression, but not FUT8 in T2D patients. NT5C2 protein expression was decreased in pancreatic β-cells from T2D mice. Transient transfection NT5C2 into RIN-m5F cells down-regulated DNA methyltransferase I (DNMT1) expression and up-regulation of the insulin receptor. Moreover, NT5C2 knockdown induced in DNMT1 overexpression and insulin receptor inhibition. Taken together, these results showed that NT5C2 epigenetically regulated insulin receptor in patients and mice with T2D, and maybe provide for T2D therapy strategy.

Genetic Variability in Exon 3 Region of POU1F1 Gene and its Effect on Body Weight and Milk Yield in Malabari Goats

Background: POU1F1 is known as a major candidate gene coding for pituitary-specific transcription factor-1 regulating the production of anterior pituitary hormones like GH, TSH, LH, FSH and prolactin in small ruminants. However, little is known about the genetic variability of caprine POU1F1 gene in Indian breeds. Hence, the present study aimed at the identification of single nucleotide polymorphisms in the exon 3 region of POU1F1 and their association with body weight and milk production in Malabari goats. Methods: The present study was conducted during 2016-2018 on 100 Malabari goats at the University Goat and Sheep Farm, Mannuthy. Genomic DNA was extracted using standard phenol-chloroform method. The POU1F1 exon 3 locus was PCR amplified using appropriate primers. The 234 bp PCR product was subjected to single-strand conformation polymorphism (SSCP) analysis on 12% PAGE gel and silver-stained. The different SSCP patterns were sequenced and homologous sequences identified using Blast algorithms. Allelic-genotypic frequencies and the observed-expected heterozygosity at the locus were estimated. Data on body weights at birth, three, six, nine months of age and parity-wise lactation milk yield were used to find the association of POU1F1 exon 3 variants with body weights and milk yield using one-way ANOVA in General Linear Models for fixed effects. Result: PCR-SSCP revealed GG, GA genotypes with frequencies of 0.44 and 0.56 and G and A alleles with frequencies of 0.72 and 0.28. The observed and expected heterozygosity for the locus were 0.5657 and 0.4077 respectively. Sequencing of the PCR products revealed a synonymous single nucleotide polymorphism (g. 42C&gt;T). GG homozygotes had higher body weight while GA heterozygotes had higher milk yield (p less than 0.05). It was concluded that the polymorphic exon 3 locus significantly contributed to variation in pre-pubertal body weight and milk yield and hence may be employed in the marker-assisted selection programmes for Malabari goats.

Association of a polymorphism in exon 3 of the IGF1R gene with growth, body size, slaughter and meat quality traits in Colored Polish Merino sheep

This study aimed to genotype the polymorphism (c.654G > A) in the exon 3 of the insulin-like growth factor 1 receptor gene (IGF1R) and to analyze its association with growth, body size, slaughter and meat quality traits in Colored Polish Merino sheep. In total, 67 traits were analyzed. The IGF1R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. The MIXED procedure of the SAS software was used to assess the genotypic effects of the polymorphism (c.654G > A) on production traits of interest. The IGF1R c.654G > A genotypes were found to have a significant effect on the average daily gain between the 56th and 78th day of life, cold carcass, leg part, leg cut, fore shank, and kidney weights, as well as eye of loin depth, intramuscular fat content, and water-holding capacity of meat. The results suggest that the studied polymorphism may provide useful information for marker-assisted selection for increased meat performance in Colored Polish Merino sheep.

Efficacy of EGFR tyrosine kinase inhibitors in patients having EGFR-activating mutations with or without BIM polymorphisms.

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer with BIM deletion polymorphism may have a limited response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, some results of previous reports are discordant. It is necessary to evaluate the relationship between BIM polymorphism and the efficacy of EGFR-TKIs. We retrospectively analyzed patients treated with EGFR-TKIs. We collected serum samples from patients before EGFR-TKI administration. We analyzed BIM deletion polymorphism and BIM single nucleotide polymorphism in exon 5 c465C > T by the Invader® assay. BIM deletion polymorphism was identified in 27 of 194 patients (13.9%). BIM single nucleotide polymorphism was identified in 29 of 194 patients (14.9%). The overall response ratio was 81.5% in patients with BIM deletion polymorphism, 89.7% with BIM single nucleotide polymorphism, and 83.6% with BIM wild type. Median progression-free survival was 10.3months with BIM deletion polymorphism, 8.5months with BIM single nucleotide polymorphism, and 10.4months with BIM wild type. Overall survival was 38.4months with BIM deletion polymorphism, 29.1months with BIM single nucleotide polymorphism, and 31.6months with BIM wild type. There were no significant differences between the groups in overall response ratio, progression-free survival, and overall survival. BIM polymorphism does not affect EGFR-TKI efficacy.

Novel Mutations and Genes That Impact on Growth in Short Stature of Undefined Aetiology: The EPIGROW Study.

BackgroundChildren with short stature of undefined aetiology (SS-UA) may have undiagnosed genetic conditions.PurposeTo identify mutations causing short stature (SS) and genes related to SS, using candidate gene sequence data from the European EPIGROW study.MethodsFirst, we selected exonic single nucleotide polymorphisms (SNPs), in cases and not controls, with minor allele frequency (MAF) < 2%, whose carriage fitted the mode of inheritance. Known mutations were identified using Ensembl and gene-specific databases. Variants were classified as pathogenic, likely pathogenic, or variant of uncertain significance using criteria from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. If predicted by ≥ 5/10 algorithms (eg, Polyphen2) to be deleterious, this was considered supporting evidence of pathogenicity. Second, gene-based burden testing determined the difference in SNP frequencies between cases and controls across all and then rare SNPs. For genotype/phenotype relationships, we used PLINK, based on haplotype, MAF > 2%, genotype present in > 75%, and Hardy Weinberg equilibrium P > 10–4.ResultsFirst, a diagnostic yield of 10% (27/263) was generated by 2 pathogenic (nonsense in ACAN) and a further 25 likely pathogenic mutations, including previously known missense mutations in FANCB, IGFIR, MMP13, NPR2, OBSL1, and PTPN11. Second, genes related to SS: all methods identified PEX2. Another 7 genes (BUB1B, FANCM, CUL7, FANCA, PTCH1, TEAD3, BCAS3) were identified by both gene-based approaches and 6 (A2M, EFEMP1, PRKCH, SOS2, RNF135, ZBTB38) were identified by gene-based testing for all SNPs and PLINK. ConclusionsSuch panels improve diagnosis in SS-UA, extending known disease phenotypes. Fourteen genes related to SS included some known to cause growth disorders as well as novel targets.

PCR-RFLP Polymorphism of Growth Hormone Gene and Its Association with Growth and Morphometric Traits in Ganjam and Baigani Goats of Odisha

Background: Growth Hormone (GH) gene codes for the growth hormone, an anabolic hormone synthesized and secreted by the somatotroph cells of pituitary. Growth hormone influences many processes such as growth, lactation, reproduction and metabolism. Genetic variation in the gene are utilized as markers for selecting animals that are superior in terms growth, production and reproduction traits. Information available on the polymorphism of growth hormone gene of Ganjam and Baigani goats of Odisha is scanty. The current investigation was done to explore the genetic variation of this gene and its association with morphometric traits. Methods: Genetic polymorphism in exon 2 and 3 of Growth hormone gene in Ganjam goat and Baigani goat was explored with sample size of 100 goats for each. The goats belonged to three locations: Khallikote, Rambha, Chattrapur of Ganjam district. The goats were recorded for their body weights, morphometric traits and morphological traits. Genomic DNA was isolated, the target segment comprising exons 2 and 3 was amplified and PCR-RFLP was carried out using Hae III restriction enzyme. Genotypes were scored. Result: PCR of the locus resulted in 422 bp PCR product. PCR-RFLP using Hae III restriction enzyme yielded only two variants in both the populations. The variant A had only one restriction recognition site on the target gene segment yielding two bands with size of 366bp and 56bp whereas the variant B did not have any restriction site with single band of 422bp. Three genotypes AA, AB and BB were found in both the population. In both the population, the gene and genotype frequency were significantly deviated from the Hardy Weinberg Equilibrium frequency. There was a significant difference in the genotype frequencies of growth hormone gene between Ganjam and Baigani goats. The AB genotype had higher mean value for all morphometric traits than AA and BB genotype though the differences were not found to be significant.