Polymorphism In Exon Research Articles

A novel single nucleotide polymorphism in exon 3 of MYOC enhances the risk of glaucoma.

Genetic polymorphismsof MYOCalter the myocilin protein,which leads to disruption of thenormal regulation of intraocular pressure (IOP) that ultimately causes glaucoma.Theaim of the present study was to identify the polymorphism in exon 3 of the MYOC gene of theglaucoma patients in Lahore, Pakistan. We conducted a case-control study with 100 patients and 100 controls subjects. We extracted DNA from blood samples,amplified the target DNA fragmentby PCR, and identifiedpolymorphisms through sequencing. We observed that the allelic and genotypic frequencies of rs74315341 and rs879255525 were associated with glaucoma in our patient population. The polymorphism atrs74315341 led to the substitutionof serine for arginine,whereas the polymorphism at rs879255525 led to the substitution ofasparagine for lysine. The haplotype TGAAGCCATTTC was associated with disease onset, whereas the haplotype GGAAGCCATTTC was protective against disease development. In conclusion, weidentified MYOC gene polymorphisms in susceptible regions that were associated withglaucoma onset among the Lahore patient population.This is the first report to identify a novel mutation in rs879255525 in exon 3 of the MYOC genethat is associated withglaucoma.

Mutation screening of the BRCA1 gene in sporadic breast cancer in the Central of Iran

The purpose of the work was to study mutation screening of BRCA1 in Iranian patients with sporadic breast cancer. We carried out a mutational analysis of BRCA1 gene in 101 breast cancer patients from a population in Central of Iran. The comparison of DNA of paraffin-embedded breast cancer tissue from patients was studied, and breast tissue from 30 unrelated normal women without cancer was selected as controls. The entire BRCA1 coding sequence was amplified by PCR with primers especially designed for comprehensive mutation screening by single-strand conformation polymorphism (SSCP) analysis. The PCR products revealing abnormal SSCP migration pattern were sequenced. Then, in silico investigation was performed to identify the effects of new mutations on stability and function of BRCA 1.A total of ten nucleotide alterations were observed in the breast cancer tissue DNA. Six cases of single nucleotide changes in BRCA1 were detected in the study without records in the BIC database consisted four polymorphism in exon 11 (1543 Del G, 1597C>T, 2246 Del T, 2612C>G), one missense mutation in exon 7 (490C>T), and one deletion mutation in exon 10 (743 Del C). No nucleotide alterations were detected in the controls. In addition, the results of in silico analysis indicated that three mutations including 2612C>G, 1543 Del G and 743 Del C were not recorded in the especial database. Furthermore, the results of molecular docking studies confirmed that 2612C>G could change physicochemical properties of BRCA1.The findings of the present study suggest that screened mutations may have an important role on the incidence of breast cancer in women.

Regulation of Monoallelic TERT Expression in Cancer Cells with Wildtype Promoters

During cell division, chromosomal telomere shortening that occurs due to the “end‐replication problem” can be compensated for by telomerase, a ribonucleoprotein enzyme that lengthens telomeres. Telomerase is active in stem cells, enabling maintenance of the telomeres, while it is normally inactive in somatic cells, leading to telomeres progressively shortening until a critical length triggers cell senescence or apoptosis. Importantly, telomerase is pathogenically reactivated in approximately 80–90% of human cancers. The expression of telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, specifically appears to be crucial to telomerase's tightly regulated activities; the Cech lab and others have shown that an absence of TERT expression is what prevents telomerase activity in human cells. While TERT expression levels are tightly regulated, with only 10–20% decrease in telomerase activity thought to be possibly deleterious for normal stem cell function, it is unclear how TERT expression becomes reactivated in many cancer types. Of particular interest is monoallelic expression (MAE) of TERT, which has been found in the majority of cancerous tissues. While some MAE cancer lines contain activating promoter mutations, other MAE cancer lines have no detectable mutations, raising the intriguing question of why TERT is reactivated in a monoallelic fashion in these wildtype (WT) cancers. To investigate the cause(s) of MAE expression in these WT cancer lines, we are investigating the allelic DNA CpG methylation pattern using bisulfite conversion cloning, histone modification markers using chromatin immunoprecipitation (ChIP), and transcription factor (TF) binding via ChIP, all within the TERT promoter region. Lines being investigated include multiple myeloma, pancreatic, lung, and glioblastoma cancer lines that have a single‐nucleotide polymorphism (SNP) in TERT exon 2 to enable identification of the active allele via reverse transcription PCR. While CpG hypermethylation is typically associated with silent gene expression, the TERT promoter paradoxically contains an apparently hypermethylated promoter in cancers actively expressing TERT. Our group recently found that in MAE cancers with TERT promoter mutations, the active allele is in fact hypomethylated (Stern et al., in press*), raising the question of whether this is similar in the WT TERT MAE lines. We have found that, in at least some of the WT MAE lines investigated, DNA CpG methylation patterns appear to be allelic, with one allele possessing hypermethylation and the other hypomethylation. We are currently investigating how this correlates with allelic expression, histone modification, and TF binding. Improved understanding of how TERT is reactivated in WT MAE cancers could help guide future drug discovery and cancer therapeutic efforts.Support or Funding InformationThis work was funded by National Institutes of Health grant R01 GM099705 to T.R.C.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differentiating causes of CSF protein increase: Barrier dysfunction or drainage reduction?

Schizophrenia is a complex neuropsychiatric disorder with deficits of multiple domains of cognitive functions, volition and emotions. Family and twin studies have provided cumulative evidence for the genetic basis of schizophrenia. The aetiolgy of this disease involves the interplay of multifactiorial inheritance operating on brain maturational processes and polygenic inheritance with some genes showing susceptibility at many genomic locations such as 22q and 11q.The catechol-O-methyltransferase (COMT-22q11) is an extensively studied candidate gene for schizophrenia. COMT acts as an enzymatic detoxicating barrier between the blood and other tissues regulating the amounts of active dopamine and norepinephrine in various parts of the brain and therefore to be associated with schizophrenia.The presence of a common functional single nucleotide polymorphism (SNP) in exon 4 [Guanine (G) Adenine (A); Val108/158Met], alters the enzymatic activity with a trimodal distribution of high-HH, intermediate-HL and low-LL activity alleles which appear to have association with schizophrenia.Brain-derived neurotrophic factor (BDNF-11q13) is a member of the nerve growth factor family working as a molecular regulator of neuronal development and plasticity. Molecules that are critical in the development and survival of neurons such as BDNF play a significant role in the neuropathology of schizophrenia. While upregulation of BDNF increases the neuronal cell size and synaptic plasticity, a functional polymorphism at codon 66 [G→A; Val66Met] down regulates this process and induces schizophrenia.In the present study, our aim was to investigate the differences in allele frequencies between schizophrenic patients [n = 97 (51 men, 46 women)] and control group [n = 376 (228 men, 148 women)] subjects.When the control and schizophrenia groups were compared for BDNFVal66Met polymorphism, we did not find a significant difference between the study groups either for genotype (χ2 = 3.370447, p > 0.05) or Val/Met haplotype analysis (χ2 = 2.840264, p > 0.05). When a comparison was revealed for COMT-Val108/158Met polymorphism, no significant difference was detected among schizophrenia and control groups for genotype (χ2 = 0.373330, p > 0.05) and Val/Met haplotype analysis (χ2 = 0.339073, p > 0.05). When the control and study groups were compared for BDNFVal66Met–COMTVal108/158Met polymorphisms compound genotype and haplotype analyses, there was no significant difference between the two groups (χ2 = 11.015; p > 0.05 and χ2 = 3.191; p > 0.05), respectively.Our results indicate that there is no association between schizophrenia and BDNF–COMT polymorphisms and haplotypes analysis. We also did not find an association between schizophrenia and BDNF–COMT compound genotype and haplotype analyses. Although our study is unique in Turkey as combining BDNF and COMT compound genotype–haplotype analyses, for a generalization of Turkish schizophrenia patient's susceptibility to schizophrenia; we need further studies with an enlarged cohort.

Cq1 Exon Polymorphisms in Caucasian and African American Systemic Lupus Erythematosus patients

C1q protein is composed of three protein chains (A, B and C) that are the products of separate genes. Genetic deficiencies in C1Q genes are important factors influencing the risk of systemic lupus erythematosus (SLE). Therefore, this study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) in the coding region of the C1Q genes with SLE. To search for potential SNPs in the encoding regions of C1q A, B and C chains, Cq1 exons were initially amplified and directly sequenced from leukocyte DNA from a subset of Caucasian and African American SLE patients and healthy controls. The sequences were analyzed by the Phrap and Phred software analysis system and the SNPs were identified by visual inspection. To test if any of these SNPs were linked to susceptibility to SLE, they were measured in 210 SLE patients ((59 African Americans and 151 Caucasians) and 129 matched healthy controls (55 African Americans and 74 Caucasians) by restriction fragment length polymorphism analysis. The sequencing phase of the study identified three synonymous SNPs: Nucleotide 276G>A in C1QA, 66C>A in C1QB and 129G>A in C1QC. Statistically, no differences were found in genotype or allele frequencies between patients and controls for the 276G>A or 66C>A SNP. However, in Caucasians, the frequencies of the 129G>A genotypes were significantly different between SLE patients and controls (P = 0.005), specifically with the GG genotype being over represented in the controls (P = 0.004). The results show that the homozygous 129GG genotype is associated with protection against SLE onset. This protection is race dependent, being observed in Caucasians but not African Americans. The mechanism of this association is currently unclear.

An examination of melanogenic traits and <i>TYRP1</i> polymorphism in Nanping and Romney Marsh sheep breeds

Abstract. The effects of mutations of the gene for tyrosinase-related protein 1 (TYRP1) on the black muscles and coat color in Nanping black-boned sheep were investigated. Tyrosinase activity and melanin content in plasma were measured and compared in three random groups of sheep: Nanping black-boned (101 heads), Nanping normal (106 heads) and Romney Marsh sheep (82 heads, Ovis aries). Eight exons and their partial flanking regions of the TYRP1 gene were amplified. Six intronic mutations and six exonic polymorphisms including two non-synonymous mutations [c.203C > T (p.A68V) and c.1202T > C (p.V401A)] were identified. Using a bi-directional polymerase chain reaction allele-specific amplification (bi-PASA) of the mutation c.203C > T it was shown that the frequencies of allele C in the Nanping black-boned, Nanping normal and Romney Marsh sheep were respectively 0.955, 0.967 and 0.744. For the mutation c.1202T > C, the frequencies of allele T in the three populations of sheep were respectively 0.777, 0.745 and 0.793 as measured using the single-strand conformation polymorphism. When the data from sheep of all three populations with the CC genotype of SNP c.203C > T were pooled, it was found that there was significantly higher (P < 0.05) tyrosinase activity, content of alkali-soluble melanin and ratio of eumelanin : total melanin than in the plasma of sheep with the CT and TT genotypes. This was not so within each of the three groups of sheep. No significant effect of the TRYP1 genotype on coat color was found. Further studies will be necessary to determine the cause of the black traits in Nanping black-boned sheep.

Investigation of PRL-RsaI and HaeIII gene polymorphisms in Anatolian water buffaloes bred by using PCR-RFLP method

ABSTRACT The objective of this study was to investigate polymorphisms both in exons 1 and 3 of prolactin (PRL) gene for milk productivity of Anatolian water buffalo breed in Sivas province in Turkey. Blood samples were collected from 129 male and female water buffaloes and DNA was isolated by using phenol/chloroform method. Samples of DNA were amplified and resulting PCR products were digested with RsaI (for exons 1 and 3) and HaeIII (for exon 1). Allelic polymorphisms were determined by [...]

LKF, the locus regulating large grains in the rice cultivar ‘Fusayoshi’, is identical to the loci encoding a serine/threonine protein phosphatase with Kelch motif

The LKF locus, which regulates grain size in the rice cultivar ‘Fusayoshi’ showing large grain, has been mapped to the proximal part of the long arm of chromosome 3. An incomplete dominant allele, Lkf, caused large grain size of Fusayoshi. The structure and function of this locus, however, have not yet been determined. In a similar position to LKF on chromosome 3, two loci, Os03g0407400 (GS3) and LOC_Os03g44500, have been already reported as loci also regulating rice grain size. The objective of the present study was to determine the nucleotide sequences of both Os03g0407400 and LOC_Os03g44500 for different alleles at the LKF locus. Results showed that only one known single nucleotide polymorphism (SNP) in exon 10 of LOC_Os03g44500 was detected between a large-grain allele (Lkf) and a small-grain allele at the LKF locus, whereas no polymorphisms in Os03g0407400. This SNP, visualized using a dCAPS marker, clearly demonstrated nearly complete co-segregation with grain length in an F2 population segregating the Lkf at LKF. Other large-grain mutant lines with large-grain alleles at the LKF locus, which originated from another cultivar ‘Gimbozu’, also showed the same SNP in exon 10 of LOC_Os03g44500. It was concluded from these results that LKF is identical to LOC_Os03g44500, and the detected SNP in exon 10, at least, which is included in Kelch-like repeat motif, could be essential for expression of the large-grain phenotype.

Unique CD44 intronic SNP is associated with tumor grade in breast cancer: a case control study and in silico analysis

BackgroundCD44 encoded by a single gene is a cell surface transmembrane glycoprotein. Exon 2 is one of the important exons to bind CD44 protein to hyaluronan. Experimental evidences show that hyaluronan–CD44 interaction intensifies the proliferation, migration, and invasion of breast cancer cells. Therefore, the current study aimed at investigating the association between specific polymorphisms in exon 2 and its flanking region of CD44 with predisposition to breast cancer.MethodsIn the current study, 175 Iranian female patients with breast cancer and 175 age-matched healthy controls were recruited in biobank, Breast Cancer Research Center, Tehran, Iran. Single nucleotide polymorphisms of CD44 exon 2 and its flanking were analyzed via polymerase chain reaction and gene sequencing techniques. Association between the observed variation with breast cancer risk and clinico-pathological characteristics were studied. Subsequently, bioinformatics analysis was conducted to predict potential exonic splicing enhancer (ESE) motifs changed as the result of a mutation.ResultsA unique polymorphism of the gene encoding CD44 was identified at position 14 nucleotide upstream of exon 2 (A37692→G) by the sequencing method. The A > G polymorphism exhibited a significant association with higher-grades of breast cancer, although no significant relation was found between this polymorphism and breast cancer risk. Finally, computational analysis revealed that the intronic mutation generated a new consensus-binding motif for the splicing factor, SC35, within intron 1.ConclusionsThe current study results indicated that A > G polymorphism was associated with breast cancer development; in addition, in silico analysis with ESE finder prediction software showed that the change created a new SC35 binding site.

The HLA-G 14 bp insertion/deletion polymorphism and its association with soluble HLA-G levels in women with recurrent miscarriages.

HLA-G, a nonclassical class-Ib gene is mainly expressed on extravillous trophoblasts at the fetal-maternal interface. HLA-G molecule is considered to play an important role in maternal immune suppression during pregnancy. The 14 bp insertion/deletion polymorphism (rs66554220) in exon eight of the HLA-G gene influences HLA-G mRNA stability and isoform splicing patterns. In this study, 202 recurrent miscarriage (RM) women with two or more than two consecutive miscarriages, their 202 partners and 204 fertile control women with at least one live birth and no miscarriages were analyzed for 14 bp insertion/deletion polymorphism. Soluble HLA-G (sHLA-G) levels were also determined and compared between randomly selected 111 RM women and 111 control women using QAYEE-Bio ELISA kits. Student's t test and χ2 test were used to depict the statistical differences. The results showed no significant differences for 14 bp allele and genotype frequencies between the study groups. However, our study showed a significant difference (P = .0107) for sHLA-G levels in RM women and control women. Furthermore, a significant difference (P = .0135) for sHLA-G levels in relation to +/-14 bp heterozygous genotype was seen between the two groups. The 14 bp allele sharing between the partners did not show any significant association with the number of miscarriages in RM couples. The association of 14 bp polymorphism and recurrent miscarriages was not significant in our study.

LIN7 Cell-Wall Invertase Orthologs in Cultivated and Wild Tomatoes (Solanum Section Lycopersicon)

Plant acid invertases are considered to be the key enzymes in sucrose unloading and carbohydrate supply to sink tissues. Acid cell-wall invertases control sucrose transport via the apoplastic pathway during sink initiation and expansion. In this study, we identified 12 LIN7 gene homologs encoding cell-wall invertases in red- and green-fruited tomato accessions (Solanum section Lycopersicon) of self-compatible and self-incompatible species. All genes consisted of six exons and five introns, including highly conserved 9-bp exon II. Identification of 226 exonic single nucleotide polymorphisms as well as extremely high intron variability indicates a significant interspecific divergence among the examined tomato accessions. Computational prediction revealed protein structure typical for the glycosyl hydrolase family 32 and conserved catalytic sites described for other plant cell-wall invertases. LIN7 expression in mature buds and flowers confirms LIN7 role in the development of pollen tubes and grains. The variability in gene and protein sequences and species-specific differences in LIN7 expression patterns may be responsible for putative functional divergence of invertases. Furthermore, we performed phylogenetic analysis of the Solanum section Lycopersicon species based on the LIN7 gene, which clearly divided the analyzed tomato accessions into two main clusters corresponding to self-compatible and self-incompatible species and was in agreement with the separation into red- and green-fruited plants. Given that LIN7 plays an essential role in tomato fertility and fruit ripening, the characterization of protein variability within species of section Lycopersicon may be useful to evaluate the potential application of the encoding genes for tomato breeding programs.

Association of polymorphic variants of IL-1β and IL-1RN genes in the development of Graves’ disease in Kashmiri population (North India)

PurposeGraves’ disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (−511 T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population. MethodsA total of 135 Graves’ disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RNVNTR and IL-1β gene polymorphisms respectively. ResultsWe found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02–8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14–4.50) in IL-1β gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11–0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20–0.48) was observed in GD cases as against controls. For IL-1RNVNTR (rs2234663), we didn’t observe any significant difference in the allelic and genotypic frequencies between cases and controls. ConclusionOur findings suggest that both promoter and exon polymorphisms of IL-1β gene have a significant role in the risk of developing GD, whereas IL-1RNVNTR has no association with GD.

Genetic Association of the Norepinephrine Transporter Gene G1287A Polymorphism with Risk of Schizophrenia: A Case-Control Study and Meta-Analysis.

The G1287A polymorphism (rs5569) in exon 9 of the norepinephrine transporter (NET) gene has been associated with schizophrenia in several populations. However, the results are conflicting. Moreover, few studies have investigated the relationship between the G1287A polymorphism and schizophrenia among the Chinese Han population. A case-control study was designed to explore whether the G1287A genetic variant is related to schizophrenia in the Chinese Han population. The results from this study were then included in the performance of a meta-analysis to further analyze the association of the G1287A polymorphism with schizophrenia. No significant differences in the genotype and allele distributions of G1287A were found between Chinese Han patients with schizophrenia and control participants. Similarly, in gender-specific analyses, no significant differences were found for G1287A genotype and allele distributions in either the male or the female case-control comparisons. Finally, the results of this meta-analysis also showed that the NET gene G1287A polymorphism was not associated with schizophrenia in the total population under allelic, recessive, dominant, or homozygous genetic models. Our case-control study and meta-analysis suggest that the NET gene G1287A polymorphism may not be involved in the etiology of schizophrenia in the Chinese Han population.

Association of PAX4 gene R192H polymorphisms in Chinese Han type 2 diabetes

The purpose of this study was to explore whether PAX4 gene R192H polymorphism plays a role in type 2 diabetes in Chinese Han population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology to detect R192H polymorphism in exon 5 of PAX4 gene in 410 cases of patients with type 2 diabetes and 95 cases of non-diabetic controls from January 2014 to January 2015. There are no significant differences in the genotypes or allele frequencies between type 2 diabetes mellitus (T2DM) and non-diabetic controls about PAX4 R192H polymorphism. Similarly, no statistical differences were observed in the T2DM and non-diabetic controls when adjusting for gender stratification and age stratification. The comparisons on the subjects in clinical characteristics including blood glucose, glycated hemoglobin, cholesterol, triglycerides, high-density lipoprotein cholesterol, and systolic blood pressure showed no difference between carriers with the GA and AA genotype except diastolic blood pressure (p value = 0.038). PAX4 gene exon 5 R192H polymorphism was not associated with type 2 diabetes in Chinese Han population.

CTLA4 gene polymorphisms associated with insulindependent diabetes mellitus (IDDM) type I in Iraqi population

This study was correlated to evaluate polymorphisms in CTLA4 associated with insulin-dependent diabetes mellitus in a Iraqi population. Blood samples were collected from 40 patient (4-25 years) from 1/6/2010- 1/2/2011, isolation of DNA were done and PCR was performed using primer for CTLA4 gene. The result shows that 31 patients have mutation in 49 position A/G polymorphism in exon 1 of CTLA4 by using BstEII enzyme. There is a highly significant correlation between diabetes and incidence of A/G 49 position in exon 1 of CTLA4 gene (X2 = 32.1, P>0.05), the conclusion is that there is enough evidence to support the claim that diabetes is related to A/G 49 transition mutation

SERT gene polymorphisms are associated with risk-taking behaviour and breeding parameters in wild great tits

Individual differences in coping with potentially dangerous situations are affected by a combination of genetic and environmental factors. How genetic polymorphisms and behavioural variations are related to fitness is unknown. One of the candidate genes affecting a variety of behavioural processes, including impulsivity, anxiety and mood fluctuations in both humans and other vertebrates, is the serotonin transporter gene (SERT/SLC6A). The aim of this study was to assess an association between SERT genotypes and novelty-seeking and risk-taking behaviours as well as breeding parameters of great tits (Parus major) in a natural environment. We associated polymorphisms in the promoter exonic regions of the SERT gene with parental risk-taking-related behaviour and fitness traits. Our results show that: (1) risk-taking behaviour in our great tit population is linked to single nucleotide polymorphisms in the SERT gene exon 3 and exon 8; (2) the genotype-behaviour associations are consistent with the presence of different stressors; and (3) polymorphisms in exon 8 could be associated with fitness-related traits, such as the start of egg-laying and hatching success. We showed for the first time that genetic variability of SERT plays an important role in shaping individual decision-making that affects fitness in a wild population. However, the results are based on one population and on the polymorphisms that are in a single gene. Therefore, replication studies are needed in order to confirm these preliminary results.

The association of gamma-synuclein autoantibodies with the polymorphism in exon 4 of the coding gene

To analyze the polymorphism in exon 4 of the gamma-synuclein gene (SNCG) in patients with autoantibodies against the gamma-synuclein protein. To identify autoantibodies against gamma-synuclein, the serum from patients with chronic cerebral ischemia and cervical osteochondrosis was used. All patients were women of the Slavic ethnic group, mean age 61±5 years. The isolated genomic DNA was used to determine the point mutation in exon 4 by the restriction endonuclease HphI and subsequent sequencing of the resulting fragments to confirm the results. Antibodies against gamma-synuclein were identified in 2 patients with chronic cerebral ischemia and 3 with cervical osteochondrosis. All five patients had a T to A substitution at position 371, which was detected by the restriction endonuclease HphI resulting in a hydrolysis of the amplicon and the formation of two fragments. The subsequent sequencing of exon 4 of the SNCG revealed no other mutations and confirmed the T to A substitution. This single nucleotide polymorphism results in the amino acid substitution of glutamic acid to valine at position 110 (out of 127), changing its physicochemical properties and the ability to form aggregates as well as post-translational modifications. The obtained results provide grounds for further association studies of SNCG polymorphism in patients with various diseases of the nervous system.

The Deletion Polymorphism in Exon 8 of Uncoupling Protein 2 is Associated with Severe Obesity in a Saudi Arabian Case-control Study.

Context:Obesity is a major health concern in Saudi Arabia. Uncoupling protein 2 (UCP2) seems to play a major role in the regulation of human metabolism; therefore, genetic polymorphisms in the UCP2 gene might contribute to obesity.Aim:This study aims to establish whether 45-blood pressure (BP) insertion (I)/deletion (D) polymorphisms in UCP2 are associated with moderate and/or severe obesity in a Saudi Arabian population.Settings and Design:Case–control study design.Materials and Methods:The study enrolled 151 male and female subjects originating from the eastern province of Saudi Arabia, and assigned each to a “nonobese,” “moderately obese,” or “severely obese” group. Genomic DNA was extracted from all subjects and screened for UCP2 I/D polymorphisms using a standard polymerase chain response protocol.Statistical Analysis Used:Analysis of variance, Chi-squared tests, and logistic regression analysis.Results:The frequencies of the UCP2 45-BP I/D genotypes D/D, I/D, and I/I within the analyzed population were 58.3%, 36.4%, and 5.3%, respectively. The D/D genotype was highly prevalent within the severely obese group (82.9%) compared to the nonobese (46.2%) and moderately obese (53.3%) groups. Using a dominance model, the conducted logistic regression analysis showed a strong association between the deletion allele and severe obesity (Odds ratio = 0.18, 95% confidence interval: 0.07–0.44, P = 0.0004).Conclusions:The present study reported that the frequency of UCP2 45-BP I/D polymorphisms in a population originating from eastern Saudi Arabia and identified a strong association between the D/D genotype and severe obesity.

Polymorphism Of Exon 2-3 Of Growth Hormone Gene In Surti and Mehsani Goats by PCR-RFLP

The investigation was planned to study GH gene exon 2-3 polymorphism using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) in Surti and Mehsani goats. GH gene exon 2-3 region was found to be polymorphic on restriction digestion with Hae III which revealed two genotypes AA and AB with genotypic frequencies of 0.24 and 0.76 in Surti goats and 0.20 and 0.80 in Mehsani goats respectively. Both the population of Surti and Mehsani goats were not found to be in genetic equilibrium for GH locus exon 2-3 indicating selection pressure for growth. Polymorphism in exon 2-3 region of GH gene in both the goat breeds can be utilized in formulating breeding strategies based on marker assisted selection in both the goat breeds.

Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus.

Purpose:To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN).Methods:Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features according to Rabinowitz's criteria (K > 47.2, I-S > 1.4 and KISA > 100%). DNA from blood samples was extracted from donors, and the exons and exon-intron boundaries of VSX1 were sequenced. The potential impact of the identified amino acid changes was assessed with Poly-Phen2, SIFT, and PMUT analysis tools. Genotyping was confirmed by RLFP technique, which was also applied to genotype non-affected individuals.Results:We found three non-synonymous substitutions (L68H, R131S, and D105E) in VSX1 exon 1, with L68H mutation as a novel variation in this gene. In silico analysis indicated that all variations found were predicted to be probably damaging to VSX1 structure and function. Examination of R131S and L68H variations segregating in one family suggested a strong effect of these variations in increasing disease severity in the proband, which presented bilateral KCN leading to corneal grafting before the age of sixteen. We found a novel synonymous substitution (P79P) and two previously described exonic polymorphisms, with unknown roles in VSX1 pathogenesis.Conclusion:VSX1 polymorphisms found in the Brazilian population support a genetic component in KCN pathogenesis. L68H is a novel mutation, and the phenotypic data suggest that this mutation might enhance disease severity when combined with other polymorphisms. However, further investigations are needed.