alleles Research Papers - Academia.edu (original) (raw)

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are... more

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at ...

In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases.... more

In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P = 0.048) and healthy controls (P = 0.0006), indepen...

1. Frog integumentary mucins (FIM-A.1, FIM-B.1 and FIM-C.1) consist of typical threonine-rich highly O-glycosylated (semi)repetitive domains, and cysteine-rich modules, i.e. the P-domain, the short consensus repeat and a region with high... more

1. Frog integumentary mucins (FIM-A.1, FIM-B.1 and FIM-C.1) consist of typical threonine-rich highly O-glycosylated (semi)repetitive domains, and cysteine-rich modules, i.e. the P-domain, the short consensus repeat and a region with high similarity to the C-terminal end of von Willebrand factor (designated here CC29-motif). 2. These modules are thought to be involved in protein-protein interactions and they have been observed in a variety of extracellular proteins. In FIMs, these modules may be involved in oligomerization processes leading to an entangled mucin network. 3. Polydispersities have been detected in FIM-B.1 and FIM-C.1 within single individuals. Multiple transcripts are probably generated by alternative splicing of a huge array of different (semi)repetitive cassettes encoding the threonine-rich domains. 4. Furthermore, genetic polymorphism is observed between different individuals, probably due to allelic variations in the number of (semi)repetitive cassettes.

Genomic selection estimates genetic merit based on dense SNP (single nucleotide polymorphism) genotypes and phenotypes. This requires that SNPs explain a large fraction of the genetic variance. The objectives of this work were: (1) to... more

Genomic selection estimates genetic merit based on dense SNP (single nucleotide polymorphism) genotypes and phenotypes. This requires that SNPs explain a large fraction of the genetic variance. The objectives of this work were: (1) to estimate the fraction of genetic variance explained by dense genome-wide markers using 54 K SNP chip genotyping, and (2) to evaluate the effect of alternative marker-based relationship matrices and corrections for the base population on the fraction of the genetic variance explained by markers. Two alternative marker-based relationship matrices were estimated using 35 706 SNPs on 1086 dairy bulls. Both pedigree- and marker-based relationship matrices were fitted simultaneously or separately in an animal model to estimate the fraction of variance not explained by the markers, i.e. the fraction explained by the pedigree. The phenotypes considered in the analysis were the deregressed estimated breeding values (dEBV) for milk, fat and protein yield and for...

Promoter polymorphism of cytokine genes may lead to inter-individual differences in cytokine levels, therefore, polymorphisms may associate with susceptibility to infectious diseases. In this study, we investigated a possible association... more

Promoter polymorphism of cytokine genes may lead to inter-individual differences in cytokine levels, therefore, polymorphisms may associate with susceptibility to infectious diseases. In this study, we investigated a possible association between interleukin-10 (IL-10) -1082A⁄G (rs1800896) and interferon (IFN)-gamma +874T/A (rs2430561) promoter polymorphisms and tuberculosis (TB) in the Azeri population of Iran. IL-10 -1082G/A and IFN-gamma +874T/A single nucleotide polymorphisms (SNPs) were genotyped by amplification refractory mutation system (ARMS)-PCR in 200 healthy controls and 124 tuberculosis patients. IL-10 -1082 A allele was more frequent in the control group than in the patient group (p=0.001, odds ratio [OR]=2.183). On the other hand, the AA genotype was significantly more frequent in the control group (p=0.0001). The frequency of IFN-gamma +874 T allele was significantly higher in the controls (p=0.013, OR=1.56). There was no significant association between IFN-gamma +874...

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and growth retardation. Clinical photosensitivity is present in... more

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and growth retardation. Clinical photosensitivity is present in approximately 50% of TTD patients but is not associated with an elevated frequency of cancers. Previous complementation studies show that the photosensitivity in nearly all of the studied patients is due to a defect in the same genetic locus that underlies the cancer-prone genetic disorder xeroderma pigmentosum group D (XP-D). Nucleotide-sequence analysis of the ERCC2 cDNA from three TTD cell strains (TTD1V1, TTD3VI, and TTD1RO) revealed mutations within the region from amino acid 713-730 and within previously identified helicase functional domains. The various clinical presentations and DNA repair characteristics of the cell strains can be correlated with the particular mutations found in the ERCC2 locus. Mutations of Arg658 to either His or Cys correlate with...

Chloroquine (CQ) remains the first-line treatment of malaria in Haiti. Given the challenges of conducting in vivo drug efficacy trials in low-endemic settings like Haiti, molecular surveillance for drug resistance markers is a reasonable... more

Chloroquine (CQ) remains the first-line treatment of malaria in Haiti. Given the challenges of conducting in vivo drug efficacy trials in low-endemic settings like Haiti, molecular surveillance for drug resistance markers is a reasonable approach for detecting resistant parasites. In this study, 349 blood spots were collected from suspected malaria cases in areas in and around Port-au-Prince from March to July 2010. Among them, 121 samples that were Plasmodium falciparum positive by polymerase chain reaction were genotyped for drug-resistant pfcrt, pfdhfr, pfdhps, and pfmdr1 alleles. Among the 108 samples that were successfully sequenced for CQ resistant markers in pfcrt, 107 were wild type (CVMNK), whereas one sample carried a CQ-resistant allele (CVIET). Neutral microsatellite genotyping revealed that the CQ-resistant isolate was distinct from all other samples in this study. Furthermore, the remaining parasite specimens appeared to be genetically distinct from other reported Cent...

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of... more

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft ...

Gender dysphoria, a marked incongruence between one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s experienced gender and biological sex, is commonly believed to arise from... more

Gender dysphoria, a marked incongruence between one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s experienced gender and biological sex, is commonly believed to arise from discrepant cerebral and genital sexual differentiation. With the discovery that estrogen receptor β is associated with female-to-male (FtM) but not with male-to-female (MtF) gender dysphoria, and given estrogen receptor α involvement in central nervous system masculinization, it was hypothesized that estrogen receptor α, encoded by the ESR1 gene, also might be implicated. To investigate whether ESR1 polymorphisms (TA)n-rs3138774, PvuII-rs2234693, and XbaI-rs9340799 and their haplotypes are associated with gender dysphoria in adults. Molecular analysis was performed in peripheral blood samples from 183 FtM subjects, 184 MtF subjects, and 394 sex- and ethnically-matched controls. Genotype and haplotype analyses of the (TA)n-rs3138774, PvuII-rs2234693, and XbaI-rs9340799 polymorphisms. Allele and genotype frequencies for the polymorphism XbaI were statistically significant only in FtM vs control XX subjects (P = .021 and P = .020). In XX individuals, the A/G genotype was associated with a low risk of gender dysphoria (odds ratio [OR] = 0.34; 95% CI = 0.16-0.74; P = .011); in XY individuals, the A/A genotype implied a low risk of gender dysphoria (OR = 0.39; 95% CI = 0.17-0.89; P = .008). Binary logistic regression showed partial effects for all three polymorphisms in FtM but not in MtF subjects. The three polymorphisms were in linkage disequilibrium: a small number of TA repeats was linked to the presence of PvuII and XbaI restriction sites (haplotype S-T-A), and a large number of TA repeats was linked to the absence of these restriction sites (haplotype L-C-G). In XX individuals, the presence of haplotype L-C-G carried a low risk of gender dysphoria (OR = 0.66; 95% CI = 0.44-0.99; P = .046), whereas the presence of haplotype L-C-A carried a high susceptibility to gender dysphoria (OR = 3.96; 95% CI = 1.04-15.02; P = .044). Global haplotype was associated with FtM gender dysphoria (P = .017) but not with MtF gender dysphoria. XbaI-rs9340799 is involved in FtM gender dysphoria in adults. Our findings suggest different genetic programs for gender dysphoria in men and women. Cortés-Cortés J, Fernández R, Teijeiro N, et al. Genotypes and Haplotypes of the Estrogen Receptor α Gene (ESR1) Are Associated With Female-to-Male Gender Dysphoria. J Sex Med 2017;14:464-472.

The present investigation was carried out using 51 diverse bitter gourd accessions as material for studying genetic diversity and relatedness using morphological and SSR markers. A wide variation was observed for morphological traits like... more

The present investigation was carried out using 51 diverse bitter gourd accessions as material for studying genetic diversity and relatedness using morphological and SSR markers. A wide variation was observed for morphological traits like the number of days to the first female flower anthesis (37.33–60.67), the number of days to the first fruit harvest (47.67–72.00), the number of fruits/plant (12.00–46.67), fruit length (5.00–22.23 cm), fruit diameter (1.05–6.38 cm), average fruit weight (20.71–77.67 g) and yield per plant (513.3–1976 g). Cluster analysis for 10 quantitative traits grouped the 51 accessions into 6 clusters. Out of 61 SSR primers screened, 30 were polymorphic and highly informative as a means to differentiate these accessions. Based on genotyping, a high level of genetic diversity was observed, with a total of 99 alleles. The polymorphic information content (PIC) values ranged from 0.038 for marker BG_SSR-8 to 0.721 for S-24, with an average of 0.429. The numbers of...

Introduction: The ACE gene encodes the angiotensin-converting enzyme (ACE), which is characterized by the presence of allele I or the absence of allele D of a 287-bp fragment. The D allele is associated with higher ACE activity and... more

Introduction: The ACE gene encodes the angiotensin-converting enzyme (ACE), which is characterized by the presence of allele I or the absence of allele D of a 287-bp fragment. The D allele is associated with higher ACE activity and increased angiotensin II levels and performance in strength-oriented exercise tasks. This study aimed to compare the genetic profile of rs4646994 single nucleotide polymorphism of the ACE gene in the elite male weightlifters and non-athletes.
Material & Methods: In total, 30 elite male weightlifters (league, country, national team, Asian, world, and Olympic champions) living in Isfahan province along with 43 healthy non-athlete volunteers who were matched in age, height, and weight to the elite group formed the subjects of the study. After completing the consent form, saliva samples were collected from the participants, and after DNA extraction, ACE genotypes were determined using PCR-RLFP and electrophoresis techniques. Data analysis was performed using independent t-test, chi-square, and logistic regression in SPSS software (version 20).
(Ethic code: 7993)
Findings: The results showed that the prevalence of D allele in elite weightlifters and non-athletes was significantly higher than allele I in their groups (P<0.05). Moreover, in the genotyping distribution, D/I was most common both in the study population (7.50%), as well as weightlifters (7.56%) and non-athletes (5.46%). However, there was no significant difference in the elite weightlifters and non-athletes regarding the distribution of D/I ACE genotyping (χ2=0/31).
Discussion & Conclusion: The study showed a positive relationship between Iranian elite weightlifters and the ACE D allele, which probably distinguishes it as one of the effective genetic factors in creating a strength phenotype of Iranian weightlifters.

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of... more

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). ...

Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in... more

Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in elite rugby athletes, we hypothesised that both SNPs would be associated with career success. In 1105 participants (RugbyGene project), comprising 460 elite rugby union (RU), 88 elite rugby league athletes and 565 non-athlete controls, DNA was collected and genotyped for the COL5A1 rs12722 and rs3196378 variants using real-time PCR. For rs12722, the injury-protective CC genotype and C allele were more common in all athletes (21% and 47%, respectively) and RU athletes (22% and 48%) than in controls (16% and 41%, P ≤ 0.01). For rs3196378, the CC genotype and C allele were overrepresented in all athletes (23% and 48%) and RU athletes (24% and 49%) compared with controls (16% and 41%, P ≤ 0.02). The CC genotype in particular was overrepresented in the back ...

Background Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring... more

Background Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring trypanotolerance could lead to effective means of genetic selection for trypanotolerance. In this context, high resolution mapping in mouse models are a promising approach to identifying the genes associated with trypanotolerance. In previous studies, using F2 C57BL/6J × A/J and C57BL/6J × BALB/cJ mouse resource populations, trypanotolerance QTL were mapped within a large genomic intervals of 20-40 cM to chromosomes MMU17, 5 and 1, and denoted Tir 1, Tir 2 and Tir 3 respectively. Subsequently, using F6 C57BL/6J × A/J and C57BL/6J × BALB/cJ F6 advanced intercross lines (AIL), Tir 1 was fine mapped to a confidence interval (CI) of less than 1 cM, while Tir 2 and Tir 3, were mapped within 5-12 cM. Tir 1 represents the major trypanotolerance QTL. Results In order...

Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially... more

Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies. Prenatal ultrasound scanning is a useful tool to detect several skeletal dysplasias and sonographic measurements serve as reliable indicators of lethality. The lethality depends on various factors including gestational age at which features are identified, size of the chest and progression of malformations. Although, it is important to type the skeletal presentation as accurately as possible, this is not always possible in an antenatal presentation and it is impor...