Biallelic Polymorphisms Research Articles

Rapidly mutating Y-STRs in rapidly expanding populations: Discrimination power of the Yfiler Plus multiplex in northern Africa

The male-specific northern African genetic pool is characterised by a high frequency of the E-M81 haplogroup, which expanded in very recent times (2–3 kiloyears ago). As a consequence of their recent coalescence, E-M81 chromosomes often cannot be completely distinguished on the basis of their Y-STR profiles, unless rapidly-mutating Y-STRs (RM Y-STRs) are analysed. In this study, we used the Yfiler® Plus kit, which includes 7 RM Y-STRs and 20 standard Y-STR, to analyse 477 unrelated males coming from 11 northern African populations sampled from Morocco, Algeria, Libya and Egypt. The Y chromosomes were assigned to monophyletic lineages after the analysis of 72 stable biallelic polymorphisms and, as expected, we found a high proportion of E-M81 subjects (about 46%), with frequencies decreasing from west to east. We found low intra-population diversity indexes, in particular in the populations that experienced long-term isolation. The AMOVA analysis showed significant differences between the countries and between most of the 11 populations, with a rough differentiation between northwestern Africa and northeastern Africa, where the Egyptians Berbers from Siwa represented an outlier population. The comparison between the Yfiler® and the Yfiler® Plus network of the E-M81 Y chromosomes confirmed the high power of discrimination of the latter kit, thanks to higher variability of the RM Y-STRs: indeed, the number of chromosomes sharing the same haplotype was drastically reduced from 201 to 81 and limited, in the latter case, to subjects from the same population.

Donor white blood cell survival and cytokine profiles following red blood cell transfusion in Australian major trauma patients

BackgroundThe potential for the co-existence of genetically disparate cells (microchimerism) and associated cytokine profiles following red blood cell (RBC) transfusion in trauma patients has not been well characterized to date. This study investigated the incidence of surviving donor white blood cells (known as transfused-associated microchimerism (TAM)) and cytokine changes following blood transfusion in trauma patients. Study design and methodsTrauma patients with an injury severity score (ISS) >12 who had been transfused between 2012–2016 with at least 5 units of RBC units over a 4 h period were recruited. Trauma patients with ISS > 12 who did not require blood transfusion were recruited as controls. The incidence of TAM was determined using a panel of insertion/deletion (InDel) bi-allelic polymorphisms. Selected pro- and anti-inflammatory cytokine profiles were analyzed using cytometric bead array. ResultsThe transfused cohort (n = 40) had median ISS of 28 [12–66], received a median of 11 RBC units [4–114] and had median hospital length of stay of 35 days [1–152]. Only 11 (27.5%) patients returned for follow-up blood sampling after discharge. Of these, one patient showed an InDel pattern indicating the presence of TAM. No patients in the control cohort (n = 49) showed TAM. Cytokines IL-10 and IL-6 were found to be elevated in the transfused trauma patients. ConclusionIn this cohort, TAM was found to occur in one patient of the 11 who received a blood transfusion. Elevated IL-6 and IL-10 cytokines were detected in those patients who were transfused. However, the incidence of TAM could not be correlated with the elevated cytokine profiles for this cohort.

Haploids, polymorphisms and fluctuating selection

I analyze the joint impact of directional and fluctuating selection with reversible mutation in finite bi-allelic haploid populations using diffusion approximations of the Moran and chemostat models. Results differ dramatically from those of the classic Wright–Fisher diffusion. There, a strong dispersive effect attributable to fluctuating selection dissipates nascent polymorphisms promoted by a relatively weak emergent frequency dependent selective effect. The dispersive effect in the Moran diffusion with fluctuations every birth–death event is trivial. The same frequency dependent selective effect now dominates and polymorphism is promoted. The dispersive effect in the chemostat diffusion with fluctuations every generation is identical to that in the Wright–Fisher diffusion. Nevertheless, polymorphism is again promoted because the emergent frequency dependent effect is doubled, an effect attributable to geometric reproduction within generations. Fluctuating selection in the Moran and chemostat diffusions can also promote bi-allelic polymorphisms when one allele confers a net benefit. Rapid fluctuations within generations are highly effective at promoting polymorphism in large populations. The bi-allelic distribution is approximately Gaussian but becomes uniform and then U-shaped as the frequency of environmental fluctuations decreases to once a generation and then once every multiple generations. Trade-offs (negative correlations in fitness) help promote polymorphisms but are not essential. In all three models the frequency dependent effect raises the probability of ultimate fixation of new alleles, but less effectively in the Wright–Fisher diffusion. Individual-based forward simulations confirm the calculations.

AB081. Biallelic and triallelic 5-HTTLPR polymorphisms and their relationship with lifelong premature ejaculation: a case-control study from a Chinese population

BackgroundThe study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications.MethodsA total of 115 outpatients who complained of ejaculating prematurely and were diagnosed as lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. Associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, and the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients were evaluated.ResultsThe patients and controls didn’t differ significantly in terms of any characteristic except age. The results showed no significant difference regarding the biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L/L genotype (OR =0.37; 95% CI: 0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes.ConclusionsContrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research of PE to avoid false negative results in future studies.

Population assignment and local adaptation along an isolation-by-distance gradient in Pacific cod (Gadus macrocephalus).

The discernment of populations as management units is a fundamental prerequisite for sustainable exploitation of species. A lack of clear stock boundaries complicates not only the identification of spatial management units, but also the assessment of mixed fisheries by population assignment and mixed stock analysis. Many marine species, such as Pacific cod, are characterized by isolation by distance, showing significant differentiation but no clear stock boundaries. Here, we used restriction‐site‐associated DNA (RAD) sequencing to investigate population structure and assess power to genetically assign Pacific cod to putative populations of origin. Samples were collected across the species range in the eastern Pacific Ocean, from the Salish Sea to the Aleutian Islands. A total of 6,425 putative biallelic single nucleotide polymorphisms were identified from 276 individuals. We found a strong isolation‐by‐distance signal along coastlines that mirrored previous microsatellite results and pronounced genetic differentiation between coastal samples and those from the inland waters of the Salish Sea, with no evidence for hybridization between these two populations. Individual assignment success based on two methods was high overall (≥84%) but decreased from south to north. Assignment to geographic location of origin also was successful, with average distance between capture and assignment location of 220 km. Outlier analyses identified more loci potentially under selection along the coast than between Salish Sea and coastal samples, suggesting more diverse adaptation to latitudinal environmental factors than inshore vs. offshore environments. Our results confirm previous observations of sharp genetic differentiation of the Salish Sea population and isolation by distance along the coast, but also highlight the feasibility of using modern genomic techniques to inform stock boundaries and fisheries management in a low F ST marine species.

The effect of kernel selection on genome wide prediction of discrete traits by Support Vector Machine

This study aimed to compare predictive performance of the linear, radial, polynomial and sigmoid kernel-based Support Vector Machine (SVM) in different scenarios of genetic architecture of a discrete trait (number of quantitative trait loci (QTL) and distribution of QTL effects) as well as heritability level. A 500 centiMorgans genome was simulated consisted of 5 chromosomes, one Morgan each, on which 10,000 bi-allelic single nucleotide polymorphisms (SNP) were distributed. To measures accuracy of prediction, Pearson's correlation between the true and predicted genomic breeding values (rp,t) was estimated. In all of the scenarios studied, increase in the heritability resulted to an increase in the accuracy of prediction. Radial and sigmoid based SVM predictors outperformed polynomial and linear kernels significantly (p < 0.05). The linear and polynomial kernel-based SVMs provided predictions with least accuracy and therefore were not recommended for genome wide prediction of discrete traits. Radial-based SVM had slightly higher predictive performance compared to sigmoid-based SVM, though the differences were non-significant. Therefore, both of them were recommended for predicting genomic breeding values. All of the studied SVM-based predictors had almost the same time and memory requirements.

Molecular Genetic Analysis of Population Structure of the Great Zhuz Kazakh Tribal Union Based on Y-Chromosome Polymorphism

Historically, the Kazakhs formed through an amalgam of nomadic tribes that previously belonged to the Golden Horde. The Kazakh tribes were geographically divided into three tribal associations—the Great, the Middle, and the Lesser zhuzes. One of the unsolved problems in the Kazakhs’ ethnic history remains the issue of the genetic relationships between tribes composing the zhuzes. The aim of the current work was to study intertribal genetic relations in the Great zhuz. To achieve this goal, we investigated the biallelic polymorphisms of Y chromosome in the 12 tribes of the Great zhuz. Twenty-seven haplogroups of Y chromosome were identified. The comparative analysis of the haplogroup distribution revealed complexity of the Great zhuz gene pool. The results obtained suggest that the Great zhuz was formed by combining not only genetically related, but also quite remote, groups of tribes.

Isolation and characterization of 41 SNP markers in Coilia nasus

Coilia nasus is an important economic fish species in China due to its excellent meat quality and wonderful flavor. The germplasm resources of C. nasus have recently been seriously degraded by human activities. It is urgent to develop the genetic markers of C. nasus in order to apply to conservation of this species. In this study, we used C. nasus transcriptomic data from GENBANK to identify single nucleotide polymorphism (SNP) markers for this species. From 148,156 unigenes with functional annotations, 85,454 putative SNPs were identified. Forty-one of the 61 SNP loci (including 31 loci that were associated with osmoregulation-related genes and 10 loci associated with other functions) were successfully validated and showed bi-allelic polymorphism in three rivers. Nine, six and eleven of these SNP loci deviated significantly from Hardy–Weinberg equilibrium (P < 0.05) in Yangtze River, Yellow River and Huai River. The average observed and expected heterozygosities ranged from 0.136827 to 0.289015, and 0.148122 to 0.314441 in three rivers, respectively. The SNP markers identified here will be useful in population conservation and management, construction of genetic linkage maps, and in molecular breeding of C. nasus.

Signatures of polygenic adaptation associated with climate across the range of a threatened fish species with high genetic connectivity.

Adaptive differences across species' ranges can have important implications for population persistence and conservation management decisions. Despite advances in genomic technologies, detecting adaptive variation in natural populations remains challenging. Key challenges in gene-environment association studies involve distinguishing the effects of drift from those of selection and identifying subtle signatures of polygenic adaptation. We used paired-end restriction site-associated DNA sequencing data (6,605 biallelic single nucleotide polymorphisms; SNPs) to examine population structure and test for signatures of adaptation across the geographic range of an iconic Australian endemic freshwater fish species, the Murray cod Maccullochella peelii. Two univariate gene-association methods identified 61 genomic regions associated with climate variation. We also tested for subtle signatures of polygenic adaptation using a multivariate method (redundancy analysis; RDA). The RDA analysis suggested that climate (temperature- and precipitation-related variables) and geography had similar magnitudes of effect in shaping the distribution of SNP genotypes across the sampled range of Murray cod. Although there was poor agreement among the candidate SNPs identified by the univariate methods, the top 5% of SNPs contributing to significant RDA axes included 67% of the SNPs identified by univariate methods. We discuss the potential implications of our findings for the management of Murray cod and other species generally, particularly in relation to informing conservation actions such as translocations to improve evolutionary resilience of natural populations. Our results highlight the value of using a combination of different approaches, including polygenic methods, when testing for signatures of adaptation in landscape genomic studies.

Performance evaluation of support vector machine (SVM)-based predictors in genomic selection

The aim was to compare predictive performance of SVM-based predictors constructed using different kernel functions (radial, sigmoid, linear and polynomial) in different genetic architectures of a trait (number of QTL, distribution of QTL effects) and heritability levels. To this end, a genome comprised of five chromosomes, oneMorgan each, was simulated on which 10,000 bi-allelic single nucleotide polymorphisms (SNP) were distributed.Cross validation employing a grid search was used to tune the meta-parameters of each kernel function. Pearson’scorrelation between the true and predicted genomic breeding values (rp,t) and mean squared error of predictedgenomic breeding values (MSEp) were used, respectively, as measures of the predictive accuracy and the overallfit. Meta-parameter optimization had a significant effect on predictive performance of SVM-based predictors insuch a way that by using improper meta-parameters, the predictive power of models decreased significantly. In allmodels, the accuracy of prediction increased following increase in heritability and decrease in the number ofQTLs. In most of scenarios, radial- and sigmoid-based SVM predictors outperformed polynomial and linear models.The linear-and polynomial-based SVM had lower rp,t and higher MSEp and, therefore, were not recommended forgenomic selection. The prediction accuracy of radial and sigmoid models was approximately the same in most ofthe studied scenarios; however, considering all pros and cons of radial and sigmoid kernels, radial kernel wasrecommended as the best kernel function for constructing SVM. All of studied SVM-based predictors were efficientusers of time and memory.

Development of novel InDel markers and genetic diversity in Chenopodium quinoa through whole-genome re-sequencing

BackgroundQuinoa (Chenopodium quinoa Willd.) is a balanced nutritional crop, but its breeding improvement has been limited by the lack of information on its genetics and genomics. Therefore, it is necessary to obtain knowledge on genomic variation, population structure, and genetic diversity and to develop novel Insertion/Deletion (InDel) markers for quinoa by whole-genome re-sequencing.ResultsWe re-sequenced 11 quinoa accessions and obtained a coverage depth between approximately 7× to 23× the quinoa genome. Based on the 1453-megabase (Mb) assembly from the reference accession Riobamba, 8,441,022 filtered bi-allelic single nucleotide polymorphisms (SNPs) and 842,783 filtered InDels were identified, with an estimated SNP and InDel density of 5.81 and 0.58 per kilobase (kb). From the genomic InDel variations, 85 dimorphic InDel markers were newly developed and validated. Together with the 62 simple sequence repeat (SSR) markers reported, a total of 147 markers were used for genotyping the 129 quinoa accessions. Molecular grouping analysis showed classification into two major groups, the Andean highland (composed of the northern and southern highland subgroups) and Chilean coastal, based on combined STRUCTURE, phylogenetic tree and PCA (Principle Component Analysis) analyses. Further analysis of the genetic diversity exhibited a decreasing tendency from the Chilean coast group to the Andean highland group, and the gene flow between subgroups was more frequent than that between the two subgroups and the Chilean coastal group. The majority of the variations (approximately 70%) were found through an analysis of molecular variation (AMOVA) due to the diversity between the groups. This was congruent with the observation of a highly significant FST value (0.705) between the groups, demonstrating significant genetic differentiation between the Andean highland type of quinoa and the Chilean coastal type. Moreover, a core set of 16 quinoa germplasms that capture all 362 alleles was selected using a simulated annealing method.ConclusionsThe large number of SNPs and InDels identified in this study demonstrated that the quinoa genome is enriched with genomic variations. Genetic population structure, genetic core germplasms and dimorphic InDel markers are useful resources for genetic analysis and quinoa breeding.

A Complete Association of an intronic SNP rs6798742 with Origin of Spinocerebellar Ataxia Type 7-CAG Expansion Loci in the Indian and Mexican Population.

Spinocerebellar ataxia type 7 (SCA7) is a rare neurogenetic disorder caused by highly unstable CAG repeat expansion mutation in coding region of SCA7. We aimed to understand the effect of diverse ATXN7 cis-element in correlation with CAG expansion mutation of SCA7. We initially performed an analysis to identify the haplotype background of CAG expanded alleles using eight bi-allelic single nucleotide polymorphisms (SNPs) flanking an ATXN7-CAG expansion in 32 individuals from nine unrelated Indian SCA7 families and 88 healthy controls. Subsequent validation of the findings was performed in 89 ATXN7-CAG mutation carriers and in 119 unrelated healthy controls of Mexican ancestry. The haplotype analyses showed a shared haplotype background and C allele of SNP rs6798742 (approximately 6 kb from the 3'-end of CAG repeats) is in complete association with expanded, premutation, intermediate, and the majority of large normal (≥12) CAG allele. The C allele (ancestral/chimp allele) association was validated in SCA7 subjects and healthy controls from Mexico, suggesting its substantial association with CAG expanded and expansion-prone chromosomes. Analysis of rs6798742 and other neighboring functional SNPs within 6 kb in experimental datasets (Encyclopedia of DNA Elements; ENCODE) shows functional marks that could affect transcription as well as histone methylation. An allelic association of the CAG region to an intronic SNP in two different ethnic and geographical populations suggests a -cis factor-dependent mechanism in ATXN7 CAG-region expansion.

Genetic and individual assignment of tetraploid green sturgeon with SNP assay data

Polyploid organisms pose substantial obstacles to genetic analysis, as molecular assay data are usually difficult to evaluate in a Mendelian framework. Green sturgeon (Acipenser medirostris) is a tetraploid species and is facing significant conservation challenges, including bycatch in ocean fisheries. We present here novel molecular genetic assays and analytical methodology for green sturgeon that allow discrimination of fish from the two visually indistinguishable distinct population segments (DPSs), and also provide individual-specific genetic tags. We show how the relative fluorescence intensity data from a standard quantitative PCR assay, designed for a biallelic single nucleotide polymorphism, can be grouped into “genotype categories” using standard analytical software and post-processing manipulation. We then show how these genotype category data can be used to discriminate green sturgeon from the southern DPS, which is protected under the US Endangered Species Act, and the northern DPS, which is not. We also show how these data can be used to reliably identify individual green sturgeon, and can therefore be used in capture/recapture analyses. Both types of identification are extremely accurate even when fewer than half of the assays are successfully called. We then apply these new techniques to show that proportions of the two green sturgeon DPSs are extremely different in the two major fishery areas where they are encountered as bycatch. While these assays and methods do not provide data that can be used in pedigree-based analyses, they are an important advance in the application of genetic analysis to conservation and management of polyploid organisms.

Development and characterization of SNP derived from spinyhead croaker (Collichthys lucidus) by RNA-seq

A novel set of SNP markers were detected from RNA-seq data of spinyhead croaker (Collichthys lucidus). Totally 49,617,970 clean reads and 78,671 putative SNPs were obtained. Among them, 40 SNPs were randomly selected to perform validation in 30 wild individuals of C. lucidus captured from 3 geographic stocks in the coast of China. Eventually, 29 SNP loci were successfully validated and showed bi-allelic polymorphism in genotyping by Sequenom MassARRAY. These novel SNPs provided useful genomic resources for C. lucidus, especially in population genetics, molecular assisted selection and conservation studies.

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer\u2019s disease

BackgroundInflammatory processes play a pivotal role in the degenerative process of Alzheimer’s disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer’s disease.MethodsWe enrolled a total of 135 patients with Alzheimer’s disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations.ResultsThere were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores.ConclusionsInterleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.

Gender-specific association between serotonin transporter polymorphisms (5-HTTLPR and rs25531) and neuroticism, anxiety and depression in well-defined healthy Han Chinese

BackgroundA tri-allelic serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) more effectively determines the levels of transcriptional efficacy than that with the bi-allelic 5-HTTLPR polymorphism in vitro. Both are reportedly associated with personality traits of negative emotionality, but with conflicting findings. One explanation for this is that a gender difference may play a role in genetic contribution. Here, we hypothesized that the tri-allelic genotype of the serotonin transporter is more closely linked to neuroticism, an anxiety- and depression-related trait, than the bi-allelic variation, particularly in a gender-dependent way. MethodsThe genotypes of the 5-HTTLPR and rs25531 loci were determined in 1139 well-defined physically and mentally healthy Han Chinese (550 men, 589 women; mean age 38.3±10.3 years). All participants completed the neuroticism measure of the short-form Maudsley Personality Inventory (MPI). The levels of anxiety and depression were assessed by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively. ResultsA significant tri-allelic genotype-by-gender interaction effect was found in the MPI-neuroticism measure. S′S′ homozygotes were associated with higher neuroticism than L′ allele carriers in men. Also, both the BAI and BDI scores were higher in the S′S′ homozygotic men. In the bi-allelic analyses, however, there was only an association between SS genotype and MPI-neuroticism in men. LimitationsSub-analyses by gender-stratification may reduce the statistical power. ConclusionsOur findings confirm that gender differences exist in the genetic contributions of the serotonin transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531, strengthening the effects of 5-HTTLPR.

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing

Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome.

Biallelic and Triallelic 5-Hydroxytyramine Transporter Gene-Linked Polymorphic Region (5- HTTLPR) Polymorphisms and Their Relationship with Lifelong Premature Ejaculation: A Case-Control Study in a Chinese Population.

BackgroundThis study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications.Material/MethodsA total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients.ResultsThe patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L’L’ genotype (OR=0.37; 95%CI=0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes.ConclusionsContrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies.

Polymorphisms of Immunoglobulin G Fc Receptors in Pediatric Guillain-Barré Syndrome.

Introduction Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy characterized by demyelination and axonal damage. Biallelic functional polymorphisms in the immunoglobulin G Fc receptors (FcγR)-FcγRIIA: H131/R131, FcγRIIIA: V158/F158, and FcγRIIIB: NA1/NA2 affect the affinity of the IgG-FcγR interaction, therefore, diseases such as GBS in which this interaction plays a critical role might be influenced by the polymorphisms. Methods We evaluated the role of FcγR polymorphisms in susceptibility to GBS in Egyptian pediatric patients and the association of the variant alleles with neurophysiological types, severity, and outcome of the disease. A total of 50 patients with GBS and 50 controls were examined for FcγR polymorphisms by allele-specific polymerase chain reaction. Results FcγRIIA H131 allele (p = < 0.0001; odds ratio [OR] = 4.78; 95% confidence interval [CI], 2.62-8.70) and FcγRIIA H/H131 genotype (p = < 0.0001 ; OR = 10.56; 95% CI, 3.59-31.06) were significantly increased in GBS patients while FcγRIIIA and FcγRIIIB allelic distributions were similar among patients and controls. The FcγR genotypes showed no association with neurophysiological types of GBS, severity or outcome of the disease. Conclusions These findings reflect that FcγRIIA H131 allele may represent a risk marker for susceptibility to GBS.

AB090. Biallelic and triallelic 5-HTTLPR polymorphisms and their relationship with lifelong premature ejaculation: a case-control study from a Chinese population

ObjectiveThe study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications.MethodsA total of 115 outpatients who complained of ejaculating prematurely and were diagnosed as LPE and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. Associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, and the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients were evaluated.ResultsThe patients and controls didn’t differ significantly in terms of any characteristic except age. The results showed no significant difference regarding the biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L’L’ genotype (OR =0.37; 95% CI =0.15–0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes.ConclusionsContrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research of PE to avoid false negative results in future studies.