Pattern analysis on grain yield performance of Chinese and CIMMYT spring wheat cultivars sown in China and CIMMYT

Understanding the relationships among testing environments is essential for better targeting cultivars to production environments. To identify patterns of cultivar, environment, cultivar-by-environment interactions, and opportunities for indirect selection for grain yield, a set of 25 spring wheat cultivars from China and the International Maize and Wheat Improvement Center (CIMMYT) was evaluated in nine environments in China and four management environments at CIMMYT in Cd. Obregon, Mexico, during two wheat seasons. Genetic background and original environment were the main factors influencing grain yield performance of the cultivars. Baviacora M 92, Xinchun 2 and Xinchun 6 showed relatively more stable and higher grain yields, whereas highly photoperiod sensitive cultivars Xinkehan 9, Kefeng 6 and Longmai 19 proved consistently inferior across environments, except in Harbin and Keshan, the two high latitude environments. Longmai 26, also from high latitude environments in the northeastern Heilongjiang province, was however probably not as photoperiodicly sensitive as other cultivars; from that region, and produced much higher grain yield and expressed a broader adaptation. None of the environments reported major diseases. Pattern analyses revealed that photoperiod response and planting option on beds were the two main factors underlying the observed interactions for grain yield. The production environment of planting on the flat in Mexico grouped together with Huhhot and Urumqi in both wheat seasons, indicating an indirect response to selection for grain yield in this CIMMYT managed environment could benefit the two Chinese environments. Both the environment of planting on the flat with Chinese Hejin and Yongning, and the three CIMMYT enviromnents planting on raised beds with Chinese Yongning grouped together only in one season, showing that repeatability may not be stable in this case.

Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia

Context: Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. Objective: To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ. Design: The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals. Setting: Research hospital. Patients: Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n=46) and the case-control analysis (n=272). Healthy white men and women participated in the cognitive (n=513) and neuroimaging (n=52) studies. Main Outcome Measures: The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging. Results: The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals. Conclusions: These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. ©2012 American Medical Association. All rights reserved.

Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining interindividual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children. Areas covered in this review: This review explores pharmacogenetic knowledge developed over the last decade regarding the impact of ABCB1 polymorphisms on tacrolimus toxicity and dosage requirements in children. What the reader will gain: A better understanding of the role of ABCB1 genetic polymorphisms (and corresponding haplotypes) and ABCB1 expression levels in various tissues and organs on tacrolimus outcomes in children with liver transplant. Take home message: Pharmacogenetics offers significant potential for optimising tacrolimus use. ABCB1 donor genotypes and ABCB1 expression level in the intestine and leukocytes may be useful in dosage selection. Large prospective studies are, however, required to further explore the potential of genetic testing in identifying children who are at risk of toxicity and to better individualise tacrolimus therapy.

An online study combining the constructs from the theory of planned behaviour and protection motivation theory in predicting intention to test for chlamydia in two testing contexts

Chlamydia is a common sexually transmitted infection that has potentially serious consequences unless detected and treated early. The health service in the UK offers clinic-based testing for chlamydia but uptake is low. Identifying the predictors of testing behaviours may inform interventions to increase uptake. Self-tests for chlamydia may facilitate testing and treatment in people who avoid clinic-based testing. Self-testing and being tested by a health care professional (HCP) involve two contrasting contexts that may influence testing behaviour. However, little is known about how predictors of behaviour differ as a function of context. In this study, theoretical models of behaviour were used to assess factors that may predict intention to test in two different contexts: self-testing and being tested by a HCP. Individuals searching for or reading about chlamydia testing online were recruited using Google Adwords. Participants completed an online questionnaire that addressed previous testing behaviour and measured constructs of the Theory of Planned Behaviour and Protection Motivation Theory, which propose a total of eight possible predictors of intention. The questionnaire was completed by 310 participants. Sufficient data for multiple regression were provided by 102 and 118 respondents for self-testing and testing by a HCP respectively. Intention to self-test was predicted by vulnerability and self-efficacy, with a trend-level effect for response efficacy. Intention to be tested by a HCP was predicted by vulnerability, attitude and subjective norm. Thus, intentions to carry out two testing behaviours with very similar goals can have different predictors depending on test context. We conclude that interventions to increase self-testing should be based on evidence specifically related to test context.

Comparison of Multivariate and Univariate Models for Genetic Evaluation of Milk Yield based on Test Day Data

2000 Mathematics Subject Classification: 62H12, 62P99

Correlates of voluntary HIV testing and counseling among middle aged and older Latinas

This study identifies and describes HIV Voluntary Counseling and Testing (VCT) of middle aged and older Latinas. The rate of new cases of HIV in people age 45 and older is rapidly increasing, with a 40.6% increase in the numbers of older Latinas infected with HIV between 1998 and 2002. Despite this increase, there is paucity of research on this population. This research seeks to address the gap through a secondary data analysis of Latina women. The aim of this study is twofold: (1) Develop and empirically test a multivariate model of VCT utilization for middle aged and older Latinas; (2) To test how the three individual components of the Andersen Behavioral Model impact VCT for middle aged and older Latinas. The study is organized around the three major domains of the Andersen Behavioral Model of service use that include: (a) predisposing factors; (b) enabling characteristics and (c) need. Logistic regression using structural equation modeling techniques were used to test multivariate relationships of variables on VCT for a sample of 135 middle age and older Latinas residing in Miami-Dade County, Florida. Over 60% of participants had been tested for HIV. Provider endorsement was found to he the strongest predictor of VCT (odds ration [OR] 6.38), followed by having a clinic as a regular source of healthcare (OR=3.88). Significant negative associations with VCT included self rated health status (OR=.592); Age (OR=.927); Spanish proficiency (OR=.927); number of sexual partners (OR=.613) and consumption of alcohol during sexual activity (.549). As this line of inquiry provides a critical glimpse into the VCT of older Latinas, recommendations for enhanced service provision and research will he offered.

Phylogenetic and ecological significance in the evolution of Cetacean tonal sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution. ^

Phylogenetic and Ecological Significance in the Evolution of Cetacean Tonal Sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution.

Functional Evaluation of Causal Mutations Identified in Human Genetic Studies

Human genetics has been experiencing a wave of genetic discoveries thanks to the development of several technologies, such as genome-wide association studies (GWAS), whole-exome sequencing, and whole genome sequencing. Despite the massive genetic discoveries of new variants associated with human diseases, several key challenges emerge following the genetic discovery. GWAS is known to be good at identifying the locus associated with the patient phenotype. However, the actually causal variants responsible for the phenotype are often elusive. Another challenge in human genetics is that even the causal mutations are already known, the underlying biological effect might remain largely ambiguous. Functional evaluation plays a key role to solve these key challenges in human genetics both to identify causal variants responsible for the phenotype, and to further develop the biological insights from the disease-causing mutations.

We adopted various methods to characterize the effects of variants identified in human genetic studies, including patient genetic and phenotypic data, RNA chemistry, molecular biology, virology, and multi-electrode array and primary neuronal culture systems. Chapter 1 is a broader introduction for the motivation and challenges for functional evaluation in human genetic studies, and the background of several genetics discoveries, such as hepatitis C treatment response, in which we performed functional characterization.

Chapter 2 focuses on the characterization of causal variants following the GWAS study for hepatitis C treatment response. We characterized a non-coding SNP (rs4803217) of IL28B (IFNL3) in high linkage disequilibrium (LD) with the discovery SNP identified in the GWAS. In this chapter, we used inter-disciplinary approaches to characterize rs4803217 on RNA structure, disease association, and protein translation.

Chapter 3 describes another avenue of functional characterization following GWAS focusing on the novel transcripts and proteins identified near the IL28B (IFNL3) locus. It has been recently speculated that this novel protein, which was named IFNL4, may affect the HCV treatment response and clearance. In this chapter, we used molecular biology, virology, and patient genetic and phenotypic data to further characterize and understand the biology of IFNL4. The efforts in chapter 2 and 3 provided new insights to the candidate causal variant(s) responsible for the GWAS for HCV treatment response, however, more evidence is still required to make claims for the exact causal roles of these variants for the GWAS association.

Chapter 4 aims to characterize a mutation already known to cause a disease (seizure) in a mouse model. We demonstrate the potential use of multi-electrode array (MEA) system for the functional characterization and drug testing on mutations found in neurological diseases, such as seizure. Functional characterization in neurological diseases is relatively challenging and available systematic tools are relatively limited. This chapter shows an exploratory research and example to establish a system for the broader use for functional characterization and translational opportunities for mutations found in neurological diseases.

Overall, this dissertation spans a range of challenges of functional evaluations in human genetics. It is expected that the functional characterization to understand human mutations will become more central in human genetics, because there are still many biological questions remaining to be answered after the explosion of human genetic discoveries. The recent advance in several technologies, including genome editing and pluripotent stem cells, is also expected to make new tools available for functional studies in human diseases.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Development, characterization and use of genomic SSR markers for assessment of genetic diversity in some Saudi date palm ( Phoenix dactylifera L.) cultivars

Background: The present study was undertaken towards the development of SSR markers and assessing genetic relationships among 32 date palm ( Phoenix dactylifera L.) representing common cultivars grown in different geographical regions in Saudi Arabia. Results: Ninety-three novel simple sequence repeat markers were developed and screened for their ability to detect polymorphism in date palm. Around 71% of genomic SSRs were dinucleotide, 25% tri, 3% tetra and 1% penta nucleotide motives. Twenty-two primers generated a total of 91 alleles with a mean of 4.14 alleles per locus and 100% polymorphism percentage. A 0.595 average polymorphic information content and 0.662 primer discrimination power values were recorded. The expected and observed heterozygosities were 0.676 and 0.763 respectively. Pair-wise similarity values ranged from 0.06 to 0.89 and the overall cultivars averaged 0.41. The UPGMA cluster analysis recovered by principal coordinate analysis illustrated that cultivars tend to group according to their class of maturity, region of cultivation, and fruit color. Analysis of molecular variations (AMOVA) revealed that genetic variation among and within cultivars were 27% and 73%, respectively according to geographical distribution of cultivars. Conclusions: The developed microsatellite markers are additional values to date palm characterization tools that can be used by researchers in population genetics, cultivar identification as well as genetic resource exploration and management. The tested cultivars exhibited a significant amount of genetic diversity and could be suitable for successful breeding program. Genomic sequences generated from this study are available at the National Center for Biotechnology Information (NCBI), Sequence Read Archive (Accession numbers. LIBGSS_039019).

Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus

Coastal lagoons are semi-isolated ecosystems exposed to wide fluctuations of environmental conditions and showing habitat fragmentation. These features may play an important role in separating species into different populations, even at small spatial scales. In this study, we evaluate the concordance between mitochondrial (previous published data) and nuclear data analyzing the genetic variability of Pomatoschistus marmoratus in five localities, inside and outside the Mar Menor coastal lagoon (SE Spain) using eight microsatellites. High genetic diversity and similar levels of allele richness were observed across all loci and localities, although significant genic and genotypic differentiation was found between populations inside and outside the lagoon. In contrast to the FST values obtained from previous mitochondrial DNA analyses (control region), the microsatellite data exhibited significant differentiation among samples inside the Mar Menor and between lagoonal and marine samples. This pattern was corroborated using Cavalli-Sforza genetic distances. The habitat fragmentation inside the coastal lagoon and among lagoon and marine localities could be acting as a barrier to gene flow and contributing to the observed genetic structure. Our results from generalized additive models point a significant link between extreme lagoonal environmental conditions (mainly maximum salinity) and P. marmoratus genetic composition. Thereby, these environmental features could be also acting on genetic structure of coastal lagoon populations of P. marmoratus favoring their genetic divergence. The mating strategy of P. marmoratus could be also influencing our results obtained from mitochondrial and nuclear DNA. Therefore, a special consideration must be done in the selection of the DNA markers depending on the reproductive strategy of the species.

Multilocus genetic analyses provide insight into speciation and hybridization in aquatic grasses, genus Ruppia

Aquatic plants of the genus Ruppia inhabit some of the most threatened habitats in the world, such as coastal lagoons and inland saline to brackish waters where their meadows play several key roles. The evolutionary history of this genus has been affected by the processes of hybridization, polyploidization, and vicariance, which have resulted in uncertainty regarding the number of species. In the present study, we apply microsatellite markers for the identification, genetic characterization, and detection of hybridization events among populations of putative Ruppia species found in the southern Iberian Peninsula, with the exception of a clearly distinct species, the diploid Ruppia maritima. Microsatellite markers group the populations into genetically distinct entities that are not coincident with geographical location and contain unique diagnostic alleles. These results support the interpretation of these entities as distinct species: designated here as (1) Ruppia drepanensis, (2) Ruppia cf. maritima, and (3) Ruppia cirrhosa. A fourth distinct genetic entity was identified as a putative hybrid between R. cf. maritima and R. cirrhosa because it contained a mixture of microsatellite alleles that are otherwise unique to these putative species. Hence, our analyses were able to discriminate among different genetic entities of Ruppia and, by adding multilocus nuclear markers, we confirm hybridization as an important process of speciation within the genus. In addition, careful taxonomic curation of the samples enabled us to determine the genotypic and genetic diversity and differentiation among populations of each putative Ruppia species. This will be important for identifying diversity hotspots and evaluating patterns of population genetic connectivity. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 00, 000–000.

Drug resistance and genetic diversity of Mycobacterium tuberculosis in Luanda, Angola: a molecular epidemiological perspective

Poster presented at the 36th Annual Congress of the European Society of Mycobacteriology. Riga, Latvia, 28 June - 1 July 2015

Association of kinase insert domain-containing receptor (KDR) gene polymorphism/ haplotypes with recurrent spontaneous abortion and genetic structure

Background: Recurrent spontaneous abortion is one of the diseases that can lead to physical, psychological, and, economical problems for both individuals and society. Recently a few numbers of genetic polymorphisms in kinase insert domain-containing receptor (KDR) gene are examined that can endanger the life of the fetus in pregnant women. Objective: The risk of KDR gene polymorphisms was investigated in Iranian women with idiopathic recurrent spontaneous abortion (RSA). Materials and Methods: A case controlled study was performed. One hundred idiopathic recurrent spontaneous abortion patients with at least two consecutive pregnancy losses before 20 weeks of gestational age with normal karyotypes were included in the study. Also, 100 healthy women with at least one natural pregnancy were studied as control group. Two functional SNPs located in KDR gene; rs1870377 (Q472H), and rs2305948 (V297I) as well as one tag SNP in the intron region (rs6838752) were genotyped by using PCR based restriction fragment length polymorphism (PCR-RFLP) technique. Haplotype frequency was determined for these three SNPs’ genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to study genetic variation. Results: Functional SNP (rs1870377) was highly linked to tag SNP (rs6838752) (D´ value=0. 214; χ2 = 16.44, p<0. 001). K means clustering showed that k = 8 as the best fit for the optimal number of genetic subgroups in our studied materials. This result was in agreement with Neighbor Joining cluster analysis. Conclusion: In our study, the allele and genotype frequencies were not associated with RSA between patient and control individuals. Inconsistent results in different populations with different allele frequencies among RSA patients and controls may be due to ethnic variation and used sample size.