Terms Of Haplotypes Research Articles

Interleukin-38 promoter variants and risk of COVID-19 among Iraqis

Coronavirus disease-19 (COVID-19) has recently emerged as a respiratory infection with a significant impact on health and society. The pathogenesis is primarily attributed to a dysregulation of cytokines, especially those with pro-inflammatory and anti-inflammatory effects. Interleukin-38 (IL-38) is a recently identified anti-inflammatory cytokine with a proposed involvement in mediating COVID-19 pathogenesis, while the association between IL38 gene variants and disease susceptibility has not been explored. Therefore, a pilot study was designed to evaluate the association of three gene variants in the promoter region of IL38 gene (rs7599662 T/A/C/G, rs28992497 T/C and rs28992498 C/A/T) with COVID-19 risk. DNA sequencing was performed to identify these variants. The study included 148 Iraqi patients with COVID-19 and 113 healthy controls (HC). Only rs7599662 showed a significant negative association with susceptibility to COVID-19. The mutant T allele was presented at a significantly lower frequency in patients compared to HC. Analysis of recessive, dominant and codominant models demonstrated that rs7599662 TT genotype frequency was significantly lower in patients than in HC. In terms of haplotypes (in order: rs7599662, rs28992497 and rs28992498), frequency of CTC haplotype was significantly increased in patients compared to HC, while TTC haplotype showed significantly lower frequency in patients. The three SNPs influenced serum IL-38 levels and homozygous genotypes of mutant alleles were associated with elevated levels. In conclusion, this study indicated that IL38 gene in terms of promoter variants and haplotypes may have important implications for COVID-19 risk.

Phylogeography of Colpomenia sinuosa (Ectocarpales, Phaeophyceae) along the Brazilian coast.

Colpomenia sinuosa is a cosmopolitan brown macroalgal species complex and hence a great candidate for evolutionary studies in the marine environment. Since 2009, three major C. sinuosa phylogenetic lineages, subdivided into eight subgroups, have been identified based on cox3 DNA sequences from worldwide collections. However, worldwide sampling remains limited and spotty. To date molecular data from Brazilian C. sinuosa populations have been limited to 10 specimens collected in a single locality. Nonetheless, C. sinuosa populations occur along the entire ~8,000 km Brazilian coast. Consequently, knowledge on population genetic diversity and spatial genetic structuring along most of the Brazilian coastline is nonexistent. To fulfill this gap in knowledge, we performed a phylogeographic analysis of C. sinuosa populations in Brazil. The highly variable cox3 marker was sequenced for 148 individuals collected in 12 localities in Brazil. Results identified two genetically distinct population groups (north vs. south) separated at 20.5° S latitude. Genetic diversity in northern populations is 14.6 and 15.5 times greater than southern populations in terms of haplotype and nucleotide diversity, respectively. Among northern populations, the Bahia state holds the largest genetic diversity. The southern populations had lower genetic diversity and no internal genetic sub-structure suggesting past bottlenecks followed by recent colonization from northern haplotypes. Our results do not indicate recent introductions of foreign haplotypes in Brazil and reinforce the crucial importance of historical and extant allopatric, parapatric, and sympatric processes driving marine macroalgal evolution in the Southwestern Atlantic Ocean.

Genetic diversity of Cyprinion macrostomus (Heckel, 1843) populations in the Euphrates and Tigris rivers based on partial cytochrome b sequences of mitochondrial DNA

Cyprinion macrostomus (Heckel, 1843), thriving in both Euphrates and Tigris river systems, is an economically important food fish species of the family Cyprinidae. It is important to know genetic structure of fis populations in terms of identification of genetic structure of stocks for facilitating sustainable fishing and conservation strategies.The present study, evaluated genetic structure of C. macrostomus populations in Euphrates and Tigris rivers using mtDNA cytochrome b sequence analysis. A total number of 44 C. macrostomus specimens were collected from Euphrates and Tigris rivers and total DNA was isolated from muscle tissue. Approximately 600 bp of mtDNA cyt b site was amplified by PCR and 8 polymorphic and 8 haplotypes were identified after sequence analysis. Mean haplotype and nucleotide diversity were calculated as 0.738 and 0.00253 respectively. Both populations had similar values in terms of haplotype as well as nucleotide diversity and neutrality tests were also found to be statistically insignificant.

First insights towards the population genetic structure and the phylogeographic status of the horse mussel (Modiolus barbatus) from the eastern Mediterranean

AbstractThe horse musselModiolus barbatusis a marine benthic bivalve, distributed mainly in the Mediterranean basin, that constitutes a fishery product of high economic importance and a promising candidate for aquaculture. The current study provides the first insights regarding the genetic profile ofM. barbatuspopulations from the eastern Mediterranean, by analysis of a partial segment of the mitochondrialCOIgene in individuals collected from five sampling localities within the Aegean Sea. To the best of our knowledge, the derived haplotypes represent the first DNA barcodes ofM. barbatusfrom the entire Mediterranean region. Maximum likelihood phylogenetic analysis revealed thatM. barbatusfrom the North Sea andM. barbatusfrom the eastern Mediterranean may not belong to the same species and as a consequence, there might be three species of the genusModiolusin Europe. On the other hand, eastern MediterraneanM. barbatushaplotypes were found to be more closely related to the Asian-PacificModiolusspecies. All geographic populations analysed displayed high levels of genetic diversity, in terms of haplotype and nucleotide diversity and a considerable number of unique alleles. Divergence among populations was found at generally low levels, corresponding with the majority of pairwiseFstvalues not being significant. These findings suggest no population structure and high levels of gene flow, a common feature observed in marine bivalves with long pelagic larval phases.

Deciphering the killer-cell immunoglobulin-like receptor system at super-resolution for natural killer and T-cell biology.

SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

Genetic risk assessment for cardiovascular disease in Azoreans (Portugal): A general population-based study

The identification of clinically validated genetic variants contributing to complex disorders raise the possibility to investigate individuals' risk. In this line of research, the present work aimed to assess the genetic risk for cardiovascular disease (CVD) in Azoreans. Genotyping of 19 SNPs – 9 on 9p21, 5 on LDLR and 5 on USF1 – was performed by TaqMan assays on 170 healthy Azorean individuals. Results demonstrate that the most frequent haplotype in 9p21, with a frequency of 41.4%, is TGGGCGCGC, which harbors all risk alleles. Considering haplotype homozygosity data show that females present higher value of homozygosity for both LDLR (13.5%) and USF1 (15.3%), whereas males present higher value for the 9p21 region (8.2%). Interestingly, genetic profile analysis revealed differences in terms of geographic and gender distribution. The Azorean Central group presented a higher risk for atherosclerosis, 2.7 times higher when compared to the Eastern group, while the Eastern group shows 1.5 times higher risk for dyslipidemias. Moreover, Azorean females demonstrated a 4 times higher risk for dyslipidemias when compared to males, whereas males have an increased risk for atherosclerosis. Although allele frequencies in Azoreans were similar to those reported for the HapMap CEU population, the differences in terms of haplotype and genetic profile distribution must be taken in consideration when assessing genetic risk. Taken together, the data here presented evidence for the need to perform biomedical research and epidemiologic analysis in Azoreans with the aim of developing strategies to CVD prevention, health promotion and population education.

HLA Class-I Diversity in Cameroon: Evidence for a North-South Structure of Genetic Variation and Relationships with African Populations

HLA class I diversity (loci A, B and C) was analysed in four populations, two from North Cameroon (Podokwo and Uldeme) and two from South Cameroon (Ewondo and Bamileke). Northern and southern Cameroon populations show a substantial genetic diversity in terms of haplotype sharing and genetic distances, even despite the low percentage of variance due to differences among populations evidenced by analysis of molecular variance. The signals of differentiation among populations are consistent with their linguistic affiliation, and support previous evidence, based on autosomal microsatellites and protein loci, which has shown that the complex pattern of genetic variation of Cameroon can in part be described by contrasting the northern and southern part of the country. Looking at our results in the more general framework of HLA diversity in sub-Saharan Africa, it turns out that the Podokwo and Uldeme show some genetic links to populations of the southern western branch of the Sahel corridor, while their high frequency of A*02 and C*04 alleles is congruent with previously hypothesised introgression of non-sub-Saharan alleles. On the other hand, signals of shared ancestry between the Bamileke and Ewondo and the Bantu speakers from central and southern Africa were detected.

Discovering novel risk factors for venous thrombosis: a candidate-gene approach

The candidate-gene approach can be used to locate and identify genetic variations that are associated with a particular phenotype. This gene-centric approach assumes that there exists important genetic variation within genes that can influence health. Identifying known genes which are candidates for the phenotype of interest can be accomplished using existing knowledge about biology or using findings from genome-wide association studies. Genetic variation can be characterized locally by single nucleotide polymorphisms (SNPs) or insertion—deletions, or it can be characterized more broadly in terms of haplotypes and diplotypes, which usually need to be inferred statistically. As an example, we present a candidate-gene approach to identify novel associations between variation in 24 clotting genes and the risk of incident venous thrombosis.

Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population

Recent investigations suggest that prostaglandin E2 (PGE2) is important in the pathogenesis of not only aspirin-intolerant asthma but also asthma unrelated to aspirin intolerance. This study was conducted to evaluate the effects of variations in the gene coding PGE2 receptor subtype EP1-4 (Ptger1-4) on the risk of asthma in the Korean population. Nineteen single nucleotide polymorphisms (SNPs) were selected after re-sequencing Ptger1-4 and were genotyped in 480 asthmatics and 140 healthy controls, who were randomly recruited. By logistic regression analyses controlling for age and sex, 1388T>C in Ptger3 was found to be significantly associated with asthma [P=0.002, odds ratio (95% confidence interval)=0.63 (0.46-0.85) in the allele model], and this remained significant after applying the Bonferroni correction. In terms of haplotype, the frequency of the C-C-A-A haplotype in Ptger3 was significantly lower in asthmatics than in healthy controls (P=0.004). Moreover, the prevalence of this haplotype was significantly lower in moderate-to-severe asthmatics than in mild asthmatics (P=0.045; mild vs. moderate and P=0.034; mild vs. severe). However, no association was found between any genetic variation in Ptger1, Ptger2, or Ptger4 and asthma. The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population.

Preliminary analysis of a KIR haplotype estimation algorithm: a simulation study

The analysis of Killer cell immunoglobulin-like receptors (KIRs) in terms of haplotypes have only been done through genotyping numerous and selected families. Consequently and schematically, KIR haplotypes have been roughly described by two groups (A and B) based on their gene contents. No further KIR adapted methods have been applied to the estimation of haplotype frequencies using unrelated data. We propose here a maximum likelihood (ML) estimation of KIR haplotype frequencies. ML estimation was developed as an extension of those successfully applied to human leukocyte antigen (HLA) data including the handling of missing values and HLA nomenclature. It has been implemented using an adapted Expectation Masimisation algorithm. KIR types on 11 loci in more than 40 Irish families were used to validate the method in a simulation study. Estimated haplotype frequencies are compared to the phase known. Various allele or gene frequency estimation methods were also compared. We demonstrated the interest and reliability of the haplotype method and underline the effect of the sample size on the quality of the estimation. The ML haplotype method also provides by collapsing more accurate estimation of allele or gene frequencies in population. Such an algorithm opens new perspectives in the analysis of KIR genotypes. Large sample size studies are required using phase-known data and/or simulations. It would allow a genotype-based approach to explore the KIR gene haplotype diversity. The haplotype frequencies may be used to compare populations.

Polymorphisms within the coding region of the bovine luteinizing hormone receptor gene and their association with fertility traits

Mutations within a number of genes have been associated with variations in fertility in various mammals. However, to date there have been no such associations reported for cattle. Herein, we describe three single nucleotide polymorphisms (SNPs) in the luteinizing hormone/choriogonadotropin receptor gene of cattle (Bos taurus). These polymorphisms include two missense mutations and one sense mutation, and all are located in areas of conserved synteny. When assessed in terms of haplotypes, these SNPs were significantly associated with variations in cattle fertility and production traits, most notably on calving interval, days to first service and production index (the UK economic index of milk yield measured in poundGB).

Inferring haplotypes at the NAT2 locus: the computational approach

BackgroundNumerous studies have attempted to relate genetic polymorphisms within the N-acetyltransferase 2 gene (NAT2) to interindividual differences in response to drugs or in disease susceptibility. However, genotyping of individuals single-nucleotide polymorphisms (SNPs) alone may not always provide enough information to reach these goals. It is important to link SNPs in terms of haplotypes which carry more information about the genotype-phenotype relationship. Special analytical techniques have been designed to unequivocally determine the allocation of mutations to either DNA strand. However, molecular haplotyping methods are labour-intensive and expensive and do not appear to be good candidates for routine clinical applications. A cheap and relatively straightforward alternative is the use of computational algorithms. The objective of this study was to assess the performance of the computational approach in NAT2 haplotype reconstruction from phase-unknown genotype data, for population samples of various ethnic origin.ResultsWe empirically evaluated the effectiveness of four haplotyping algorithms in predicting haplotype phases at NAT2, by comparing the results with those directly obtained through molecular haplotyping. All computational methods provided remarkably accurate and reliable estimates for NAT2 haplotype frequencies and individual haplotype phases. The Bayesian algorithm implemented in the PHASE program performed the best.ConclusionThis investigation provides a solid basis for the confident and rational use of computational methods which appear to be a good alternative to infer haplotype phases in the particular case of the NAT2 gene, where there is near complete linkage disequilibrium between polymorphic markers.

Haplotype analysis of VDR gene polymorphisms: a meta-analysis.

Although many studies have addressed the relationship between multiple individual polymorphisms in the vitamin D receptor (VDR) gene and bone health, few have analyzed this data in terms of haplotypes. We performed a meta-analysis of studies with data on the BsmI, ApaI, and TaqI polymorphisms in order to (a) estimate haplotype frequencies, (b) determine linkage disequilibrium (LD), and (c) estimate the magnitude of the association between haplotypes and osteoporosis/bone mineral density (BMD). Haplotypes were inferred using the expectation-maximization algorithm (EM); log-linear models were used to determine association with osteoporosis; and regression analysis with variance components was used to determine association with BMD. Our results indicate that the most common haplotype for the VDR gene, regardless of ethnicity, is baT, followed by BAt and bAT in Caucasians, and bAT and BaT in Asians. This indicates strong LD between the BsmI and TaqI polymorphisms. We demonstrate a gain in power when considering the haplotypes rather than the individual polymorphisms separately, i.e., although BsmI, ApaI, and TaqI were not significantly associated with osteoporosis on their own, the haplotypes Bat and BAt were significantly associated, with an OR of approximately 4. We have applied haplotype analysis to the VDR polymorphisms and bone measures. We also highlight a number of methodologic issues, including linkage disequilibrium, the robustness of the EM algorithm in this context, and the potential for exploring effect modification.

The Gm--Pi linkage heterogeneity in view of Pi M subtypes.

In this study linkage between the loci for Gm (gamma-type heavy-chain immunoglobulin markers) and Pi (alpha 1-antitrypsin/alpha 1-protease inhibitor) has been shown in families segregating for the Pi M subtypes (M1, M2, M3 and Msal) as identified by separator isoelectric focusing . The estimate for the Gm--Pi (M type) recombination is 0.29 (95% limits 0.24--0.37) at a peak lod score of 4.31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm--Pi in Pi MS (0.26) and Pi MZ, SZ and FZ families (0.21). The overall Gm--Pi recombination fraction estimate of 0.26 (95% limits 0.23--0.30) at a peak lod score of 20.75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M = 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the alpha 1-antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.