Association of FTO and TMEM18 polymorphisms with overweight and obesity in the population of Polish children

Published Online: 2016-03-16The objective of the study was to verify whether or not FTO rs9939609, rs9926289 and TMEM18 rs4854344, rs6548238, rs2867125 variants are important risk factors for overweight and/or obesity in Polish children aged 6-16 (n=283). FTO rs 9939609 and rs9926289 exhibited a strong codominant obesity-predisposing effect of genotypes homozygous for minor alleles (OR=5.42, 95% CI: 2.04-14.39, p=0.0006). The important finding of the study is increased risk of overweight (OR=5.03, 95% CI: 1.15-21.93, p=0.0306) in individuals homozygous for the minor alleles rs4854344, rs6548238 and rs2867125 in the recessive inheritance model, while no other significant associations between TMEM18 variants and risk of obesity were found. Given the identified interaction TMEM18 genotype × BMI category (p=0.0077), it seems that the effect of homozygous for the minor alleles may be compared to a “weight guard”, which significantly increases the risk of overweight, but not of obesity, because it promotes weight gain only up to the threshold of obesity. Conclusion: The proposed hypothetical effect (“weight guard”) of homozygous for the minor alleles in the TMEM18 based on a rather small sample is a possible explanation of the effects of minor alleles, which minimize the risk of obesity.Iwona Rosset, Dominik Strapagiel, Aneta Sitek, Małgorzata Majewska, Lidia Ostrowska-Nawarycz, Elżbieta Żądzińsk

Association of FTO gene with obesity in Polish schoolchildren

The goal of the study was verification of fat mass and obesity-associated (FTO) gene polymorphisms as significant risk factors of obesity in the population of Polish children. Body mass index (BMI) and DNA were evaluated, where DNA was extracted from saliva, collected from 213 children at the age of 6-13 years. DNA was genotyped by PCR (polymerase chain reaction) and HRM (high resolution melting) techniques, as well as by direct sequencing. Three (3) FTO polymorphisms were identified: rs9939609, rs9926289 and rs76804286, the last polymorphism located between the first two. For the first time, absolute linkage disequilibrium (LD) of FTO gene rs9939609 and rs9926289 polymorphisms was confirmed in data for the Polish population (D’=1, r2=1). The lack of a complete dependence among the three single nucleotide polymorphisms (SNPs) of the FTO gene was a consequence of the concurrence of homozygotes with minor alleles A of rs9939609+rs9926289 of FTO (AA+AA) with major alleles of rs76804286 (GG). A case-control association analysis for BMI in obese children (n=51), as compared to normal-weight children (n=162), was based on the effects of genotypes homozygous for the minor alleles of the studied SNPs in recessive and codominant inheritance models (assuming an independent effect of each genotype). A comparison of children with normal BMI with obese children indicate a strong co-dominant effect of a genotype in homozygotes of minor alleles (AA+AA) of completely linked rs9939609+rs9926289 (OR at age 8.89 ± 1.54 years=4.87, 95% CI 1.81-13.12, p=0.002). An almost five-fold increase of obesity risk in the examined children indicates that the genetic factors, associated with excessive body weight gain, exert stronger effects in the early period of ontogenetic development vs. puberty and adulthood. The role of genetic factors in predisposing to obesity declines with age.Aneta Sitek, Iwona Rosset, Dominik Strapagiel, Małgorzata Majewska, Lidia Ostrowska-Nawarycz, Elżbieta Żądzińsk

A genomic Neolithic time transect of hunter-farmer admixture in central Poland.

Ancient DNA genome-wide analyses of Neolithic individuals from central and southern Europe indicate an overall population turnover pattern in which migrating farmers from Anatolia and the Near East largely replaced autochthonous Mesolithic hunter-gatherers. However, the genetic history of the Neolithic transition in areas lying north of the European Neolithic core region involved different levels of admixture with hunter-gatherers. Here we analyse genome-wide data of 17 individuals spanning from the Middle Neolithic to the Early Bronze Age (4300-1900 BCE) in order to assess the Neolithic transition in north-central Poland, and the local impacts of hunter-farmer contacts and Late Neolithic steppe migrations. We evaluate the influence of these on local populations and assess if and how they change through time, reporting evidence of recurrent hunter-farmer admixture over three millennia, and the co-existence of unadmixed hunter-gatherers as late as 4300 BCE. During the Late Neolithic we report the appearance of steppe ancestry, but on a lesser scale than previously described for other central European regions, with evidence of stronger affinities to hunter-gatherers than to steppe pastoralists. These results help understand the Neolithic palaeogenomics of another central European area, Kuyavia, and highlight the complexity of population interactions during those times

Fungal Planet description sheets: 1436–1477

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilax glyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Screening the Expression of ABCB6 in Erythrocytes Reveals an Unexpectedly High Frequency of Lan Mutations in Healthy Individuals

Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9) and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689) and G588 S (rs145526996)). The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.This work was supported by the Lendulet Program of the Hungarian Academy of Sciences (GS), OTKA 83533 and by the Polish POIG grant 01.01.02-10-005/08 TESTOPLEK, supported by the EU through the European Regional Development Fund. Hajnalka Andrikovics is a recipient of the Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Camilo Toro and Dr. William Gahl of the NIH Undiagnosed Diseases Program for an affected patient specimen; that work was supported by the Intramural Research Program of the National Human Genome Research Institute and the Office of the Director of the NIH. We thank Lionel Arnaud (National Institute of Blood Transfusion (INTS), Paris, France) for helpful discussions

Association of five SNPs with human hair colour in the Polish population

AbstractTwenty-two variants of the genes involved in hair pigmentation (OCA2, HERC2, MC1R, SLC24A5, SLC45A2, TPCN2, TYR, TYRP1) were genotyped in a group of 186 Polish subjects, representing a range of hair colours (45 red, 64 blond, 77 dark). A genotype-phenotype association analysis was performed.Using z-statistics and the associated p-value, we identified three variants highly associated with different hair colour categories (rs12913832:A&gt;G in HERC2, rs1805007:T&gt;C and rs1805008:C&gt;T in MC1R). Two variants: rs1800401:C&gt;T in OCA2 and rs16891982:C&gt;G in SLC45A2 showed a high probability of a relation with hair colour, although that probability did not exceed the threshold of statistical significance after applying the Bonferroni correction. We created and validated mathematical logistic regression models in order to test the usefulness of the sets of polymorphisms for hair colour prediction in the Polish population. We subjected four models to stratified cross-validation. The first model consisted of three polymorphisms that proved to be important in the associative analysis. The second model included, apart from the mentioned polymorphisms, additionally rs16891982:C&gt;G in SLC45A. The third model included, apart from the variants relevant in the associative analysis, rs1800401:C&gt;T in OCA. The fourth model consisted of the set of polymorphisms from the first model supplemented with rs16891982:C&gt;G in SLC45A and rs1800401:C&gt;T in OCA. The validation of our models showed that the inclusion of rs16891982:C&gt;G in SLC45A and rs1800401:C&gt;T in OCA increases the prediction of red hair in comparison with the algorithm only including rs12913832:A&gt;G in HERC2, rs1805007:T&gt;C and rs1805008:C&gt;T in MC1R. The model consisting of all the five above-mentioned genetic variants showed good prediction accuracies, expressed by the area under the curve (AUC) of the receiver operating characteristics: 0.84 for the red-haired, 0.82 for the dark-haired and 0.71 for the blond-haired. A genotype-phenotype association analysis brought results similar to those in other studies and confirmed the role of rs16891982:C&gt;G, rs12913832:A&gt;G, rs1805007:T&gt;C and rs1805008:C&gt;T in hair colour determination in the Polish population. Our study demonstrated for the first time the possibility of a share of the rs1800401:C&gt;T SNP in the OCA2 gene in hair colour determination. Including this SNP in the actual hair colour predicting models would improve their predictive accuracy.</jats:p