Chromosomal Polymorphism Research Articles

The pink salmon genome: Uncovering the genomic consequences of a two-year life cycle.

Pink salmon (Oncorhynchus gorbuscha) adults are the smallest of the five Pacific salmon native to the western Pacific Ocean. Pink salmon are also the most abundant of these species and account for a large proportion of the commercial value of the salmon fishery worldwide. A two-year life history of pink salmon generates temporally isolated populations that spawn either in even-years or odd-years. To uncover the influence of this genetic isolation, reference genome assemblies were generated for each year-class and whole genome re-sequencing data was collected from salmon of both year-classes. The salmon were sampled from six Canadian rivers and one Japanese river. At multiple centromeres we identified peaks of Fst between year-classes that were millions of base-pairs long. The largest Fst peak was also associated with a million base-pair chromosomal polymorphism found in the odd-year genome near a centromere. These Fst peaks may be the result of a centromere drive or a combination of reduced recombination and genetic drift, and they could influence speciation. Other regions of the genome influenced by odd-year and even-year temporal isolation and tentatively under selection were mostly associated with genes related to immune function, organ development/maintenance, and behaviour.

A rare chromosomal polymorphism in a Kangayam bull (Bosindicus) of south India.

A chromosomal polymorphism was detected on karyological screening of Kangayam breeding sires prior to subjecting them for frozen semen collection. One bull possessed the chromosomal complement 2n = 60, consisting of 58 acrocentric autosomes, one large sub-metacentric X-chromosome, and one small acrocentric Y-chromosome with a small visible p-arm, which was further confirmed using CBG- and GTG-banding. This polymorphism was attributed to a heterochromatin variation of the acrocentric Y-chromosome routine in the Bosindicus Linnaeus, 1758 cattle.

CHROMOSOMAL POLYMORPHISM IN BULGARIAN PATIENTS WITH REPRODUCTIVE PROBLEMS – ONE GENETIC CENTRE EXPERIENCE

Chromosomal polymorphism is described as normal variants at chromosomal regions with no impact on the phenotype but a possible correlation to infertility and recurrent spontaneous abortions. The aim of this study was to evaluate the effect of the chromosomal polymorphisms involved in families with reproductive failures in the Bulgarian population. Material and methods: A total of 1733 patients with unexplained reproductive failures who visited the Laboratory of Medical Genetics – Varna, Bulgaria, (2004 - 2019) were investigated by conventional cytogenetic analysis GTG and CBG differential banding techniques and analyzed at the resolution 400-550 GTG bands. Results: Chromosomal polymorphisms were found in 173 infertile patients (9,98%). The sex distribution was 6,52% males and 3,46% females. The most frequent finding was inv(9)(qh) (23,7%). The other chromosomal variants, which were found, consisted: 9qh+/- variants (15,1%); polymorphisms on the short arms of the acrocentric chromosomes (21,4%); 16qh+ (12,7%) and 1qh+ (6,9%). Y chromosome polymorphism was found in 27,4% of the males with polymorphisms. Two rare cases of polymorphism involving the centromere regions - 19qcenh+ and 20pcenh+ were also found. Conclusion: There is growing evidence that polymorphisms may have a clinical impact on fertility and could take part in the etiology of RF. In this study, we found a significantly high percentage of polymorphisms (9,98%) among the tested patients, and they were more common among males. The statistical significance of increased incidence of chromosome variations found in our study emphasizes the need for routine evaluation of their role in families with RF in our country.

Highly divergent karyotypes and barcoding of the East African genus Gonatoxia Karsch (Orthoptera: Phaneropterinae)

East Africa is a hotspot of biodiversity of many orthopteran taxa, including bushcrickets. Gonatoxia Karsch, 1889 species are fully alate Phaneropterinae, which are perfectly adapted to the foliage of forests. We examined five species using combined cytogenetic and molecular data to determine the inter- and intraspecific genetic diversity. The variation in the diploid number of chromosomes in males ranged from 2n = 28 + X0 and 26 + X0 to 2n = 6 + X0. Fluorescence in situ hybridization showed from one to many 18S rDNA loci as well as interstitial sequences, especially in G. helleri. 18S rDNA loci coincided with active NOR and C-banding patterns. The isolation of populations of the species explains differences in the number of chromosomes (G. maculata), chromosomal polymorphism and chromosomal heterozygosity (G. helleri). Our molecular phylogeny based on the COI locus supported the monophyly of the genus Gonatoxia and separateness of the five examined species in accordance with their morphological features and chromosome numbers as well as the species’ distribution.

Peculiarities of karyotype in patients with miscarriage

Objective. To study the features of the karyotype in patients with miscarriage. This article is devoted to the role of maternal chromosome polymorphisms and their role in the genesis of miscarriage.
 Materials and methods. A comparative assessment of the karyotypes in women, whose pregnancy proceeded without complications and ended in the birth of a healthy child (75 persons, group I), and a group of patients with NB (135 persons, group II) was carried out. Group IIa consisted of 68 women with the first pregnancy that ended in spontaneous abortion in the first trimester, group IIb - 67 women with the first and subsequent pregnancy, interrupted in the first trimester. Statistical processing of the obtained material was carried out using the Exel program, and StatTech v.2.1.0.
 Results. A significantly greater number of patients with normal karyotype was in group I 72 persons (98.1 %). Data on the structure of chromosome polymorphisms showed that in patients of group II, changes in one chromosome are found in 8.8 % (3 people), two chromosomes in 23.5 % (8 persons). Analysis of the data of group II showed significant differences in the subgroups in the frequency of chromosome polymorphisms, in patients of group IIa changes were noted only in one chromosome, and in IIc, every fifth patient had polymorphism of two chromosomes.
 Conclusion. Despite the fact that genetic breakdowns are uncontrollable factors and it is not possible to directly influence them, the search for possible mechanisms leading to them is promising.

The Kengyiliahirsuta karyotype polymorphisms as revealed by FISH with tandem repeats and single-gene probes.

Kengyiliahirsuta (Keng, 1959) J. L. Yang, C. Yen et B. R. Baum, 1992, a perennial hexaploidy species, is a wild relative species to wheat with great potential for wheat improvement and domestication. The genome structure and cross-species homoeology of K.hirsuta chromosomes with wheat were assayed using 14 single-gene probes covering all seven homoeologous groups, and four repetitive sequence probes 45S rDNA, 5S rDNA, pAs1, and (AAG)10 by FISH. Each chromosome of K.hirsuta was well characterized by homoeological determination and repeats distribution patterns. The synteny of chromosomes was strongly conserved in the St genome, whereas synteny of the Y and P genomes was more distorted. The collinearity of 1Y, 2Y, 3Y and 7Y might be interrupted in the Y genome. A new 5S rDNA site on 2Y might be translocated from 1Y. The short arm of 3Y might involve translocated segments from 7Y. The 7 Y was identified as involving a pericentric inversion. A reciprocal translocation between 2P and 4P, and tentative structural aberrations in the subtelomeric region of 1PL and 4PL, were observed in the P genome. Chromosome polymorphisms, which were mostly characterized by repeats amplification and deletion, varied between chromosomes, genomes, and different populations. However, two translocations involving a P genome segmental in 3YL and a non-Robertsonial reciprocal translocation between 4Y and 3P were identified in two independent populations. Moreover, the proportion of heterozygous karyotypes reached almost 35% in all materials, and almost 80% in the specific population. These results provide new insights into the genome organization of K.hirsuta and will facilitate genome dissection and germplasm utilization of this species.

Triatoma sordida (Hemiptera, Triatominae) from La Paz, Bolivia: an incipient species or an intraspecific chromosomal polymorphism?

BackgroundTriatoma sordida is one of the main Chagas disease vectors in Brazil. In addition to Brazil, this species has already been reported in Bolivia, Argentina, Paraguay, and Uruguay. It is hypothesized that the insects currently identified as T. sordida are a species subcomplex formed by three cytotypes (T. sordida sensu stricto [s.s.], T. sordida La Paz, and T. sordida Argentina). With the recent description of T. rosai from the Argentinean specimens, it became necessary to assess the taxonomic status of T. sordida from La Paz, Bolivia, since it was suggested that it may represent a new species, which has taxonomic, evolutionary, and epidemiological implications. Based on the above, we carried out molecular and experimental crossover studies to assess the specific status of T. sordida La Paz.MethodsTo evaluate the pre- and postzygotic barriers between T. sordida La Paz and T. sordida s.s., experimental crosses and intercrosses between F1 hybrids and between F2 hybrids were conducted. In addition, cytogenetic analyses of the F1 and F2 hybrids were applied with an emphasis on the degree of pairing between the homeologous chromosomes, and morphological analyses of the male gonads were performed to evaluate the presence of gonadal dysgenesis. Lastly, the genetic distance between T. sordida La Paz and T. sordida s.s. was calculated for the CYTB, ND1, and ITS1 genes.ResultsRegardless of the gene used, T. sordida La Paz showed low genetic distance compared to T. sordida s.s. (below 2%). Experimental crosses resulted in offspring for both directions, demonstrating that there are no prezygotic barriers installed between these allopatric populations. Furthermore, postzygotic barriers were not observed either (since the F1 × F1 and F2 × F2 intercrosses resulted in viable offspring). Morphological and cytogenetic analyses of the male gonads of the F1 and F2 offspring demonstrated that the testes were not atrophied and did not show chromosome pairing errors.ConclusionBased on the low genetic distance (which configures intraspecific variation), associated with the absence of prezygotic and postzygotic reproductive barriers, we confirm that T. sordida La Paz represents only a chromosomal polymorphism of T. sordida s.s.Graphical abstract

Autosexing strains to control populations of fruit flies (DIPTERA: Tephritidae): why do they fail to succeed?

The development of a unique genetic sexing strain to control fruit fly populations has repetedly failed. But why do they fail to succed? We previously demonstrated in Certitis capitata (Wied.) that the autosexing mechanism must be developed on the germplasm of the population to be controled. The present integrative study addresses the causes for the lack of success, thus studying: 1- compatibility tests between Anastrepha fraterculus (Wied.) germplasms from different geographic origins; 2- the genotype by environment interaction component of phenotypic variation in A. fraterculus and 3- essential knowledge on polymorphisms of the Y-chromosome carrying the marker linked to male sex. Our hypothesis: a- chromosomal and morphological variants are associated to different argentinian geographic populations of C. capitata; b- chromosomal variants are not randomly distributed in A. fraterculus populations. We sampled guava fruits during 30 years to recover larvae and adult flies from both species, in order to study the chromosomal pattern of larvae from wild populations and derived strains. Banding patterns were obtained with routine and molecular cytogenetics. Sexual chromosome variants were associated to different strains. Analysis showed ten sexual chromosome variants in A. fraterculus. In C. capitata we found sexual chromosome polymorphisms for the X as well as for the Y. Our results -throughout the years- show the necessity of performing periodically genetic samplings of the populations to be treated in order to detect new mutations affecting mating beahaviour between laboratory and wild populations or lack of compatibiliy when applying the sterile male technique. The study of genotype by environment interaction parameter is mandatory to identify the right germplasms on which to develop the autosexing mechanism in order to successfully control populations of both fruit flies species

Folate metabolism modifies chromosomal damage induced by 1,3-butadiene: results from a match-up study in China and in vitro experiments

ObjectivesTo explore the role of folate metabolism in 1,3-Butadiene (BD)'s genotoxicity, we conducted a match-up study in BD-exposed workers in China to analyze the associations between the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the chromosomal damage induced by BD exposure, and culture-based experiments in TK-6 cells to examine the global DNA methylation levels and chromosomal damage when exposed both to BD’s genotoxic metabolite, 1,2:3,4-diepoxybutane (DEB), and MTHFR’s direct catalytic product, 5-methyltetrahydrofolate (5-MTHF).MethodsCytokinesis block micronucleus assay (CBMN) was used to examine the chromosomal damage induced by BD or DEB. Poisson regression models were produced to quantify the relationship of chromosomal damage and genetic polymorphisms in the BD-exposed workers. Global DNA methylation levels in TK6 cells were examined using DNA Methylation Quantification Kit.ResultsWe found that BD-exposed workers carrying MTHFR C677T CC (2.00 ± 2.00‰) (FR = 0.36, 95%CI: 0.20–0.67, P < 0.01) or MTHFR C677T CT (2.87 ± 1.98‰) (FR = 0.49, 95%CI: 0.32–0.77, P < 0.01) genotypes had significantly lower nuclear bud (NBUD) frequencies than those carrying genotype MTHFR 677 TT (5.33 ± 2.60‰), respectively. The results in TK6 cells showed that there was a significant increment in frequencies of micronucleus (MN), nucleoplasmic bridge (NPB) and nuclear bud (NBUD) with exposure to DEB at each 5-MTHF dose (ANOVA, P < 0.01). Additionally, there was a significant decrease in frequencies of MN, NPB and NBUD in DEB-exposed cultures with increasing concentration of 5-MTHF (ANOVA, P < 0.05). The levels of global DNA methylation were significantly decreased by DEB treatment in a dose-dependent manner within each 5-MTHF concentration in TK-6 cells (ANOVA, P < 0.01), and were significantly increased by 5-MTHF supplementation within each DEB concentration (ANOVA, P < 0.01).ConclusionWe reported that folate metabolism could modify the association between BD exposure and chromosomal damage, and such effect may be partially mediated by DNA hypomethylation, and 5-MTHF supplementation could rescue it.

Reproductive health of parents

The reproductive health of parents is the onset and further physiological course of pregnancy, childbirth and health of the unborn child. Saving of reproductive health can be considered as protecting the family from factors with “reproductive toxicity”, that is lead to morphological and functional changes in the germ cells, organs and systems of embryo. The risk of infertility and miscarriage is significantly higher in couples where a man and a woman have balanced chromosomal rearrangements or gene polymorphisms. In the future, we will be able to block genotoxic lesions of the genome at the gene level.Research and development of experience on this issue continues. Now there are already some promising methods, which include nutritional support at the stage of pregnancy planning using folic acid and myo-inositol. New guidelines have been developed for folic acid, metafolin, MTHFR gene variants, and others. Neural tube defects are more common in people with MTHFR 677 CT and TT genotypes in countries where food folate fortification is not used, so they did not get enough of it. Women who are planning a pregnancy and have previously children with malformations are recommended to intake folic acid 4000 µg daily, starting 1 month before pregnancy and during the first 3 months of gestation.However, getting ready for pregnancy is much more than 3 or 12 months before conception. Preparing for pregnancy is a healthy lifestyle for parents from the moment they are conceived to their reproductive years. Saving of reproductive health is protection against genotoxic damage. Genotoxic substances act in different periods of life with different intensity of strength and time, therefore, the program for maintaining reproductive health should begin from the moment of conception of future parents. At the same time, the reproductive health saving program applies to both women and men.

A Draft Genome of the Ginger Species Alpinia nigra and New Insights into the Genetic Basis of Flexistyly.

Angiosperms possess various strategies to ensure reproductive success, such as stylar polymorphisms that encourage outcrossing. Here, we investigate the genetic basis of one such dimorphism that combines both temporal and spatial separation of sexual function, termed flexistyly. It is a floral strategy characterised by the presence of two morphs that differ in the timing of stylar movement. We performed a de novo assembly of the genome of Alpinia nigra using high-depth genomic sequencing. We then used Pool-seq to identify candidate regions for flexistyly based on allele frequency or coverage differences between pools of anaflexistylous and cataflexistylous morphs. The final genome assembly size was 2 Gb, and showed no evidence of recent polyploidy. The Pool-seq did not reveal large regions with high FST values, suggesting large structural chromosomal polymorphisms are unlikely to underlie differences between morphs. Similarly, no region had a 1:2 mapping depth ratio which would be indicative of hemizygosity. We propose that flexistyly is governed by a small genomic region that might be difficult to detect with Pool-seq, or a complex genomic region that proved difficult to assemble. Our genome will be a valuable resource for future studies of gingers, and provides the first steps towards characterising this complex floral phenotype.

O-175 Impact of female chromosomal polymorphic variants on ovarian reserve markers and fertility treatments prognosis

Abstract Study question Could the presence of chromosomal polymorphisms in women undergoing fertility treatments influence ovarian reserve, oocyte preservation or IVF clinical outcomes? Summary answer Polymorphic variants of chromosomes seem to adversely influence the Anti-Müllerian Hormone (AMH) serum levels and the post-thawing oocyte survival rate. What is known already Infertile couples have been reported to have a higher incidence of karyotype abnormalities than the general population, which could lead to lower fertility rates. However, few studies have demonstrated the controversial relationship between these karyotype alterations in women and the specific involvement of these variants and their combinations in an IVF cycle. Therefore, there is a growing interest in categorizing chromosomal polymorphic variants and relating them to the subsequent evolution in ART cycles. Study design, size, duration Retrospective evaluation of a cohort of women undergoing IVF cycles in a private fertility center. The sample included 280 cycles performed between July 2017 and December 2020. The study explored the correlation between karyotype polymorphisms and IVF outcomes in terms of: Anti-Müllerian Hormone (AMH) level, Antral Follicle Count (AFC), Oocyte Maturity (MII), Oocyte Survival after Thawing (TS), Fertilization (FZ), Useful Embryos (UE), Biochemical (BP) and Clinical Pregnancy (CP), Miscarriage (M) and Live Birth (LB) rates. Participants/materials, setting, methods Women with karyotype performed before an IVF cycle. Chromosome analysis was carried out according to the International System for Human Cytogenetic Nomenclature guidelines (ISCN). Only own eggs cycles were included, and testicular sperm cycles were excluded. The normality of the distribution of the variables was assessed using the Shapiro-Wilk test. The association between IVF cycle parameters and the presence of polymorphisms was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Main results and the role of chance From a total of 280 IVF cycles, 198 met the inclusion criteria: Control Group (CG) with normal karyotype (94) and Study Group (SG) with presence of polymorphisms (104) were analyzed. Cycles with fresh (136) and warmed (62) oocytes were included. Mean female age was 37.66 ± 3.99 (CG) and 36.61 ± 3.72 (SG). The overall outcome rates were: 75.82% MII, 81.39% TS, 72.78% FZ, 49.07% UE on day 5, 21.82% BP, 78.18% CP, 14.53% M and 63.65% LB. Statistically significant differences were found between the presence of polymorphisms and mean AMH serum level between CG (2.36 ng/mL) and SG (1.74 ng/mL) (p = 0.04), especially when the type “qh+” was detected (1.01 ng/mL) (p = 0.02). Furthermore, statistically significant differences were found regarding oocyte thawing survival rate, which decreased in the SG (78.94%) compared to the CG (93.69%) (p = 0.02), mainly when the type “ps+” was detected (75.13%) (p &amp;lt; 0.01). No statistically significant differences were found between the presence of polymorphism and the AFC (p = 0.25), MII (p = 0.10), FZ (p = 0.93) or UE (p = 0.52) rate on day 5. In the same way, from 106 embryo transfers (ET) performed, no significant differences were found for BP, CP, M and LB rates (p &amp;gt; 0.05). Limitations, reasons for caution Larger prospective studies including homogeneous cohorts are needed in order to corroborate our initial results. Wider implications of the findings Our findings may represent a practical tool in order to advise these patients about their reproductive success, especially, in terms of post-thawing oocyte survival prognosis. Therefore, it could be provided more personalized prognostic information before embarking on IVF treatments. Trial registration number Not Applicable

Investigation on combined copy number variation sequencing and cytogenetic karyotyping for prenatal diagnosis

BackgroundWe aimed to evaluate the clinical value of copy number variation-sequencing (CNV-Seq) in combination with cytogenetic karyotyping in prenatal diagnosis.MethodsCNV-Seq and cytogenetic karyotyping were performed in parallel for 9452 prenatal samples for comparison of the diagnostic performance of the two methods, and to evaluate the screening performance of maternal age, maternal serum screening, fetal ultrasound scanning and noninvasive prenatal testing (NIPT) for fetal pathogenic copy number variation (CNV).ResultsAmong the 9452 prenatal samples, traditional karyotyping detected 704 cases (7.5%) of abnormal cytogenetic karyotypes, 171 (1.8%) chromosome polymorphism, 20 (0.2%) subtle structural variations, 74 (0.7%) mutual translocation (possibly balanced), 52 (0.6%) without karyotyping results, and 8431 (89.2%) normal cytogenetic karyotypes. Among the 8705 cases with normal karyotype, polymorphism, mutual translocation, or marker chromosome, CNV-Seq detected 63 cases (0.7%) of pathogenic chromosome microdeletion/duplication. Retrospectively, noninvasive prenatal testing (NIPT) had high sensitivity and specificity for the screening of fetal pathogenic CNV, and NIPT combining with maternal age, maternal serum screening or fetal ultrasound scanning, which improved the screening performance.ConclusionThe combined application of cytogenetic karyotyping and CNV-Seq significantly improved the detection rate of fetal pathogenic chromosome microdeletion/duplication. NIPT was recommended for the screening of pathogenic chromosome microdeletion/duplication, and NIPT combining with other screening methods further improved the screening performance for pathogenic fetal CNV.

Phylogeographic review of Y chromosome haplogroups in Europe.

The Y chromosome has been widely explored for the study of human migrations. Due to its paternal inheritance, the Y chromosome polymorphisms are helpful tools for understanding the geographical distribution of populations all over the world and for inferring their origin, which is really useful in forensics. The remarkable historical context of Europe, with numerous migrations and invasions, has turned this continent into a melting pot. For this reason, it is interesting to study the Y chromosome variability and how it has contributed to improving our knowledge of the distribution and development of European male genetic pool as it is today. The analysis of Y lineages in Europe shows the predominance of four haplogroups, R1b-M269, I1-M253, I2-M438 and R1a-M420. However, other haplogroups have been identified which, although less frequent, provide significant evidence about the paternal origin of the populations. In addition, the study of the Y chromosome in Europe is a valuable tool for revealing the genetic trace of the different European colonizations, mainly in several American countries, where the European ancestry is mostly detected by the presence of the R1b-M269 haplogroup. Therefore, the objective of this review is to compile the studies of the Y chromosome haplogroups in current European populations, in order to provide an outline of these haplogroups which facilitate their use in forensic studies.

Sparrows and supergenes: Ecological epigenetics in action.

Despite the promise of ecological epigenetics, there remain few cases that clearly link epigenetic variation in wild animal populations to evolutionary change. In this issue of Molecular Ecology, Sun et al. provide such an example in white-throated sparrows-a fascinating system in which a large chromosomal rearrangement generates a "supergene" polymorphism linked to plumage colour, aggression and parenting behaviour. By combining whole genome bisulphite sequencing with RNA-sequencing and chromatin accessibility data, they show that the two alleles of this chromosomal polymorphism also exhibit substantial differences in DNA methylation levels, with implications for gene expression and transposable element activity. Their results provide a compelling case study for how genetic and epigenetic evolution proceed in concert. They also demonstrate the importance of integrating multiple types of genomic information to understand how gene regulation evolves, providing a model for future work in nonmodel species.

Association between 9p21 Chromosome Polymorphisms rs1333040 and rs7865618 and Chronic Myeloid Leukemia

Introduction: During the last decade, single nucleotide polymorphisms (SNPs) on the chromosomal locus 9p21 have been associated with several cardiovascular (CV) diseases, such as stroke and myocardial infarction. In this study, we evaluated the association between two SNPs on 9p21 and Chronic Myeloid Leukemia (CML). As CML is generally treated with tyrosine kinase inhibitors (TKIs) and TKI therapy has been associated with increased vascular events by itself, we investigated the influence of SNPs on chromosome 9p21 on the incidence of CV events in subjects affected by CML who were in treatment with TKIs.Patients and Methods: We studied 185 patients with CML and 171 unaffected controls. The median age at the diagnosis of CML was 55 years (range 17-84) and we enrolled 99 males and 86 females. All patients were treated with at least 1 TKI, with Imatinib being the most commonly used as first line therapy (71%). Previous CV diseases were taken into account and new CV events were recorded during follow-up. The median follow-up was 91,5 months (range 14-301). Genomic DNA was isolated from peripheral blood collected during follow-up and the rs1333040C>T and rs7865618A>G polymorphisms were assessed by PCR-RFLP using restriction endonucleases. For each SNP, we performed dominant, recessive, and additive genetic models. The association between SNPs on 9p21 and CML was evaluated using Chi-square test. In subjects affected by CML, to study the association between SNPs on 9p21 and CV events, Fisher's exact test was performed. In CML patients we also analyzed the correlation between SNP on 9p21 and age at diagnosis, sex, ethnic group, Sokal, Euro and Eutos risk, response to therapy.Results: The distribution of the three possible genotypes of rs1333040 (TT, TC and CC) was statistically different between cases and controls (p=0.0006; Table 1). The TT genotype was significantly associated with CML in the dominant model (p=0.0001) but not in the recessive model (p=0.09). The T allele was significantly associated with CML in the additive model (p=0.004). Also, the distribution of the three possible genotypes of rs7865618 (GG, AG and AA) was statistically different between cases and controls (p=0.015; Table 2), and the GG genotype and the G allele were significantly associated with CML in the dominant (p=0.05), recessive (p=0.009), and additive models (p=0.009). We registered 37 CV events among patients affected by CML. Most of them (26) occurred before the introduction of TKI therapy. In patients taking TKI, 11 events were recorded. The TT genotype of rs1333040 was associated with an increased risk of CV events in CML patients (p=0.05) with no difference between patients taking or not taking TKI. Differently, patients carrying the “at risk” genotype of rs7865618 (GG) did not show increased risk of CV events compared to the control population. No correlation was found between CML patients characteristics and response to therapy and studied genotypes.Discussion: Polymorphisms on chromosome 9p21 have been consistently associated with CV diseases in the general population. In this study, we demonstrate that the TT genotype of rs1333040 and the GG genotype of rs7865618 are significantly associated with CML. Patients affected by CML who are carriers of the TT genotype of rs1333040 show increased risk of CV events compared with non-carriers. The use of TKIs is not associated with increased risk of CV events in both carriers and non-carriers. The 9p21 chromosomal region deserves further investigation for its potential role in the genetic susceptibility to CML and associated CV events. [Display omitted] DisclosuresAbruzzese:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; ARIAD: Consultancy; Novartis: Consultancy.

Debaryomyces hansenii Strains Isolated From Danish Cheese Brines Act as Biocontrol Agents to Inhibit Germination and Growth of Contaminating Molds.

The antagonistic activities of native Debaryomyces hansenii strains isolated from Danish cheese brines were evaluated against contaminating molds in the dairy industry. Determination of chromosome polymorphism by use of pulsed-field gel electrophoresis (PFGE) revealed a huge genetic heterogeneity among the D. hansenii strains, which was reflected in intra-species variation at the phenotypic level. 11 D. hansenii strains were tested for their ability to inhibit germination and growth of contaminating molds, frequently occurring at Danish dairies, i.e., Cladosporium inversicolor, Cladosporium sinuosum, Fusarium avenaceum, Mucor racemosus, and Penicillium roqueforti. Especially the germination of C. inversicolor and P. roqueforti was significantly inhibited by cell-free supernatants of all D. hansenii strains. The underlying factors behind the inhibitory effects of the D. hansenii cell-free supernatants were investigated. Based on dynamic headspace sampling followed by gas chromatography-mass spectrometry (DHS-GC-MS), 71 volatile compounds (VOCs) produced by the D. hansenii strains were identified, including 6 acids, 22 alcohols, 15 aldehydes, 3 benzene derivatives, 8 esters, 3 heterocyclic compounds, 12 ketones, and 2 phenols. Among the 71 identified VOCs, inhibition of germination of C. inversicolor correlated strongly with three VOCs, i.e., 3-methylbutanoic acid, 2-pentanone as well as acetic acid. For P. roqueforti, two VOCs correlated with inhibition of germination, i.e., acetone and 2-phenylethanol, of which the latter also correlated strongly with inhibition of mycelium growth. Low half-maximal inhibitory concentrations (IC50) were especially observed for 3-methylbutanoic acid, i.e., 6.32–9.53 × 10–5 and 2.00–2.67 × 10–4 mol/L for C. inversicolor and P. roqueforti, respectively. For 2-phenylethanol, a well-known quorum sensing molecule, the IC50 was 1.99–7.49 × 10–3 and 1.73–3.45 × 10–3 mol/L for C. inversicolor and P. roqueforti, respectively. For acetic acid, the IC50 was 1.35–2.47 × 10–3 and 1.19–2.80 × 10–3 mol/L for C. inversicolor and P. roqueforti, respectively. Finally, relative weak inhibition was observed for 2-pentanone and acetone. The current study shows that native strains of D. hansenii isolated from Danish brines have antagonistic effects against specific contaminating molds and points to the development of D. hansenii strains as bioprotective cultures, targeting cheese brines and cheese surfaces.

Differentiation of the frog sculpin Myoxocephalus stelleri Tilesius, 1811 (Actinopterygii, Cottidae) based on mtDNA and karyotype analyses.

A molecular genetic and karyological study of the frog sculpin Myoxocephalus stelleri Tilesius, 1811 was carried out on an extensive sample from a large area of the species’ range. A total of 42 specimens was sampled from the Sea of Japan, Sea of Okhotsk, and coastal waters off the southern Kuril Islands, which makes this sampling scheme the most comprehensive to date. The level of mtDNA polymorphism was found to be low. The haplotypes of the species formed three phylogenetic groups. The unique M. stelleri haplotype from the coast of Shikotan Island linked all the studied groups, indicating that it is likely ancestral. Robertsonian polymorphism was identified in the species. In all five cytotypes (I – 2n = 44, II – 2n = 43, III – 2n = 42, IV – 2n = 41, V – 2n = 40; NF = 44+2) were identified, all of which were present in the Sea of Japan. Only one (cytotype I) was found in the Sea of Okhotsk, which is probably the closest to the ancestral karyotype. The significant chromosomal polymorphism and the presence of common haplotypes in the studied samples indicate their recent origin from a common ancestor and/or relatively recent contacts within the range. The discrepancies between mtDNA and karyotypes in assigning the ancestral M. stelleri to the coastal waters off Shikotan Island (southern Kuril Islands) and the Sea of Okhotsk, respectively, can be explained by the different inheritance mechanisms and the rates of evolution of molecular genetic and karyological traits.

Genetic structuring of Drosophila bipectinata in Indian natural populations based on the distribution of cosmopolitan inversions

Genetic differentiation among different natural populations of a species depends upon the environmental factors and the evolutionary forces that operate on them. In this study, seven Indian natural populations of D. bipectinata, two from north and five from south India, have been studied for their chromosomal inversion polymorphism. A total of nine paracentric autosomal inversions were recorded from these seven places but only three of them, present on the 2L, 2R and 3L were found to be cosmopolitan in distribution. In all the populations, the frequency of standard gene arrangement was found to be high than their respective cosmopolitan inversion gene arrangement. The average heterozygosity (Ho) of cosmopolitan inversions increases from north to south. There is a latitudinal cline in the distribution of three cosmopolitan inversion arrangements because their frequency increases with the decreasing latitude, i.e. from north to south India. A comparison of the genetic profile of two north Indian and five south Indian natural populations of D. bipectinata reveals the role of natural selection as well as bottleneck effect in the genetic structuring of these populations which may be due to their varying ecological conditions to which they are constantly encountered. Further, the presence of all kinds of paracentric inversions in individual populations was analysed following Poisson distribution to see whether these inversions occur randomly in natural populations or not and the results indicate that north Indian populations show the random occurrence of these inversions than the populations derived from the south.

Unusual chromosomal polymorphism of the common shrew, Sorex araneus L., in southern Belarus.

Analysis of the frequency of karyotypes and chromosomal rearrangements in the distributional ranges of four metacentric races of Sorex araneus Linnaeus, 1758 has revealed features that are not typical for polymorphic populations of this species. The frequency of the acrocentric karyotype and heterozygotes for fusion of acrocentric chromosomes turned out to be significantly higher than expected in case of random crossing. As an explanation for the unusual polymorphism, it has been suggested that metacentric races may hybridize with acrocentric populations that remained from the ancient chromosomal form.