DG - Artículos
https://hdl.handle.net/10481/31028
2024-03-28T19:19:38ZInterpopulation spread of a parasitic B chromosome is unlikely through males in the grasshopper Eyprepocnemis plorans
https://hdl.handle.net/10481/89784
Interpopulation spread of a parasitic B chromosome is unlikely through males in the grasshopper Eyprepocnemis plorans
Manrique-Poyato, María Inmaculada; Cabrero Hurtado, Josefa; López León, María Dolores; Perfectti Álvarez, Francisco; Gómez, Ricardo; Martínez Camacho, Juan Pedro
The near-neutral model of B chromosome evolution predicts that population invasion is quite fast. To test this prediction, in 1994, we introduced males of the grasshopper Eyprepocnemis plorans from a B-carrying population into a B-lacking population and monitored the evolution of B-chromosome frequency up to 2013. We observed fluctuating very low B frequency across years but, remarkably, the B chromosome introduced (the B2 variant) was found up to 1996 only, whereas the B1 variant was present from 1996 onwards, presumably introduced by fishermen using E. plorans males as bait. Effective introgression of genetic material from the donor population was evidenced by the presence of a satellite DNA on autosome 9 (up to 1999) and the presence of one individual in 2006 showing an ISSR marker profile being highly similar to that found in the donor population. This indicated that the males introduced by us effectively mated with resident females, but donor genes rapidly decreased in frequency after this non-recurrent migration event. Taken together, our results indicated: (i) that the non-recurrent migration event had a slight, transient genetic effect on the recipient population, which was diluted in only a few generations; and (ii) that even with recurrent migration (forced by fishermen) the B chromosome failed to increase in frequency. Bearing in mind that B chromosomes in this species drive through females only, we hypothesize that B chromosomes most likely failed invasion in both migration events because the migrating sex shows no B-drive.
This study was supported by grants from the Spanish Secretaría de Estado de Investigación,
Desarrollo e Innovación (CGL2015-70750-P), and was partially performed by FEDER funds.
Eight Million Years of Satellite DNA Evolution in Grasshoppers of the Genus Schistocerca Illuminate the Ins and Outs of the Library Hypothesis
https://hdl.handle.net/10481/89757
Eight Million Years of Satellite DNA Evolution in Grasshoppers of the Genus Schistocerca Illuminate the Ins and Outs of the Library Hypothesis
Palacios-Giménez, Octavio Manuel; Milani, Diogo; Song, Hojun; Marti, Dardo A.; María Dolores López León; Ruiz-Ruano, Francisco J.; M. Camacho, Juan Pedro; Cabral-de-Mello, Diogo C.
Satellite DNA (satDNA) is an abundant class of tandemly repeated noncoding sequences, showing high rate of change in sequence, abundance, and physical location. However, the mechanisms promoting these changes are still controversial. The library model was put forward to explain the conservation of some satDNAs for long periods, predicting that related species share a common collection of satDNAs, which mostly experience quantitative changes. Here, we tested the library model by analyzing three satDNAs in ten species of Schistocerca grasshoppers. This group represents a valuable material because it diversified during the last 7.9 Myr across the American continent from the African desert locust (Schistocerca gregaria), and this thus illuminates the direction of evolutionary changes. By combining bioinformatic and cytogenetic, we tested whether these three satDNA families found in S. gregaria are also present in nine American species, and whether differential gains and/or losses have occurred in the lineages. We found that the three satDNAs are present in all species but display remarkable interspecies differences in their abundance and sequences while being highly consistent with genus phylogeny. The number of chromosomal loci where satDNA is present was also consistent with phylogeny for two satDNA families but not for the other. Our results suggest eminently chance events for satDNA evolution. Several evolutionary trends clearly imply either massive amplifications or contractions, thus closely fitting the library model prediction that changes are mostly quantitative. Finally, we found that satDNA amplifications or contractions may influence the evolution of monomer consensus sequences and by chance playing a major role in driftlike dynamics.
This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP (process number 2014/11763-8) and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior-CAPES. The authors are grateful to anonymous reviewers for valuable comments. O.M.P.-G. and F.J.R.-R. acknowledge the scholarship obtained from the Lawski Foundation (Sweden), H.S. to the U.S. National Science Foundation (Grant No. IOS-1253493) and the United State Department of Agriculture (Hatch Grant TEX0-1-6584), D.A.M. was supported by Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET from Argentina. D.C.C.-d.-M. is recipient of a research productivity fellowship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (process number 304758/2014-0). Computing ran on resources provided by the Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX). We also thank Alexander Suh (Uppsala University, Uppsala/Sweden) for helpful comments on an earlier version of this manuscript and to Cristiane Mileo (UNESP-Rio Claro/SP) for helping with some figures.
A distal enhancer at the 11q13.5 risk locus promotes Treg-mediated suppression of colitis
https://hdl.handle.net/10481/88835
A distal enhancer at the 11q13.5 risk locus promotes Treg-mediated suppression of colitis
Nasrallah, Nasrallah; Bossini Castillo, Lara María
Genetic variations underlying susceptibility to complex autoimmune and allergic diseases are concentrated within noncoding regulatory elements termed enhancers1. The functions of a large majority of disease-associated enhancers are unknown, in part owing to their distance from the genes they regulate, a lack of understanding of the cell types in which they operate, and our inability to recapitulate the biology of immune diseases in vitro. Here, using shared synteny to guide loss-of-function analysis of homologues of human enhancers in mice, we show that the prominent autoimmune and allergic disease risk locus at chromosome 11q13.52-7 contains a distal enhancer that is functional in CD4+ regulatory T (Treg) cells and required for Treg-mediated suppression of colitis. The enhancer recruits the transcription factors STAT5 and NF-κB to mediate signal-driven expression of Lrrc32, which encodes the protein glycoprotein A repetitions predominant (GARP). Whereas disruption of the Lrrc32 gene results in early lethality, mice lacking the enhancer are viable but lack GARP expression in Foxp3+ Treg cells, which are unable to control colitis in a cell-transfer model of the disease. In human Treg cells, the enhancer forms conformational interactions with the promoter of LRRC32 and enhancer risk variants are associated with reduced histone acetylation and GARP expression. Finally, functional fine-mapping of 11q13.5 using CRISPR-activation (CRISPRa) identifies a CRISPRa-responsive element in the vicinity of risk variant rs11236797 capable of driving GARP expression. These findings provide a mechanistic basis for association of the 11q13.5 risk locus with immune-mediated diseases and identify GARP as a potential target in their therapy.
Versión de acceso abierto proporcionada por Europe PMC Funders Group
Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility
https://hdl.handle.net/10481/88816
Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility
Bossini Castillo, Lara María
Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure.
Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure.
Materials and methods: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted.
Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern.
Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.
Versión Open Access de la web de la revista
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort
https://hdl.handle.net/10481/88814
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort
Bossini Castillo, Lara María
Background: Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non-obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes).
Objectives: The main objective of the present study is to analyze in the Iberian population the effect of 6 single-nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome-wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns.
Materials and methods: We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS-associated variants PRMT6-rs12097821, PEX10-rs2477686, CDC42BPA-rs3000811, IL17A-rs13206743, ABLIM1-rs7099208, and SOX5-rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources.
Results: ABLIM1-rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA-rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10-rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis-specific expression of nearby genes and that lincRNA may play a role in SpF.
Conclusions: Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1-rs7099208, CDC42BPA-rs3000811, and PEX10-rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.