A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate cytoskeleton defects to ...autoinflammatory diseases and primary immunodeficiencies. We reviewed the pathways of actin cytoskeleton remodeling in order to identify inflammatory and immunological manifestations associated to pathological variants. We list more than twenty monogenic diseases, ranging from pure autoinflammatory conditions as familial Mediterranean fever, mevalonate kinase deficiency and PAPA syndrome, to classic and novel primary immunodeficiencies as Wiskott-Aldrich syndrome and DOCK8 deficiency, characterized by the presence of concomitant inflammatory and autoimmune manifestations, such as vasculitis and cytopenia, to severe and recurrent infections. We classify these disorders according to the role of the mutant gene in actin cytoskeleton remodeling, and in particular as disorders of transcription, elongation, branching and activation of actin. This expanding field of rare immune disorders offers a new perspective to all immunologists to better understand the physiological and pathological role of actin cytoskeleton in cells of innate and adaptive immunity.
Secondary, AA, Amyloidosis Papa, Riccardo; Lachmann, Helen J
Rheumatic diseases clinics of North America,
11/2018, Letnik:
44, Številka:
4
Journal Article
Recenzirano
Secondary, AA, amyloidosis is a rare systemic complication that can develop in any long-term inflammatory disorder, and is characterized by the extracellular deposition of fibrils derived from serum ...amyloid A (SAA) protein. SAA is an acute-phase reactant synthetized largely by hepatocytes under the transcriptional regulation of proinflammatory cytokines. The kidney is the major involved organ with proteinuria as first clinical manifestation; renal biopsy is the commonest diagnostic investigation. Targeted anti-inflammatory treatment promotes normalization of circulating SAA levels preventing amyloid deposition and renal damage. Novel therapies aimed at promoting clearance of existing amyloid deposits soon may be an effective treatment approach.
An Update on Familial Mediterranean Fever Lancieri, Maddalena; Bustaffa, Marta; Palmeri, Serena ...
International journal of molecular sciences,
05/2023, Letnik:
24, Številka:
11
Journal Article
Recenzirano
Odprti dostop
(1) Background: Familial Mediterranean Fever (FMF) is the prototypal autoinflammatory disease, characterized by recurrent bursts of neutrophilic inflammation. (2) Methods: In this study we look at ...the most recent literature on this condition and integrate it with novel information on treatment resistance and compliance. (3) Results: The canonical clinical presentation of FMF is in children with self-limited episodes of fever and polyserositis, associated with severe long-term complications, such as renal amyloidosis. It has been described anecdotally since ancient times, however only recently it has been characterized more accurately. We propose an updated overview on the main aspects of pathophysiology, genetics, diagnosis and treatment of this intriguing disease. (4) Conclusions: Overall, this review presents the all the main aspects, including real life outcome of the latest recommendation on treatment resistance of FMF, a disease, that not only helped understanding the pathophysiology of the auto inflammatory process but also the functioning of the innate immune system itself.
Color pattern mimicry in Heliconius butterflies is a classic case study of complex trait adaptation via selection on a few large effect genes. Association studies have linked color pattern variation ...to a handful of noncoding regions, yet the presumptive cis-regulatory elements (CREs) that control color patterning remain unknown. Here we combine chromatin assays, DNA sequence associations, and genome editing to functionally characterize 5 cis-regulatory elements of the color pattern gene optix. We were surprised to find that the cis-regulatory architecture of optix is characterized by pleiotropy and regulatory fragility, where deletion of individual cis-regulatory elements has broad effects on both color pattern and wing vein development. Remarkably, we found orthologous cis-regulatory elements associate with wing pattern convergence of distantly related comimics, suggesting that parallel coevolution of ancestral elements facilitated pattern mimicry. Our results support a model of color pattern evolution in Heliconius where changes to ancient, multifunctional cis-regulatory elements underlie adaptive radiation.
Invasive populations of green iguanas (Iguanidae:
Iguana iguana
) are widely established beyond their native Central, South American, and Lesser Antillean range in various islands of the Pacific, ...Florida USA, and in the Greater Caribbean Region. Although widespread, information about these invasions is scarce. Here we determine the origin of invasive populations of green iguanas in Puerto Rico, Fiji, The Caymans, Florida USA, The Dominican Republic, the US Virgin Islands (USVI) of St. Thomas and St. Croix, and a U.S.A pet store. We sampled 120 individuals from these locations and sequenced one mitochondrial (
ND4
) and two nuclear (
PAC
and
NT3
) loci. We also include a preliminary characterization of population structure throughout Puerto Rico using six microsatellite loci to genotype individuals across 10 sampling sites. Comparing the genealogical relationships of all our samples to published sequencing data from the native range, we found that sampled populations were largely a product of populations from Colombia and El Salvador; two countries with multiple, industrial-size pet iguana farming operations. Notably, we found that haplotypes detected exclusively in the USVI and Puerto Rico’s outlying island of Vieques are closely linked to green iguanas native to Saba and Montserrat (Lesser Antilles); a clade not reported in the pet trade. Our population genetic analyses did not reveal isolation among sampling sites in Puerto Rico, rather the evidence supported admixture across the island. This study highlights the roles of the pet trade and lack of regulation in the spread of green iguanas beyond their native range.
In
butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic ...radiation. One of these genes,
, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple
species and show that
is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified
-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the
lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that
-regulatory structural variation underlies these mimetic adaptations. Our work shows that
functionally controls scale colour fate and that its
-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.
Abstract
Many animal species remain separate not because their individuals fail to produce viable hybrids but because they “choose” not to mate. However, we still know very little of the genetic ...mechanisms underlying changes in these mate preference behaviours.
Heliconius
butterflies display bright warning patterns, which they also use to recognize conspecifics. Here, we couple QTL for divergence in visual preference behaviours with population genomic and gene expression analyses of neural tissue (central brain, optic lobes and ommatidia) across development in two sympatric
Heliconius
species. Within a region containing 200 genes, we identify five genes that are strongly associated with divergent visual preferences. Three of these have previously been implicated in key components of neural signalling (specifically an
ionotropic glutamate receptor
and two
regucalcins
), and overall our candidates suggest shifts in behaviour involve changes in visual integration or processing. This would allow preference evolution without altering perception of the wider environment.
Although animals display a rich variety of shapes and patterns, the genetic changes that explain how complex forms arise are still unclear. Here we take advantage of the extensive diversity of ...Heliconius butterflies to identify a gene that causes adaptive variation of black wing patterns within and between species. Linkage mapping in two species groups, gene-expression analysis in seven species, and pharmacological treatments all indicate that cis -regulatory evolution of the WntA ligand underpins discrete changes in color pattern features across the Heliconius genus. These results illustrate how the direct modulation of morphogen sources can generate a wide array of unique morphologies, thus providing a link between natural genetic variation, pattern formation, and adaptation.
Heliconius butterflies, a speciose genus of Müllerian mimics, represent a classic example of an adaptive radiation that includes a range of derived dietary, life history, physiological and neural ...traits. However, key lineages within the genus, and across the broader Heliconiini tribe, lack genomic resources, limiting our understanding of how adaptive and neutral processes shaped genome evolution during their radiation. Here, we generate highly contiguous genome assemblies for nine Heliconiini, 29 additional reference-assembled genomes, and improve 10 existing assemblies. Altogether, we provide a dataset of annotated genomes for a total of 63 species, including 58 species within the Heliconiini tribe. We use this extensive dataset to generate a robust and dated heliconiine phylogeny, describe major patterns of introgression, explore the evolution of genome architecture, and the genomic basis of key innovations in this enigmatic group, including an assessment of the evolution of putative regulatory regions at the Heliconius stem. Our work illustrates how the increased resolution provided by such dense genomic sampling improves our power to generate and test gene-phenotype hypotheses, and precisely characterize how genomes evolve.
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