An Appraisal of Genetic Studies on Leprosy

1972 ◽  
Vol 21 (1-2) ◽  
pp. 21-52 ◽  
Author(s):  
Bernardo Beiguelman
Keyword(s):  
Racial Differences ◽  
Genetic Markers ◽  
Genetic Factors ◽  
Twin Pair ◽  
Critical Discussion ◽  
Australia Antigen ◽  
Genetic Studies ◽  
Mechanism Of Resistance ◽  
Familial Association

SummaryThe present paper reviews the research lines which have been explored to evaluate to what extent genetic factors are intervening on the mechanism of resistance and susceptibility to leprosy.It presents a critical discussion of the investigations on the familial association of leprosy, familial association of leprosy types, intrafamilial contagion of leprosy, concordance of leprosy in twinpairs, racial differences on leprosy prevalence and lepromatous rate, pedigree studies, association of leprosy to genetic markers, Australia antigen, and dermatoglyphic patterns. Space was also allotted to review family and twin-pair studies on the Mitsuda reaction, as well as to the investigation on the in vitro behaviour of blood macrophages against killed M. leprae.Some areas in which further research on leprosy and genetics may be considered as prioritary are outlined with some detail.

Implications of genetics for the epidemiology and control of leprosy

1988 ◽  
Vol 321 (1207) ◽  
pp. 365-376 ◽  
Keyword(s):  
Racial Differences ◽  
Genetic Studies ◽  
Disease Clusters ◽  
Hla Dr ◽  
History Of ◽  
Genetic Mechanisms ◽  
Specific Reactions ◽  
And Control

This paper reviews the rationale and history of genetic studies related to leprosy, and considers their implications for the epidemiology and control of the disease. A long tradition of genetic studies in leprosy was initiated by early impressions that the disease clusters within families. Investigations were first motivated by an attempt to understand population patterns, and the focus shifted from investigations of racial differences to investigations of families, of twins and ultimately of genetic markers. The strongest evidence for genetic influence has come from studies of HLA segregation patterns within families, and this has led to elegant in vitro work demonstrating the role of HLA-DR alleles in mediating T-cell reactions in conjunction with antigens of Mycobacterium leprae . The epidemiological implications of this work are not yet clear. The emphasis on family-segregation studies may have given a biased impression because of their requirement for multi-case families. There is evidence that the genetic mechanisms underlying leprosy differ within and between populations. One possible application of the current work would be the use of HLA-DR-specific reactions to identify epitopes of M. leprae which should be excluded from future vaccine preparations.

Bestimmung der DNA-Schädigung in vitro

2010 ◽  
Vol 49 (S 01) ◽  
pp. S64-S68
Author(s):  
E. Dikomey
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Chromosome Aberrations ◽  
Genetic Factors ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Cell Inactivation ◽  
Repair Mechanisms ◽  
Break Repair

SummaryIonising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.

scholarly journals Substantiation inEnterococcus faecalisof Dose-Dependent Resistance and Cross-Resistance to Pore-Forming Antimicrobial Peptides by Use of a Polydiacetylene-Based Colorimetric Assay

2010 ◽  
Vol 77 (3) ◽  
pp. 786-793 ◽  
Author(s):  
Jitender Mehla ◽  
S. K. Sood
Keyword(s):  
Colorimetric Assay ◽  
Physiological Activity ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Common Mechanism ◽  
Membrane Phospholipids ◽  
Mechanism Of Resistance ◽  
Colorimetric Response ◽  
Dose Dependent

ABSTRACTA better understanding of the antimicrobial peptide (AMP) resistance mechanisms of bacteria will facilitate the design of effective and potent AMPs. Therefore, to understand resistance mechanisms and forin vitroassessment, variants ofEnterococcus faecalisthat are resistant to different doses of the fungal AMP alamethicin (Almr) were selected and characterized. The resistance developed was dose dependent, as both doses of alamethicin and degrees of resistance were colinear. The formation of bacterial cell aggregates observed in resistant cells may be the prime mechanism of resistance because overall, a smaller cell surface in aggregated cells is exposed to AMPs. Increased rigidity of the membranes of Almrvariants, because of their altered fatty acids, was correlated with limited membrane penetration by alamethicin. Thus, resistance developed against alamethicin was an adaptation of the bacterial cells through changes in their morphological features and physiological activity and the composition of membrane phospholipids. The Almrvariants showed cross-resistance to pediocin, which indicated that resistance developed against both AMPs may share a mechanism, i.e., an alteration in the cell membrane. High percentages of colorimetric response by both AMPs against polydiacetylene/lipid biomimetic membranes of Almrvariants confirmed that altered phospholipid and fatty acid compositions were responsible for acquisition of resistance. So far, this is the only report of quantification of resistance and cross-resistance using anin vitrocolorimetric approach. Our results imply that a single AMP or AMP analog may be effective against bacterial strains having a common mechanism of resistance. Therefore, an understanding of resistance would contribute to the development of a single efficient, potent AMP against resistant strains that share a mechanism of resistance.

scholarly journals Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein

2006 ◽  
Vol 395 (3) ◽  
pp. 587-598 ◽  
Author(s):  
Ramin Nazarian ◽  
Marta Starcevic ◽  
Melissa J. Spencer ◽  
Esteban C. Dell'Angelica
Keyword(s):  
Recombinant Proteins ◽  
Binding Protein ◽  
Coiled Coil ◽  
Direct Interaction ◽  
Muscle Pathology ◽  
Binding Assays ◽  
Genetic Studies ◽  
Binding Interface ◽  
Lysosome Related Organelles

Dysbindin was identified as a dystrobrevin-binding protein potentially involved in the pathogenesis of muscular dystrophy. Subsequently, genetic studies have implicated variants of the human dysbindin-encoding gene, DTNBP1, in the pathogeneses of Hermansky–Pudlak syndrome and schizophrenia. The protein is a stable component of a multisubunit complex termed BLOC-1 (biogenesis of lysosome-related organelles complex-1). In the present study, the significance of the dystrobrevin–dysbindin interaction for BLOC-1 function was examined. Yeast two-hybrid analyses, and binding assays using recombinant proteins, demonstrated direct interaction involving coiled-coil-forming regions in both dysbindin and the dystrobrevins. However, recombinant proteins bearing the coiled-coil-forming regions of the dystrobrevins failed to bind endogenous BLOC-1 from HeLa cells or mouse brain or muscle, under conditions in which they bound the Dp71 isoform of dystrophin. Immunoprecipitation of endogenous dysbindin from brain or muscle resulted in robust co-immunoprecipitation of the pallidin subunit of BLOC-1 but no specific co-immunoprecipitation of dystrobrevin isoforms. Within BLOC-1, dysbindin is engaged in interactions with three other subunits, named pallidin, snapin and muted. We herein provide evidence that the same 69-residue region of dysbindin that is sufficient for dystrobrevin binding in vitro also contains the binding sites for pallidin and snapin, and at least part of the muted-binding interface. Functional, histological and immunohistochemical analyses failed to detect any sign of muscle pathology in BLOC-1-deficient, homozygous pallid mice. Taken together, these results suggest that dysbindin assembled into BLOC-1 is not a physiological binding partner of the dystrobrevins, likely due to engagement of its dystrobrevin-binding region in interactions with other subunits.

Toll-like receptor polymorphisms and susceptibility to human disease

2008 ◽  
Vol 114 (5) ◽  
pp. 347-360 ◽  
Author(s):  
E. Ann Misch ◽  
Thomas R. Hawn
Keyword(s):  
Immune Response ◽  
Disease Susceptibility ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Genetic Studies ◽  
The Past ◽  
Molecular Studies ◽  
Cellular Immune ◽  
Lines Of Evidence

Although several lines of evidence suggest that variation in human inflammation is genetically controlled, the genes which regulate these responses are largely unknown. TLRs (Toll-like receptors) mediate recognition of microbes, regulate activation of the innate immune response and influence the formation of adaptive immunity. Cellular and molecular studies over the past several years have identified a number of common TLR polymorphisms that modify the cellular immune response and production of cytokines in vitro. In addition, human genetic studies suggest that some of these polymorphisms are associated with susceptibility to a spectrum of diseases. In this review, we summarize studies of common TLR polymorphisms and how this work is beginning to illuminate the influence of human variation on inflammation and disease susceptibility.

Differentiating closely affiliated Dehalococcoides lineages by a novel genetic marker identified via computational pangenome analysis

2021 ◽  
Author(s):  
Siyan Zhao ◽  
Chen Zhang ◽  
Matthew J. Rogers ◽  
Xuejie Zhao ◽  
Jianzhong He
Keyword(s):  
Amino Acid ◽  
Microbial Communities ◽  
Genetic Marker ◽  
Genetic Markers ◽  
Unknown Function ◽  
Computational Approach ◽  
Amino Acid Sequences ◽  
Reductive Dehalogenation ◽  
Wide Range

As a group, Dehalococcoides dehalogenate a wide range of organohalide pollutants but the range of organohalide compounds that can be utilized for reductive dehalogenation differs among the Dehalococcoides strains. Dehalococcoides lineages cannot be reliably disambiguated in mixed communities using typical phylogenetic markers, which often confounds bioremediation efforts. Here, we describe a computational approach to identify Dehalococcoides genetic markers with improved discriminatory resolution. Screening core genes from the Dehalococcoides pangenome for degree of similarity and frequency of 100% identity found a candidate genetic marker encoding a bacterial neuraminidase repeat (BNR)-containing protein of unknown function. This gene exhibits the fewest completely identical amino acid sequences and among the lowest average amino acid sequence identity in the core pangenome. Primers targeting BNR could effectively discriminate between 40 available BNR sequences ( in silico ) and 10 different Dehalococcoides isolates ( in vitro ). Amplicon sequencing of BNR fragments generated from 22 subsurface soil samples revealed a total of 109 amplicon sequence variants, suggesting a high diversity of Dehalococcoides distributed in environment. Therefore, the BNR gene can serve as an alternative genetic marker to differentiate strains of Dehalococcoides in complicated microbial communities. Importance The challenge of discriminating between phylogenetically similar but functionally distinct bacterial lineages is particularly relevant to the development of technologies seeking to exploit the metabolic or physiological characteristics of specific members of bacterial genera. A computational approach was developed to expedite screening of potential genetic markers among phylogenetically affiliated bacteria. Using this approach, a gene encoding a bacterial neuraminidase repeat (BNR)-containing protein of unknown function was selected and evaluated as a genetic marker to differentiate strains of Dehalococcoides , an environmentally relevant genus of bacteria whose members can transform and detoxify a range of halogenated organic solvents and persistent organic pollutants, in complex microbial communities to demonstrate the validity of the approach. Moreover, many apparently phylogenetically distinct, currently uncharacterized Dehalococcoides were detected in environmental samples derived from contaminated sites.

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