scholarly journals Genetics of susceptibility to tuberculosis in humans

2004 ◽  
Vol 61 (2) ◽  
Author(s):  
M.J. Newport ◽  
S. Nejentsev
Keyword(s):  
Complex Disease ◽  
Single Gene ◽  
Mycobacterial Infection ◽  
Disease Genes ◽  
Epidemiological Evidence ◽  
Host Genetic ◽  
Different Populations ◽  
Single Gene Defect ◽  
Increased Susceptibility ◽  
Made In

There is substantial epidemiological evidence that host genetic factors in part determine susceptibility to mycobacteria, and many approaches have been applied to identify the specific genes involved. These include the study of single genes in ‘knockout’ mouse models and rare human families in which increased susceptibility to mycobacterial infection segregates as a single gene defect. Several genes have now been studied in many different populations. This review gives an overview of the progress made in the field of genetic susceptibility to tuberculosis and highlights more generally some of the challenges involved in the identification of complex disease genes.

THE CAT, THE FLY AND THE BEETLE — WHY GENETICS NEEDS A SEMANTIC EDUCATION

2009 ◽  
Vol 03 (01) ◽  
pp. 77-90
Author(s):  
SANDOSH PADMANABHAN ◽  
CLAIRE HASTIE ◽  
CHRISTOPHER A. SAINSBURY ◽  
MARTIN W. MCBRIDE ◽  
JOHN M. CONNELL ◽  
...  
Keyword(s):  
Public Health ◽  
Plant Breeding ◽  
Genetic Basis ◽  
Complex Disease ◽  
Single Gene ◽  
Current Understanding ◽  
The Public ◽  
Monogenic Disorders ◽  
Disease Causation ◽  
Made In

Major advances have been made in the understanding of the genetic basis of diseases since Mendel's publication of the results of plant breeding experiments in 1866. To date these advances have been largely confined to the monogenic disorders — caused by mutations in a single gene. The public-health implications of these advances is relatively limited. In this review we explore our current understanding of the genetic basis of human traits and the reasons why current theories may account for the difficulties in identifying the genes for common diseases. We then postulate that semantic computing may be rightly poised to help understand complex disease causation, and explore the efforts that have been made to date to develop the necessary technological approach to the problem.

scholarly journals A gene co-association network regulating gut microbial communities in a Duroc pig population

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Antonio Reverter ◽  
Maria Ballester ◽  
Pamela A. Alexandre ◽  
Emilio Mármol-Sánchez ◽  
Antoni Dalmau ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Candidate Genes ◽  
Relative Abundance ◽  
Association Studies ◽  
Single Gene ◽  
Host Genome ◽  
Genome Wide Association Studies ◽  
Vaccine Response ◽  
Microbiome Composition ◽  
Host Genetic

Abstract Background Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately. Results In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance. Conclusions Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.

Structural and Genetic Aspects of Proline-rich Proteins

1987 ◽  
Vol 66 (2) ◽  
pp. 457-461 ◽  
Author(s):  
A. Bennick
Keyword(s):  
General Structure ◽  
Single Gene ◽  
Conclusive Evidence ◽  
In Vitro Translation ◽  
Binding Studies ◽  
Nmr Studies ◽  
Post Translational Modifications ◽  
Single Precursor ◽  
Made In

Considerable advances have been made in the genetics of salivary proline-rich proteins (PRP). The genes for acidic, basic, and glycosylated PRP have been cloned. They code for precursor proteins that all have an acidic N-terminal followed by proline-rich repeat sequences. Structural studies on secreted proteins have demonstrated that not only acidic but also some basic PRPs have this general structure. It is possible that mRNA for different PRP may have originated from a single gene by differential mRNA splicing, but post-translational cleavages of the primary translation product apparently also occur. In vitro translation of salivary gland mRNA results in a single precursor protein for acidic PRP. Such in vitro translated protein can be cleaved by salivary kallikrein, giving rise to two commonly secreted acidic PRPs, and kallikrein or kallikrein-like enzymes may be responsible for other post-translational cleavages of PRPs. Acidic as well as some basic PRPs are phosphorylated. A protein kinase has been demonstrated in salivary glands which phosphorylates the PRPs and other secreted salivary proteins in a cAMP and Ca2+-calmodulinindependent manner. Knowledge of the conformation of PRPs is limited. There is no conclusive evidence of polyproline-like structure in the proline-rich part of PRPs. Ca2+ binding studies on acidic PRPs indicate that there is interaction between the Ca2+ binding N-terminal end and the proline-rich C-terminal part. This interaction is relieved by modification of arginine side-chains. 1H, 32P, and 43Ca NMR studies have further elucidated the conformation of acidic PRPs in solution. Present evidence shows that salivary PRPs constitute a unique superfamily of proteins which pose a number of interesting questions concerning gene structure, pre- and post-translational modifications, and protein conformation.

Shaking the tree: mapping complex disease genes with linkage disequilibrium

The Lancet ◽  
2005 ◽  
Vol 366 (9492) ◽  
pp. 1223-1234 ◽  
Author(s):  
Lyle J Palmer ◽  
Lon R Cardon
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Disease ◽  
Disease Genes

scholarly journals Genotyping Error Detection Through Tightly Linked Markers

Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 1161-1173
Author(s):  
Guohua Zou ◽  
Deyun Pan ◽  
Hongyu Zhao
Keyword(s):  
Error Detection ◽  
Complex Disease ◽  
Disease Genes ◽  
Genotyping Error ◽  
Genotyping Errors ◽  
Detection Rates ◽  
Nuclear Families ◽  
Additional Information ◽  
Number Of Children ◽  
Multiple Markers

Abstract The identification of genotyping errors is an important issue in mapping complex disease genes. Although it is common practice to genotype multiple markers in a candidate region in genetic studies, the potential benefit of jointly analyzing multiple markers to detect genotyping errors has not been investigated. In this article, we discuss genotyping error detections for a set of tightly linked markers in nuclear families, and the objective is to identify families likely to have genotyping errors at one or more markers. We make use of the fact that recombination is a very unlikely event among these markers. We first show that, with family trios, no extra information can be gained by jointly analyzing markers if no phase information is available, and error detection rates are usually low if Mendelian consistency is used as the only standard for checking errors. However, for nuclear families with more than one child, error detection rates can be greatly increased with the consideration of more markers. Error detection rates also increase with the number of children in each family. Because families displaying Mendelian consistency may still have genotyping errors, we calculate the probability that a family displaying Mendelian consistency has correct genotypes. These probabilities can help identify families that, although showing Mendelian consistency, may have genotyping errors. In addition, we examine the benefit of available haplotype frequencies in the general population on genotyping error detections. We show that both error detection rates and the probability that an observed family displaying Mendelian consistency has correct genotypes can be greatly increased when such additional information is available.

Complex cardiovascular diseases: the genetics of arterial hypertension

ESC CardioMed ◽  
2018 ◽  
pp. 732-736
Author(s):  
Georg Ehret
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Genetic Variants ◽  
Single Gene ◽  
Primary Hypertension ◽  
Genetic Types ◽  
Risk Variants ◽  
Cardiovascular Risk Prediction ◽  
Single Gene Defect ◽  
Substantial Extent

Arterial hypertension appears as two genetic types: primary hypertension is to a substantial extent determined by a large number of genetic risk variants, whereas rare patients with a familial hypertensive syndrome have a single gene defect that drives the elevated blood pressure. The familial hypertensive syndromes have been instrumental in highlighting blood pressure-regulating pathways that almost exclusively cluster in the kidney and in the mineralocorticoid pathways. Conversely, hundreds or more genetic variants cause the genetic component of primary hypertension and each risk variant causes a small blood pressure increase. The blood vessels appear to be one tissue in which these variants principally act and surprisingly there is little overlap with pathways of kidney and hormone pathways. Genetic testing is useful for the rare familial hypertensive syndrome, but in primary hypertension cardiovascular risk prediction can currently not be improved by genotyping.

scholarly journals “Touching Triton”:

2016 ◽  
Vol 78 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Madelene Loftin ◽  
Kelly East ◽  
Adam Hott ◽  
Neil Lamb
Keyword(s):  
Student Performance ◽  
Complex Disease ◽  
Disease Risk ◽  
Single Gene ◽  
Mendelian Inheritance ◽  
Serious Game ◽  
Genetic Technologies ◽  
Genetic And Environmental Factors ◽  
High Level ◽  
Unrealistic Expectations

Life science classrooms often emphasize the exception to the rule when it comes to teaching genetics, focusing heavily on rare single-gene and Mendelian traits. By contrast, the vast majority of human traits and diseases are caused by more complicated interactions between genetic and environmental factors. Research indicates that students have a deterministic view of genetics, generalize Mendelian inheritance patterns to all traits, and have unrealistic expectations of genetic technologies. The challenge lies in how to help students analyze complex disease risk with a lack of curriculum materials. Providing open access to both content resources and an engaging storyline can be achieved using a “serious game” model. “Touching Triton” was developed as a serious game in which students are asked to analyze data from a medical record, family history, and genomic report in order to develop an overall lifetime risk estimate of six common, complex diseases. Evaluation of student performance shows significant learning gains in key content areas along with a high level of engagement.

scholarly journals Disease Ionomics: Understanding the Role of Ions in Complex Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8646
Author(s):  
Yan Zhang ◽  
Yinzhen Xu ◽  
Lin Zheng
Keyword(s):  
Complex Disease ◽  
Dynamic Network ◽  
Complex Diseases ◽  
Living Organism ◽  
Future Trends ◽  
Pathological Conditions ◽  
Systematic Understanding ◽  
Elemental Profiling ◽  
Made In

Ionomics is a novel multidisciplinary field that uses advanced techniques to investigate the composition and distribution of all minerals and trace elements in a living organism and their variations under diverse physiological and pathological conditions. It involves both high-throughput elemental profiling technologies and bioinformatic methods, providing opportunities to study the molecular mechanism underlying the metabolism, homeostasis, and cross-talk of these elements. While much effort has been made in exploring the ionomic traits relating to plant physiology and nutrition, the use of ionomics in the research of serious diseases is still in progress. In recent years, a number of ionomic studies have been carried out for a variety of complex diseases, which offer theoretical and practical insights into the etiology, early diagnosis, prognosis, and therapy of them. This review aims to give an overview of recent applications of ionomics in the study of complex diseases and discuss the latest advances and future trends in this area. Overall, disease ionomics may provide substantial information for systematic understanding of the properties of the elements and the dynamic network of elements involved in the onset and development of diseases.

scholarly journals Analysis of Topological Parameters of Complex Disease Genes Reveals the Importance of Location in a Biomolecular Network

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 143 ◽  
Author(s):  
Xiaohui Zhao ◽  
Zhi-Ping Liu
Keyword(s):  
Complex Disease ◽  
Significant Degree ◽  
Clustering Coefficient ◽  
Gene Location ◽  
Disease Genes ◽  
Complex Disorders ◽  
Topological Parameters ◽  
Topological Features ◽  
Disease Mechanisms ◽  
Biomolecular Network

Network biology and medicine provide unprecedented opportunities and challenges for deciphering disease mechanisms from integrative viewpoints. The disease genes and their products perform their dysfunctions via physical and biochemical interactions in the form of a molecular network. The topological parameters of these disease genes in the interactome are of prominent interest to the understanding of their functionality from a systematic perspective. In this work, we provide a systems biology analysis of the topological features of complex disease genes in an integrated biomolecular network. Firstly, we identify the characteristics of four network parameters in the ten most frequently studied disease genes and identify several specific patterns of their topologies. Then, we confirm our findings in the other disease genes of three complex disorders (i.e., Alzheimer’s disease, diabetes mellitus, and hepatocellular carcinoma). The results reveal that the disease genes tend to have a higher betweenness centrality, a smaller average shortest path length, and a smaller clustering coefficient when compared to normal genes, whereas they have no significant degree prominence. The features highlight the importance of gene location in the integrated functional linkages.

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