scholarly journals Causal Genomic and Epigenomic Network Analysis emerges as a New Generation of Genetic Studies of Complex Diseases

2015 ◽  
Vol 03 (02) ◽  
Author(s):  
Momiao Xiong
Keyword(s):  
Network Analysis ◽  
Complex Diseases ◽  
Genetic Studies ◽  
New Generation

scholarly journals A Systematic Review on Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders

2020 ◽  
Author(s):  
Sana Amanat ◽  
Teresa Requena ◽  
Jose Antonio Lopez-Escamez
Keyword(s):  
Systematic Review ◽  
Candidate Genes ◽  
Rare Variants ◽  
De Novo ◽  
Complex Diseases ◽  
De Novo Mutations ◽  
Genetic Studies ◽  
Complex Disorders ◽  
Extreme Phenotype ◽  
Age Related

Exome sequencing has been commonly used in rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) to search for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to heritability in complex clinical traits. We have conducted a systematic review to find evidence supporting the use of EP strategies to search for rare variants in genetic studies of complex diseases, to highlight the contribution of rare variation to the genetic structure of multiallelic conditions. After performing the quality assessment of the retrieved records, we selected 19 genetic studies considering EP to demonstrate genetic association. All the studies successfully identified several rare variants, de novo mutations and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach in patients with an early onset of the disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.

scholarly journals Identification of Key Genes Affecting Porcine Fat Deposition Based on Co-Expression Network Analysis of Weighted Genes

2021 ◽  
Author(s):  
Kai Xing ◽  
Huatao Liu ◽  
Fengxia Zhang ◽  
Yibing Liu ◽  
Yong Shi ◽  
...  
Keyword(s):  
Network Analysis ◽  
Production Efficiency ◽  
Fat Deposition ◽  
Rna Seq ◽  
Genetic Studies ◽  
Gene Expression Matrix ◽  
Differential Gene ◽  
Key Genes ◽  
Strong Candidate ◽  
Molecular Regulatory Mechanisms

Abstract Background: Fat deposition is an important economic consideration for pig production. The amount of fat deposition in pigs seriously affects production efficiency, quality, and reproductive performance, while also affecting consumers' choice of pork. Weighted gene co-expression network analysis (WGCNA) has been shown to be effective in pig genetic studies. Therefore, this study aimed to identify modules that co-express genes associated with fat deposition in pigs (Songliao black and Landrace breeds) with extreme levels of backfat (high and low), and to identify the central genes in each of these modules. Results: We used RNA-seq of different pig tissues to construct a gene expression matrix consisting of 12 862 genes from 36 samples. Eleven co-expression modules were identified using WGCNA; the number of genes in these modules ranged from 39 to 3363. We found four co-expression modules were significantly correlated with backfat thickness. A total of 14 genes ( RAD9A , IGF2R , SCAP , TCAP , DGAT1 , GPS2 , IGF1 , MAPK8 , FABP , FABP5 , LEPR , UCP3 , APOF , and FASN ) were found to be related to fat deposition. Conclusions: RAD9A , TCAP , GPS2 , and APOF were found to be the key genes in the four modules according to the degree of gene connectivity. Combining the results of differential gene analysis, APOF was proposed as a strong candidate gene for body size traits. This study explores the key genes that regulate porcine fat deposition and lays the foundation for further research into the molecular regulatory mechanisms behind porcine fat deposition.

scholarly journals A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 987
Author(s):  
Sana Amanat ◽  
Teresa Requena ◽  
Jose Antonio Lopez-Escamez
Keyword(s):  
Systematic Review ◽  
Candidate Genes ◽  
Rare Variants ◽  
De Novo ◽  
Complex Diseases ◽  
Genetic Studies ◽  
Complex Disorders ◽  
Extreme Phenotype ◽  
Disease Spectrum ◽  
Age Related

Exome sequencing has been commonly used to characterize rare diseases by selecting multiplex families or singletons with an extreme phenotype (EP) and searching for rare variants in coding regions. The EP strategy covers both extreme ends of a disease spectrum and it has been also used to investigate the contribution of rare variants to the heritability of complex clinical traits. We conducted a systematic review to find evidence supporting the use of EP strategies in the search for rare variants in genetic studies of complex diseases and highlight the contribution of rare variations to the genetic structure of polygenic conditions. After assessing the quality of the retrieved records, we selected 19 genetic studies considering EPs to demonstrate genetic association. All studies successfully identified several rare or de novo variants, and many novel candidate genes were also identified by selecting an EP. There is enough evidence to support that the EP approach for patients with an early onset of a disease can contribute to the identification of rare variants in candidate genes or pathways involved in complex diseases. EP patients may contribute to a better understanding of the underlying genetic architecture of common heterogeneous disorders such as tinnitus or age-related hearing loss.

Nonreplication in Genetic Studies of Complex Diseases-Lessons Learned From Studies of Osteoporosis and Tentative Remedies

2004 ◽  
Vol 20 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Hui Shen ◽  
Yongjun Liu ◽  
Pengyuan Liu ◽  
Robert R Recker ◽  
Hong-Wen Deng
Keyword(s):  
Complex Diseases ◽  
Lessons Learned ◽  
Genetic Studies

scholarly journals Phenotype Heritability in holobionts: An Evolutionary Model

2020 ◽  
Author(s):  
Saúl Huitzil ◽  
Santiago Sandoval-Motta ◽  
Alejandro Frank ◽  
Maximino Aldana
Keyword(s):  
Regulatory Networks ◽  
Evolutionary Model ◽  
Complex Diseases ◽  
Missing Heritability ◽  
Phenotypic Characteristics ◽  
Genetic Studies ◽  
Genomic Signatures ◽  
High Incidence ◽  
Gene Regulatory ◽  
Missing Heritability Problem

AbstractMany complex diseases are expressed with high incidence only in certain populations. Genealogy studies determine that these diseases are inherited with a high probability. However, genetic studies have been unable to identify the genomic signatures responsible for such heritability, as identifying the genetic variants that make a population prone to a given disease is not enough to explain its high occurrence within the population. This gap is known as the missing heritability problem. We know that the microbiota plays a very important role in determining many important phenotypic characteristics of its host, in particular, the complex diseases for which the missing heritability occurs. Therefore, when computing the heritability of a phenotype it is important to consider not only the genetic variation in the host but also in its microbiota. Here we test this hypothesis by studying an evolutionary model based on gene regulatory networks. Our results show that the holobiont (the host plus its microbiota) is capable of generating a much larger variability than the host alone, greatly reducing the missing heritability of the phenotype. This result strongly suggests that a considerably large part of the missing heritability can be attributed to the microbiome.

scholarly journals A systems biology approach to genetic studies of complex diseases

FEBS Letters ◽  
2005 ◽  
Vol 579 (24) ◽  
pp. 5325-5332 ◽  
Author(s):  
Momiao Xiong ◽  
Carol A. Feghali-Bostwick ◽  
Frank C Arnett ◽  
Xiaodong Zhou
Keyword(s):  
Systems Biology ◽  
Complex Diseases ◽  
Genetic Studies

scholarly journals Decoding and modulating multiregional communication in the mood processing network

2019 ◽  
Author(s):  
Shaoyu Qiao ◽  
J. Isaac Sedillo ◽  
Kevin A. Brown ◽  
Breonna Ferrentino ◽  
Bijan Pesaran
Keyword(s):  
Network Analysis ◽  
Neural Activity ◽  
Network Communication ◽  
Great Promise ◽  
Causal Network ◽  
Neural Decoding ◽  
Brain Disorders ◽  
Functional Brain Networks ◽  
New Generation ◽  
Processing Network

ABSTRACTNeural decoding and neuromodulation technologies hold great promise for treating mood and other brain disorders in next-generation therapies that manipulate functional brain networks. Here, we perform a novel causal network analysis to decode multiregional communication in the primate mood processing network and determine how neuromodulation, short-burst tetanic microstimulation (SB-TetMS), alters multiregional network communication. The causal network analysis revealed a mechanism of network excitability that regulates when a sender stimulation site communicates with receiver sites. Decoding network excitability from neural activity at modulator sites predicted sender-receiver communication while SB-TetMS neuromodulation specifically disrupted sender-receiver communication. These results reveal specific network mechanisms of multiregional communication and suggest a new generation of brain therapies that combine neural decoding to predict multiregional communication with neuromodulation to disrupt multiregional communication.One Sentence SummaryDecoding and modulating multiregional network communication.

scholarly journals Mutations in the ghrelin receptor gene GHSR in congenital hypopituitarism

2017 ◽  
Vol 63 (2) ◽  
pp. 98-102
Author(s):  
Elena B. Bashnina ◽  
Olga S. Berseneva ◽  
Andrey S. Glotov ◽  
Oleg S. Glotov ◽  
Mariia E. Turkunova ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Molecular Genetic ◽  
Pituitary Hormones ◽  
Malabsorption Syndrome ◽  
Hormone Deficiency ◽  
Genetic Studies ◽  
Ghrelin Receptor ◽  
New Generation Sequencing ◽  
New Generation ◽  
Congenital Hypopituitarism

The results of molecular genetic studies indicate the potential involvement of ghrelin in the pathogenesis of some dwarfism forms. However, in the case of isolated somatotropin insufficiency, mutations in the ghrelin receptor gene are a rare cause of the disease. The article describes a case of identification, based on new generation sequencing (NGS) using the AmpliSeq technology, of a functionally significant marker ― the c.837C>A substitution in the ghrelin receptor gene GHSR (OMIM: 615925) in the heterozygous state in two sisters with isolated growth hormone deficiency and the clinical picture of malabsorption syndrome. We have supposed that mutations in the GHSR gene may be an etiological factor of isolated somatotropin insufficiency in a combination with malabsorption syndrome and eating disorders. Mutations in the GHSR gene enable predicting the development of somatotropin insufficiency not associated with abnormality of other pituitary hormones.

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