Abstract:
:In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value ≤ 5 × 10-6). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 × 10-7 and p < 1 × 10-20). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Ziliotto N,Marchetti G,Scapoli C,Bovolenta M,Meneghetti S,Benazzo A,Lunghi B,Balestra D,Laino LA,Bozzini N,Guidi I,Salvi F,Straudi S,Gemmati D,Menegatti E,Zamboni P,Bernardi Fdoi
10.3389/fgene.2019.00573subject
Has Abstractpub_date
2019-06-26 00:00:00pages
573issn
1664-8021journal_volume
10pub_type
杂志文章abstract::Several authors have acknowledged that testing mediational hypotheses between treatments, genes, physiological measures, and behaviors may substantially advance our understanding of how these associations operate. In psychiatric research, the costs of measuring the putative mediator or the outcome can be prohibitive. ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2011.00075
更新日期:2011-10-31 00:00:00
abstract::Mosquitoes are one of the deadliest animals on earth because of their ability to transmit a wide range of human pathogens. Traditional mosquito control methods use chemical insecticides, but with dwindling long-term effectiveness and negative effects on the environment, microbial forms of control have become common al...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.504354
更新日期:2020-10-07 00:00:00
abstract::Identifying driver genes that contribute to cancer progression from numerous passenger genes, although a central goal, is a major challenge. The protein-protein interaction network provides convenient and reasonable assistance for driver gene discovery. Random walk-based methods have been widely used to prioritize nod...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00377
更新日期:2020-04-28 00:00:00
abstract::Cardiovascular diseases such as atherosclerosis are one of the leading causes of morbidity and mortality worldwide. The clinical manifestations of atherosclerosis, which include heart attack and stroke, occur several decades after initiation of the disease and become more severe with age. Inflammation of blood vessels...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2014.00422
更新日期:2014-12-10 00:00:00
abstract::Plant basic helix-loop-helix (bHLH) transcription factors are involved in the regulation of various biological processes in plant growth, development, and stress response. However, members of this important transcription factor family have not been systematically identified and analyzed in pepper (Capsicum annuum L.)....
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.570156
更新日期:2020-09-25 00:00:00
abstract::The genetic diversity of the sheep breeds in the Arab countries might be considered to be a mirror of the ecology of the region. In this study, the genetic structure and diversity of sheep breeds from Saudi Arabia (Harri, Najdi, Naemi, Arb, and Rufidi) and Awassi sheep from Jordan as an out-group were investigated usi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00408
更新日期:2018-09-25 00:00:00
abstract::Pervasive allelic variation at both gene and single nucleotide level (SNV) between individuals is commonly associated with complex traits in humans and animals. Allele-specific expression (ASE) analysis, using RNA-Seq, can provide a detailed annotation of allelic imbalance and infer the existence of cis-acting transcr...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00863
更新日期:2019-09-19 00:00:00
abstract::Bamboo is one of the fastest-growing non-timber forest plants. Moso bamboo (Phyllostachys edulis) is the most economically valuable bamboo in Asia, especially in China. With the release of the whole-genome sequence of moso bamboo, there are increasing demands for refined annotation of bamboo genes. Recently, large amo...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00574
更新日期:2018-11-27 00:00:00
abstract::Oxidative stress is one of the crucial mediators of varicocele-related male infertility. Recently, roles of long noncoding RNAs (lncRNAs) in oxidative stress have begun to emerge, however, little is known about their role in male infertility. The aim of this study was to determine the role of lncRNA SLC7A11-AS1 in var...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.01015
更新日期:2020-09-11 00:00:00
abstract::Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In th...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00267
更新日期:2015-08-18 00:00:00
abstract::Selective breeding programs aiming to increase the productivity and profitability of the sheep meat industry use elite, progeny tested sires. The broad genetic traits of primary interest in the progeny of these sires include skeletal muscle yield, fat content, eating quality, and reproductive efficiency. Natural mutat...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00164
更新日期:2012-08-29 00:00:00
abstract::The unique structure of the X chromosome shaped by evolution has led to the present gender-specific genetic differences, which are not shared by its counterpart, the Y chromosome, and neither by the autosomes. In males, recombination between the X and Y chromosomes is limited to the pseudoautosomal regions, PAR1 and P...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.00926
更新日期:2020-09-17 00:00:00
abstract:Background:This study aimed to investigate the genetic causes of hypohidrotic ectodermal dysplasia (HED) in two families and elucidate the molecular pathogenesis of HED in Chinese Han patients. Methods:Whole-exome sequencing (WES) was used to screen HED-related genes in two family members, followed by confirmatory San...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00021
更新日期:2020-02-04 00:00:00
abstract::Homozygous and compound heterozygous mutations in GNB5 gene have been associated with a wide spectrum of clinical presentations, ranging from neurodevelopmental issues with or without cardiac arrhythmia (LADCI) to severe developmental delay with epileptic encephalopathy, retinal dystrophy, and heart rhythm abnormaliti...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00399
更新日期:2020-05-13 00:00:00
abstract::It is believed that recombination in meiosis serves to reshuffle genetic material from both parents to increase genetic variation in the progeny. At the same time, the number of crossovers is usually kept at a very low level. As a consequence, many organisms need to make the best possible use from the one or two cross...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00609
更新日期:2018-12-12 00:00:00
abstract::The goal of any plant breeding program is to improve quality of a target crop. Crop quality is a comprehensive feature largely determined by biological background. To improve the quality parameters of crops grown for the production of fiber, a functional approach was used to search for genes suitable for the effective...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.589881
更新日期:2020-11-12 00:00:00
abstract::Previous efforts to characterize conservation between the human and mouse genomes focused largely on sequence comparisons. These studies are inherently limited because they don't account for gene structure differences, which may exist despite genomic sequence conservation. Recent high-throughput transcriptome studies ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2013.00183
更新日期:2013-09-26 00:00:00
abstract::The development of whole-genome bisulfite sequencing (WGBS) has resulted in a number of exciting discoveries about the role of DNA methylation leading to a plethora of novel testable hypotheses. Methods for constructing sodium bisulfite-converted and amplified libraries have recently advanced to the point that the bot...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00341
更新日期:2014-10-21 00:00:00
abstract::Satellite DNA is a class of repetitive sequences that are organized in long arrays of tandemly repeated units in most eukaryotes. Long considered as selfish DNA, satellite sequences are now proposed to contribute to genome integrity. Despite their potential impact on the architecture and evolution of the genome, satel...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00557
更新日期:2020-06-05 00:00:00
abstract::Behavioral and cognitive traits have a genetic component even though contributions from individual genes and genomic loci are in many cases modest. Changes in the environment can alter genotype-phenotype relationships. Space travel, which includes exposure to ionizing radiation, constitutes environmental challenges an...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00404
更新日期:2018-10-09 00:00:00
abstract::Tolerance to infections is defined as the ability of a host to limit the impact of a given pathogen burden on host performance. Uncoupling resistance and tolerance is a challenge, and there is a need to be able to separate them using specific trait recording or statistical methods. We present three statistical methods...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00262
更新日期:2012-12-14 00:00:00
abstract::The switch to a modern lifestyle in recent decades has coincided with a rapid increase in prevalence of obesity and other diseases. These shifts in prevalence could be explained by the release of genetic susceptibility for disease in the form of gene-by-environment (GxE) interactions. Yet, the detection of interaction...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00225
更新日期:2014-07-21 00:00:00
abstract::Understanding the processes that cause speciation is a key aim of evolutionary biology. Lineages or biomes that exhibit recent and rapid diversification are ideal model systems for determining these processes. Species rich biomes reported to be of relatively recent origin, i.e., since the beginning of the Miocene, inc...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2013.00192
更新日期:2013-10-09 00:00:00
abstract::Abundant genomic heterozygosity can be found in wild strains of the budding yeast Saccharomyces cerevisiae isolated from industrial and clinical environments. The extent to which heterozygosity influences the phenotypes of these isolates is not fully understood. One such case is the PE-2/JAY270 strain, a natural hybri...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00782
更新日期:2019-09-11 00:00:00
abstract::Diabetes mellitus represents a group of complex metabolic diseases that result in impaired glucose homeostasis, which includes destruction of β-cells or the failure of these insulin-secreting cells to compensate for increased metabolic demand. Despite a strong interest in characterizing the transcriptome of the differ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2014.00200
更新日期:2014-07-01 00:00:00
abstract::The study of microorganisms that pervade each and every part of this planet has encountered many challenges through time such as the discovery of unknown organisms and the understanding of how they interact with their environment. The aim of this review is to take the reader along the timeline and major milestones tha...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2015.00348
更新日期:2015-12-17 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal cancer, with a poor prognosis. Our study aimed to identify a biomarker that is significantly associated with ccRCC prognosis and novel immunotherapeutic targets, as well as some novel molecular drugs for ccRCC. Based on th...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00810
更新日期:2020-08-18 00:00:00
abstract::Fragile X syndrome (FXS) is mostly caused by two distinct events that occur in the FMR1 gene (Xq27.3): an expansion above 200 repeats of a CGG triplet located in the 5'UTR of the gene, and methylation of the cytosines located in the CpG islands upstream of the CGG repeats. Here, we describe two unrelated families with...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00442
更新日期:2018-11-02 00:00:00
abstract::At the time of translation, nascent proteins are thought to be sorted into their final subcellular localization sites, based on the part of their amino acid sequences (i.e., sorting or targeting signals). Thus, it is interesting to computationally recognize these signals from the amino acid sequences of any given prot...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.607812
更新日期:2020-11-25 00:00:00
abstract::Commensal gut bacteria in many species including flies are integral part of their host, and are known to influence its development and homeostasis within generation. Here we report an unexpected impact of host-microbe interactions, which mediates multi-generational, non-Mendelian inheritance of a stress-induced phenot...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00027
更新日期:2014-02-25 00:00:00