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Basal Cell Nevus Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Priyanka Chhadva, Pete Setabutr
BCNS has a variable phenotypic expression, which reflects as differences in penetrance. This also contributes to the variations in the effects of environmental factors, modifier genes, and expression of various mutations within the same gene. Therefore, there is a variety of genetic and clinical manifestations expressed in patients and their family members affected by BCNS [7,25].
Liver Disease in Cystic Fibrosis
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Carla Colombo, Pier Maria Battezzati, Clara Fredella, Andrea Crosignani
A few genes encoding elements of host defense have been also considered, including the TGF-beta cytokine and mannose-binding lectin, a protein of the innate immune system.33 Candidate modifiers genes or chromosomal regions for CF-liver disease and the presumed mechanisms of liver damage are reported in Tables 2 and 3. Studies so far carried out on relatively small number of patients have indicated an increased frequency of heterozygous carriers for the αl-antitripsine deficiency Ζ allele and an allelic variant of mannose-binding lectin among CF patients with liver disease.33,34 There is also evidence that the structural deficiency variants of MBL2 and high-expression variant of the TGF-beta may interact with the proteinase inhibitor gene mutations and potentiate their adverse effects.34 The frequency of a particular polymorphism of the glutathione S-transferase P1 was also found to be higher in CF patients with liver disease. The presumed mechanism of liver damage may therefore differ depending on type of modifier gene involved (Table 3).
Respiratory Medicine
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Colin Wallis, Helen Spencer, Sam Sonnappa
Cystic fibrosis (CF) is an autosomal recessive disease caused by a gene defect on the long arm of chromosome 7. The most common mutation in Caucasians is ΔF508, accounting for some 70% of the gene mutations seen in Northern Europeans. Over 1,000 other mutations have been described, a number of which are specific to other ethnic groups. Although there is some evidence of a phenotype – genotype correlation especially in relation to pancreatic sufficiency, the phenotype is unpredictable. A number of environmental factors as well as phenotypical impact from modifier genes will all influence the final clinical phenotype.
The desaturase1 gene affects reproduction before, during and after copulation in Drosophila melanogaster
Published in Journal of Neurogenetics, 2019
Tetsuya Nojima, Isabelle Chauvel, Benjamin Houot, François Bousquet, Jean-Pierre Farine, Claude Everaerts, Daisuke Yamamoto, Jean-François Ferveur
Given that each gene establishes a network with multiple genetic partners, any defect induced in a single gene of the network could either be enhanced or compensated by the activity of other interconnected genes (Greenspan, 2001). Given the almost unlimited number of interactions and networks, the whole genome could resemble an infinite network of gene networks (without mentioning the extra layer of complexity provided by epigenetic interactions). The concept of modifier genes has been postulated for a long time (Gardner & Stott, 1951), and has been validated by the more recent transcriptomics methods which allowed researchers to quantify inter-genes relationship, and detect the potential involvement of each genetic unit independently of its interconnected partners. Measuring the simultaneous variation of potentially connected genes is a useful method to reveal the real involvement of each gene in the phenotype of interest, independently of compensatory or enhancing mechanisms (Houot, Fraichard, Greenspan, & Ferveur, 2012; Toma, White, Hirsch, & Greenspan, 2002). Transcriptomics also offered a breakthrough to compare the simultaneous variation of multiple genes between (i) natural populations living in different environments (Greenspan, 1997; Kent, Daskalchuk, Cook, Sokolowski, & Greenspan, 2009; Sawyer et al., 1997) , and (ii) laboratory lines subjected experimental selection during many generations (Dierick & Greenspan, 2006; Houot et al., 2012).
Krüppel-Like Factor 1 Gene Mutations in Thalassemia Patients from North Iran: Report of a New Mutation Associated with β-Thalassemia Intermedia
Published in Hemoglobin, 2019
Ahmad Tamaddoni, Sahar Khabaz Astaneh, Reza Tabaripour, Haleh Akhavan-Niaki
In most cases, disease phenotype is best predicted by assessment of the β-globin gene mutation itself. However, the situation becomes complicated as phenotypes may vary according to the type of β-globin gene mutation or polymorphisms in the β-globin gene cluster as is the case of γ-globin promoter [9–12]. Alternatively, modifier genes may also influence β-thal phenotypes [13,14]. One of the important modifier genes is KLF1 (Krüppel-like factor 1). The KLF1 gene comprises three exons spanning 2782 bp on chromosome 19p13.13 that encodes a zinc finger protein with 362 amino acids, and acts as hematopoietic-specific transcription factor, which binds to the CCACACCCT DNA sequence on the HBB gene promoter, and subsequently increases the expression level of adult β-globin [15]. Some diseases that have been shown to be associated with KLF1 genes are dyserythropoietic anemia and hereditary persistence of fetal Hb (HPFH) [16,17]. The aim of this study was to investigate the presence of possible KLF1 gene mutations in patients with a β-thal minor phenotype or β-thal intermedia (β-TI), with no mutations on the HBA and HBB genes.
Perry disease: recent advances and perspectives
Published in Expert Opinion on Orphan Drugs, 2019
Takayasu Mishima, Shinsuke Fujioka, Yoshio Tsuboi
Monogenic disorders are affected by modifier genes that modulate the phenotypic manifestation of target genes. These modifier genes do not function by themselves, but rather act with other genes in a network. Most phenotypes, however, result from the complex actions of multiple genes and environmental factors [60]. This phenomenon has recently been reported for other genetic disorders [61,62]. The role of modifier genes is likely important for phenotypic manifestation of Perry disease, but their role has not been fully clarified. Therefore, further studies will be needed to understand the epistatic regulation of Perry disease pathogenesis.