Search results for "Genetics"

A low-frequency haplotype spanning SLX4/FANCP constitutes a new risk locus for early-onset breast cancer (<60 years) and is associated with reduce…

2017

Only a fraction of breast cancer (BC) cases can be yet explained by mutations in genes or genomic variants discovered in linkage, genome-wide association and sequencing studies. The known genes entailing medium or high risk for BC are strongly enriched for a function in DNA double strand repair. Thus, aiming at identifying low frequency variants conferring an intermediate risk, we here investigated 17 variants (MAF: 0.01-0.1) in 10 candidate genes involved in DNA repair or cell cycle control. In an exploration cohort of 437 cases and 1189 controls, we show the variant rs3810813 in the SLX4/FANCP gene to be significantly associated with both BC (≤60 years; OR = 2.6(1.6-3.9), p = 1.6E-05) and…

2018

Secondary sexual trait expression can be influenced by fixed individual factors (such as genetic quality) as well as by dynamic factors (such as age and environmentally induced gene expression) that may be associated with variation in condition or quality. In particular, melanin-based traits are known to relate to condition and there is a well-characterized genetic pathway underpinning their expression. However, the mechanisms linking variable trait expression to genetic quality remain unclear. One plausible mechanism is that genetic quality could influence trait expression via differential methylation and differential gene expression. We therefore conducted a pilot study examining DNA meth…

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

2021

PURPOSE: ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized.METHODS: International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing.RESULTS: We identified 13 individuals with heterozygous…

Caretakers and Gatekeepers

2017

It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis. Keywords: gatekeeper genes; caretaker genes; tumor suppressor genes; cell cycle; hereditary syndromes

Update on oral-facial-digital syndromes (OFDS)

2016

Oral-facial-digital syndromes (OFDS) represent a heterogeneous group of rare developmental disorders affecting the mouth, the face and the digits. Additional signs may involve brain, kidneys and other organs thus better defining the different clinical subtypes. With the exception of OFD types I and VIII, which are X-linked, the majority of OFDS is transmitted as an autosomal recessive syndrome. A number of genes have already found to be mutated in OFDS and most of the encoded proteins are predicted or proven to be involved in primary cilia/basal body function. Preliminary data indicate a physical interaction among some of those proteins and future studies will clarify whether all OFDS prote…

Ethical Aspects of Nuclear and Mitochondrial DNA Transfer

2016

Somatic cell nuclear transfer (SCNT) (cloning), as a reproductive or therapeutic method, and mitochondrial DNA transfer, as a method to prevent the transmission of mitochondrial diseases, are analyzed in this paper from a bioethics perspective. The licit purpose of being able to treat certain diseases, as in the case of SCNT, cannot justify, in any case, resorting to illicit means such as the manipulation, selection, and elimination of human embryos in the blastocyst phase, by using cell lines obtained from them. Crossing this line paves the way (as utilitarian ethics advocates) to assuming any cost in scientific experimentation so long as satisfactory results are obtained. With mitochondr…

Epigenetic regulation of DNA repair genes and implications for tumor therapy

2017

DNA repair represents the first barrier against genotoxic stress causing metabolic changes, inflammation and cancer. Besides its role in preventing cancer, DNA repair needs also to be considered during cancer treatment with radiation and DNA damaging drugs as it impacts therapy outcome. The DNA repair capacity is mainly governed by the expression level of repair genes. Alterations in the expression of repair genes can occur due to mutations in their coding or promoter region, changes in the expression of transcription factors activating or repressing these genes, and/or epigenetic factors changing histone modifications and CpG promoter methylation or demethylation levels. In this review we …

Whole genome sequences reveal Vibrio hemicentroti Kim et al. 2013 as a later heterotypic synonym of Vibrio splendidus (Beijerinck 1900) Baumann et al…

2017

The synonymy between Vibrio hemicentroti Kim et al. 2013 and Vibrio splendidus (Beijerinck 1900) Baumann et al. 1981 was suggested after a recent multilocus sequence analysis of the Splendidus clade, which included the type strains of both species. To clarify their status, we have determined genomic indexes from whole genome sequences of strains V. hemicentroti CECT 8714T and V. splendidus NCCB 53037T. Average Nucleotide Identities of 96.0–96.7 % and an in silico DNA–DNA hybridization value of 70.2 %, as well as similarity levels of selected housekeeping gene sequences support the consideration of V. hemicentroti as a later heterotypic synonym of V. splendidus .

2015

Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation pa…

5' and 3' RACE Method to Obtain Full-Length 5' and 3' Ends of Ciona robusta Macrophage Migration Inhibitory Factors Mif1 and Mif2 cDNA

2019

The 5' and 3' RACE is a method to obtain full-length 5' and 3' ends of cDNA using known cDNA sequences from expressed sequence tags (ESTs), subtracted cDNA, differential display, or library screening. Here is described the identification of full-length 5' and 3' ends of Ciona robusta Mif1 and Mif2 cDNA by using 5' and 3' RACE method.