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Public health and genetics
Published in Siân Griffiths, Davide J Hunter, Sir Kenneth Calman, New Perspectives in Public Health, 2017
Mark Kroese, Ron Zimmern, Simon Sanderson
The exact definition of a genetic test is still debated but the term ‘genetic test’ should be regarded as a shorthand to describe a test to detect (a) a particular genetic variant (or set of variants), (b) for a particular disease, (c) in a particular population and (d) for a particular purpose (Kroese et al. 2004). The specification of all these factors is essential for test evaluation since validity will be to a large extent determined by them. The predictive value of tests will be dependent, for example, on the prevalence of the disease in the population; it is also well known that many individual variants on a gene (allelic heterogeneity) or that variants in more than one gene (locus heterogeneity) may give rise to the same disease. A genetic test should also be considered as part of an integrated package of care rather than as an isolated investigation.
Genetic Factors in Parkinson's Disease
Published in Lucien Côté, Lola L. Sprinzeles, Robin Elliott, Austin H. Kutscher, Parkinson's Disease and Quality of Life, 2014
In conclusion, there is now compelling evidence that PD is a genetic disorder. Families with multiple cases of PD are now well documented. Modern techniques of molecular analysis of DNA make it possible to map the location of the responsible gene mutation on the human genome in these families. The effort to map the gene is now underway and it appears probable that a gene locus will soon be found. Once the gene is identified and its function clarified, it will then be possible to clarify the mechanism of the disease process. Our understanding of PD will be profoundly changed and entirely new methods of treatment, prevention and even a cure will become possible.
Genetics of heart failure
Published in ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP, The Year in Heart Failure, 2005
RAY HERSHBERGER, EMILY BURKETT
from one of his or her parents who also carried the mutation, or (2) as a new mutation (that occurred in one of the parents' gametes during meiosis). Individuals who carry a mutation for a dominant trait have a 50% chance of passing on the mutation and a 50% chance of passing on the normal allele to each of their offspring. Recessive traits require two copies of the gene mutation at the locus for obvious expression of the condition. For an individual to be affected with a recessive condition, they must have received a mutant allele from each of their parents. X-linked traits are those caused by mutations in genes on the X chromosome. Males who carry an X-linked gene mutation will express the trait; in contrast, females, who have two copies of the X chromosome, may carry the mutant gene but not express it, or may express a much milder form of the condition. Females carrying the mutation have a 50% chance of transmitting the gene to each son or daughter. The genetic constitution of an individual-or the specific genetic make-up at a particular gene locus-is referred to as his or her genotype. The expression of the individual's genotype (which includes environmental influences on the genotype) is referred to as his or her phenotype. The concept of variable expression refers to the extent to which a genotype is expressed, since even in individuals with identical genotypes the phenotype may vary from person to person. Variable expression is seen extensively with the genes known to cause DCM in families, which are reviewed later in the chapter. Penetrance refers to the all-or-none expression of a mutation. For example, if a phenotype is expressed in fewer than 100% of the individuals who carry the deleterious genotype, it is said to have reduced penetrance. Dilated cardiomyopathy is often said to have age-dependent penetrance; that is, as individuals who carry a deleterious gene for DCM get older, they have an increased chance of expressing the DCM phenotype.
High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation
Published in The World Journal of Biological Psychiatry, 2018
Miriam Kesselmeier, Carolin Pütter, Anna-Lena Volckmar, Hansjörg Baurecht, Harald Grallert, Thomas Illig, Khadeeja Ismail, Miina Ollikainen, Yasmina Silén, Anna Keski-Rahkonen, Cynthia M. Bulik, David A. Collier, Eleftheria Zeggini, Johannes Hebebrand, André Scherag, Anke Hinney
Interestingly, moving from CpG sites to genes, we confirmed one previously described AN candidate gene locus. Similar to Booij et al. (2015), we detected that multiple CpG sites at the TNXB gene were hypermethylated in our AN patients compared to both our control groups. The TNXB (Tenascin XB gene) encodes an extracellular matrix glycoprotein with anti-adhesive effects (Bristow et al. 1993). Absence of the protein in humans has been associated with the Ehlers-Danlos syndrome, a connective tissue disorder (Chen et al. 2009). Localization of the gene on chromosome 6 is within the major histocompatibility complex class III region (Weissensteiner & Lanchbury 1997). In a study based on a small sample size, gene expression levels of TNXB have been proposed as a potential diagnostic tumour marker to discriminate malignant mesothelioma from metastatic carcinoma in effusions (Yuan et al. 2009). There are hints for association of SNPs in the TNXB region with age-related macular degeneration; however, the result was not genome-wide significant (Cipriani et al 2012). It was recently shown that mutations in TNXB can cause hereditary primary vesicoureteral reflux, which is the most common congenital kidney and urinary tract anomaly (Gbadegesin et al. 2013). However, an effect on body weight regulation, starvation or AN has not yet been described.
Aggressive Initial Presentation of HLA-B27 Uveitis in Older Individuals: A Case Series
Published in Ocular Immunology and Inflammation, 2018
Preethi S. Ganapathy, Careen Y. Lowder, Sunil K. Srivastava
The HLA-B27 polymorphism has a well-known association with acute anterior uveitis. Its locus is on chromosome 6, and the protein encodes a major histocompatibility complex class I molecule.1 Variants in the gene locus predispose affected individuals to increased inflammatory conditions, including ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel disease.2 Ophthalmologic presentation is typically acute, unilateral inflammation, although asymmetric bilateral inflammation is also seen frequently. Episodes resolve within a mean of 6 weeks, and recurrences are common.3,4 HLA-B27-positive patients have an earlier onset of uveitis compared with HLA-B27-negative patients5 and it is classically thought to be a condition of the young with a median age of onset in their 30s.3,6 Here, we describe cases of HLA-B27 positive anterior uveitis that first presented in older individuals.
PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue – prognostic implications and rationale for immunotherapy
Published in OncoImmunology, 2018
Melanie Boxberg, Katja Steiger, Ulrich Lenze, Hans Rechl, Rüdiger von Eisenhart-Rothe, Klaus Wörtler, Wilko Weichert, Rupert Langer, Katja Specht
Amplification of the CD274/PD-L1 gene locus was present in 9/128 (7.1%) cases, including 8 cases with high-level and one case with low-level amplification. Information regarding the PD-L1/CEP9 ratio is given in Supplementary Table 3. In 32/128 (25.0%) cases, polysomy of the gene locus was detected, whereas 81/128 (63.3%) cases were disomic. In 2/128 (1.6%) cases, one allele of the CD274/PD-L1 gene was deleted. In amplified cases, concordant PD-L1 protein expression assessed by immunohistochemistry, was present in 6/9 (66.7%) cases, and was significantly more frequent in comparison to cases with PD-L1 polysomy, disomy or deletion (p = 0.015). PD-L1 expression assessed by immunohistochemistry did not show a correlation with the presence of a copy number variation (CNV) of the CD274/PD-L1 gene locus. To exclude any possible bias due to tissue heterogeneity, staining results based on TMAs were confirmed by staining of whole slide sections in CD274/PD-L1 amplified cases (correlation coefficient r = 0.991; p = 0.001). The gene locus for PD-L1 is in close proximity to the gene locus for PD-L2. We therefore also analyzed expression of PD-L2 by immunohistochemistry in these 9 amplified cases by staining whole slides of the respective cases. PD-L2 was not expressed in any of these cases (0/9) (data not shown).