Posts By: Yannis Trakadis

Rate of de novo mutations, father’s age and disease risk

Posted by & filed under Exome sequencing.

Whole-genome sequencing of 78 parent–offspring trios in Iceland was used to study the de novo genome-wide mutation rates. Fathers on average passed more de novo mutations than mothers. The overall de novo genome-wide mutation rate is reported to increase by about two mutations a year as a function of the increasing age of the father […]

Biomarkers for AD Alzheimer’s Disease

Posted by & filed under Part 28: NEUROGENETICS.

Bateman et al. performed a prospective, longitudinal study about Autosomal dominant Alzheimer’s disease. 128 participants went through baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. Cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset were conducted in order to determine the relative order and […]

A new approach to advance clinical genomics?

Posted by & filed under Exome sequencing, Part 02: PERSPECTIVES, Part 03: GENERAL THEMES, Part 06: DIAGNOSTIC APPROACHES, Tools.

It is now feasible to sequence an individual’s whole genome at a relatively low cost. However, for genome sequencing to be implemented clinically, a number of major challenges need to be overcome. I hereby discuss the challenges associated with integrating genomic technologies into clinical practice and describe a novel approach, namely, “Individualized Mutation-weighed On-line Phenotype […]

APP variant protective against Alzheimer’s disease

Posted by & filed under Part 28: NEUROGENETICS.

Alzheimer’s disease is characterized by amyloid plaques formed via cleavage of amyloid precursor protein (APP). Jonsson et al. studied coding variants in APP gene in a set of whole-genome sequence data from 1,795 Icelanders, searching for low-frequency variants in APP gene with a significant effect on the risk of Alzheimer’s disease. A coding mutation (A673T) […]

Targeting nuclear RNA for in vivo correction of myotonic dystrophy.

Posted by & filed under Part 25: MUSCLE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, Treatment.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder characterized by myotonia, weakness, cardiac arrhythmias, diabetes and cognitive deficits. Patients carry an expansion of the CTG DNA repeat sequence in the DMPK gene. As a result, when the mutant gene is expressed, it yields a toxic messenger RNA molecule (a gain-of-function effect). In addition […]

Noninvasive whole-genome fetal sequencing

Posted by & filed under Part 06: DIAGNOSTIC APPROACHES.

Approximately 10% of DNA floating freely in a pregnant woman’s plasma originates from the fetus that she carries. Analysis of cell-free fetal DNA in maternal plasma has formed the basis for the development of noninvasive prenatal genetic diagnostics for detection of fetal trisomies and specific paternally inherited mutations. Kitzman et al. in this study reconstructed […]

redundancy of the human genome

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Genome-sequencing studies indicate that all humans carry multiple genetic variants predicted to cause loss of function (LoF) of protein-coding genes. McArthur et al. estimated that human genomes contain ~100 genuine LoF variants with ~20 genes completely inactivated. They also described a method for using the differences found between LoF-tolerant and recessive disease genes to prioritize […]

Targeted aCGH for mitochondrial and metabolic disorders

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Tools.

Targeted aCGH can be useful in the diagnosis of mitochondrial and metabolic disorders. Wang et al. have developed a custom designed oligonucleotide aCGH platform targeting the entire mitochondrial genome and a set of nuclear genes involving mitochondrial and metabolic disorders. This technology can be used to evaluate large deletions, particularly as a complementary diagnostic test […]

Exome sequencing-GWAS applications

Posted by & filed under Exome sequencing.

Genome-wide association studies (GWAS) have been used to idnetify SNPs associated with complex traits. SNP arrays that assay up to 2.5 million polymorphisms have been used and these data have often been augmented by imputation of non-genotyped variants using information from the HapMap or 1000 Genomes Project. The recent decrease in Exome-sequencing cost has provided […]

Oxidative stress & Wilson disease

Posted by & filed under Part 14: METALS.

A recent study by Bruha et al. suggests that increased oxidative stress may contribute significantly to the clinical manifestation of Wilson disease, an inherited disorder of copper disposition caused by an ATP7B transporter gene mutations. Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms. Bruha et al. J Inherit Metab […]