Posts Categorized: Exome sequencing



DOOR syndrome (or DOORS syndrome) genetics

Posted by & filed under Exome sequencing, Part 28: NEUROGENETICS.

In this post, I will describe one of my main research projects, the study of DOOR syndrome, or DOORS syndrome, which stands for : – Deafness (sensorineural) – Onychodystrophy (abnormal nails) – Osteodystrophy (abnormal bones, especially in the digits) – Retardation, mental (now know as intellectual disability) – Seizures The acronym was first used by […]



Actionable Incidental Findings in 1,000 Participants’ Exomes

Posted by & filed under Exome sequencing, Treatment.

Dorschner et al. estimated the number of expected actionable findings in a cohort of 1,000 participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project (500 European; 500 African-descent individuals). The participants were screened for variants in 114 genes pre-selected by an expert panel for their association with medically actionable genetic […]



Archived neonatal dried blood spot samples for accurate whole genome sequencing

Posted by & filed under Exome sequencing, Newborn screening, Part 06: DIAGNOSTIC APPROACHES.

Hollegaard et al. have demonstrated in the past that DNA extracted from a fraction (2 × 3.2 mm discs) of an archived Dried blood spot sample (DBSS) can be whole genome amplified (wgaDNA) and used for accurate array genotyping. In this study, they compared whole-blood DNA next-generation sequencing (NGS) results to results from DBSS and concluded that DBSS […]



Incidental Findings in Clinical Exome/Genome Sequencing

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES.

During the Annual Clinical Genetics Meeting of the American College of Medical Genetics and Genomics (ACMG) in Phoenix, the “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing” were released. This report includes recommendations for management of incidental findings and for a minimum list of conditions, genes, and variants to be […]



Diagnostic exome sequencing in intellectual disability.

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Tools.

de Ligt et al. evaluated patients with intellectual disability to exclude known causes and then sequenced the coding regions of more than 21,000 genes obtained from 100 patients with an IQ below 50 and their unaffected parents. The total diagnostic yield was 16%, mostly involving de novo mutations. The authors conclude that de novo mutations […]



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 […]



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 […]



Collaboration effort for discovery of genes responsible for Mendelian diseases

Posted by & filed under Exome sequencing.

Exome and whole genome sequencing by next generation sequencing have shown tremendous potential for discovery of genes underlying Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Genomics at Yale University; and the Baylor–Johns Hopkins […]



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 […]



Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.

Posted by & filed under Exome sequencing, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Sorry to blow my own horn but I’m quite passionate about the findings described below. Late last year, the group of Clayton-Smith et al. identified mutations in KAT6B in Ohdo syndrome, a condition characterized by blepharophimosis and developmental delay. Shortly after, our group and the group of Simpson et al. identified mutations in the same […]