Related Experiment Video

Updated: Jun 14, 2025

In Vivo Modeling of the Morbid Human Genome using Danio rerio
12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

20.7K

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease

Eleanor C Broeren1, Vanessa N Gitau1, Alicia B Byrne1

  • 1Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.

Genetics in Medicine Open
|June 11, 2025
PubMed

Insights

The ClinGen Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) evaluated 111 gene-disease relationships for rare syndromic disorders. This work enhances clinical testing by assessing gene validity for complex genetic conditions.

Area of Science:

  • Genetics
  • Genomic Medicine
  • Rare Diseases

Background:

  • Gene curation efforts historically focused on specific organ systems or phenotypes.
  • An unmet need existed for evaluating genes associated with syndromic disorders.
  • The Clinical Genome Resource (ClinGen) established the Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) to address this gap.

Purpose of the Study:

  • To apply the ClinGen framework for evaluating the clinical validity of genes linked to rare syndromic disorders.
  • To curate gene-disease relationships (GDRs) within the spectrum of syndromic conditions.
  • To address the need for comprehensive gene assessment in syndromic genetic disorders.

Main Methods:

  • Evaluated 111 gene-disease relationships (GDRs) involving 100 genes.
  • Conducted 38 precurations to refine gene-disease classifications (lumping/splitting entities).
  • Classified GDRs based on clinical validity: Definitive (78), Strong (9), Moderate (15), Limited (9).

Main Results:

  • A total of 111 GDRs for 100 genes were curated.
  • 78 GDRs were classified as Definitive, indicating strong evidence.
  • The majority of diseases (79.2%) affected five or more organ systems, reflecting syndromic complexity.

Conclusions:

  • The SD-GCEP successfully addresses a critical gap in gene curation for syndromic disorders.
  • This work facilitates the inclusion of genes for syndromic conditions in clinical testing.
  • The panel's efforts help keep pace with the rapid discovery of new genetic syndromes.
Abstract

Keywords:
ClinGenGene curationGene-disease relationshipRare diseaseSyndromic disorders

More Related Videos

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

10.1K
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

33.7K

Related Concept Videos

Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
4.9K
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
13.2K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
14.9K
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
22.1K
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
36.2K