Related Experiment Video
Updated: Jan 21, 2026
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model
Yaoqiang Du1, Zhongshan Li1, Zhenwei Liu1
1Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.
Purpose:
Elucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis.
Methods:
A comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients.
Results:
We observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1.
Conclusions:
Our findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.
Related Concept Videos
02:39lncRNA - Long Non-coding RNAs
02:39lncRNA - Long Non-coding RNAs
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
02:30Histone Variants at the Centromere
01:21Types of Reports II: Incident or Occurrence Report
Purposes:
In the healthcare industry, reports play a crucial role in documenting incidents within an agency. The primary objective of these reports is to ensure patient safety, uphold the...
01:29Nursing Code of Ethics