In a genome-wide association study of 2165 participants from the Autism Genetic Resource Exchange (AGRE) performed to examine associations between genomic loci and endophenotypes associated with ASDs, it was shown that item 85 (faints, fits, or blackouts referring to an unexplained change in level of consciousness with or without falling or jerking movements of the limbs) on the Autism Diagnostic Interview-Related (ADIR is significantly associated with the NELL1 gene (Connolly et al., 2012).
Molecular Function
This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social res...
A Nell-1 haploinsufficiency mouse model shows autism-like phenotypes, including increased repetitive behavior and decreased social approach. Older mice also show spontaneous seizures. Although expressed in craniofacial tissue, the haploinsufficiency model shows no deformity in cranial structure. Genes that are associated with bipolar disorder, autism spectrum disorder, epilepsy and craniofacial syndromes show changes in alternative splicing. Risperidone, a drug used to treat bipolar disorder and autism, has a restorative effect on repetitive and social behaviors.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
The Nell1^I7R6-6R allele (MGI:3626314) originates from an N-ethyl-N-nitrosourea (ENU)-induced point mutation that truncates an 810 amino acid Nell-1 protein at residue 502. In its homozygous state, the mutation induces neonatal death. Therefore, the Nell1 heterozygote mutant mouse is used as an established loss-of-function model.
Allele Type: Knockout
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Oak Ridge National Laboratory
Description: 64% of the tested 3-month-old Nell-1 heterozygote mice experienced hair loss due to overgrooming repetitive behavior. In contrast, none of the wildtype littermates experienced hair loss. Mild hair loss cases mostly occurred in whiskers, perinasal, and periorbital areas of Nell-1 heterozygote mice, moderate cases exhibited large areas of facial hair loss, and in severe cases, full-body hair loss.
Description: In the three-chamber social approach test, Nell-1 heterozygote mice did not prefer a companion over the empty space when wildtype mice engaged more with other mice.
Description: Comprehensive alternative splicing hunting (CASH) method identified ten genes with significantly different alternative splicing events in the Nell1 heterozygote, most of which have known functions in bipolar, epilepsy, autism, and craniofacial syndromes.
Exp Paradigm: comprehensive alternative splicing hunting (CASH) method
Description: The initial global transcriptomic analyses identified 269 differential expressed genes (DEGs) in the Nell-1 heterozygote mouse hippocampus compared to their wildtype counterparts. Among the top 10 downregulated DEGs, several encode functional proteins in the nervous system.
