Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder

Borges-Monroy, Rebeca; Chu, Chong; Dias, Caroline; Choi, Jaejoon; Lee, Soohyun; Gao, Yue; Shin, Taehwan; Park, Peter J.; Walsh, Christopher A.; Lee, Eunjung Alice

doi:10.1186/s13100-021-00256-w

Mobile DNA

Table 1 Select de novo insertions in ASD and high pLI genes in affected individuals

From: Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder

Proband ID	TE Type	Gene	SFARI Classification^a	pLI	Genic Region	Validation Status	Observed Phenotype	Previous Neurodevelopmental Phenotype associated with gene	Reference
11,859.p1	Alu	CSDE1	No	1	Exon	Validated	ASD, language delay, ID, macrocephaly, history of vision correction, normal EEG at 4 years	LGD variants associated with ASD, developmental delay, ID, seizures, macrocephaly, ADHD, anxiety, ocular abnormalities	Guo et al. 2019 [22]
14,565.p1	Alu	KBTBD6	No	0.935	Exon	Validated	ASD, macrocephaly, uncoordinated, normal IQ, BMI Z-score − 3.91
12,548.p1	Alu	APPBP2	No	0.999	Intron	Validated	ASD, normal IQ, macrocephaly
12,748.p1	Alu	SYT1	Syndromic	0.837	Intron	Validated	ASD, normal IQ, uncoordinated	Developmental delays, autistic features, hypotonia, ocular abnormalities, hyperkinetic movements associated with de novo missense variation	Baker et al., 2018 [23]
13,931.p1	Alu	OTUD7A	Suggestive evidence	0.975	Intron	Validated	ASD, borderline IQ, normal EEG, and brain imaging	Neurodevelopmental phenotype of ASD, developmental delay, ID, seizures associated with 15q13.3 microdeletion syndrome	Yin et al. 2018 [24], Uddin et al. 2018 [25]
13,107.p1	Alu	TOX3	No	0.994	Intron	Validated	ASD, normal IQ
14,315.p1	Alu	JAZF1	No	0.958	Intron	Validated	ASD, borderline verbal IQ, normal nonverbal IQ, normal EEG
11,196.p1	L1	SRGAP3	Minimal Evidence	1	Intron	Validated	ASD, above average IQ, no history of seizures, heart problems reported	Case report of translocation breakpoint at loci posited to be LoF associated with hypotonia and severe ID	Endris et al. 2002 [26]
13,684.p1	L1	HCN1	Syndromic	0.953	Intron	NA	ASD, Tourette syndrome, above average IQ, GI problems, uncoordinated	Missense variation associated with a syndrome of seizures, intellectual disability, and autistic features, gene also implicated in Tourette syndrome, role in striatal neuronal function and enteric nervous system	Nava et al. 2014 [27], Tsetsos et al. [28] 2021
14,080.p1	L1	DAB1	Hypothesized	0.981	Intron	Validated	ASD, uncoordinated, GI problems	ASD, GI problems, schizophrenia, spinocerebellar ataxia-37 associated with non-coding nucleotide repeats	Corral-Juan et al. 2018 [29], Nawa et al. 2020 [30]
14,282.p1	L1	DPYD	Suggestive evidence	0	Intron	Not in LCL DNA, predicted blood mosaic	ASD, normal IQ	ASD, ID	Carter et al. 2011 [31], Willemsen et al. 2011 [32]
11,234.p1	L1	NOTCH2	No	1	Intron	NA	ASD, above average IQ
13,451.p1	L1	DPP10	Suggestive evidence	1	Intron	NA	ASD, borderline IQ	ASD	Marshall et al. 2008 [33]
14,404.p1	SVA	GRAMD1B	No	0.985	Intron	NA, predicted blood mosaic	ASD, non-verbal, IQ in profound intellectual disability range, macrocephaly	Autosomal recessive intellectual disability	Santos-Cortez et al. 2018 [34]
14,523.p1	SVA	ACACA	No	1	Intron	NA	ASD, above average IQ, macrocephaly	Acetyl-CoA carboxylase deficiency	Blom et al. 1981 [35]

A subset of de novo TEIs observed in individuals with ASD in genes relevant to ASD or with a high probability of being loss-of-function intolerant (pLI > 0.9). ^aSFARI annotations were obtained in 2019. LCL Lymphoblastoid cell line, LGD Likely gene disrupting, ID Intellectual disability, LoF Loss of function, ADHD Attention-deficit hyperactivity disorder, GI Gastrointestinal.

Back to article page

ISSN: 1759-8753

Contact us

General enquiries: journalsubmissions@springernature.com