Table 2.

Zebrafish models of genes in 16p11.2 interval.

Human Gene(s)	Zebrafish Gene(s)	Disorder*	Method**	Phenotype(s)	Rescue	Reference
21 genes#	22 orthologs#	ASD SCZ ID	MO	Brain or eye abnormalities at 24 hpf (20/22 genes) Muscle and tail abnormalities at 24 hpf for most genes Decreased spontaneous movement at 24 hpf (7 genes), touch response at 48 hpf (14 genes) Abnormal axon tract development at 36 hpf (6 genes); altered pigmentation (8 genes)	Human or zebrafish mRNA rescue phenotypes for all genes (except mvp)	Blaker-Lee et al. (2012)
29 genes##	kctd13	ASD SCZ ID	OE (Human mRNA in zebrafish); MO (kctd13)	KCTD13 is only human mRNA where OE causes head size PT Human KCTD13 mRNA OE in zebrafish: - Microcephaly; fewer neurons in telencephalon (4.5 dpf) - Increased apoptosis in brain (3 dpf) - Decreased cell proliferation in brain (2 dpf) kctd13 MO: - Macrocephaly; increased neurons in telencephalon (4.5 dpf) - Increased cell proliferation in brain (2 dpf) Mouse Kctd13 knockdown in vitro/in vivo: Increased cell proliferation	Human mRNA + kcdt13 MO rescue head size phenotypes	Golzio et al. (2012)
KCTD13	kctd13	−	CRISPR Mutant	Zebrafish and mouse KCTD13 mutants: - No changes in head size or cell proliferation (4.5 dpf) - Increased RhoA in brain (adult zebrafish; mice ≥ P18) Decreased synaptic transmission in mice	RhoA inhibitor rescues synaptic transmission defects in mice	Escamilla et al. (2017)
DOC2A FAM57B	doc2a fam57ba	−	MO; TALEN Mutant	Genetic interactions between 16 pairs of genes in 16p11.2 interval, including fam57ba and doc2a, in MO screen for brain/ventricle morphology phenotypes at 24 hpf doc2a+/−fam57ba+/−: - Hyperactivity and seizure sensitivity (7 dpf) - Increased body length and some head size dimensions (12 dpf) fam57ba−/–: - Hyperactivity and seizure sensitivity (7 dpf), less than in double heterozygotes - Strong increase in body length and head size (12 dpf) - Increased lipid content	Valproic acid and carbamazepine rescue drug-induced seizures	McCammon et al. (2017)

Key: hpf, hours post fertilization; dpf, days post fertilization; *Disorder: ASD, autism spectrum disorder; EP, Epilepsy; ID, intellectual disability; SCZ, schizophrenia; **Methods of Risk Gene Disruption: CRISPR, clustered regularly interspaced short palindromic repeats; MO, Morpholino; OE, overexpression; TALEN, transcription activator-like effector nuclease; ^#Human Genes in 16p11.2 interval in Blaker-Lee et al. (2012): ALDOA, ASPHD1, C16orf53, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, KIF22, MAPK3, MAZ, MVP, PPP4C, PRRT2, SEZ6L2, TAOK2, TBX6, YPEL3; Zebrafish Orthologs: aldoaa, asphd1, c16orf53, cdipt, coro1a, doc2a, fam57ba, gdpd3, hirip3, ino80e, kctd13, kif22, mapk3, maz, mvp, ppp4ca, prrt2, sez6l2, taok2a, taok2b, tbx24, ypel3; ^##Human Genes in 16p11.2 interval in Golzio et al. (2012): ALDOA, ASPHD1, BOLA2, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, GIYD2, KCTD13, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3.