The birth of a human-specific neural gene by incomplete duplication and gene fusion

Table 1 Likely gene-disruptive events detected in HYDIN/HYDIN2 by MIP-based sequencing of exons in cases and controls

Paralog^a	Variant	Exon	Intron	Protein position	Amino acid	Cases (n = 3483)			Controls (n = 2629)
Paralog^a	Variant	Exon	Intron	Protein position	Amino acid	n	Freq.	Number genotyped^b	n	Freq.	Number genotyped^b
Cases only
HYDIN2	splice_donor	-	66/85	-	-	1	0.03%	3431	0	0.00%	2604
HYDIN2	splice_acceptor	-	53/85	-	-	1	0.03%	3432	0	0.00%	2599
HYDIN	stop_gained	48/86	-	2690	Q/*	1	0.03%	3433	0	0.00%	2603
HYDIN2	stop_gained	46/86	-	2540	R/*	1	0.03%	3425	0	0.00%	2598
Controls only
HYDIN2	stop_gained	80/86	-	4563	W/*	0	0.00%	3429	1	0.04%	2599
HYDIN2	Frameshift	48/86	-	2680	G/X	0	0.00%	3427	1	0.04%	2598
HYDIN2	splice_donor	-	42/85	-	-	0	0.00%	3428	1	0.04%	2599
HYDIN	splice_donor	-	29/85	-	-	0	0.00%	3434	1	0.04%	2603
HYDIN	stop_gained	11/86	-	1330	R/*	0	0.00%	3429	1	0.04%	2599
Found in both cases and controls
HYDIN2	splice_acceptor	-	67/85	-	-	11	0.32%	3430	6	0.23%	2601
HYDIN2	splice_acceptor	-	54/85	-	-	1	0.03%	3426	1	0.04%	2595
HYDIN2	frameshift	46/86	-	2485	A/X	1	0.03%	3428	1	0.04%	2600
HYDIN2	frameshift	41/86	-	2115-2116	VI/VSX	11	0.32%	3427	10	0.38%	2598
HYDIN2	splice_donor	-	28/85	-	-	1	0.03%	3430	1	0.04%	2600
HYDIN2	frameshift	19/86	-	2531-2532	A/X	1	0.03%	3434	1	0.04%	2607
HYDIN2	splice_acceptor	-	14/85	-	-	4	0.12%	3429	2	0.08%	2605

We genotyped 3483 probands and 2629 healthy controls from families with autism using a MIP-based genotyping assay that targeted coding exons and at least five flanking intronic nucleotides. LGD variants (frameshift, stop-gain, stop-loss, and splice-site) were called using FreeBayes. Only variants that could be definitively assigned to HYDIN or HYDIN2 based on the presence of an identifying SUN are shown. Variants include those seen only in cases, seen only in controls, and those seen in both cases and controls. Most of the variants seen in HYDIN2 occur outside of the putative coding sequence
^aParalog determined by presence of SUN(s) on variant-containing MIP reads; variants identified by MIP reads that did not intersect a SUN could not be assigned. Variants in HYDIN2 are annotated with the exon numbering scheme from HYDIN
^bNumber of samples successfully genotyped for this variant (FreeBayes)

ISSN: 1474-760X