Table 6.

Lack of Segregation Distortion

Gene Group	Proband	Sibling	Proband & Sibling	Neither	Total
(A) Segregation of Rare Nonsense and Splice Site Variants
FMRP-associated	9	15	16	20	60
CNV candidates	3	1	3	0	7
De novo LGD	0	6	4	3	13
All of the above	12	22	20	23	77
All well-annotated	666	726	750	692	2,834
(B) Segregation of Rare Missense Variants
FMRP-associated	1,784	1,808	1,924	1,591	7,107
CNV candidates	99	99	116	108	422
De novo LGD	165	189	200	214	768
All of the above	1,973	2,017	2,168	1,833	7,991
All well-annotated	22,267	22,379	24,255	20,875	89,776
(C) Genes with Compound Heterozygosity (Rare Nonsense, Splice Site, and Missense)
FMRP-associated	28	31			59
CNV candidates	1	0			1
De novo LGD	4	3			7
All of the above	32	33			65
All well-annotated	242	224			466

Rare SNVs (those observed only once in the 686 parents in this study) are classified based on the children to whom they were transmitted: only to the proband (“proband”); only to the unaffected sibling (“sibling”); to both children (“proband & sibling”) or to “neither” child.

(A) We classified rare variants by the gene they target. The segregation of several target groups of rare nonsense and splice site variants is indicated. The “FMRP-associated” group is all variants that occur within the coding region of FMRP-associated genes; “CNV candidates” are defined as in Table 5; “de novo LGD” are the variants that occur in the 59 genes affected by de novo LGD in probands from this study; “all of the above” represents the variants in at least one of the previous three target sets; and “all well-annotated” are variants that target well-annotated CCDS genes (Pruitt et al., 2009).

(B) Segregation of rare missense variants categorized as in (A).

(C) Compound heterozygosity in probands and unaffected siblings. A compound heterozygote was defined as an instance in which a gene was affected by two different rare variants—one from the mother and one from the father—in the same child. Genes are classified as in (A) and (B).