New insights into the generation and role of de novo mutations in health and disease

Table 1 Comparison of inherited and de novo variants

	Inherited variants	De novo mutations
Single-nucleotide variants (SNVs)	3.5 to 4.4 million [4]	44 to 82 [9, 10, 12, 13, 15]
Number of coding SNVs	22,186 [10]	1–2 [25]
Insertions and deletions (indels <50 bp)	~550,000 [4]	2.9–9 [26, 91]
Large indels (50–5000 bp)^a	~1000 [4]	0.16 [26]
Copy-number variations (CNVs)	~160 [4]	0.0154 [26]^b
Selection pressure in previous generation(s)	High	None
Damaging capacity of variants	Majority with small effect	High
Differences in population	Yes	None
Parental/paternal age effect	None	Strong
Detection of variants	Imputable	Not imputable
Amenable to positional cloning^c	Yes	No

^aOwing to technical limitations, the number and mutation rate for large indels ranging between 50 and 5000 bp remain uncertain. Novel sequencing approaches will likely provide more-accurate estimates (see Chaisson et al. [205])
^bPer generation for CNVs larger than 100 kb
^cPositional cloning by linkage analysis or homozygosity mapping

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