Estimation of the frequency of inherited germline mutations by whole exome sequencing in ethyl nitrosourea-treated and untreated gpt delta mice

Table 2 Mutation spectra in the offspring and somatic tissues of ENU-treated mice

			Control		ENU
			NGS (this study)		NGS (this study)		Genome-wide screening^1a		Transgenic reporter gene mutation assays										Endogenous gene mutation assays
Target sequences			Whole exome		Whole exome		63 loci (197 Mb)		gpt (this study)		gpt ²		lacZ ³		lacZ ⁴		lacI ⁵		Hprt (cDNA)⁶		Hprt (exon 3)⁷
Target tissues			Offspring		Offspring		Offspring		Sperm		Bone marow		Liver		Bone marrow		Splenic lymphocytes		Splenic lymphocytes		Splenic lymphocytes
Mutations			No.	%	No.	%	No.	%	No.	%	No.	%	No.	%	No.	%	No.	%	No.	%	No.	%
Base substitution
Transition
G:C	to	A:T	1	33.3	21	17.1	32	22.4	11	22.4	17	28.3	6	24.0	7	35.0	13	29.5	4	12.9	2	3.9
A:T	to	G:C	1	33.3	52	42.3	53	37.1	8	16.3	12	20.0	1	4.0	2	10.0	10	22.7	7	22.6	14	27.5
Transversion
G:C	to	T:A	0	0.0	12	9.8	13	9.1	7	14.3	9	15.0	6	24.0	4	20.0	4	9.1	1	3.2	1	2.0
G:C	to	C:G	0	0.0	0	0.0	1	0.7	1	2.0	0	0.0	0	0.0	0	0.0	1	2.3	1	3.2	0	0.0
A:T	to	T:A	0	0.0	33	26.8	35	24.5	17	34.7	17	28.3	7	28.0	6	30.0	10	22.7	13	41.9	28	54.9
A:T	to	C:G	0	0.0	5	4.1	8	5.6	4	8.2	3	5.0	3	12.0	0	0.0	4	9.1	5	16.1	6	11.8
Deletion			1	33.3	0	0.0	1	0.7	1	2.0	2	3.3	1	4.0	1	5.0	1	2.3	0	0.0	0	0.0
Insertion			0	0.0	0	0.0	0	0.0	0	0.0	0	0.0	1	4.0	0	0.0	1	2.3	0	0.0	0	0.0
Total			3	100	123	100	143	100	49	100	60	100	25	100	20	100	44	100	31	100	51	100

¹Male F1 mice by crossing C57BL/6 × DBA/2 or C3H/He [12]
²Male BDF1 gpt delta mice [10]
³Female CD2F1 Muta^TM mice [17]
⁴Male CD2F1 Muta^TM mice [18]
⁵Male B6C3F1 Big Blue® mice [19]
⁶C57BL/6 mice [30]
⁷Male B6C3F1 mice [19]
^aTemperature gradient capillary electrophoresis (TGCE) and Sanger sequencing methods

ISSN: 1880-7062