Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Chromosomes	Codominant	Dominant	Recessive	Overdominant	Log-additive
1	BICF2P448058 BICF2P501513 BICF2P776685	BICF2P448058 BICF2P501513	BICF2S2334324	BICF2P343250	BICF2P825735 BICF2P501513 BICF2P776685 BICF2P345133
2	-	TIGRP2P33447_rs8 841788	-	-	-
3	-	BICF2G630704243	BICF2S23125394	-	BICF2G630704243 BICF2G630704438
8	TIGRP2P107898_rs 9044787	BICF2S2308912	TIGRP2P107898_rs 9044787	BICF2P158200	TIGRP2P107898_rs 9044787*
10	-	-	-	BICF2S23760334	-
11	-	-	BICF2P576198	BICF2S23118240	-
12	-	BICF2S23638049	-	-	-
13	-	TIGRP2P176993_rs 9197628	-	-	TIGRP2P176993_rs 9197628
14	BICF2P797481	-	-	-	BICF2P797481 BICF2P720053
15	-	TIGRP2P201649_rs 8752112 BICF2S23334099 BICF2P352914	-	-	-
16	BICF2P1314057	BICF2P1314057	-	-	BICF2P1314057
19	TIGRP2P268994_rs 8894778	-	-	TIGRP2P268994_rs 8894778	-
22	-	-	BICF2P801296	-	-
23	BICF2P373712	BICF2P373712	-	-	BICF2P373712
24	-	-	-	-	BICF2S23648284
28	-	BICF2G630269882	-	-	-
30	-	-	-	-	BICF2G630397948
32	-	BICF2S23661944	-	-	-
34	-	-	BICF2S23049081	-	BICF2S23049081
35	-	-	BICF2S23219997	-	BICF2P28560
37	BICF2G630136001	-	-	BICF2G630129768 BICF2G630136001*	BICF2G630127550
X	-	-	-	BICF2S23347259	-

1 The effect of single nucleotide polymorphisms marked with * was statistically significant at the level 5⁻⁸

Table 2.

Summary of single nucleotide polymorphisms (SNPs) statistically significantly associated with the occurrence of mammary gland tumours

SNP	CHR	Location (bp)	Minor allele	MAF (%)	MAF_control (%)	MAF_case (%)	HWE P-value	Candidate gene or locus/nearest gene or locus
BICF2P448058	1	65,212,166	G	46.19	37.20	66.67	0.85	LOC111096229 / TRMT11
BICF2P501513	1	65,293,673	A	42.37	32.93	63.89	1.00	- / LOC111096229, LOC111096230
BICF2P776685	1	65,819,801	A	46.61	56.71	23.61	0.46	- / LOC100684456, LOC102153070
BICF2S2334324	1	14,217,295	G	47.03	52.44	34.72	0.47	ZCCHC2 / -
BICF2P343250	1	67,922,585	A	27.97	32.32	18.06	0.25	LAMA2 / -
BICF2P825735	1	41,988,950	A	14.83	6.71	33.33	0.00	ARMT1
BICF2P345133	1	66,185,882	A	36.86	26.22	61.11	0.00	- / LOC111096246
TIGRP2P33447_rs8841788	2	82,135,437	G	39.32	32.93	54.29	0.70	ARHGEF19 / -
BICF2G630704243	3	27,421,551	G	41.53	51.22	19.44	0.34	HOMER1 / -
BICF2S23125394	3	36,857,983	A	49.57	57.93	30.00	0.06	- / MKRN3
BICF2G630704438	3	27,777,144	A	49.57	59.76	26.39	0.03	DMGDH / -
TIGRP2P107898_rs9044787	8	12664933	A	36.75	24.07	65.28	0.05	NPAS3 / -
BICF2S2308912	8	49,696,532	A	19.07	26.83	1.39	0.00	- / LOC111097115
BICF2P158200	8	34,943,508	A	17.37	11.59	30.56	0.34	CCDC175, JKAMP / -
BICF2P441276	8	56,964,583	A	39.57	37.80	43.94	0.02	LOC111097128 / FLRT2
BICF2S23760334	10	47,442,988	A	36.44	33.53	43.06	0.00	- /LOC100687001, PPM1B
BICF2P576198	11	61,345,663	G	47.88	56.71	27.78	0.01	- / LOC102156133, LOC612266, SMC2
BICF2S23118240	11	52,671,467	A	23.73	26.22	18.06	0.01	- / DNAJB5, C11H9orf131
BICF2S23638049	12	19,343,255	A	26.50	19.51	42.86	1.00	- / LOC119876904, LOC119874254
TIGRP2P176993_rs9197628	13	39,050,399	A	19.49	10.98	38.89	0.38	LIMCH1 / -
BICF2P797481	14	45,742,638	A	42.80	53.05	19.44	0.19	- / LOC106559680
BICF2P720053	14	45,744,668	G	42.37	52.44	19.44	0.19	- / LOC106559680
TIGRP2P201649_rs8752112	15	42,346,461	A	27.12	35.37	8.33	0.00	LOC119869373 / ASCL1
BICF2P352914	15	42,358,113	G	27.12	35.37	8.33	0.00	ASCL1 / -
BICF2S23334099	15	42,352,911	A	27.54	35.98	8.33	0.00	ASCL1 / -
BICF2P1314057	16	35,869,183	A	23.28	14.63	44.12	1.00	RBPMS / -
TIGRP2P268994_rs8894778	19	46,961,958	A	27.35	22.56	38.57	0.06	ARHGAP15 / -
BICF2P801296	22	7,706,835	A	49.15	56.10	32.86	0.10	ENOX1 / -
BICF2P373712	23	51,871,689	G	43.53	55.63	16.67	0.00	- / LOC111092021, VEPH1
BICF2S23648284	24	29,281,559	T	25.42	17.07	44.44	1.00	LOC119865549 / -
BICF2G630269882	28	20,841,387	A	29.91	21.95	48.57	1.00	- / LOC111092968
BICF2G630397948	30	35,183,072	A	42.37	31.71	66.67	0.00	THSD4 / -
BICF2S23661944	32	29,141,932	A	16.53	23.17	1.39	0.09	LOC106558120 / -
BICF2S23049081	34	30,205,708	G	49.58	39.02	73.61	0.07	- / LOC111093899
BICF2S23219997	35	20,654,940	A	22.03	14.63	38.89	0.01	- / LOC119867672
BICF2P28560	35	15,603,710	A	36.44	46.34	13.89	0.05	ATXN1 / -
BICF2G630136001	37	30,735,796	A	38.46	34.76	47.14	0.56	DLGAP2 / -
BICF2G630129768	37	24,240,716	G	38.98	35.98	45.83	0.44	- / LOC102156106, LOC111094390
BICF2G630127550	37	9,335,944	G	40.25	50.00	18.06	0.03	SPATS2L / -
BICF2S23347259	X	32,408,330	A	31.62	25.61	45.71	0.20	LANCL3 / -

1 CHR – chromosome; MAF – minor allele frequency; MAF_control – minor allele frequency in the control group; MAF_case – minor allele frequency in the case group; HWE – Hardy–Weinberg equilibrium

Table 3.

The risk of mammary gland tumours associated with particular genotypes within single nucleotide polymorphisms (SNPs) for the dominant model

CHR	SNP	Genotype	Genotype number (percentage)		OR (95% CI)	P-value
CHR	SNP	Genotype	Control	Case
1	BICF2P448058	A/A	34 (41.5%)	1 (2.5%)	24.79	1.57 × 10⁻⁶
	BICF2P448058	G/A-G/G	48 (58.5)	35 (97.2%)	(3.24; 189.80)	1.57 × 10⁻⁶
	BICF2P501513	G/G	37 (45.1%)	2 (5.6%)	13.98	7.08 × 10⁻⁶
	BICF2P501513	A/G-A/A	45 (54.9%)	34 (94.4%)	(3.15; 62.08)	7.08 × 10⁻⁶
2	TIGRP2P33447_rs8841788	A/A	41 (50.0%)	3 (8.6%)	10.67	5.15 × 10⁻⁶
2	TIGRP2P33447_rs8841788	G/A-G/G	41 (50.0%)	32 (91.4%)	(3.03; 37.61)	5.15 × 10⁻⁶
3	BICF2G630704243	A/A	19 (23.2%)	24 (66.7%)	0.15	7.02 × 10⁻⁶
3	BICF2G630704243	G/A-G/G	63 (76.8%)	12 (33.3%)	(0.06; 0.36)	7.02 × 10⁻⁶
8	BICF2S2308912	G/G	49 (59.8%)	35 (97.2%)	0.04	2.67 × 10⁻⁶
8	BICF2S2308912	A/G-A/A	33 (40.2%)	1 (2.8%)	(0.01; 0.33)	2.67 × 10⁻⁶
12	BICF2S23638049	G/G	55 (67.1%)	8 (22.9%)	6.87	7.92 × 10⁻⁶
12	BICF2S23638049	A/G-A/A	27 (32.9%)	27 (77.1%)	(2.76; 17.14)	7.92 × 10⁻⁶
13	TIGRP2P176993_rs9197628	G/G	65 (79.3%)	13 (36.1%)	6.76	6.52 × 10⁻⁶
	TIGRP2P176993_rs9197628	A/G-A/A	17 (20.7%)	23 (63.9%)	(2.85; 16.06)	6.52 × 10⁻⁶
	TIGRP2P201649_rs8752112	G/G	38 (46.3%)	32 (88.9%)	0.11	4.35 × 10⁻⁶
	TIGRP2P201649_rs8752112	A/G-A/A	44 (53.7%)	4 (11.1%)	(0.03; 0.33)	4.35 × 10⁻⁶
15	BICF2S23334099	G/G	37 (45.1%)	32 (88.9%)	0.10	2.50 × 10⁻⁶
	BICF2S23334099	A/G-A/A	45 (54.9%)	4 (11.1%)	(0.03; 0.32)	2.50 × 10⁻⁶
	BICF2P352914	A/A	38 (46.3%)	32 (88.9%)	0.11	4.35 × 10⁻⁶
	BICF2P352914	G/A-G/G	44 (53.7%)	4 (11.1%)	(0.03; 0.33)	4.35 × 10⁻⁶
16	BICF2P1314057	G/G	60 (73.2%)	8 (23.5%)	8.86	6.14 × 10⁻⁷
16	BICF2P1314057	A/G-A/A	22 (26.8%)	26 (76.5%)	(3.49; 22.48)	6.14 × 10⁻⁷
23	BICF2P373712	A/A	21 (26.2%)	26 (72.2%)	0.14	2.77 × 10⁻⁶
23	BICF2P373712	G/A-G/G	59 (73.8%)	10 (27.8%)	(0.06; 0.33)	2.77 × 10⁻⁶
28	BICF2G630269882	C/C	51 (62.2%)	6 (17.1%)	7.95	3.93 × 10⁻⁶
28	BICF2G630269882	A/C-A/A	31 (37.8%)	29 (82.9%)	(2.97; 21.31)	3.93 × 10⁻⁶
32	BICF2S23661944	G/G	50 (61.0%)	35 (97.2%)	0.04	4.52 × 10⁻⁶
32	BICF2S23661944	A/G-A/A	32 (39.0%)	1 (2.8%)	(0.01; 0.34)	4.52 × 10⁻⁶

1 CHR – chromosome; OR – odds ratio; CI – confidence interval

Table 4.

The risk of mammary gland tumours associated with particular genotypes within single nucleotide polymorphisms (SNPs) for the recessive model

CHR	SNP	Genotype	Genotype number (percentage)		OR (95% CI)	P-value
CHR	SNP	Genotype	Control	Case	OR (95% CI)	P-value
1	BICF2S2334324	A/A-G/A	54 (65.9%)	36 (100%)	0	9.24 × 10⁻⁶
1	BICF2S2334324	G/G	28 (34.1%)	0 (0%)	0	9.24 × 10⁻⁶
3	BICF2S23125394	C/C-A/C	49 (59.8%)	34 (97.1%)	0.04	3.70 × 10⁻⁶
3	BICF2S23125394	A/A	33 (40.2%)	1 (2.9%)	(0.01; 0.33)	3.70 × 10⁻⁶
8	TIGRP2P107898_rs9044787	G/G-A/G	77 (95.1%)	19 (52.8%)	17.22	9.55 × 10⁻⁸
8	TIGRP2P107898_rs9044787	A/A	4 (4.9%)	17 (47.2%)	(5.19; 57.15)	9.55 × 10⁻⁸
11	BICF2P576198	A/A-G/A	49 (59.8%)	35 (97.2%)	0.04	2.67 × 10⁻⁶
11	BICF2P576198	G/G	33 (40.2%)	1 (2.8%)	(0.01; 0.33)	2.67 × 10⁻⁶
22	BICF2P801296	G/G-A/G	50 (61.0%)	34 (97.1%)	0.05	6.19 × 10⁻⁶
22	BICF2P801296	A/A	32 (39.0%)	1 (2.9%)	(0.01; 0.35)	6.19 × 10⁻⁶
34	BICF2S23049081	A/A-G/A	69 (84.1%)	15 (41.7%)	7.43	4.35 × 10⁻⁶
34	BICF2S23049081	G/G	13 (15.9%)	21 (58.3%)	(3.05; 18.08)	4.35 × 10⁻⁶
35	BICF2S23219997	G/G-A/G	81 (98.8%)	26 (72.2%)	31.15	8.60 ×10⁻⁶
35	BICF2S23219997	A/A	1 (1.2%)	(27.8%)	(3.81; 255.00)	8.60 ×10⁻⁶

1 CHR – chromosome; OR – odds ratio; CI – confidence interval

Table 5.

The risk of mammary gland tumours associated with particular genotypes within single nucleotide polymorphisms (SNPs) for the codominant model

CHR	SNP	Genotype	Genotype number (percentage)		OR	95% CI	P-value
CHR	SNP	Genotype	Control	Case	OR	95% CI	P-value
1	BICF2P448058	A/A	34 (41.5%)	1 (2.8%)	1.00
		G/A	35 (42.7%)	22 (61.1%)	2.73	(2.73; 167.5)	6.1 × 10⁻⁶
		G/G	13 (15.9%)	13 (36.1%)	4.03	(4.03; 286.7)
	BICF2P501513	G/G	37 (45.1%)	2 (5.6%)	1.00
		A/G	36 (43.9%)	22 (61.1%)	11.31	(2.48; 51.61)	7.1 × 10⁻⁶
		A/A	9 (11.0%)	12 (33.3%)	24.67	(4.67; 130.35)
	BICF2P776685	G/G	16 (19.5%)	20 (55.6%)	1.00
		A/G	39 (47.6%)	15 (41.7%)	0.13	(0.13; 0.75)	8.9 × 10⁻⁶
		A/A	27 (32.9%)	1 (2.8%)	0.00	(0.00; 0.24)
8	TIGRP2P107898_rs9044787	G/G	46 (56.8%)	6 (16.7%)	1.00
		A/G	31 (38.3%)	13 (36.1%)	3.22	(1.10; 9.37)	5.7 × 10⁻⁸
		A/A	4 (4.9%)	17 (47.2%)	32.58	(8.18; 129.78)
14	BICF2P797481	G/G	19 (23.2%)	23 (63.9%)	1.00
		A/G	39 (47.6%)	12 (33.3%)	0.25	(0.10; 0.62)	8.8 × 10⁻⁶
		A/A	24 (29.3%)	1 (2.8%)	0.03	(0.00; 0.28)
16	BICF2P1314057	G/G	60 (73.2%)	8 (23.5%)	1.00
		A/G	20 (24.4%)	22 (64.7%)	8.25	(3.18; 21.43)	3.2 × 10⁻⁶
		A/A	2 (2.4%)	4 (11.8%)	15.00	(2.36; 95.47)
19	TIGRP2P268994_rs8894778	G/G	56 (68.3%)	10 (28.6%)	1.00
		A/G	15 (18.3%)	23 (65.7%)	8.59	(3.37; 21.89)	4.8 × 10⁻⁶
		A/A	11 (13.4%)	2 (5.7%)	1.02	(0.20; 5.30)
23	BICF2P373712	A/A	21 (26.2%)	26 (72.2%)	1.00
		G/A	29 (36.2%)	8 (22.2%)	0.22	(0.08; 0.59)	2.9 × 10⁻⁶
		G/G	30 (37.5%)	2 (5.6%)	0.05	(0.01; 0.25)
37	BICF2G630136001	G/G	42 (51.2%)	4 (11.4%)	1.00
		A/G	23 (28.0%)	29 (82.9%)	13.24	(4.14; 42.34)	1.5 × 10⁻⁷
		A/A	17 (20.7%)	2 (5.7%)	1.24	(0.21; 7.39)

1 CHR – chromosome; OR – odds ratio; CI – confidence interval

Table 6.

The risk of mammary gland tumours associated with particular genotypes within single nucleotide polymorphisms (SNPs) for the overdominant model

CHR	SNP	Genotype	Genotype number (percentage)		OR (95% CI)	P-value
CHR	SNP	Genotype	Control	Case	OR (95% CI)	P-value
1	BICF2P343250	G/G-A/A	43 (52.4%)	33 (91.7%)	0.10	9.99 × 10⁻⁶
1	BICF2P343250	A/G	39 (47.6%)	3 (8.3%)	(0.03; 0.35)	9.99 × 10⁻⁶
8	BICF2P158200	G/G-A/A	71 (86.6%)	16 (44.4%)	8.07	3.03 × 10⁻⁶
	BICF2P158200	A/G	11 (13.4%)	20 (55.6%)	(3.23; 20.13)	3.03 × 10⁻⁶
	BICF2P441276	G/G-A/A	62 (75.6%)	10 (30.3%)	7.13	6.16 × 10⁻⁶
	BICF2P441276	A/G	20 (24.4%)	23 (69.7%)	(2.91; 17.49)	6.16 × 10⁻⁶
10	BICF2S23760334	G/G-A/A	65 (79.3%)	13 (36.1%)	6.76	6.52 × 10⁻⁶
10	BICF2S23760334	A/G	17 (20.7%)	23 (63.9%)	(2.85; 16.06)	6.52 × 10⁻⁶
11	BICF2S23118240	G/G-A/A	51 (62.2%)	35 (97.2%)	0.05	7.59 × 10⁻⁶
11	BICF2S23118240	A/G	31 (37.8%)	1 (2.8%)	(0.01; 0.36)	7.59 × 10⁻⁶
19	TIGRP2P268994_rs8894778	G/G-A/A	67 (81.7%)	12 (34.3%)	8.56	7.49 × 10⁻⁷
19	TIGRP2P268994_rs8894778	A/G	15 (18.3%)	23 (65.7%)	(3.50; 20.95)	7.49 × 10⁻⁷
37	BICF2G630129768	A/A-G/G	57 (69.5%)	9 (25.0%)	6.84	5.72 × 10⁻⁶
	BICF2G630129768	G/A	25 (30.5%)	27 (75.0%)	(2.81; 16.64)	5.72 × 10⁻⁶
	BICF2G630136001	G/G-A/A	59 (72.0%)	6 (17.1%)	12.4	2.14 × 10⁻⁸
	BICF2G630136001	A/G	23 (28.0%)	29 (82.9%)	(4.55; 33.78)	2.14 × 10⁻⁸
X	BICF2S23347259	G/G-A/A	62 (75.6%)	11 (31.4%)	6.76	6.79 × 10⁻⁶
X	BICF2S23347259	A/G	20 (24.4%)	24 (68.6%)	(2.82; 16.20)	6.79 × 10⁻⁶

1 CHR – chromosome; OR – odds ratio; CI – confidence interval

Table 7.

The risk of mammary gland tumours associated with particular genotypes within single nucleotide polymorphisms (SNPs) for the log-additive model

CHR	SNP	Genotype	OR	95% CI	P-value
1	BICF2P825735	0, 1, 2	4.66	(2.17; 9.99)	9.95 × 10⁻⁶
	BICF2P501513	0, 1, 2	4.21	(2.11; 8.37)	5.17 × 10⁻⁶
	BICF2P776685	0, 1, 2	0.23	(0.12; 0.46)	2.40 × 10⁻⁶
	BICF2P345133	0, 1, 2	3.25	(1.87; 5.67)	8.34 × 10⁻⁶
3	BICF2G630704243	0, 1, 2	0.23	(0.11; 0.47)	4.23 × 10⁻⁶
3	BICF2G630704438	0, 1, 2	0.28	(0.15; 0.52)	8.86 × 10⁻⁶
8	TIGRP2P107898_rs9044787	0, 1, 2	5.46	(2.76; 10.81)	1.60 × 10⁻⁸
13	TIGRP2P176993_rs9197628	0, 1, 2	5.39	(2.50; 11.61)	2.19 × 10⁻⁶
14	BICF2P797481	0, 1, 2	0.22	(0.11; 0.45)	1.62 × 10⁻⁶
14	BICF2P720053	0, 1, 2	0.23	(0.12; 0.46)	2.89 × 10⁻⁶
16	BICF2P1314057	0, 1, 2	5.87	(2.65; 13.03)	1.16 × 10⁻⁶
23	BICF2P373712	0, 1, 2	0.23	(0.12; 0.45)	4.49 × 10⁻⁷
24	BICF2S23648284	0, 1, 2	4.78	(2.27; 10.08)	6.34 × 10⁻⁶
30	BICF2G630397948	0, 1, 2	3.39	(1.91; 6.03)	6.58 × 10⁻⁶
34	BICF2S23049081	0, 1, 2	3.92	(2.07; 7.41)	2.84 × 10⁻⁶
35	BICF2P28560	0, 1, 2	0.22	(0.10; 0.46)	2.81 × 10⁻⁶
37	BICF2G630127550	0, 1, 2	0.26	(0.13; 0.51)	9.59 × 10⁻⁶

1 CHR – chromosome; OR – odds ratio; CI – confidence interval

References

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Articles in this issue

DOI: https://doi.org/10.2478/jvetres-2023-0040 | Journal eISSN: 2450-8608 (formerly 2300-3235)

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Language: English

Page range: 427 - 436

Submitted on: Jan 21, 2023

Accepted on: Jun 28, 2023

Published on: Sep 20, 2023

Published by: National Veterinary Research Institute in Pulawy

In partnership with: Paradigm Publishing Services

Keywords:

dogs,

canine mammary tumours,

genetic marker,

genome-wide association studies,

SNP

Related subjects:

Life sciences,

Molecular biology,

Microbiology and virology,

Life sciences, other,

Medicine,

Veterinary medicine

© 2023 Anna Mucha, Błażej Nowak, Stanisław Dzimira, Bartłomiej Liszka, Magdalena Zatoń-Dobrowolska, published by National Veterinary Research Institute in Pulawy
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Volume 67 (2023): Issue 3 (September 2023)

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

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Paradigm

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