Table 2.
The most promising candidate genes found by matching data sets from independent studies and their in silico analysis (level of expression in lactating mouse mammary gland, genetic variability in cattle and their functions).
| List of the most promising candidate genes and number of independent studies by approach |
In silico analysis |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Association studies |
Expression studies |
Number of SNPs |
|||||||||||||
| Gene | Gene name | Mouse KOs and transgenic experiments | Milk traits | Mastitis traits | Milk traits1 | Mastitis traits | Milk protein genetic variants | Epigenetic studies | Expression in lactating mammary gland2 (mouse) | Promoter (5 kb upstream) | 5′UTR | Exons3 | Introns (context 100 bp) | 3′UTR | Functions4 |
| Associated with milk production | |||||||||||||||
| ABCG2 | ATP-binding cassette, sub-family G (WHITE), member 2 | + + + | + | *** | 0 | 0 | 1 | 1 | 0 | E | |||||
| ATP2B2 | ATPase, Ca++ transporting, plasma membrane 2 | + | + | * | 1 | 0 | 1 | 3 | 0 | D | |||||
| B4GALT1 | UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1 | + | + | ** | 0 | 0 | 0 | 1 | 0 | A | |||||
| BTN1A1 | Butyrophilin, subfamily 1, member A1 | + | + | *** | 0 | 0 | 3 (2) | 0 | 0 | C | |||||
| CSN1S1 | Casein alpha s1 | + + + | + | + | + | *** | 0 | 0 | 1 (1) | 0 | 0 | C | |||
| CSN1S2 | Casein alpha s2 | + | + | NA | 0 | 0 | 0 | 0 | 0 | NA | |||||
| CSN2 | Casein beta | + | + | *** | 0 | 0 | 3 (3) | 0 | 0 | B | |||||
| CSN3 | Casein kappa | + | + + + | + | + | *** | 0 | 0 | 0 | 3 | 0 | B | |||
| DGAT1 | Diacylglycerol O-acyltransferase 1 | + | + + + + + + + | ** | NA | NA | NA | NA | NA | A | |||||
| EGF | Epidermal growth factor (beta urogastrone) | + | + | NA | 0 | 0 | 0 | 0 | 0 | B | |||||
| GHR | Growth hormone receptor | + + + + | ** | 0 | 0 | 0 | 0 | 0 | B | ||||||
| ID2 | Inhibitor of DNA binding 2, dominant negative helix-loop-helix protein | + | + | * | 0 | 0 | 0 | 1 | 0 | B | |||||
| LALBA | Lactalbumin, alpha | + | + | + | *** | 0 | 0 | 0 | 0 | 1 | A | ||||
| LEP | Leptin | + | + + + | + | ** | 0 | 0 | 8 (3) | 4 | 8 | B | ||||
| LGB | Lactoglobulin, beta | + + | + | NA | 0 | 1 | 1 | 0 | 0 | NA | |||||
| MFGE8 | Milk fat globule-EGF factor 8 protein | + | + | *** | 0 | 0 | 0 | 0 | 1 | A | |||||
| NME1 | Non-metastatic cells 1, protein (NM23A) expressed in | + | + | NA | 0 | 0 | 3 (2) | 0 | 1 | D | |||||
| PRL | Prolactin | + | + + | NA | 0 | 0 | 0 | 0 | 0 | B | |||||
| PTHLH | Parathyroid hormone-like peptide | + | + | ** | 0 | 0 | 0 | 0 | 0 | C | |||||
| STAT5A | Signal transducer and activator of transcription 5A | + | + + | ** | 0 | 0 | 0 | 0 | 0 | B | |||||
| XDH | Xanthine dehydrogenase | + | + | *** | 0 | 0 | 2 (1) | 1 | 0 | C | |||||
| Associated with mastitis resistance | |||||||||||||||
| ACTB | Actin, beta, cytoplasmic | + | + | * | 0 | 0 | 0 | 0 | 1 | D | |||||
| C5AR1 | Complement component 5a receptor 1 | + + | ** | 0 | 0 | 1 | 0 | 0 | B | ||||||
| CD14 | CD14 antigen | + + + + | *** | 0 | 1 | 1 | 0 | 0 | A | ||||||
| ETS2 | E26 avian leukaemia oncogene 2, 3′ domain | + | + | * | 0 | 0 | 0 | 1 | 1 | C | |||||
| FEZF2 | fez family zinc finger 2 | + | + | ** | 0 | 0 | 1 (1) | 1 | 0 | E | |||||
| IFNG | Interferon gamma | + + + | ** | 0 | 0 | 0 | 1 | 2 | D | ||||||
| IL1B | Interleukin 1 beta | + + + + | ** | 0 | 0 | 2 | 0 | 7 | D | ||||||
| IL6 | Interleukin 6 | + + | ** | 0 | 0 | 1 | 1 | 1 | B | ||||||
| IL8 | Interleukin 8 | + + + | NA | 0 | 0 | 0 | 5 | 7 | C | ||||||
| IL8RA | Interleukin 8 receptor, alpha | + + | ** | 0 | 0 | 0 | 0 | 0 | C | ||||||
| LBP | Lipopolysaccharide binding protein | + + | *** | 2 | 0 | 5 (2) | 0 | 0 | A | ||||||
| PTGS1 | Prostaglandin-endoperoxide synthase 1 | + | + | ** | 0 | 0 | 0 | 0 | 0 | A | |||||
| SAA3 | Serum amyloid A3 | + + | ** | 0 | 0 | 0 | 0 | 0 | A | ||||||
| TLR-2 | Toll-like receptor 2 | + + | ** | 0 | 0 | 3 (2) | 0 | 0 | A | ||||||
| TLR-4 | Toll-like receptor 4 | + + | + + | ** | 0 | 1 | 28 (8) | 4 | 2 | A | |||||
| TNF | Tumor necrosis factor | + + + + | ** | 0 | 0 | 0 | 0 | 0 | A | ||||||
| Associated with milk production and mastitis resistance | |||||||||||||||
| ACLY | ATP citrate lyase | + | + | ** | 0 | 0 | 2 | 3 | 0 | D | |||||
| BoLA-DRB3 | Major histocompatibility complex, class II, DRB3 | + + + | + + + | NA | 1 | 0 | 5 (5) | 0 | 0 | NA | |||||
| CCL2 | Chemokine (C-C motif) ligand 20 | + | + | * | 1 | 0 | 2 (2) | 1 | 0 | C | |||||
| KCNK1 | Potassium channel, subfamily K, member 1 | + | + | *** | 1 | 0 | 3 (1) | 1 | 0 | E | |||||
| LTF | Lactoferrin | + + | + | + | + | ** | 0 | 2 | 4 | 1 | 0 | A | |||
| RORA | RAR-related orphan receptor alpha | + | + | ** | 0 | 0 | 0 | 0 | 0 | D | |||||
| TP53 | Transformation related protein 53 | + | + | + | * | 0 | 0 | 1 | 1 | 0 | D | ||||
+, independent study.
Candidates suggested by Ron et al. (2007) on the basis of three independent expression experiments.
Mouse mammary gland expression score: *below median, **median to 10× median, ***above 10× median.
Number in brackets represents number of non-synonymous coding SNPs.
Top functions: A – inflammatory disease, inflammatory response, antigen presentation, B – connective tissue development and function, skeletal and muscular system development and function, endocrine system development and function, C – cancer, cellular movement and cellular development, D – cell-mediated immune response, lymphoid tissue structure and development, cancer, E – organ morphology, reproductive system development and function and amino acid metabolism.