Table 1.
Results of the Whole Genome Sequencing and filtering approach.
| Defect | Coverage; Gaps | Het. variants | Priv. het. variants | Delet. priv. het. variants | Candidate mutation | Human syndromes (MIM #) |
|---|---|---|---|---|---|---|
| Glass-Eyed Albino (GEA) | 11.5 x; 1.5% | 3.1 × 106 | 4.4 × 103 | 3 | MITF p.R211del | Tietz syndrome (103500) |
| Dominant Red (DR) | 13.4 x; 1.2% | 3.4 × 106 | 3.2 × 103 | 3 | COPA p.R160C | — |
| Neurocristopathy (NC) | 13.4 x; 0.9% | 3.8 × 106 | 9.7 × 103 | 15 | CHD7 p.K594AfsX29 | CHARGE syndrome (214800) |
| Osteogenesis imperfecta type 2(OI)* | 20.7 x; 1.1% | 3.5 × 106 | 4.5 × 103 | 12 | COL1A1 p.A1049_P1050delinsS | Osteogenesis imperfecta type 2 (166210) |
| Bulldog Calf Syndrome (BD1) | 12.9 x; 1.2% | 3.8 × 106 | 28.4 × 103 | 29 | COL2A1 p.G600D | Achondrogenesis type II (200610) |
| Bulldog calf syndrome (BD2)** | 9.0 x; 1.6% | 1.9 × 106 | 4.2 × 103 | 28 | COL2A1 p.G996S | |
| Bulldog calf syndrome (BD3) | 15.1 x; 1.1% (15.8 x; 1.2% & 16.2 x; 1.4%) | 3.2 × 106 | 9.0 × 103 (200) | 9 (1) | COL2A1 p.G720S |
Het. variants: number of heterozygous variants; Priv. het. variants: number of private heterozygous variants; and Delet. priv. het. variants: number of deleterious private heterozygous variants after filtering for variants presents in 1230 control genomes or, between brackets, with 1230 control genomes and both parents. x: unit corresponding to the average number of time that one base pair of the genome is read. Gaps: percentage of the UMD3.1 bovine sequence assembly that is not covered by sequence reads. *: the sequenced animal was the mosaic sire. **: to identify mutations compatible with BD2 syndrome in Holstein cattle, we applied a less stringent quality threshold (quality score = 15 instead of 30) compared to the other defects due to the lower genome coverage (9.0 x) of the BD2 sequencing data (see Methods). Note that for the Holstein GEA, DR, BD2 and BD3 animals, the number of private heterozygous variants is inferior or close to the number of de novo mutations which may have accumulated since the creation of this breed considering that approximately 200 mutations accumulated at each generation over 20 generations. This illustrates how the small effective size of the worldwide Holstein population (Ne ~100) combined with the high number of control genomes for this breed (n = 345) enable to capture most of its genetic diversity. In contrast, the elevated number of private heterozygous variants for the Charolais X Salers crossbred calf BD1 reflects the small number of control genomes available for the Salers breed (n = 4).