Phenotypes

Charlier et al. (2016): nonsense (stop-gain) p.Lys693∗

Using mate-pair libraries from one affected and three controls, Charlier et al. (2012) obtained around 3.4Gb of sequence from each animal. Comparison of sequence in the candidate BTA21 region "revealed a 3.3 Kb deletion removing exons 25–27 of the 37 composing the FANCI (Fanconi anemia complementation-group I) gene". Noting that the carrier frequency is far too high (up to 7.4%) to be consistent with a relatively rare autosomal recessive disor...

Within the mapped candidate region (see Mapping section), Fritz et al. (2018) identified a likely causal variant as "an A-to-G transition at position 29,773,628 bp on chromosome 16 (g.29773628A>G; rs434666183)". The authors explained that "This A-to-G transition changes the initiator ATG (methionine) codon to ACG because the gene is transcribed on the reverse strand. . . . Initiation of translation at the closest in-frame Met codon would tr...

Comparison of sequence of the 713kb candidate region (mentioned in the mapping section above) in an obligate carrier, one of its offspring, 43 members of the Fleckvieh breed (in which the disorder has never been reported) and 191 non-Fleckviehs from the 1000-bulls project revealed 2 candidate causal SNVs: a coding variant and an intronic variant of the gene UBE3B, which encodes ubiquitin protein ligase E3B, and mutations in which cause a simil...

By examining three comparative positional candidate genes from their mapping results (see Mapping section), Krebs et al. (2007) reported strong evidence that this disorder in cattle is due to a mutation in "FVT1, encoding 3-ketodihydrosphingosine reductase, which catalyzes a crucial step in the glycosphingolipid metabolism". Specifically, the mutation is "a G-to-A missense mutation that changes Ala-175 to Thr". Interestingly, the FVT1 gene, of...