Three novel nonsense mutations of prolactin receptor found in heat‐tolerant <i>Bos taurus</i> breeds of the Caribbean Basin

Murillo, Julio Mateo Flórez; Landaeta-Hernández, Antonio; Kim, Eui-Soo; Bostrom, Jonathan R.; Larson, Sabreena; O'Brien, Ana M. Pérez; Montero-Urdaneta, Merilio; Garcia, José Fernando; Sonstegard, Tad S.

doi:10.1111/age.13027

Cited by 16 publications

(15 citation statements)

References 8 publications

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“…We aimed at introducing natural sequence variants in the PMEL and PRLR genes thought to increase thermotolerance of cattle ( Schmutz and Dreger, 2013 ; Littlejohn et al, 2014 ; Porto-Neto et al, 2018 ; Flórez Murillo et al, 2021 ; Laible et al, 2021 ). To edit the p .Leu18del PMEL mutation, caused by a 3bp deletion associated with coat color dilution, we tested gRNA 129F/Cas9, previously used to generate fully edited calves by cell-mediated HDR editing ( Laible et al, 2021 ), and the TALEN pair TL17/TR217 ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

“…Lightening the coat color will reduce the radiative heat gain from sunlight which impacts on heat stress ( Hansen, 1990 ). The other sequence variants comprised single base pair changes in the prolactin receptor ( PRLR ) gene known from tropical cattle, all generating pre-mature stop codons associated with the slick coat phenotype and improved thermotolerance ( Littlejohn et al, 2014 ; Porto-Neto et al, 2018 ; Flórez Murillo et al, 2021 ). These editing targets were then used to determine the impact of TALEN and gRNA/Cas9 editors, the time of injection, donor templates and delivery of the editors as DNA, RNA or as ribonucleoprotein (RNP) complexes (for gRNA/Cas9 editors) on the conversion efficiency into completely edited genotypes.…”

Section: Introductionmentioning

confidence: 99%

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Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos

et al. 2022

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Genome editing provides opportunities to improve current cattle breeding strategies through targeted introduction of natural sequence variants, accelerating genetic gain. This can be achieved by harnessing homology-directed repair mechanisms following editor-induced cleavage of the genome in the presence of a repair template. Introducing the genome editors into zygotes and editing in embryos has the advantage of uncompromised development into live animals and alignment with contemporary embryo-based improvement practices. In our study, we investigated the potential to introduce sequence variants, known from the pre-melanosomal protein 17 (PMEL) and prolactin receptor (PRLR) genes, and produce non-mosaic, edited embryos, completely converted into the precision genotype. Injection of gRNA/Cas9 editors into bovine zygotes to introduce a 3 bp deletion variant into the PMEL gene produced up to 11% fully converted embryos. The conversion rate was increased to up to 48% with the use of TALEN but only when delivered by plasmid. Testing three gRNA/Cas9 editors in the context of several known PRLR sequence variants, different repair template designs and delivery as DNA, RNA or ribonucleoprotein achieved full conversion rates up to 8%. Furthermore, we developed a biopsy-based screening strategy for non-mosaic embryos which has the potential for exclusively producing non-mosaic animals with intended precision edits.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos

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“…A frameshift mutation resulting from a single cystine deletion caused a premature stop codon (p.Leu462*) in the resulting protein. This mutation became known as the SLICK1 allele and, although the SLICK1 has been the best characterized mutation so far, additional variants of the PRLR have been reported that result in truncation of the protein at different points and causing the similar slick phenotype observed in criollo-derived B. taurus breeds ( Porto-Neto et al, 2018 ; Flórez Murillo et al, 2021 ). These alleles have been named SLICK2-SLICK6 ( Flórez Murillo et al, 2021 ).…”

Section: Gene Editing To Alleviate the Effects Of Heat Stress On Euro...mentioning

confidence: 99%

Perspectives of gene editing for cattle farming in tropical and subtropical regions

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“…2018; Flórez Murillo et␣al . 2021). The first slick mutation to be described, SLICK1, is prevalent in the Senepol breed from the US Virgin Islands and has been introduced into Holstein and Jersey by crossbreeding.…”

Section: Breed Mating (Male × Female) Expected Frequency a Number Of ...mentioning

confidence: 99%

“…The slick-hair phenotype in cattle is due to one of a series of mutations in the prolactin receptor (PRLR) that arose in Criollo-type cattle. The mutations cause truncation of the Cterminal region of the protein involved in STAT5 activation during prolactin signaling (Littlejohn et al 2014;Porto-Neto et al 2018;Fl orez Murillo et al 2021). The first slick mutation to be described, SLICK1, is prevalent in the Senepol breed from the US Virgin Islands and has been introduced into Holstein and Jersey by crossbreeding.…”

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Inheritance of the SLICK1 allele of PRLR in cattle

et al. 2021

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The slick-hair phenotype in cattle is due to one of a series of mutations in the prolactin receptor (PRLR) that cause truncation of the C-terminal region of the protein involved in JAK2/STAT5 activation during prolactin signaling. Here we evaluated whether the inheritance of the SLICK1 allele, the first slick mutation discovered, is inherited in a fashion consistent with Hardy-Weinberg equilibrium. It was hypothesized that any deleterious effect of inheriting the allele on embryonic or fetal function would result in reduced frequency of the allele in offspring. A total of 525 Holstein and Senepol cattle produced from matings involving one or both parents with the SLICK1 allele were genotyped. The observed frequency of the SLICK1 allele (0.247) was not significantly different than the expected frequency of 0.269. These results support the idea that inheritance of the SLICK1 allele does not act in the embryo or fetus to modify its competence to complete development to term.

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Three novel nonsense mutations of prolactin receptor found in heat‐tolerant Bos taurus breeds of the Caribbean Basin

Cited by 16 publications

References 8 publications

Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos

Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos

Perspectives of gene editing for cattle farming in tropical and subtropical regions

Inheritance of the SLICK1 allele of PRLR in cattle

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