Lethal genetic disorder in Poll Merino/Merino sheep in Australia

Shariflou,; Wade, Claire M.; Windsor, Peter; Tammen, Imke; James, J. W.; Nicholas, F. W.

doi:10.1111/j.1751-0813.2011.00789.x

“…Breeding programs resulting in high rates of inbreeding should be avoided due to the likelihood of declines in fitness [ 36 , 37 ] and homozygous recessive genotypes that are lethal [ 38 ]. However, if inbreeding is penalized too heavily, genetic diversity is maintained but with low rates of genetic gain (Figs.…”

Section: Discussionmentioning

confidence: 99%

Increased genetic gains in sheep, beef and dairy breeding programs from using female reproductive technologies combined with optimal contribution selection and genomic breeding values

Granleese

¹

,

Clark

²

,

Swan

³

et al. 2015

View full text Add to dashboard Cite

BackgroundFemale reproductive technologies such as multiple ovulation and embryo transfer (MOET) and juvenile in vitro embryo production and embryo transfer (JIVET) can boost rates of genetic gain but they can also increase rates of inbreeding. Inbreeding can be managed using the principles of optimal contribution selection (OCS), which maximizes genetic gain while placing a penalty on the rate of inbreeding. We evaluated the potential benefits and synergies that exist between genomic selection (GS) and reproductive technologies under OCS for sheep and cattle breeding programs.MethodsVarious breeding program scenarios were simulated stochastically including: (1) a sheep breeding program for the selection of a single trait that could be measured either early or late in life; (2) a beef breeding program with an early or late trait; and (3) a dairy breeding program with a sex limited trait. OCS was applied using a range of penalties (severe to no penalty) on co-ancestry of selection candidates, with the possibility of using multiple ovulation and embryo transfer (MOET) and/or juvenile in vitro embryo production and embryo transfer (JIVET) for females. Each breeding program was simulated with and without genomic selection.ResultsAll breeding programs could be penalized to result in an inbreeding rate of 1 % increase per generation. The addition of MOET to artificial insemination or natural breeding (AI/N), without the use of GS yielded an extra 25 to 60 % genetic gain. The further addition of JIVET did not yield an extra genetic gain. When GS was used, MOET and MOET + JIVET programs increased rates of genetic gain by 38 to 76 % and 51 to 81 % compared to AI/N, respectively.ConclusionsLarge increases in genetic gain were found across species when female reproductive technologies combined with genomic selection were applied and inbreeding was managed, especially for breeding programs that focus on the selection of traits measured late in life or that are sex-limited. Optimal contribution selection was an effective tool to optimally allocate different combinations of reproductive technologies. Applying a range of penalties to co-ancestry of selection candidates allows a comprehensive exploration of the inbreeding vs. genetic gain space.

show abstract

“…A third production animal paper continues the theme, and characterises a lethal genetic disorder that was found in Poll Merino/Merino sheep 4 . The study includes descriptions of a new congenital multisystem disorder, named brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in a commercial sheep flock.…”

Section: Production Animalsmentioning

confidence: 98%

In this issue – July 2011

Jackson¹

2011

Aust Veterinary J

0

View full text Add to dashboard Cite

show abstract

“…Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595–9940 ) is a previously reported lethal inherited disorder in Australian Poll Merino/Merino sheep [ 1 , 2 ] that, to the best of our knowledge, has not been reported in other sheep breeds in Australia. This disorder is characterized by a range of congenital defects and conforms with an autosomal recessive mode of inheritance based on previous pedigree information and segregation analyses [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595–9940 ) is a previously reported lethal inherited disorder in Australian Poll Merino/Merino sheep [ 1 , 2 ] that, to the best of our knowledge, has not been reported in other sheep breeds in Australia. This disorder is characterized by a range of congenital defects and conforms with an autosomal recessive mode of inheritance based on previous pedigree information and segregation analyses [ 1 ]. Affected lambs are stillborn and the primary defects associated with this disorder are brachygnathia, cardiomegaly and renal hypoplasia, with additional skeletal defects including short stature, a short and broad cranium, a small thoracic cavity reduced in size by approximately 25%, thin ribs and brachysternum (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular basis of a new ovine model for human 3M syndrome-2

Woolley

¹

,

Hayes

²

,

Shariflou

³

et al. 2020

View full text Add to dashboard Cite

Background Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595–9940) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2. Results Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%. Conclusions The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.

show abstract

Lethal genetic disorder in Poll Merino/Merino sheep in Australia

Cited by 9 publications

References 15 publications

Increased genetic gains in sheep, beef and dairy breeding programs from using female reproductive technologies combined with optimal contribution selection and genomic breeding values

Increased genetic gains in sheep, beef and dairy breeding programs from using female reproductive technologies combined with optimal contribution selection and genomic breeding values

In this issue – July 2011

Molecular basis of a new ovine model for human 3M syndrome-2

Contact Info

Product

Resources

About