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dc.contributor.authorWhitacre, L.en
dc.contributor.authorHoff, J.en
dc.contributor.authorSchnabel, R.en
dc.contributor.authorAlbarella, S.en
dc.contributor.authorCiotola, F.en
dc.contributor.authorPeretti, V.en
dc.contributor.authorStrozzi, F.en
dc.contributor.authorFerrandi, C.en
dc.contributor.authorRamunno, L.en
dc.contributor.authorSonstegard, T.en
dc.contributor.authorWilliams, J.en
dc.contributor.authorTaylor, J.en
dc.contributor.authorDecker, J.en
dc.identifier.citationScientific Reports, 2017; 7(1):39719-1-39719-9en
dc.description.abstractRecent strong selection for dairy traits in water buffalo has been associated with higher levels of inbreeding, leading to an increase in the prevalence of genetic diseases such as transverse hemimelia (TH), a congenital developmental abnormality characterized by absence of a variable distal portion of the hindlimbs. Limited genomic resources available for water buffalo required an original approach to identify genetic variants associated with the disease. The genomes of 4 bilateral and 7 unilateral affected cases and 14 controls were sequenced. A concordance analysis of SNPs and INDELs requiring homozygosity unique to all unilateral and bilateral cases revealed two genes, WNT7A and SMARCA4, known to play a role in embryonic hindlimb development. Additionally, SNP alleles in NOTCH1 and RARB were homozygous exclusively in the bilateral cases, suggesting an oligogenic mode of inheritance. Homozygosity mapping by whole genome de novo assembly also supported oligogenic inheritance; implicating 13 genes involved in hindlimb development in bilateral cases and 11 in unilateral cases. A genome-wide association study (GWAS) predicted additional modifier genes. Although our data show a complex inheritance of TH, we predict that homozygous variants in WNT7A and SMARCA4 are necessary for expression of TH and selection against these variants should eradicate TH.en
dc.description.statementofresponsibilityLynsey K. Whitacre, Jesse L. Hoff, Robert D. Schnabel, Sara Albarella, Francesca Ciotola, Vincenzo Peretti, Francesco Strozzi, Chiara Ferrandi, Luigi Ramunno, Tad S. Sonstegard, John L. Williams, Jeremy F. Taylor & Jared E. Deckeren
dc.publisherNature Publishing Groupen
dc.rights© The Author(s) 2017 . This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
dc.subjectAnimals; Buffaloes; Cattle; Ectromelia; Animal Diseases; DNA Helicases; Receptors, Retinoic Acid; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Wnt Proteins; Receptor, Notch1; Genome-Wide Association Study; Genes, Modifier; Whole Genome Sequencingen
dc.titleElucidating the genetic basis of an oligogenic birth defect using whole genome sequence data in a non-model organism, Bubalus bubalisen
dc.typeJournal articleen
pubs.library.collectionAnimal and Veterinary Sciences publicationsen
dc.identifier.orcidWilliams, J. [0000-0001-5188-7957]en
Appears in Collections:Animal and Veterinary Sciences publications

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