Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/103946
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Type: Journal article
Title: Elucidating the genetic basis of an oligogenic birth defect using whole genome sequence data in a non-model organism, Bubalus bubalis
Author: Whitacre, L.
Hoff, J.
Schnabel, R.
Albarella, S.
Ciotola, F.
Peretti, V.
Strozzi, F.
Ferrandi, C.
Ramunno, L.
Sonstegard, T.
Williams, J.
Taylor, J.
Decker, J.
Citation: Scientific Reports, 2017; 7(1):39719-1-39719-9
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Lynsey 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. Decker
Abstract: Recent 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.
Keywords: Animals
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 Sequencing
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 http://creativecommons.org/licenses/by/4.0/
DOI: 10.1038/srep39719
Published version: http://dx.doi.org/10.1038/srep39719
Appears in Collections:Animal and Veterinary Sciences publications
Aurora harvest 3

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