@article{46002c12f27943ca9efc757b19d2e7e0,
title = "A deletion in GDF7 is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats",
abstract = "An inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test and a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3. Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats, by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing and genotyped by fragment analyses. This variant was not identified in 192 unaffected cats in the 99 Lives dataset. The variant segregated concordantly in an extended pedigree. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.",
keywords = "BMP12, Brain malformation, Feline, Felis catus, Genetics, Genome-wide association study, Genomics, Mendelian traits, Neurodevelopment, Whole genome sequencing",
author = "Yoshihiko Yu and Creighton, {Erica K.} and Buckley, {Reuben M.} and Lyons, {Leslie A.} and Buckley, {Reuben M.} and Danielle Aberdein and Alves, {Paulo C.} and Barsh, {Gregory S.} and Bellone, {Rebecca R.} and Bergstr{\"o}m, {Tomas F.} and Boyko, {Adam R.} and Brockman, {Jeffrey A.} and Casal, {Margret L.} and Castelhano, {Marta G.} and Ottmar Distl and Dodman, {Nicholas H.} and Ellinwood, {N. Matthew} and Fogle, {Jonathan E.} and Forman, {Oliver P.} and Garrick, {Dorian J.} and Ginns, {Edward I.} and Jens H{\"a}ggstr{\"o}m and Harvey, {Robert J.} and Daisuke Hasegawa and Bianca Haase and Helps, {Christopher R.} and Isabel Hernandez and Hyt{\"o}nen, {Marjo K.} and Maria Kaukonen and Kaelin, {Christopher B.} and Tomoki Kosho and Emilie Leclerc and Lear, {Teri L.} and Tosso Leeb and Li, {Ronald H.L.} and Hannes Lohi and Maria Longeri and Magnuson, {Mark A.} and Richard Malik and Mane, {Shrinivasrao P.} and Munday, {John S.} and Murphy, {William J.} and Pedersen, {Niels C.} and Peterson-Jones, {Simon M.} and Rothschild, {Max F.} and Clare Rusbridge and Beth Shapiro and Stern, {Joshua A.} and Swanson, {William F.} and Terio, {Karen A.} and Todhunter, {Rory J.} and Warren, {Wesley C.} and Wilcox, {Elizabeth A.} and Wildschutte, {Julia H.} and Yoshihiko Yu and Lyons, {Leslie A.}",
note = "Funding Information: Funding: This study was supported by in part by NIH Office of Research Infrastructure Programs (OD R24OD01092), Winn Feline Foundation (MT-13-010), the Cat Health Network (D14FE-552) and the MU Gilbreath McLorn Endowment for Comparative Medicine (L.A.L.). The authors thank the JSPS Overseas Challenge Program for Young Researchers (2017–2018) for sponsoring the visiting scholarship (Y.Y.) and the financial support from Mars, Inc. (R.M.B.). Publisher Copyright: {\textcopyright} 2020 by the authors.",
year = "2020",
month = jun,
doi = "10.3390/genes11060672",
language = "English (US)",
volume = "11",
pages = "1--15",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",
}