Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 locus

Autor: Carneiro, Miguel, Hu, Dou, Archer, John, Feng, Chungang, Afonso, Sandra, Chen, Congying, Blanco-Aguiar, José Antonio, Garreau, Hervé, Boucher, Samuel, Ferreira, Paula G., Ferrand, Nuno, Rubin, Carl-Johan, Andersson, Leif
Přispěvatelé: Ctr Invest Biodiversidade & Recursos Genet - CIBIO InBIO, Universidade do Porto, Fac Ciencias, Dept Biol, Dept Med Biochem & Microbiol, Sci Life Lab Uppsala, Uppsala University, State Key Lab Pig Genet Improvement & Prod Techno, Jiangxi Agricultural University, IREC CSIC UCLM JCCM, Instituto de Investigación en Recursos Cinegéticos (IREC), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Fédération Française pour les sciences de la Chimie (FFC), ICBAS, Dept Anat, UMIB, Department of Zoology [University of Johannesburg], University of Johannesburg (UJ), Department of Animal Bredding and Genetics, Swedish University of Agricultural Sciences (SLU), Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, Texas A&M University System, Quadro de Referência Estratégico Nacional (Portugal), Fundação para a Ciência e a Tecnologia (Portugal), European Research Council, Programa Operacional do Potencial Humano (Portugal), European Commission, Universidade do Porto [Porto], Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Dept Anim Breeding & Genet
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Genetics
Genetics, Genetics Society of America, 2017, 205 (2), pp.955-965. ⟨10.1534/genetics.116.196667⟩
Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 0016-6731
DOI: 10.1534/genetics.116.196667⟩
Popis: The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a ~ 12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4–29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2. Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.
The work was supported by POPH-QREN funds from the European Social Fund and Portuguese MCTES [Fundação para a Ciência e a Tecnologia Investigator, IF/00283/2014/CP1256/CT0012) and postdoc grants to M.C. (SFRH/BPD/72343/2010)]; by the European Research Council project BATESON to L.A.; by FEDER funds through the COMPETE program and Portuguese national funds through the Fundação para a Ciência e a Tecnologia (project PTDC/CVT/122943/2010); by the projects “Genomics and Evolutionary Biology” and “Genomics Applied to Genetic Resources” cofinanced by North Portugal Regional Operational Programme 2007/2013 (ON.2 – O Novo Norte) under the National Strategic Reference Framework and the European Regional Development Fund ERDF; by a European Union FP7 REGPOT grant [CIBIO-New-Gen] [286431]; and by travel grants to M.C. (COST Action TD1101).
Databáze: OpenAIRE
Externí odkaz: