The Second Case of Non-Mosaic Trisomy of Chromosome 26 with Homologous Fusion 26q;26q in the Horse.
Abstract: We present cytogenetic and genotyping analysis of a Thoroughbred foal with congenital neurologic disorders and its phenotypically normal dam. We show that the foal has non-mosaic trisomy for chromosome 26 (ECA26) but normal 2n = 64 diploid number because two copies of ECA26 form a metacentric derivative chromosome der(26q;26q). The dam has normal 64,XX karyotype indicating that der(26q;26q) in the foal originates from errors in parental meiosis or post-fertilization events. Genotyping ECA26 microsatellites in the foal and its dam suggests that trisomy ECA26 is likely of maternal origin and that der(26q;26q) resulted from Robertsonian fusion. We demonstrate that conventional and molecular cytogenetic approaches can accurately identify aneuploidy with a derivative chromosome but determining the mechanism and parental origin of the rearrangement requires genotyping with chromosome-specific polymorphic markers. Most curiously, this is the second case of trisomy ECA26 with der(26q;26q) in the horse, whereas all other equine autosomal trisomies are 'traditional' with three separate chromosomes. We discuss possible ECA26 instability as a contributing factor for the aberration and likely ECA26-specific genetic effects on the clinical phenotype. Finally, because ECA26 shares evolutionary homology with human chromosome 21, which trisomy causes Down syndrome, cytogenetic, molecular, and phenotypic similarities between trisomies ECA26 and HSA21 are discussed.
Publication Date: 2022-03-22 PubMed ID: 35405793PubMed Central: PMC8996834DOI: 10.3390/ani12070803Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Case Reports
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article explores the cytogenetic and genotyping analysis of a Thoroughbred foal with congenital neurologic disorders. The study concludes that the foal’s condition is likely due to non-mosaic trisomy of chromosome 26, an abnormality obtained from the mother, resulting in a unique derivative chromosome.
Cytogenetic and Genotyping Analysis in Horses
- The research starts with the examination of a Thoroughbred foal exhibiting congenital neurologic disorders. The scientists conducted intensive cytogenetic and genotyping analyses on this foal and its phenotypically normal mother.
- Through their assessment, they determined that the foal has non-mosaic trisomy for chromosome 26 (ECA26), where it possesses three copies of chromosome 26 instead of the standard two. However, the foal’s total number of chromosomes remains normal at 64.
- Two of the ECA26s have uniquely formed a single metacentric derivative chromosome, designated as der(26q;26q).
Genetic Origin and Decision of the Abnormality
- The mother horse carries no abnormality, possessing a normal karyotype of 64,XX. With this in mind, the scientists suggest that the foal’s der(26q;26q) chromosome likely emerges from errors during parental meiosis or during post-fertilization events.
- The occurrence of trisomy ECA26, in this case, is likely to have originated from the mother. The derivative chromosome der(26q;26q) is speculated to be a result of a Robertsonian fusion, an unusual type of chromosomal rearrangement.
Detection and Identification Process of Aneuploidy
- The study showcases that conventional and molecular cytogenetic approaches can be rely upon to pinpoint aneuploidy with a derivative chromosome. However, the identification of the method and parental origin of the rearrangement demands genotyping with chromosome-specific polymorphic markers.
Unique Case of Trisomy ECA26 with der(26q;26q)
- This anomaly stands out as only the second known case of trisomy ECA26 with der(26q;26q) in horses. In contrast, every other autosomal trisomies in horses involve ‘traditional’ formation with three separate chromosomes.
- The researchers speculate on possible ECA26 instability as a factor contributing to the aberration, and probable genetic effects from ECA26 on the clinical phenotype of the foal.
Comparative Study with Human Chromosomal Disorders
- Due to evolutionary homology between horse chromosome 26 (ECA26) and human chromosome 21, whose trisomy leads to Down Syndrome, the research also recognises potential similarities in cytogenetic, molecular, and phenotypic traits between trisomies ECA26 and HSA21 (human chromosome 21).
Cite This Article
APA
Ghosh S, Kjöllerström J, Metcalfe L, Reed S, Juras R, Raudsepp T.
(2022).
The Second Case of Non-Mosaic Trisomy of Chromosome 26 with Homologous Fusion 26q;26q in the Horse.
Animals (Basel), 12(7), 803.
https://doi.org/10.3390/ani12070803 Publication
Researcher Affiliations
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
- Rood & Riddle Equine Hospital, Lexington, KY 40580, USA.
- Rood & Riddle Equine Hospital, Lexington, KY 40580, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
Grant Funding
- na / Texas A&M Molecular Cytogenetics and Animal Genetics Laboratories
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 41 references
- Lear TL, Bailey E. Equine clinical cytogenetics: the past and future.. Cytogenet Genome Res 2008;120(1-2):42-9.
- Bugno-Poniewierska M, Raudsepp T. Horse Clinical Cytogenetics: Recurrent Themes and Novel Findings.. Animals (Basel) 2021 Mar 16;11(3).
- Raudsepp T, Chowdhary BP. Chromosome Aberrations and Fertility Disorders in Domestic Animals.. Annu Rev Anim Biosci 2016;4:15-43.
- Raudsepp T, Durkin K, Lear TL, Das PJ, Avila F, Kachroo P, Chowdhary BP. Molecular heterogeneity of XY sex reversal in horses.. Anim Genet 2010 Dec;41 Suppl 2:41-52.
- Janečka JE, Davis BW, Ghosh S, Paria N, Das PJ, Orlando L, Schubert M, Nielsen MK, Stout TAE, Brashear W, Li G, Johnson CD, Metz RP, Zadjali AMA, Love CC, Varner DD, Bellott DW, Murphy WJ, Chowdhary BP, Raudsepp T. Horse Y chromosome assembly displays unique evolutionary features and putative stallion fertility genes.. Nat Commun 2018 Jul 27;9(1):2945.
- Shilton CA, Kahler A, Davis BW, Crabtree JR, Crowhurst J, McGladdery AJ, Wathes DC, Raudsepp T, de Mestre AM. Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse.. Sci Rep 2020 Aug 7;10(1):13314.
- Brito L, Sertich P, Durkin K, Chowdhary B, Turner R, Greene L, McDonnell S. Autosomic 27 Trisomy in a Standardbred Colt. J. Equine Vet. Sci. 2008;28:431–436.
- Holečková B, Schwarzbacherová V, Galdíková M, Koleničová S, Halušková J, Staničová J, Verebová V, Jutková A. Chromosomal Aberrations in Cattle.. Genes (Basel) 2021 Aug 27;12(9).
- Iannuzzi A, Parma P, Iannuzzi L. Chromosome Abnormalities and Fertility in Domestic Bovids: A Review.. Animals (Basel) 2021 Mar 12;11(3).
- Donaldson B, Villagomez DAF, King WA. Classical, Molecular, and Genomic Cytogenetics of the Pig, a Clinical Perspective.. Animals (Basel) 2021 Apr 27;11(5).
- Szczerbal I, Switonski M. Clinical Cytogenetics of the Dog: A Review.. Animals (Basel) 2021 Mar 27;11(4).
- Chen S, Liu D, Zhang J, Li S, Zhang L, Fan J, Luo Y, Qian Y, Huang H, Liu C, Zhu H, Jiang Z, Xu C. A copy number variation genotyping method for aneuploidy detection in spontaneous abortion specimens.. Prenat Diagn 2017 Feb;37(2):176-183.
- Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy.. Nat Rev Genet 2001 Apr;2(4):280-91.
- Hassold T, Maylor-Hagen H, Wood A, Gruhn J, Hoffmann E, Broman KW, Hunt P. Failure to recombine is a common feature of human oogenesis.. Am J Hum Genet 2021 Jan 7;108(1):16-24.
- Hervé B, Quibel T, Taieb S, Ruiz M, Molina-Gomes D, Vialard F. Are de novo rea(21;21) chromosomes really de novo?. Clin Case Rep 2015 Oct;3(10):786-9.
- Antonarakis SE, Adelsberger PA, Petersen MB, Binkert F, Schinzel AA. Analysis of DNA polymorphisms suggests that most de novo dup(21q) chromosomes in patients with Down syndrome are isochromosomes and not translocations.. Am J Hum Genet 1990 Dec;47(6):968-72.
- Bandyopadhyay R, McCaskill C, Knox-Du Bois C, Zhou Y, Berend SA, Bijlsma E, Shaffer LG. Mosaicism in a patient with Down syndrome reveals post-fertilization formation of a Robertsonian translocation and isochromosome.. Am J Med Genet A 2003 Jan 15;116A(2):159-63.
- Shaffer LG, Lupski JR. Molecular mechanisms for constitutional chromosomal rearrangements in humans.. Annu Rev Genet 2000;34:297-329.
- Israni A, Mandal A. De Novo Robertsonian Translocation t(21; 21) in a Child with Down Syndrome. J. Nepal Paediatr. Soc. 2017;37:92–94.
- Bowling AT, Millon L, Hughes JP. An update of chromosomal abnormalities in mares.. J Reprod Fertil Suppl 1987;35:149-55.
- Bowling AT, Millon LV. Two autosomal trisomies in the horse: 64,XX,-26,+t(26q26q) and 65,XX,+30.. Genome 1990 Oct;33(5):679-82.
- Raudsepp T, Chowdhary BP. FISH for mapping single copy genes.. Methods Mol Biol 2008;422:31-49.
- Seabright M. A rapid banding technique for human chromosomes.. Lancet 1971 Oct 30;2(7731):971-2.
- Bowling AT, Breen M, Chowdhary BP, Hirota K, Lear T, Millon LV, Ponce de Leon FA, Raudsepp T, Stranzinger G. International system for cytogenetic nomenclature of the domestic horse. Report of the Third International Committee for the Standardization of the domestic horse karyotype, Davis, CA, USA, 1996.. Chromosome Res 1997 Nov;5(7):433-43.
- McGowan-Jordan J, Simons A, Schmid M. An International System for Human Cytogenomic Nomenclature. 2020. p. 163.
- Raudsepp T, Gustafson-Seabury A, Durkin K, Wagner ML, Goh G, Seabury CM, Brinkmeyer-Langford C, Lee EJ, Agarwala R, Stallknecht-Rice E, Schäffer AA, Skow LC, Tozaki T, Yasue H, Penedo MC, Lyons LA, Khazanehdari KA, Binns MM, MacLeod JN, Distl O, Guérin G, Leeb T, Mickelson JR, Chowdhary BP. A 4,103 marker integrated physical and comparative map of the horse genome.. Cytogenet Genome Res 2008;122(1):28-36.
- Ghosh S, Carden CF, Juras R, Mendoza MN, Jevit MJ, Castaneda C, Phelps O, Dube J, Kelley DE, Varner DD, Love CC, Raudsepp T. Two Novel Cases of Autosomal Translocations in the Horse: Warmblood Family Segregating t(4;30) and a Cloned Arabian with a de novo t(12;25).. Cytogenet Genome Res 2020;160(11-12):688-697.
- Khanshour A, Conant E, Juras R, Cothran EG. Microsatellite analysis of genetic diversity and population structure of Arabian horse populations.. J Hered 2013 May-Jun;104(3):386-98.
- Juras R, Cothran EG, Klimas R. Genetic analysis of three Lithuanian native horse breeds. Acta Agric. Scand. Sect. A Anim. Sci. 2003;53:180–185.
- Schuelke M. An economic method for the fluorescent labeling of PCR fragments.. Nat Biotechnol 2000 Feb;18(2):233-4.
- Tozaki T, Penedo MC, Oliveira RP, Katz JP, Millon LV, Ward T, Pettigrew DC, Brault LS, Tomita M, Kurosawa M, Hasegawa T, Hirota K. Isolation, characterization and chromosome assignment of 341 newly isolated equine TKY microsatellite markers.. Anim Genet 2004 Dec;35(6):487-96.
- Shaffer LG, Jackson-Cook CK, Meyer JM, Brown JA, Spence JE. A molecular genetic approach to the identification of isochromosomes of chromosome 21.. Hum Genet 1991 Feb;86(4):375-82.
- Harel T, Pehlivan D, Caskey CT, Lupski JR. Mendelian, Non-Mendelian, Multigenic Inheritance, and Epigenetics. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease 2015. pp. 3–27.
- Trifonov VA, Stanyon R, Nesterenko AI, Fu B, Perelman PL, O'Brien PC, Stone G, Rubtsova NV, Houck ML, Robinson TJ, Ferguson-Smith MA, Dobigny G, Graphodatsky AS, Yang F. Multidirectional cross-species painting illuminates the history of karyotypic evolution in Perissodactyla.. Chromosome Res 2008;16(1):89-107.
- Shaffer LG, McCaskill C, Haller V, Brown JA, Jackson-Cook CK. Further characterization of 19 cases of rea(21q21q) and delineation as isochromosomes or Robertsonian translocations in Down syndrome.. Am J Med Genet 1993 Dec 1;47(8):1218-22.
- Shaffer LG, McCaskill C, Han JY, Choo KH, Cutillo DM, Donnenfeld AE, Weiss L, Van Dyke DL. Molecular characterization of de novo secondary trisomy 13.. Am J Hum Genet 1994 Nov;55(5):968-74.
- Kalbfleisch TS, Rice ES, DePriest MS Jr, Walenz BP, Hestand MS, Vermeesch JR, O Connell BL, Fiddes IT, Vershinina AO, Saremi NF, Petersen JL, Finno CJ, Bellone RR, McCue ME, Brooks SA, Bailey E, Orlando L, Green RE, Miller DC, Antczak DF, MacLeod JN. Improved reference genome for the domestic horse increases assembly contiguity and composition.. Commun Biol 2018;1:197.
- Yang F, Fu B, O'Brien PC, Nie W, Ryder OA, Ferguson-Smith MA. Refined genome-wide comparative map of the domestic horse, donkey and human based on cross-species chromosome painting: insight into the occasional fertility of mules.. Chromosome Res 2004;12(1):65-76.
- Burns EN, Finno CJ. Equine degenerative myeloencephalopathy: prevalence, impact, and management.. Vet Med (Auckl) 2018;9:63-67.
- Parizot E, Dard R, Janel N, Vialard F. Down syndrome and infertility: what support should we provide?. J Assist Reprod Genet 2019 Jun;36(6):1063-1067.
- Bull MJ. Down Syndrome.. N Engl J Med 2020 Jun 11;382(24):2344-2352.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
