Advertisement

Case Study: Polymelia in a Holstein calf

      ABSTRACT

      Polymelia, the manifestation of extra limbs or parts of limbs, occurs when there is a developmental duplication in the novel NHL repeat domain containing protein (NHLRC2) gene in Angus cattle. In Holstein cattle, little is known about the etiology of polymelia. To determine the genetic etiology of polymelia in a Holstein calf, genotyping and sequencing of the Angus developmental duplication locus, karyotyping, and a genome-wide association analysis were performed. The genome-wide association analysis compared the polymelia calf (case) to 2,650 control (normal) Holstein calves using EMMAX-GRM (Efficient Mixed-Model Association eXpedited-Genomic Relationship Matrix) software. In addition, homozygous loci within genes in the case that were never found in a control were also evaluated as putative loci. The polymelia calf had a normal Angus developmental duplication genotype that was confirmed by sequencing. Karyotyping revealed no evidence of chromosomal breakage or gross chromosomal abnormalities in the polymelia calf. The additive genome-wide association analysis identified loci associated with polymelia on BTA13 (P < 1 × 10−281) and BTA10 (P < 2 × 10−110). Seventy-nine candidate genes were identified that contained homozygous genotypes in the case that were never identified in 2,650 controls. Candidate genes include MSH homeobox 2 (MSX2) on BTA20, which has been associated with limb development in mice, and GINS complex subunit 1 (GINS1) on BTA13, which is involved in early embryogenesis in mice. In summary, these results suggest that the etiology of polymelia differs by cattle breed and is the result of genetic variants at more than one locus.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      LITERATURE CITED

        • Albarella S.
        • Ciotola F.
        • Dario C.
        • Iannuzzi L.
        • Barbieri V.
        • Peretti V.
        Chromosome instability in Mediterranean Italian buffaloes affected by limb malformation (transversal hemimelia).
        10.1093/mutage/gep030
        19640928
        Mutagenesis. 2009; 24: 471-474
        • Beever J.E.
        Likely Presence of Genetic Condition in a Line of Angus Cattle.
        2013 (Accessed Aug. 2016)
        • Bensoussan-Trigano V.
        • Lallemand Y.
        • Saint Cloment C.
        • Robert B.
        Msx1 and Msx2 in limb mesenchyme modulate digit number and identity.
        10.1002/dvdy.22619
        21465616
        Dev. Dyn. 2011; 240: 1190-1202
        • Debeer P.
        • Bacchelli C.
        • Scambler P.J.
        • De Smet L.
        • Fryns J.-P.
        • Goodman F.R.
        Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.
        10.1136/jmg.39.11.852
        12414828
        J. Med. Genet. 2002; 39: 852-856
        • Denholm L.
        • Martin L.
        • Denman A.
        Polymelia (supernumerary limbs) in Angus calves.
        2011 (Accessed Oct. 2016)
        • Fourie S.L.
        Congenital supernumerary ectopic limbs in a Brahman-cross calf.
        2286989
        J. S. Afr. Vet. Assoc. 1990; 61: 68-70
        • Goodman F.R.
        Limb malformations and the human HOX genes.
        10.1002/ajmg.10776
        12357469
        Am. J. Med. Genet. 2002; 112: 256-265
        • Hirsbrunner G.
        • Keller C.
        • Dolf G.
        Polymelia in a Holstein Friesian calf.
        10.1024/0036-7281.144.6.289
        12125240
        Schweiz. Arch. Tierheilkd. 2002; 144: 289-291
        • Johnston A.
        Polymelia in a Hereford-cross calf.
        10.1136/vr.116.22.585
        4013047
        Vet. Rec. 1985; 116: 585-586
        • Kim C.
        • Yeo S.
        • Cho G.
        • Lee J.
        • Choi M.
        • Won C.
        • Kim J.
        • Lee S.
        Polymelia with two extra forelimbs at the right scapular region in a male Korean native calf.
        10.1292/jvms.63.1161
        11714039
        J. Vet. Med. Sci. 2001; 63: 1161-1164
        • Koshiba K.
        • Kuroiwa A.
        • Yamamoto H.
        • Tamura K.
        • Ide H.
        Expression of Msx genes in regenerating and developing limbs of axolotl.
        9846382
        J. Exp. Zool. 1998; 282: 703-714
        • Muirhead T.L.
        • Pack L.
        • Radtke C.L.
        Unilateral notomelia in a newborn Holstein calf.
        24982517
        Can. Vet. J. 2014; 55: 659-662
        • Murondoti A.
        • Busayi R.M.
        Perineomelia, polydactyly and other malformations in a Mashona calf.
        10.1136/vr.148.16.512
        11345996
        Vet. Rec. 2001; 148: 512-513
        • Nagahama Y.
        • Ueno M.
        • Miyamoto S.
        • Morii E.
        • Minami T.
        • Mochizuki N.
        • Saya H.
        • Takakura N.
        PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties.
        10.1158/0008-5472.CAN-09-3662
        20103637
        Cancer Res. 2010; 70: 1215-1224
        • Neibergs H.L.
        • Seabury C.M.
        • Wojtowicz A.J.
        • Wang Z.
        • Scraggs E.
        • Kiser J.N.
        • Neupane M.
        • Womack J.E.
        • Van Eenennaam A.
        • Hagevoort G.R.
        • Lehenbauer T.W.
        • Aly S.
        • Davis J.
        • Taylor J.F.
        Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned Holstein calves.
        10.1186/1471-2164-15-1164
        25534905
        BMC Genomics. 2014; 15: 1164
        • Nowacka J.
        • Urbaniak K.
        • Antosik P.
        • Jaskowski J.M.
        • Frackowiak H.
        • Switonski M.
        Polymelia associated with frequent chromosome breaks in a heifer.
        10.1136/vr.161.8.276
        17720968
        Vet. Rec. 2007; 161: 276-277
        • Raudsepp T.
        • Chowdhary B.P.
        Murphy W. Molecular Biology. Humana Press, Totowa, NJ2008: 31-49
        • Rousseaux C.G.
        • Ribble C.S.
        Developmental anomalies in farm animals: II. Defining etiology.
        17422944
        Can. Vet. J. 1988; 29: 30-40
        • Talamillo A.
        • Bastida M.F.
        • Fernandez-Teran M.
        • Ros M.A.
        The developing limb and the control of the number of digits.
        10.1111/j.1399-0004.2005.00404.x
        15679824
        Clin. Genet. 2005; 67: 143-153
        • Ueno M.
        • Itoh M.
        • Kong L.
        • Sugihara K.
        • Asano M.
        • Takakura N.
        PSF1 is essential for early embryogenesis in mice.
        10.1128/MCB.25.23.10528-10532.2005
        16287864
        Mol. Cell. Biol. 2005; 25: 10528-10532