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Ghosh Et Al-2016-Reproduction in Domestic Animals
Ghosh Et Al-2016-Reproduction in Domestic Animals
Ghosh Et Al-2016-Reproduction in Domestic Animals
12636
ISSN 09366768
Short Communication
A Non-Reciprocal Autosomal Translocation 64,XX, t(4;10)(q21;p15) in an Arabian
Mare with Repeated Early Embryonic Loss
S Ghosh1, PJ Das2, F Avila3, BK Thwaits4, BP Chowdhary5 and T Raudsepp1
1
Texas A&M University, College Station, TX, USA; 2National Research Centre on Yak, Dirang, Arunachal Pradesh, India; 3Department of
Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA; 4Rogers Bandalero Ranch, Benson, AZ, USA; 5Qatar University,
Doha, Qatar
Contents
Balanced autosomal translocations are a known cause for
repeated early embryonic loss (REEL) in horses. In most cases,
carriers of such translocations are phenotypically normal, but
the chromosomal aberration negatively aects gametogenesis
giving rise to both genetically balanced and unbalanced
gametes. The latter, if involved in fertilization, result in
REEL, whereas gametes with the balanced form of translocation will pass the defect into next generation. Therefore, in
order to reduce the incidence of REEL, identication of
translocation carriers is critical. Here, we report about a
phenotypically normal 3-year-old Arabian mare that had
repeated resorption of conceptuses prior to day 45 of gestation
and was diagnosed with REEL. Conventional and molecular
cytogenetic analyses revealed that the mare had normal
chromosome number 64,XX but carried a non-mosaic and
non-reciprocal autosomal translocation t(4;10)(q21;p15). This
is a novel translocation described in horses with REEL and the
rst such report in Arabians. Previous cases of REEL due to
autosomal translocations have exclusively involved Thoroughbreds. The ndings underscore the importance of routine
cytogenetic screening of breeding animals.
Introduction
Subfertility due to early pregnancy failure before days
4060 of gestation is a recognized economic problem for
the equine industry (Ball 1988; Vanderwall 2008). In
case of repeated early embryonic loss (REEL), the
frequency of pregnancy failure can be as high as 50%
(Ball 1988). Several factors have been associated with
REEL, including the eect of uterine and oviduct
environment, hormonal imbalance, maternal age,
embryonic defects and genetic factors (Ball 1988).
Knowledge about the latter is currently limited to a
handful of cases with balanced chromosomal aberrations (Lear and Bailey 2008).
Balanced translocations result from reciprocal or
non-reciprocal exchange between non-homologous
chromosomes so that, overall, no genetic material is
lost or gained (see Villagomez and Pinton 2008).
Therefore, balanced translocations typically do not
aect the health or viability of the carrier, but they
disturb chromosome pairing and segregation during
gametogenesis, resulting in the formation of both
172
Table 1. Markers used for FISH analysis; EquCab2 horse reference genome (UCSC Genome Browser http://genome.ucsc.edu/)
Gene/marker symbol
NPY
ASB22
UMNe104
PEX7
URI1
PRKAG2
(a)
Cytogenetic location
CHORI-241 BAC
4:55,708,297-55,715,462
4:59,506,355-59,506,518
4:64,143,130-64,143,285
10:82,269,103-82,357,588
10:1,696,921-1,723,107
4:103,079,760-103,357,356
4q21.1-q21.3
4q21
4q21.1-q21.3
10q22-q23
10p15
4q26-q27
42L1
158I3
141L20
83E10
40B19
109O22
Reference
Raudsepp et al.
This study
Raudsepp et al.
Lear et al. 2001
Raudsepp et al.
Raudsepp et al.
2008
2008
2008
2008
(b)
(c)
Fig. 1. Cytogenetic characterization of the translocation. (a) A GTG-banded metaphase spread and (b) corresponding karyogram; (c) GTGbanded normal and aberrant chr4 and chr10 from four dierent cells; dotted line indicates the translocation breakpoint
(a)
173
(b)
(c)
(d)
(e)
Fig. 2. Translocation analysis by FISH. (ad) inverted DAPI-stained normal and aberrant chr4 and chr10 after FISH with selected markers (see
Table 1 for details); (e) schematic drawings of normal and aberrant chr4 and chr10; cytogenetic locations of six selected markers are shown to the
right of ideograms; deleted segment in chr4 is demarcated with red dotted line; translocation of 4q21-qter is indicated with a red arrow and shown
as red/white ideogram
Results
Initial karyotyping of Giemsa-stained metaphases
revealed 64 chromosomes, including two normal X
chromosomes. The latter was conrmed by CBG banding. However, in each cell we observed the presence of
two derivative submetacentric chromosomes: one very
small and another abnormally large. Further analysis by
GTG banding determined that the small chromosome
was chr4 that was missing a large segment of the long (q)
arm, and the large chromosome was composed of the
missing part of chr4q and the entire chr10 (Fig. 1a,b).
Analysis of 20 GTG-banded cells conrmed the presence
of the translocation in all cells and indicated that the
translocation break and fusion points were approximately at 4q21 and 10p15, respectively (Fig. 1c).
Table 2. Summary data about balanced autosomal translocations in horses with REEL
Karyotype
64,XX,t(1q;3q)
64,XY,t(1;30)
64,XX,t(1;16)
64,XX,t(1;21)
64,XX,t(16;22)
64,XX,t(4;13)
64,XY,t(5;16)+mar
64,XX,t(2;13)
64,XX,t(4;10)
Breakpoints
q14;q13
pter;qcen
q16;q21.3
q14;qter
q13;q18
pqcen;pqcen
qcen;p17
p13;pter
q21;p15
Type
Breed
Reference
Reciprocal
Nonreciprocal
Reciprocal
Nonreciprocal
Reciprocal
Reciprocal
Nonreciprocal
Nonreciprocal
Nonreciprocal
Thoroughbred
Thoroughbred
Thoroughbred
Thoroughbred
Thoroughbred
Thoroughbred
Thoroughbred
Thoroughbred
Arabian
Power 1991
Long 1996
Lear and Layton 2002
Lear et al. 2008
Lear et al. 2008
Lear et al. 2008
Durkin et al. 2011
Lear et al. 2014
This study
174
We concluded that the Arabian mare carried a nonmosaic and non-reciprocal balanced autosomal translocation t(4;10)(q21;p15), which was the most likely cause
of REEL.
Discussion
We characterized a novel autosomal translocation
t(4;10)(q21;p15) in the horse and reported a new case
in which subfertility due to REEL was associated with
chromosomal abnormality. While eight similar cases
have been previously described in Thoroughbred horses
(Table 2), this is the rst found in Arabians. As we had
no access to fertility records or samples for the dam and
sire of the case, we cannot speculate on whether this was
a de novo or inherited condition.
Examination of all REEL-associated translocations in
horses (Table 2) shows that none is recurrent. Even
though chrs1, 4, 13 and 16 are involved more than once,
chromosome combinations and translocation breakpoints are dierent in each case (Table 2). On the other
hand, only 11 of the 31 equine autosomes have been
engaged in these translocations which might be due to
very few available reports or because these equine
chromosomes are more prone for rearrangements.
Evidence for the latter is sparse (Lear et al. 2008), and
References
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Vaala WE, Varner DD (eds), Equine
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Cothran EG, McDonell S, Kenney DG,
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cytogenetics: the past and future. Cytogenet Genome Res 120, 4249.
Lear TL, Layton G, 2002: Use of zoo-FISH
to characterise a reciprocal translocation
in a thoroughbred mare: t(1;1 6)(q16;
q21.3). Equine Vet J 34, 207209.
Lear TL, Brandon R, Piumi F, Terry RR,
Guerin G, Thomas S, Bailey E, 2001:
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Author contributions
Clinical data and samples were provided by BKT; the study was
designed by TR and BPC; experiments were conducted, analysed and
interpreted by SG, PJD, FA and TR, and the manuscript was drafted
by TR, SG, PJD, FA and BPC.