Cytogenetic and Molecular Characterization of Y Isochromosome in a 63XO/64Xi(Yq) Mosaic Karyotype of an Intersex Horse

Abstract

Sex chromosome aberrations commonly lead to abnormal sexual development. Here we cytogenetically and molecularly characterized Y isochromosome in an intersex horse. Blood lymphocyte analysis showed a mosaic karyotype with 96% 63,XO and 4% 64,Xi(Y) cells. Molecular analysis of the isochromosome was carried out by fluorescence in situ hybridization and polymerase chain reaction with male-specific and pseudoautosomal markers from the horse Y chromosome. We found that the isochromosome was monocentric, composed of 2 long arms, carrying 2 sets of genes of the pseudoautosomal region (PAR) and the male-specific region of the Y (MSY), including the SRY - thus being genetically equivalent to Y disomy. Sequence analysis of a 1,955-bp region including the SRY exon, the promoter and the UTRs, revealed no mutations in the aberrant Y. The presence of an intact SRY in a small proportion of cells is the proposed cause for the intersex phenotype. Given that the i(Yq) was present in a mosaic form, both post-zygotic and meiotic mechanisms of its origin were proposed. We speculated that nonmosaic 64,Xi(Yq) karyotypes might be rare or absent because of the likely instability of the i(Yq) during cell division. Genetic and phenotypic implications of Y isochromosome formation in other mammals are discussed in the light of the diversity of Y chromosome organization between species.

Horse Y chromosome assembly displays unique evolutionary features and putative stallion fertility genes

“…1 Horse Y chromosome organization. a Cytogenetic features of the horse Y chromosome: G-band positive material corresponds to MSY (green FISH signal); C-band positive material corresponds to ETSTY7 ampliconic arrays; centromere is denoted by a red FISH signal (from published molecular profile of horse Y 68 ); b Horse MSY sequence classes and gene map; c Triangular dot-plot showing the location of 100% identical sequences in MSY (with a 100 bp motif and a 20 bp step) …”

Disorder of Sexual Development in a Mare with an Unusual Tentative Mosaic Karyotype: 63,X/64,Xdel(Y)

“…However, this horse had a small penis inside the vulva and small inguinal testes, indicating an effect through a SRY gene product during development. Two other chromosomally mosaic horses with a Y isochromosome (Yq) in conjunction with a 63,X cell line were reported [Herzog et al, 1989;Das et al, 2012]. Both cases had the Y isochromosomes which were composed of 2 long arms, resulting in genetic Y disomy and overdose of PAR genes.…”

“…Pure monosomy X [Mäkinen et al, 2001;Di Meo et al, 2009;Moreno-Millán et al, 2012] and its mosaic forms [Moreno-Millán et al, 2012;Pieńkowska-Schelling et al, 2016] as well as DSD with sex reversal [Bannasch et al, 2007;Bodvarsdottir et al, 2009;Raudsepp et al, 2010;Villagómez et al, 2011;Peer et al, 2012;Anaya et al, 2014;Pieńkowska-Schelling et al, 2014] are the most common findings in mares with fertility problems [Lear and McGee, 2012]. In addition, translocations [Lear et al, 2008], trisomies [Moreno-Millán et al, 1989;Lear et al, 1999;Mäkinen et al, 1999;Brito et al, 2008], deletions [Halnan, 1985;Raudsepp et al, 2010], isochromosomes [Herzog et al, 1989;Mäkelä et al, 1994;Das et al, 2012], and copy number variations [Ghosh et al, 2014] have been reported less frequently.…”

The Eutherian Pseudoautosomal Region

“…Thus, a crossover error can easily move SRY from the Y to the X The Eutherian PAR Cytogenet Genome Res 2015;147:81-94 DOI: 10.1159/000443157 91 chromosome and give rise to XX males [Ergun-Longmire et al, 2005]. However, SRY is not close to the PAB in any other eutherian species studied so far [Raudsepp et al, 2010[Raudsepp et al, , 2012Das et al, 2012], explaining why SRY -positive XX males are very rare or not found in other eutherian species [Raudsepp et al, 2010]. Therefore, a recent report about an SRY -positive 38,XX virilized tortoiseshell cat with Xp;Yp translocation [Szczerbal et al, 2015] is exceptional, particularly because the feline SRY is located 1.7 Mb proximal from the PAB [Li et al, 2013].…”