Molecular heterogeneity of XY sex reversal in horses

Abstract

SummaryMale-to-female 64,XY sex reversal is a frequently reported chromosome abnormality in horses. Despite this, the molecular causes of the condition are as yet poorly understood. This is partially because only limited molecular information is available for the horse Y chromosome (ECAY). Here, we used the recently developed ECAY map and carried out the first comprehensive study of the Y chromosome in XY mares (n = 18). The integrity of the ECAY in XY females was studied by FISH and PCR using markers evenly distributed along the euchromatic region. The results showed that the XY sex reversal condition in horses has two molecularly distinct forms: (i) a Y-linked form that is characterized by Y chromosome deletions and (ii) a non-Y-linked form where the Y chromosome of affected females is molecularly the same as in normal males. Further analysis of the Y-linked form (13 cases) showed that the condition is molecularly heterogeneous: the smallest deletions spanned about 21 kb, while the largest involved the entire euchromatic region. Regardless of the size, all deletions included the SRY gene. We show that the deletions were likely caused by inter-chromatid recombination events between repeated sequences in ECAY. Further, we hypothesize that the occurrence of SRY-negative XY females in some species (horse, human) but not in others (pig, dog) is because of differences in the organization of the Y chromosome. Finally, in contrast to the Y-linked SRY-negative form of equine XY sex reversal, the molecular causes of SRY-positive XY mares (5 cases) remain as yet undefined.

A method for isolating and culturing placental cells from failed early equine pregnancies

“…A polymerase chain reaction was performed on gDNA using sex specific primers for sex determining region Y (SRY) (Y chromosome) and androgen receptor (AR) (X chromosome) [13]. …”

“…Mononuclear cells (PBMC) as previously described [13]. PBMC from a gelding acted as a positive control for both PCRs and gDNA isolated from PBMC from a mare acted as a negative control for SRY and positive control for AR PCR reactions.…”

Disorders of Sexual Development in the Domestic Horse, <i>Equus caballus</i>

“…[ Bannasch et al, 2007] [ Raudsepp et al, 2010] [ McGee, 2011] [ Bowling et al, 1987] Arabian Andalusian Quarter Horse Appaloosa Arabian [Miyake et al, 1979;Halnan, 1985;Bowling et al, 1987;Paget et al, 2001] [ Buoen et al, 2000;Villagomez et al, 2011] [ Raudsepp et al, 2010;Villagomez et al, 2011] [ Raudsepp et al, 2010] [ Kent et al, 1986;Bowling et al, 1987;Kent et al, 1988] Half-bred Anglo-Arabian Appaloosa Standardbred Mixed Warmblood Morgan [Bugno et al, 2007] [ Buoen et al, 2000] [ Pailhoux et al, 1995;Mäkinen et al, 1999;Makinen et al, 2001;Raudsepp et al, 2010;Villagomez et al, 2011] [ Raudsepp et al, 2010] [ Bowling et al, 1987] Half-Arabian Arabian Thoroughbred Oldenburg Pasa Fino [Gill et al, 1988] [ Buoen et al, 2000;Villagomez et al, 2011] [ Abe et al, 1999;Bugno et al, 2003;Raudsepp et al, 2010;Villagomez et al, 2011] [ Kuiper et al, 2010] [ Kent et al, 1986;Kent et al, 1988] Clydesdale Belgian Quarter Horse Quarter Horse [Klunder et al, 1990] [ Villagomez et al, 2011] [ Raudsepp et al, 2010;Villagomez et al, 2011] [ Kent et al, 1986;Bowling et al, 1987;Kent et al, 1988] Fjord Konik Polski Sta...…”

Natural Exceptions to Normal Gonad Development in Mammals

“…In most of the cases described, the molecular aetiology of the XY sex reversal is a Y chromosome deletion that includes the sexdetermining gene SRY . However, the condition is molecularly heterogeneous, with deletions in the Y chromosome ranging from approximately 21 kb to large deletions that can include the entire euchromatic region [Pailhoux et al, 1995;Bugno et al, 2003;Raudsepp et al, 2010].…”