Classical and Molecular Cytogenetics of Disorders of Sex Development in Domestic Animals

Abstract

The association of abnormal chromosome constitutions and disorders of sex development in domestic animals has been recorded since the beginnings of conventional cytogenetic analysis. Deviated karyotypes consisting of abnormal sex chromosome sets (e.g. aneuploidy) and/or the coexistence of cells with different sex chromosome constitutions (e.g. mosaicism or chimerism) in an individual seem to be the main causes of anomalies of sex determination and sex differentiation. Molecular cytogenetics and genetics have increased our understanding of these pathologies, where human and mouse models have provided a substantial amount of knowledge, leading to the discovery of a number of genes implicated in mammalian sex determination and differentiation. Additionally, other genes, which appeared to be involved in ovary differentiation, have been found by investigations in domestic species such as the goat. In this paper, we present an overview of the biology of mammalian sex development as a scientific background for better understanding the body of knowledge of the clinical cytogenetics of disorders of sex development in domestic animals. An attempt to summarize of what has been described in that particular subject of veterinary medicine for each of the main mammalian domestic species is presented here.

A high incidence of leukocyte chimerism (60,XX/60,XY) in single born heifers culled due to underdevelopment of internal reproductive tracts

“…There are very few reports on DSD females with a male karyotype (60,XY) and a lack of the SRY gene (Kawakura et al 1996;Payan-Carreira et al 2008). On the other hand, the hereditary testicular or ovotesticular DSD (the female karyotype and a lack of the SRY gene), well-known in goat, pig, horse, and dog, was not reported in cattle (Villagomez et al 2009). Classification of the testicular or ovotesticular DSD is based on three major criteria: (1) the female karyotype, (2) a lack of the SRY gene, and (3) histologically detected testicular or ovotesticular gonads.…”

Equine Disorders of Sexual Development in 17 Mares Including XX, <i>SRY</i>-Negative, XY, <i>SRY</i>-Negative and XY, <i>SRY</i>-Positive Genotypes

“…XY, SRY -negative mares seem to be the equine representatives of a well-known human syndrome named XY complete gonadal dysgenesis (bilateral streak gonads), which is due to either a deletion or mutation of the SRY locus [Abe et al, 1999;Mäkinen et al, 1999Mäkinen et al, , 2001Harley et al, 2003;Chowdhary et al, 2008]. This appears to be one of the most common chromosome abnormalities described in horses, second only to X monosomy [Villagómez et al, 2009]. In mammals, it is generally agreed that the function of one nuclear transcription factor is the key event for testicular differentiation, which has been taken as equivalent of sex determination.…”

“…Genetically they fall into 4 broad categories: XX karyotype, SRYnegative genotype with ovotestis or testis; XY, SRY -negative with gonadal dysgenesis; and XY, SRY -positive with testis or gonadal dysgenesis [Pailhoux et al, 1995;Mäki-nen et al, 1999;Bugno et al, 2003;Switonski et al, 2005;Kuiper and Distl, 2007]. In contrast to that reported in humans [de la Chapelle, 1987], where translocations of the SRY gene from the Y chromosome to the X chromosome explains the occurrence of XX-males, there are no reports documenting an XX, SRY -positive sex reversal in mammalian domestic animals [Villagómez et al, 2009]. We report on the clinical, cytogenetic and molecular findings of 15 phenotypic mares, a young filly and a new foal female with DSD, the human medicine terminology for DSD classification being adopted here [Lee et al, 2006].…”

Numerical Sex Chromosome Aberrations and Abnormal Sex Development in Horse and Sheep

“…5 ). Although the frequency of twin births is much higher in sheep than in cattle, the frequency of freemartin twins is very low in sheep (between 1.6 and 8.0%) [Smith et al, 2003;Padula, 2005;Brace et al, 2008;Villagomez et al, 2009]. Since also the type of placental anastomosis is very similar in the 2 species, the differing A B Fig.…”

“…Patients with Turner syndrome present amenorrhoea and sterility [reviewed in Bondy and Cheng, 2009]. This syndrome has been rarely found in domestic animals [Gustavsson, 1980;Iannuzzi et al, 2000;Di Meo et al, 2008;Ducos et al, 2008;Villagomez et al, 2009], although in mares it represents about 1/3 of chromosome abnormalities found among carriers of sex chromosome abnormalities [Power, 1990]. Of 180 mares affected by gonadal dysgenesis, 54% showed sex chromosome abnormalities, 31% of which included X monosomy [Bowling et al, 1987].…”