The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.

Multi-copied gene families are prevalent in mammalian genomes, especially within the Y chromosome. Testis specific protein Y-encoded (TSPY) is present in variable copy number in many mammalian species. Previous studies have estimated that TSPY ranges from 50–200 copies in cattle. To examine TSPY localization on the Y chromosome we employed fluorescence in situ hybridization (FISH) and fiber-FISH. The results show a strong signal on the short arm of the Y chromosome (Yp). To investigate TSPY copy number we used relative real-time polymerase chain reaction (PCR) to analyze the DNA of 14 different cattle breeds. Variation both within and between breeds was observed. All breeds show significant variation in TSPY copy number among individual members. Brown Swiss (161 copies, CI = 133–195) had higher average levels of TSPY and Western Fjord Cattle (63 copies, CI = 45–86) had lower levels than some breeds. Overall, however, most breeds had a similar average TSPY copy number. The pooled average was 94 copies (CI = 88–100). The significance of the TSPY array remains uncertain, but as the function of TSPY is unraveled the purpose of the array may become clearer.

Comparative FISH-mapping among Y chromosomes of cattle (Bos taurus, 2n = 60, BTA, submetacentric Y chromosome), zebu (Bos indicus, 2n = 60, BIN, acrocentric Y chromosome but with visible small p-arms), river buffalo (Bubalus bubalis, 2n = 50, BBU, acrocentric Y chromosome), sheep (Ovis aries, 2n = 54, OAR, small metacentric Y chromosome) and goat (Capra hircus, 2n = 60, CHI, Y-chromosome as in sheep) was performed to extend the existing cytogenetic maps and improve the understanding of karyotype evolution of these small chromosomes in bovids. C- and R-banding comparison were also performed and both bovine and caprine BAC clones containing the SRY, ZFY, UMN0504, UMN0301, UMN0304 and DYZ10 loci in cattle and DXYS3 and SLC25A6 in goat were hybridized on R-banded chromosomes by FISH. The main results were the following: (a) Y-chromosomes of all species show a typical distal positive C-band which seems to be located at the same region of the typical distal R-band positive; (b) the PAR is located at the telomeres but close to both R-band positive and ZFY in all species; (c) ZFY is located opposite SRYand on different arms of BTA, BIN, OAR/CHI Y chromosomes and distal (but centromeric to ZFY) in BBU-Y; (d) BTA-Y and BIN-Y differ as a result of a centromere transposition or pericentric inversion since they retain the same gene order along their distal chromosome regions and have chromosome arms of different size; (e) BTA-Y and BBU-Y differ in a pericentric inversion with a concomitant loss or gain of heterochromatin; (f) OAR/CHI-Y differs from BBU-Y for a pericentric inversion with a major loss of heterochromatin and from BTA and BIN for a centromere transposition followed by the loss of heterochromatin.

A new physical map of the bovine genome has been constructed by integrating data from genetic and radiation hybrid maps, and a new bovine BAC map, with the bovine genome draft assembly.

Neuropathies are neurodegenerative diseases affecting humans and other mammals. Many genetic causes have been identified so far, including mutations of genes encoding proteins involved in mitochondrial dynamics. Recently, the “Turning calves syndrome”, a novel sensorimotor polyneuropathy was described in the French Rouge-des-Prés cattle breed. In the present study, we determined that this hereditary disease resulted from a single nucleotide substitution in SLC25A46, a gene encoding a protein of the mitochondrial carrier family. This mutation caused an apparent damaging amino-acid substitution. To better understand the function of this protein, we knocked out the Slc25a46 gene in a mouse model. This alteration affected not only the nervous system but also altered general metabolism, resulting in premature mortality. Based on optic microscopy examination, electron microscopy and on biochemical, metabolic and proteomic analyses, we showed that the Slc25a46 disruption caused a fusion/fission imbalance and an abnormal mitochondrial architecture that disturbed mitochondrial metabolism. These data extended the range of phenotypes associated with Slc25a46 dysfunction. Moreover, this Slc25a46 knock-out mouse model should be useful to further elucidate the role of SLC25A46 in mitochondrial dynamics.