A splice-site mutation causing ovine McArdle's disease

McArdle's disease is an autosomal recessive myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme muscle glycogen phosphorylase which releases glucose for contraction during exercise. The human cDNA has been sequenced and disease-causing mutations identified. An ovine equivalent of McArdle's disease has been diagnosed and the mutation responsible identified by PCR-amplification of the ovine glycogen myophosphorylase cDNA in six overlapping fragments followed by single strand conformation polymorphism (SSCP) analysis. Two fragments showed SSCPs in the glycogen myophosphorylase cDNA from affected sheep. The SSCP in fragment one was a silent polymorphism, while that in fragment six, was an eight base deletion at the 5′ end of exon 20. This deletion will cause a frame-shift, a premature stop codon and remove the last 31 amino-acid residues from the protein. The cDNA deletion suggested that the genomic mutation most likely involved a splice-site. Sequencing intron 19 identified the mutation as an adenine for guanine substitution at the intron 19 3′ splice-site. This eliminated an XbaI site present in normal sheep allowing diagnosis of normal, affected and carrier sheep. This ovine model of McArdle's disease is now available for therapeutic trials

Dimorphism and evolution of Albarracinites (Ammonoidea, Lower Bajocian) from the Iberian Range (Spain)

Several tens of specimens of Lower Bajocian Albarracinites (type species A. albarraciniensis Fernandez-Lopez, 1985), including microconchs and macroconchs from the Iberian Range, have been studied. This ammonite genus ranges in the Iberian Range from at least the Ovale Zone to the uppermost Laeviuscula Zone of the Lower Bajocian (Middle Jurassic). The macroconch counterpart is thought to be a group of stephanoceratids previously attributed to Mollistephanus, Riccardiceras and other new forms described in this paper. Two chronologically successive species of Albarracinites have been identified: A. albarraciniensis and A. submediterraneus sp. nov. The evolution of the Albarracinites lineage represents a hypermorphic peramorphocline starting from depressed, small and slender serpenticones of A. westermanni, to larger planorbicones with more cadiconic phragmocones and body chamber of subcircular cross section belonging to A. submediterraneus sp. nov., through A. albarraciniensis Fernandez-Lopez. In contrast, Mollistephanus planulatus (Buckman), M. cockroadensis Chandler & Dietze and M. mollis Buckman represent a peramorphocline by acceleration, producing adults of similar size but more compressed and with increasing ontogenic variation of shell ornament. Albarracinites and Mollistephanus subsequently developed two opposite peramorphoclines or gradational series of morphological changes undergoing greater development and ontogenic variation. These two genera show diverse palaeobiogeographical distributions too. Albarracinites is rarely recorded in the Mediterranean and Submediterranean from the Discites to the Laeviuscula Zone, whereas Mollistephanus is more common in north-western Europe and other biochoremas of the western Tethys from the Discites Zone to the Sauzei Zone. Albarracinites seems to be the earliest stephanoceratid lineage in western Tethys, branching off from the otoitid Riccardiceras by proterogenetic change and resulting in paedomorphosis at the Aalenian/Bajocian boundary