Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome

Lavender Foal Syndrome (LFS) is a lethal inherited disease of horses with a suspected autosomal recessive mode of inheritance. LFS has been primarily diagnosed in a subgroup of the Arabian breed, the Egyptian Arabian horse. The condition is characterized by multiple neurological abnormalities and a dilute coat color. Candidate genes based on comparative phenotypes in mice and humans include the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A). Here we report mapping of the locus responsible for LFS using a small set of 36 horses segregating for LFS. These horses were genotyped using a newly available single nucleotide polymorphism (SNP) chip containing 56,402 discriminatory elements. The whole genome scan identified an associated region containing these two functional candidate genes. Exon sequencing of the MYO5A gene from an affected foal revealed a single base deletion in exon 30 that changes the reading frame and introduces a premature stop codon. A PCR–based Restriction Fragment Length Polymorphism (PCR–RFLP) assay was designed and used to investigate the frequency of the mutant gene. All affected horses tested were homozygous for this mutation. Heterozygous carriers were detected in high frequency in families segregating for this trait, and the frequency of carriers in unrelated Egyptian Arabians was 10.3%. The mapping and discovery of the LFS mutation represents the first successful use of whole-genome SNP scanning in the horse for any trait. The RFLP assay can be used to assist breeders in avoiding carrier-to-carrier matings and thus in preventing the birth of affected foals

Cluster Analysis of Symptoms Among Patients with Upper Extremity Musculoskeletal Disorders

Introduction Some musculoskeletal disorders of the upper extremity are not readily classified. The study objective was to determine if there were symptom patterns in self-identified repetitive strain injury (RSI) patients. Methods Members (n = 700) of the Dutch RSI Patients Association filled out a detailed symptom questionnaire. Factor analysis followed by cluster analysis grouped correlated symptoms. Results Eight clusters, based largely on symptom severity and quality were formulated. All but one cluster showed diffuse symptoms; the exception was characterized by bilateral symptoms of stiffness and aching pain in the shoulder/neck. Conclusions Case definitions which localize upper extremity musculoskeletal disorders to a specific anatomical area may be incomplete. Future clustering studies should rely on both signs and symptoms. Data could be collected from health care providers prospectively to determine the possible prognostic value of the identified clusters with respect to natural history, chronicity, and return to work

Tephrochronology

Tephrochronology is the use of primary, characterized tephras or cryptotephras as chronostratigraphic marker beds to connect and synchronize geological, paleoenvironmental, or archaeological sequences or events, or soils/paleosols, and, uniquely, to transfer relative or numerical ages or dates to them using stratigraphic and age information together with mineralogical and geochemical compositional data, especially from individual glass-shard analyses, obtained for the tephra/cryptotephra deposits. To function as an age-equivalent correlation and chronostratigraphic dating tool, tephrochronology may be undertaken in three steps: (i) mapping and describing tephras and determining their stratigraphic relationships, (ii) characterizing tephras or cryptotephras in the laboratory, and (iii) dating them using a wide range of geochronological methods. Tephrochronology is also an important tool in volcanology, informing studies on volcanic petrology, volcano eruption histories and hazards, and volcano-climate forcing. Although limitations and challenges remain, multidisciplinary applications of tephrochronology continue to grow markedly