LAXiTY Release Packager V0.9
LAXiTY Release Packager V0.9
the portable nature and adaptability of this technology can assist in the greater deployment of physiotherapy interventions to improve recovery. for example, by providing objective and accurate measurements of knee laxity, this device will allow physiotherapists to determine when patients are likely to improve with targeted exercise programs, and the provision of a range of treatment options, to maximize patient progress [ 42 ]. laxity represents a significant development in reducing intra-operative time and peri-operative morbidity associated with knee surgery. it can not only assist surgeons in determining the surgical correction required to treat knee instability but can assist physiotherapists in determining the most effective post-operative rehabilitation program. laxity also has the potential to enable the development of automated knee instability evaluation algorithms, which could ultimately create a completely objective knee instability evaluation, providing a reliable alternative to conventional evaluations, which are subjective and highly variable. furthermore, by providing a precise and reliable assessment of knee instability, laxity may contribute to improved outcomes following knee surgery by allowing clinicians to tailor their post-operative rehabilitation programs to patients who are likely to develop recurrent instability [ 41 ].
lastly, if the laxity device is shown to be effective in reducing post-operative morbidity and improving function, we believe that laxity will have significant impact on knee surgery in general, by lowering the incidence of complications from surgery. given its non-invasive nature, it may also have applications in non-surgical populations, where the use of continuous physiotherapy is part of everyday practice.
friesian horses are the most common horse breed in the netherlands and are known to be especially sensitive to draught work. in the friesian horse breed, dwarfism is an inherited autosomal recessive trait and has a prevalence rate between 5–10%. twenty horses (15 females, 5 males) with dwarfism were taken from a single farm with a total population of about 1800 horses and were tested for the disease. all 20 dwarfs were mixed or wild-type foals. some of the dwarfs were born to a dwarf mare and some from a normal mare. although the mother and the sire of each of the five dwarfs are known, it was not possible to determine the pedigree of the other 15 dwarfs. the genotype data were recorded from a snp chip (illumina equine ovine genotype chip, illumina inc.). in the equine reference genome for every snp three phenotypes were recorded, what we will call flanking, adjacent and nearest. in the friesian horse, we have 21,093 snps within 3 mb on eca 14. due to population structure we were mainly interested in the 2.5mb region on eca14 from the telomere to 3 mb and excluded the more centromeric region. we plotted the correlation of the alleles of all snps within the single chromosome eca14. we plotted the flanking snps and the sire snp haplotype against the alleles in the adjacent snp and the nearest snp (see fig. 2c, d and e). for all pairs of alleles the correlation was highly significant. this indicates that the flanking snps are significantly correlated with the flanking snp.
following the data processing and quality control steps 23 horses remained and were assigned to three groups. the first group consisted of 14 unaffected dwarf horses from the friesian horse breed and the second group included 9 unaffected normal horses. all male horses were used in the study. the third group contained 9 dwarf horses that were lame at the time of the study. the lame horses had a history of recurring inflammation in the medial, lateral or both collateral ligaments of the tibia or hock joint, as well as degenerative changes in the medial collateral ligament and meniscal injury in the affected horses. they were all treated and had shown a significant improvement in gait as of the day of assessment. all horses were presented in two age groups. the younger group of 9 horses that was used for the association study were 5 to 8 years of age (mean 6.25 years, median 6 years) and the older group contained 14 horses between 20 and 31 years of age (mean 26.54 years, median 24 years). due to the limited availability of funds (nia r01 ag015021-01a1), only 20 individuals were genotyped using the golden gate equine genome beadchip (illumina inc. san diego, ca). additional genotypes from 3 horses were obtained using single nucleotide polymorphism (snp) chip based genotyping, and one snp was genotyped manually. the whole genome sequencing data were obtained from the same set of individuals, which included six animals with the dwarfism phenotype, and a control horse for each individual. the size of the raw data set for each group was as follows; 1095kb×(dwarf (n=6), control (n=6)), 1101kb×(control (n=6)), 3689kb×(dwarf (n=3)), 5488kb×(control (n=3)). bwa [ 22 ] was used to map the quality scored sequence reads against the equine reference genome. the horse genome was chosen as reference due to higher number of base pairs at both ends of the reference. variants were identified with samtools [ 23 ] and vcftools [ 24 ] as per the equine genome annotation release 101 [ 25 ]. we removed variants that were not found in at least two of the six samples in the control group. one of the samples was excluded as it was a control that also had a significant amount of next-generation sequencing data generated. the quality score data were used as a guide to filter the vcf files for snps and indels. variants with a quality score of 30 and over were included in the study.
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