Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses.

BackgroundDistichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait.ResultsA genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10- 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10- 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder.ConclusionsThis study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance

Fast turnaround fabrication of silicon point-contact quantum-dot transistors using combined thermal scanning probe lithography and laser writing.

The fabrication of high-performance solid-state silicon quantum-devices requires high resolution patterning with minimal substrate damage. We have fabricated room temperature single-electron transistors (SETs) based on point-contact tunnel junctions using a hybrid lithography tool capable of both high resolution thermal scanning probe lithography and high throughput direct laser writing. The best focal z-position and the offset of the tip- and the laser-writing positions were determined in-situ with the scanning probe. We demonstrate < 100 nm precision in the registration between the high resolution and high throughput lithographies. The SET devices were fabricated on degenerately doped n-type > 1020/cm3 silicon on insulator (SOI) chips using a CMOS compatible geometric oxidation process. The characteristics of the three devices investigated were dominated by the presence of Si nanocrystals or phosphorous atoms embedded within the SiO2, forming quantum dots (QDs). The small size and strong localisation of electrons on the QDs facilitated SET operation even at room temperature. Temperature measurements showed that in the range 300 K > T > ~100 K, the current flow was thermally activated but at < 100 K, it was dominated by tunnelling

Philosophical intuitions, heuristics, and metaphors

Psychological explanations of philosophical intuitions can help us assess their evidentiary value, and our warrant for accepting them. To explain and assess conceptual or classificatory intuitions about specific situations, some philosophers have suggested explanations which invoke heuristic rules proposed by cognitive psychologists. The present paper extends this approach of intuition assessment by heuristics-based explanation, in two ways: It motivates the proposal of a new heuristic, and shows that this metaphor heuristic helps explain important but neglected intuitions: general factual intuitions which have been highly influential in the philosophies of mind and perception but neglected in ongoing debates in the epistemology of philosophy. To do so, the paper integrates results from three philosophically pertinent but hitherto largely unconnected strands of psychological research: research on intuitive judgement, analogy and metaphor, and memory-based processing, respectively. The paper shows that the heuristics-based explanation thus obtained satisfies the key requirements cognitive psychologists impose on such explanations, that it can explain the philosophical intuitions targeted, and that this explanation supports normative assessment of the intuitions' evidentiary value: It reveals whether particular intuitions are due to proper exercise of cognitive competencies or constitute cognitive illusions