👤 Carrie J Finno

Single-cell RNA-sequencing has identified that Alzheimer's disease (AD) pathology in humans is associated with activation of disease-associated microglia (DAM). Microglial signatures of human AD have not been consistently identified in AD mouse models. Since the inflammatory response of rats is more like humans, we profiled microglial transcriptomes in aging TgF344-AD rats, which overexpress two human AD risk genes. Classic DAM gene activation ( Show less

Genome-wide association (GWA) studies are widely used to investigate the genetic etiology of diseases in domestic animals. In the horse, GWA studies using 40-50,000 single nucleotide polymorphisms (SNPs) in sample sizes of 30-40 individuals, consisting of only 6-14 affected horses, have led to the discovery of genetic mutations for simple monogenic traits. Equine neuroaxonal dystrophy is a common inherited neurological disorder characterized by symmetric ataxia. A case-control GWA study was performed using genotypes from 42,819 SNP marker loci distributed across the genome in 99 clinically phenotyped Quarter horses (37 affected, 62 unaffected). A significant GWA was not achieved although a suggestive association was uncovered when only the most stringently phenotyped NAD-affected horses (n = 10) were included (chromosome 8:62130605 and 62134644 [log(1/P) = 5.56]). Candidate genes (PIK3C3, RIT2, and SYT4) within the associated region were excluded through sequencing, association testing of uncovered variants and quantitative RT-PCR. It was concluded that variants in PIK3C3, RIT2, and SYT4 are not responsible for equine neuroaxonal dystrophy. This study demonstrates the risk of false positive associations when performing GWA studies on complex traits and underlying population structure when using 40-50,000 SNP markers and small sample size. Show less