Alan Renton, PhD

Dr. Renton’s expertise is the generation and analysis of genomic and functional data to identify and characterize neurodegenerative disease genes. His interests have encompassed a range of disorders, specifically Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson’s disease (PD), and progressive supranuclear palsy (PSP). His ongoing and future research arc emanates from two central themes: i) Phenotypic heterogeneity. Dr. Renton’s broad background facilitates the detection of overlaps across diseases, the elucidation of fundamental biological processes driving neuronal death, and the evolution of nosological concepts. His team is undertaking genetic and functional fine mapping of the 17q21 MAPT locus, because the H1 haplotype is associated with several neurodegenerative disorders, including PSP, PD, and APOE-ε4- negative AD. They are integrating data from multiple modalities, including imputed genome-wide arrays, targeted PacBio long read sequencing, RNAseq, co-expression networks, histopathology, and induced pluripotent stem cell models. If successful, this will correlate novel genetic variation with AD and other H1-associated conditions to pinpoint functional alleles, and untangle H1-associated phenotypic heterogeneity.

ii) Resilience alleles. Phenotypic extremes analysis can identify disease resilience alleles and address the inadequate statistical power characteristic of next generation sequencing cohorts. They are conducting a phenotypic extremes rare variant association study of AD. The basic premise is to compare younger AD cases with older cognitively intact controls. They have selected subjects from the Alzheimer’s Disease Sequencing Project case-control exome sequencing dataset and are performing variant and gene level association. If successful, this will elucidate AD genomic architecture, identify resilience alleles, and generate novel therapeutic targets.

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