Genetic Phenomena Commons^™

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline In Preclinical Alzheimer’S Disease, Tenielle Porter, Samantha C. Burnham, Greg Savage, Yen Ying Lim, Paul Maruff, Lidija Milicic, Madeline Peretti, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Kevin Taddei, David Groth, Guiseppe Verdile, Victor L. Villemagne, Simon M. Laws

Research outputs 2014 to 2021

Studies of Alzheimer’s disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted PRS (emPRS) was derived and assessed against decline in cognitive performance in 226 healthy cognitively normal older adults with high brain Aβ-amyloid burden participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. The effect size for decline in a verbal episodic memory …

Metabolomic Investigation Of A New Rat Model Of Autosomal Recessive Polycystic Kidney Disease, Hayley White

Theses : Honours

Metabolomics is complementary to genomics, transcriptomics and proteomics; however, it has the capacity to reflect the activities of the organism at a functional level. Metabolomics can therefore be used as a diagnostic tool by identifying the up- or down-regulation of metabolites in the cell, tissue, plasma, serum or urine. Specifically, these are, but are not limited to, identifying biomarkers of disease, monitoring drug treatments, and monitoring surgical procedures such as organ transplant. Autosomal recessive polycystic kidney disease (ARPKD) makes up 5-8% of patients requiring kidney dialysis and/or transplantation and of these, an estimated 50% of patients progress to end-stage renal …

Molecular Investigations In The Role Of The Galk1 Gene In Galactokinase Deficiency, Michael L. Hunter

Theses : Honours

Galactokinase deficiency is an autosomal-recessive inborn error of galactose metabolism whose major clinical manifestation is the development of cataracts during the first months of life. This metabolic disorder is caused by defects in the first enzyme of the Leloir pathway, galactokinase, encoded by the gene GALK1 on chromosome 17q24. Despite the identification of a number of conserved domains in GALK1, understanding of the functional significance of these regions and the molecular basis of the disorder is limited. This is largely due to the rarity of the disease and the fact that the small number of GALK1 mutations identified to-date are …

A Linkage Study Of Autism Using Multipoint Sib-Pair Analysis, Tamara Rogers

Theses: Doctorates and Masters

Autism is a severe developmental disorder that was first described by Kanner in 1943. It is characterised by four major criteria: marked social deficits, delay in language development, a restricted range of stereotyped repetitive behaviours and onset of the disease within the first three years of life. The last decade of research has provided support for a strong genetic basis in the aetiology of autism. Firstly, a number of genetic conditions, such as fragile X syndrome, chromosome 15 anomalies and tuberous sclerosis, have been associated with autism. Secondly, family studies have demonstrated that the recurrence risk for autism among siblings …

Molecular Studies Of Splice Sites In The Canine Dystrophin Gene, Hayley Durling

Theses : Honours

The development of an effective therapy for Duchenne Muscular Dystrophy (DMD) is one of the primary goals of all DMD/Becker Muscular Dystrophy (BMD) research. Golden Retriever Muscular Dystrophy (GRMD), an animal model of DMD is a fatal degenerative myopathy. Unlike the mdx model, the GRMD dog more accurately reflects the phenotype shown by human DMG patients, making the model better suited for the investigation and assessment of potential therapeutic approaches. The GRMD mutation, a base change from A to G in the 3' splice acceptor site of intron 6, results in exon 7 skipping which disrupts the translational reading frame. …

Detection Of Point Mutations In The Dystrophin Gene, John Pedretti

Theses : Honours

The dystrophin gene has been localised to Xp 21.1. Mutations of this gene can lead to the clinical manifestations of Duchenne and Becker muscular dystrophies (DMD/BMD). In the majority of DMD and BMD patients the disease-causing mutation is a deletion detectable by southern analysis or multiplex PCR, however in 30% of patients no deletion is observed using these conventional tests. Using PCR amplification of cDNA it was possible to detect a deletion in the product of the dystrophin gene of one such individual affected with BMD. It was then necessary to characterise the mutation in order to determine whether this …