Dr Sarra E Jamieson

CRISPR single base editing, neuronal disease modelling and functional genomics for genetic variant analysis: pipeline validation using Kleefstra syndrome EHMT1 haploinsufficiency

Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing identifies potential disease causative genetic variants. However, many are identified as variants of uncertain significance and require functional laboratory validation to determine pathogenicity, and this creates major diagnostic delays.

Common and Rare Genetic Variants That Could Contribute to Severe Otitis Media in an Australian Aboriginal Population

Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians.

Reduced socs1 expression in lung fibroblasts from patients with ipf is not mediated by promoter methylation or mir155

The interleukin (IL)-6 family of cytokines and exaggerated signal transducer and activator of transcription (STAT)3 signaling is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis, but the mechanisms regulating STAT3 expression and function are unknown. Suppressor of cytokine signaling (SOCS)1 and SOCS3 block STAT3, and low SOCS1 levels have been reported in IPF fibroblasts and shown to facilitate collagen production. Fibroblasts and lung tissue from IPF patients and controls were used to examine the mechanisms underlying SOCS1 down-regulation in IPF.

A flexible computational pipeline for research analyses of unsolved clinical exome cases

Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar.

Reviewing the Pathogenic Potential of the Otitis-Associated Bacteria Alloiococcus otitidis and Turicella otitidis

There is insufficient evidence available to determine whether these organisms are pathogens, commensals or contribute indirectly to the pathogenesis of OM

Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years

We provide new evidence to support current guidelines for orchidopexy before age 18 months to decrease the risk of future testicular cancer and infertility

Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years

Undescended testes is associated with an increased risk of testicular cancer and male infertility, and decreased paternity

Epigenetic dysregulation of host gene expression in Toxoplasma infection with specific reference to dopamine and amyloid pathways

Our results provide a possible functional link between Toxoplasma gondii infection and congenital/early life and adult neurological clinical signs

Arylsulphatase A Pseudodeficiency (ARSA-PD), hypertension and chronic renal disease in Aboriginal Australians

Traits associated with CVD, CRD and T2D in Aboriginal Australians provide novel insight into function of Arylsulphatase A Pseudodeficiency variants

Does otitis media in early childhood affect later behavioural development? Results from the Western Australian Pregnancy Cohort (Raine) Study

The relationship between early life episodes of otitis media and later behavioural development with adjustment for confounders.

A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera

We characterised the nasopharyngeal microbiome of these children in comparison to children with rAOM to identify potentially protective bacteria.

An in silico pipeline to filter the Toxoplasma gondii proteome for proteins that could traffic to the host cell nucleus and influence host cell epigenetic regulation

To identify genes with putative epigenetic functions, we developed an in silico pipeline to interrogate the T. gondii proteome of 8313 proteins

Protective benefit of predominant breastfeeding against otitis media may be limited to early childhood: results from a prospective birth cohort study

Our findings are in line with a number of epidemiological studies which show a positive association between breastfeeding and OM in early childhood

Analysis of expression of FLI1 and MMP1 in American cutaneous leishmaniasis caused by Leishmania braziliensis infection

MMP1 is regulated by factors other than FLI1, and that the influence of IL-6 on MMP1 was independent of its effect on FLI1 in Leishmania braziliensis

Early childhood development of boys with genital anomalies

We found no increased risk of poor development among boys with hypospadias or undescended testis

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer.

Toxoplasma gondii infection is associated with mitochondrial dysfunction in-vitro

Our results show perturbation of host mitochondrial function following T. gondii infection that likely impacts on pathogenesis of disease.

No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene

The methylation variation in the promoter region of CD14 gene did not explain the asthma and allergy contrast between Finnish and Russian Karelian children

Reference genotype and exome data from an Australian Aboriginal population for health-based research

This data set provides a useful reference point for genomic studies on Aboriginal Australians

Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan

The rare and undiagnosed diseases diagnostic service – application of massively parallel sequencing in a state-wide clinical service

The Rare and Undiagnosed Diseases Diagnostic Service refers to a genomic diagnostic platform operating within the Genetic Services of Western Australia

The -308 bp TNF gene polymorphism influences tumor necrosis factor expression in leprosy patients in Bahia State, Brazil

TNF mRNA expression was higher in leprosy patients compared to endemic controls, but did not differ significantly between clinical subgroups

Age at surgery and outcomes of an undescended testis

We investigated the prevalence of UDT and examined rates of surgery and age at surgery in an Australian population.

Epigenetics in infectious diseases

Viruses, bacteria, and parasites have developed strategies to invade and establish long-term infections in their hosts.

Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukaemia

Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukaemia (ALL).

Genetic and environmental factors in the aetiology of hypospadias

The increasing use of assisted reproductive techniques and hormonal manipulation during pregnancy may have been associated with an apparent rise in the...

Prevalence and risk factors for parent-reported recurrent otitis media during early childhood

The prevalence of parent-reported rOM was 26.8% (611/2280) and 5.5% (125/2280) for severe rOM in the Study.

Folate pathway gene polymorphisms and risk of childhood brain tumors: Results from an Australian case-control study

Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate...

First genome-wide association study in an Australian Aboriginal population provides insights into genetic risk factors for body mass index and type 2 diabetes

A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians.

Prevalence and risk factors for parent-reported recurrent otitis media during early childhood

The objective was to describe the prevalence and risk factors of recurrent otitis media (rOM) in an urban Australian population at 3 years of age.

Confirmation of childhood acute lymphoblastic leukemia Variants, ARID5B and IKZF1, and interaction with parental environmental exposures

The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology.

Host genetic factors in American cutaneous leishmaniasis: A critical appraisal of studies conducted in an endemic area of Brazil

This paper reviews American cutaneous leishmaniasis (ACL) immunogenetics in the state of Bahia (BA), northeastern Brazil, highlighting the interacting roles...

Genetic and functional evidence for a locus controlling otitis media at chromosome 10q26.3

Otitis media (OM) is a common childhood disease characterised by middle ear effusion and inflammation.

Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen's disease) in Brazil

This study examines whether polymorphisms in the ERBB2 gene were associated with leprosy in primary and replication cohorts from northeastern Brazil.

A Genome-Wide Search for Type 2 Diabetes Susceptibility Genes in an Extended Arab Family

We performed a discovery GWAS in an extended UAE family (N = 178; 66 diabetic; 112 healthy) genotyped on the Illumina Human 660 Quad Beadchip, with...

Genetic and epigenetic susceptibility to early life infection

To date there have been relatively few studies on genetic determinants of susceptibility to neonatal infection and many of these have methodological...

Alternative Recruitment Strategies Influence Saliva Sample Return Rates in Community-Based Genetic Association Studies

Using data from three large-scale genetic association studies we compared recruitment strategy and sample return rates.

Genetic and functional evidence for a role for SLC11A1 in susceptibility to otitis media in early childhood in a Western Australian population

Otitis media (OM) is a common disease in early childhood characterised by inflammation of the middle ear.

Genetic Research and Aboriginal and Torres Strait Islander Australians

Human genetic research promises to deliver a range of health benefits to the population. Here we consider how the different levels of Indigenous research...

New findings in the pathogenesis of otitis media

This study was the first to concurrently identify middle ear pathogens in both bacterial biofilm and intracellularly in the middle ear mucosa of children and to identify extensive DNA stranding in the MEF from children with AOM

Statistical adjustment of genotyping error in a case-control study of childhood leukaemia

Genotyping has become more cost-effective and less invasive with the use of buccal cell...

Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil

Leishmania braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. In the mouse, Fli1 was identified as a gene influencing enhanced wound healing...

Genetic susceptibility to otitis media in childhood

Reviewed in this article these studies have identified positive association at 21 genes with association at five of these replicated in independent populations.

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

We identified several novel candidate genes which warrant further analysis in cohorts matched more precisely for clinical phenotypes.

Genetic and functional evaluation of the role of CXCR1 and CXCR2 in susceptibility to visceral leishmaniasis in north-east India

IL8RA and IL8RB, encoded by CXCR1 and CXCR2, are receptors for interleukin (IL)-8 and other CXC chemokines involved in chemotaxis and activation of...

FLI1 polymorphism affects susceptibility to cutaneous leishmaniasis in Brazil

Mapping murine genes controlling cutaneous leishmaniasis (CL) identified Fli1 as a candidate influencing resistance to L. major and enhanced wound healing.

FBXO11, a regulator of the TGFΒ pathway, is associated with severe otitis media in Western Australian children

Otitis media (OM) is a common childhood disease characterised by middle ear inflammation following infection

Genetic and functional evidence implicating DLL1 as the gene that influences susceptibility

Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified...

Unraveling the genetics of otitis media: From mouse to human and back again

Otitis media (OM) is among the most common illnesses of early childhood, characterised by the presence of inflammation in the middle ear cavity...

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated

The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized

Mucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.

P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

The P2X7R is highly expressed on the macrophage cell surface, and activation of infected cells by extracellular ATP has been shown to kill intracellular bacte