The Bahlo lab works on two retinal disorders: Macular Telangiectasia Type 2 (MacTel) and Age-related Macular Degeneration (AMD). Using genome-wide association analysis (GWAS) methods for both diseases we discovered the first loci for MacTel in 2017. In recent years we have combined genomic data with metabolomic data as well as analysing and further combining extensive data generated by collaborators from the MacTel consortium. In the past two years the Bahlo lab has started a collaboration to work on a subtype of AMD with poorer prognostic outcome. This will involve using GWAS and related methods to investigate the genetic basis of this AMD subtype.

Bahlo Lab | WEHI

Q: Genetics of speech disorders

One in five Australian children start school with a speech or language disorder. While some children will grow out of it, many others will go on to have persistent speech difficulties. Such disorders can have a profound effect on an individual’s social and mental wellbeing. Speech disorders are thought to be caused by a combination of genetic, neurological and environmental factors. Understanding more about the genetic causes of speech disorders may improve developments in treatment and help us to identify individuals most at risk of these disorders. In this project, we take several approaches to investigate the genetics underlying speech problems. Through whole exome and whole genome sequencing (WES/WGS) of families, we have identified causal variants responsible for rare forms of familial speech disorders. We are working to assemble an international cohort of people who stutter, with which we shall undertake a genome-wide association study (GWAS) to identify common genetic variation, influencing risk of stuttering in the general population.

Q: Detecting repeat expansions

Short tandem repeats are short repetitive elements of the genome, which can vary in length between individuals. Some repeats are unstable and can expand in length. Repeat expansions cause a number of neurological disorders, such as Huntington's disease and spinocerebellar ataxias as well as other more common neurological disorders, such as epilepsy and motor neuron disease. Identifying repeat expansions is difficult as their length can greatly exceeds the read lengths of short read sequencing. Standard clinical tests are specialised and expensive and not routinely performed for the majority of patients. The Bahlo lab has developed new methods to identify repeat expansions in whole exome and whole genome sequencing data. We are interested in searching for known or novel repeat expansions associated with a variety of neurological disorders and indeed have discovered novel repeat expansions. Our work has also provided diagnosis for patients where it had previously not been possible to detect repeat expansions, even though they were the cause of their disorders.

Q: Identity by descent methods and applications

Genomic regions that are inherited from a common ancestor are said to be identical by descent (IBD). Identification of such regions has proven useful in human studies with application including discovery of familial relatedness, disease mapping and determining loci under selection. The Bahlo lab has developed multiple implementations of IBD methods including: - IBD methods applicable to the X-chromosome, a special case - IBD methods to mixed samples, such as those seen in microorganisms that recombine and multiply infect humans, for example those that cause malaria. The Bahlo lab has published many applications of IBD methods to refine the genomic location of disease-causing variants.

Q: Genome-wide association study investigations

The Bahlo lab has been involved and also led several genome-wide association studies (GWAS) and has previously worked on X chromosome analysis methods, as well as demonstrating that saliva derived DNA achieves high quality data of an equivalent standard to that derived from blood samples. We are continuing to perform GWAS studies in AMD, MacTel and stuttering, combining these basic analyses with techniques such as expression QTL and metabolomic QTL studies making use of modern analysis methods such as Mendelian Randomisation. The lab is also applying these methods to epilepsy through collaborations with the International League against Epilepsy (ILAE) consortium.

Q: Genomics to accelerate precision dementia research

Dementia is a heterogeneous disorder with many different subtypes that are driven by dysregulation of biological pathways. Treatment selection for dementias is based on subtype, but accurate diagnosis in the clinical setting is very challenging early on in the disease when therapies have their greatest potential. Vast improvement in dementia diagnostics is required for truly targeted treatments. We aim to supercharge dementia research by overlaying personalised genomics to WEHI’s current and future multi-disciplinary dementia projects. Conducting whole genome sequencing on patients and analysing the data will help tease apart this heterogenous patient cohort, providing greater understanding of dementia sub-types and facilitate more suitable selection of clinical trials and therapies. It will also reveal if women are genetically pre-disposed to developing dementia. Furthermore, working closely with the experts above and combining their projects’ data with the genomics information will generate an enormous, complex, and critical data set on dementia. This invaluable resource will fast track our biomarker development and diagnostic tests, advance our understanding of the disease to help identify potential targets for therapeutic development, and likely aid prognosis. This four-year project launched with a $1million flagship grant from the Alfred Felton Bequest will involve conducting whole genome sequencing on 500 Victorian patients (recruited via Royal Melbourne Hospital, the Alfred Hospital, and others), then performing comprehensive data analysis on those results, as well as other WEHI dementia projects, to facilitate precision dementia research.

About the lab

Our group develops and applies state-of-the-art methods to analyse and comprehend complex genetic datasets. These methods are used to discover the genetic causes of human disorders such as epilepsy, ataxia, dementia, motor neuron disease and Parkinson’s disease, speech disorders and retinal disorders.

We are a highly collaborative laboratory, working closely with clinician researchers to reach important outcomes for families with genetic disorders.

Our research is focused on brain (neurological) and retinal disorders, but we have also worked on infectious diseases such as malaria and tuberculosis (TB). Our analysis of data produced by new genomic technologies is identifying genetic causes for diseases that have previously proven intractable to analysis.

We routinely work with multiple, internationally leading, biobanks, such as the UK Biobank and all AllofUs (USA).

These biobanks have >500,000 individuals included and are thus repositories of a vast range of human genetic variation. Additionally, biobanks include data on a huge range of variables including clinical variables, imaging variables, proteomics, metabolomics and so on. See https://www.ukbiobank.ac.uk/about-our-data/types-of-data/ for details for the UK Biobank.

We have methods and in house expertise to interrogate biobank data for your favourite gene(s)/pathway of interest. Please see us if this is of interest! We have done a bit of work with several labs at WEHI already using biobank data and this has been very fruitful. Examples include: 1) Chiu et al, Cell 2026 (Feltham lab), 2) Bennett et al, Blood 2023 (Pasricha lab). Relevant methods publication (Tool): GeneSetPheno – see Han J, Gerring ZF, Wang L, Bahlo M. GeneSetPheno: a web application for the integration, summary, and visualization of gene and variant-phenotype associations across gene sets. Bioinform Adv. 2025 Apr 17;5(1):vbaf078. doi: 10.1093/bioadv/vbaf078. PubMed ID 40260119.

We are giving the July 22nd 2026 WEHI posgraduate seminar on utility of biobanks for WEHI researchers. Hopefully we’ll see you there or you can catch the recording.

Our mission

Detection and understanding of genetic risk factors in complex and monogenic diseases using human cohort data by integrating multi -omic data.

Impact

The Bahlo laboratory has developed innovative methods and software for genetic analysis that have led to major genetic discoveries, including diagnostically critical identification of new genes and genetic pathways implicated in neurological and retinal disorders.

Key discoveries include:
Discovery of new genes for ataxia and epilepsy.
Discovery of the genetic drivers for MacTel, a retinal disorder.
Development of pipelines for the analysis of data to: (i) faciliate understanding of genetic drivers in large datasets, (ii) to improve diagnostics.
Development of novel methods to identify repeat expansions, a type of genetic mutation that causes disease.
Bespoke analyses of complex data sets that outline new avenues for future bench work, often working closely with clinician collaborators.

Highlights

Lab research projects

Genetics of speech disorders

Detecting repeat expansions

Retinal disorders

Identity by descent methods and applications

Genome-wide association study investigations

Genomics to accelerate precision dementia research

Lab team

Our lab’s work is highly collaborative usually working in a team with wet lab scientists and clinician scientists. Most of our lab members have backgrounds in the statistical, mathematical and physical sciences.

At WEHI, we collaborate closely with labs in the Genetics and Gene Regulation Division and also have collaborations with other labs throughout the institute including the Feltham, Pasricha, Dewson, Blewitt, Wickramasingha, King labs.

We welcome PhD enquiries from individuals wishing to become involved in statistical genetics to investigate genetic risk factors through analysis of cohort data but only from individuals with strong quantitative backgrounds.

25 members

Prof Melanie Bahlo AM

Lab head