Genetics of Type 1 Diabetes Mairead Bermingham Centre for Genomic and Experimental Medicine Science Insights 24th July 2017

Monogenic Inheritance Maturity onset diabetes of the young (MODY) Mutations in glucokinase gene Normal Mutant MODY MODY Normal Normal If a parent has this gene mutation, any child they have, has a 50% chance of inheriting it from them.

Finding a gene challenge

Complex Inheritance

Incomplete Penetrance Not all individuals that inherit a particular genotype at a locus will develop the associated phenotype, or the phenotype may depend on other factors such as age, gender, or environment Example disease susceptibility genes HLA & IL2RA genes for diabetes BRCA1 and BRCA2 genes for breast cancer Both examples actually have high penetrance relative to other disease susceptibility genes, BUT their penetrance is not 100%

Polygenic Traits When a phenotype is caused by the contributions of two or more genes 2 types: Discrete traits (e.g., eye color) Continuous traits (e.g., height) AA + CG  disease AA only  no disease CG only  no disease AA + CG  metastatic cancer AA only  pre-cancerous cells CG only  localized tumor

Polygenic pedigree challenge

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Animal models

Mouse model in type 1 diabetes Type 1 diabetes is generally regarded as genetic New experiments on mice show that mouse mothers can protect their pups from developing type 1 diabetes by eating a gluten-free diet Non-obese diabetic (NOD) mouse

Breed an animal model GENIQUEST

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