Table 1.

Identifying the Genes for Type 2 Diabetes

Studies of Monogenic Forms of Type 2 Diabetes

Maturity Onset Diabetes of the Young (MODY)

Rare forms of severe insulin resistance

Neonatal diabetes

Mitochondrial syndromes of diabetes

Candidate Gene Approach

Functional

Genes involved in insulin action and insulin secretion

Genes associated with diseases associated with diabetes (obesity, genetic syndromes, etc)

Genes identified in animal models of diabetes

Positional

Genes in linked intervals identified through family studies

Useful for monogenic forms of diabetes (e.g., MODY)

Challenging for common, multifactorial Type 2 diabetes

Finding Genes with Altered Levels of Expression

Subtraction cloning and differential display

Microarray analysis (gene expression arrays)

Genome-wide Association Studies

Microarray-based typing of ≥ 100K SNPs spanning the entire genome

Large populations of diabetic cases and non-diabetic controls

Populations with intermediate phenotypes – obesity, insulin resistance, polycystic ovarian disease