Mutations in the insulin receptor gene are known to be a cause of some form of extreme insulin resistance. In a few patients similar mutations have been associated with the mild to moderate forms of insulin resistance observed in patients with NIDDM. It is currently unknown how wildly present this defect is. At present the PCR methods used to screen for point mutations (DGGE, SSCP, heteroduplex analysis) are extremely sensitive and allow researchers to study relatively large populations. However, these methods will fail to detect a partial or complete deletion. The methods currently used to screen for gene deletions (Southern blot analysis, RFLPs, quantitative Southern blot analysis) are troublesome, time consuming and require a large quantity of genomic DNA. We plan to use a novel PCR method developed in our laboratory to screen for gene deletions in a large population of NIDDM patients from the greater Baltimore area as well as populations with a high prevalence of NIDDM (Pima native Americans, Nauruans, Mexican Americans).