Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort.

Variations in the calpain-10 gene have recently been reported to be associated with type 2 diabetes in a Mexican-American population. We typed three single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNPs 43, 56, and 63) to test for association between variation at these loci and type 2 diabetes and diabetes-related traits in 1,603 Finnish subjects: two samples of 526 (Finland-U.S. Investigation of NIDDM Genetics [FUSION] 1) and 255 (FUSION 2) index case subjects with type 2 diabetes, 185 and 414 unaffected spouses and offspring of FUSION 1 index case subjects or their affected siblings, and 223 elderly normal glucose-tolerant control subjects. We found no significant differences in allele, genotype, haplotype, or haplogenotype frequencies between index case subjects with diabetes and the elderly and spouse control populations (all P > 0.087). Although variation in these three SNPs was associated with variation in some type 2 diabetes-related traits within each of the case and control groups, no consistent pattern of the implicated variant or combination of variants was discerned. We conclude that variation in these three SNPs in the calpain-10 gene is unlikely to confer susceptibility to type 2 diabetes in this Finnish cohort.

A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14.

The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.

Implementation of an error-reporting module within a biorepository IT application to enhance operations.

The Collaborative (formerly the Cooperative) Human Tissue Network (CHTN) is a federally funded service oriented grant that provides high-quality biospecimens and services to the research community. The CHTN consists of six institutions located throughout the United States to assist investigators in obtaining research specimens required for basic research. The CHTN divisions have similar operating goals: however, each division is responsible for maintaining operations at their local institutions. This requires the divisions to identify ways to maintain and sustain operations in a challenging federally funded environment, especially when the number of investigators requesting services drives the operation. Sustainability plans and goals are often times patched together out of necessity rather than taking a thoughtful approach by clearly defining and aligning activities with business strategy and priorities. The CHTN Western Division at Vanderbilt University Medical Center (CHTN-WD) has responded to this challenge of biospecimen resource sustainability in the face of diminished funding by continually identifying ways to innovate our processes through IT enhancements and requiring that the innovation produce measurable and relevant criteria for credibly reporting our operations progress and performance issues. With these overarching goals in mind, CHTN-WD underwent a Lean Six Sigma (LSS) series to identify operational inefficiencies that could be addressed with redesigning workflow and innovating the processes using IT solutions. The result of this internal collaborative innovation process was the implementation of an error-reporting module (ERM) hosted within our biorepository donor IT application, which allowed staff to report errors immediately; determine the operational area responsible; assess the severity of the error; determine course of action; determine if standard operating procedure (SOPs) revisions were required; and through automated e-mails, alert the area personnel responsible. The module provides a data-reporting feature by date range and area of operation for management and analysis.