In the San Antonio Family Diabetes Study (SAFADS) the investigators have enrolled 579 low income Mexican Americans in 31 families (median family size, 19). The purpose of this project is to identify type II diabetes susceptibility genes. Lymphoblastoid cell lines have been established on 544 subjects. They are also creating a 15 centimorgan gene map using highly polymorphic microsatellite markers on a subset of 452 highly informative individuals from 25 of the 31 families. This effort is supported by a separate, but closely related grant (DK47482). All candidate genes and microsatellite markers are screened for linkage to the following traits: diabetes, fasting and 2-hour glucose, fasting and 2-hour insulin, fasting proinsulin, fasting proinsulin split products, and a panel of anthropometric measures. The investigators propose to increase the density of their gene map to 5cM (total of 750 markers). They will screen each marker for linkage to the above traits using: a multipoint variance components approach based on sibships; affected pedigree method; and segregation-model-based linkage analysis. For markers giving a lod score >=0.834 (equal to a nominal p-value of 0.05), they will attempt to boost the signal using """"""""refined"""""""" screening tests: multipoint variance components approach based on full pedigrees; pseudo-multipoint segregation-model-based linkage analysis; and combined segregation and linkage analysis. For lod scores >=1.25 on """"""""refined"""""""" screening analysis, or >=2.00 on the primary screening analysis, they will attempt confirmation of linkage in a completely independent set of low-income Mexican American families who have participated in the Family Heart Study. They also plan to recall current families to reclassify prediabetics and enroll new families. These updated and augmented data will be used in years 9 and 10 to screen for possible linkages which could have been missed in the original dataset and to perform high resolution mapping for confirmed linkages.
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