NIDDM SUSCEPTIBILITY GENES IN MEXICAN-AMERICANS

Project: Research project

Project Details

Description

The purpose of this project is to carry out a systematic search of the
genome for susceptibility genes for non-insulin dependent diabetes
(NIDDM). The study will be carried out in Mexican American families
currently enrolled in the San Antonio Family Diabetes Study (SAFADS), a
project currently funded by NIDDKD (R01 DK42273, N. Stern, PI). To date,
432 individuals from 29 different families have been enrolled into the
SAFADS; our recruitment target is 720 total individuals, and we anticipate
achieving this target by June 1994. SAFADS families are ascertained on a
low-income Mexican American NIDDM proband. Blood lymphocytes are
currently being EBV transformed for SAFADS participants and cell lines
have been/are being established to provide a renewable source of DNA. The current project will use SAFADS families as a resource for conducting
a gene search. Our strategy will be first to seek preliminary evidence
for linkage by typing markers on an initial set of 177 individuals from 23
families already enrolled and secondly, to verify suspected linkages by
typing markers on additional family members from the initial pedigrees and
by typing other SAFADS families. We will use approximately 250 highly
polymorphic PCR-based microsatellite markers that span the entire genome
at regular intervals and then use linkage analysis to search for linkage
between these markers and NIDDM or its precursor traits (i.e., glucose,
insulin, or C-peptide levels). Our simulations indicate that if NIDDM
were inherited as a Mendelian dominant trait, we would have excellent
power of detecting evidence for linkage on the initial set of pedigrees.
As new markers are typed and added to the database, we will perform two-
point linkage analyses to screen for linkage. Those markers with
suggestive evidence for linkage will be used in combined segregation and
linkage analyses and in multipoint analysis. If evidence for linkage
persists, additional markers will be typed in that region to "zero in" on
the NIDDM susceptibility gene(s). The phenotypes to be considered in
these analyses are NIDDM, the quantitative traits, glucose, insulin, and
C-peptide levels, and a risk score derived from a predictive model for
NIDDM.
StatusFinished
Effective start/end date9/30/938/31/14

Funding

  • National Institutes of Health: $620,874.00
  • National Institutes of Health: $597,031.00
  • National Institutes of Health: $610,396.00
  • National Institutes of Health: $593,886.00

ASJC

  • Medicine(all)

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