Enhanced linkage maps from family-based genetics studies

Project Details


DESCRIPTION (provided by applicant):
Meiotic linkage maps are the foundation of both linkage and linkage
disequilibrium studies for mapping disease genes. Despite the importance of
precise maps, existing genome-wide linkage maps were built using only a small
collection of pedigrees, and so have wide confidence intervals surrounding
estimates of map distance. Incorrect marker order and map distances can have
a profound effect on linkage analyses. Using a sex-averaged map instead of a
sex-specific map biases the lod scores upward, markedly increasing the false
positive rate. Since it is very costly to follow-up many false-positive
results, there is a clear need for more precise and accurate sex-specific
genetic maps. Accurate estimates of meiotic map distance cannot be obtained
by any means other than by linkage analysis using genotype data. We propose
to build improved highly-precise sex-specific linkage maps utilizing thousands
of individuals who have previously been genotyped. After filtering out
obvious relationship and genotype errors, we will incorporate methods that
properly model for genotyping errors. In addition to creating precise maps
for the scientific community, we also propose to use these genotype data to
study how recombination may vary between ethnic groups. The genotypes
generated by the NHLBI Mammalian Genotyping Service are precisely the type of
data required to produce more accurate maps. These data collections contain
over 3,400 pedigrees with more than a 1 00-fold increase in information
compared to that contained in the 8 CEPH families that have been used to
construct current genome-wide linkage maps. Our new maps will be made
publicly available and the genotype data from our study will be accessible by
the MAP-0-MAT linkage mapping server. In the future, we anticipate broadening
our study to incorporate genotype data from additional genotyping centers such
as the Center for Inherited Disease Research (CIDR). The inaccuracies present
in current maps can contribute to misleading results, and may be one of the
reasons that disappointingly few genes have been definitively identified that
contribute to such complex diseases as asthma, cardiovascular disease,
hypertension, hypercholesterolemia, diabetes, obesity, and cancer. The more
precise maps that we propose to construct will improve the power and value of
many ongoing and new disease studies.
Effective start/end date9/1/028/31/05


  • National Heart, Lung, and Blood Institute: $155,500.00
  • National Heart, Lung, and Blood Institute: $147,415.00


  • Genetics


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