The main goal of this project is to develop a general statistical theory for making inferences about the gene order on a chromosome. Besides its theoretical relevance, it leads to important practical applications: the construction of the human gene map and the improvement of the accuracy of genetic counseling and prenatal diagnosis.
We aim at developing optimal decision procedures to order an arbitrarily high number of genes. This will be accomplished by constructing multiple-step decision procedures (procedures where multiple nonindependent tests are performed to order overlapping sequences of genes). Since one-step procedures (procedures where all the hypotheses are considered simultaneously) are repeatedly used in multiple-step procedures, we shall derive efficient one-step procedures. To develop optimal one- and multiple-step procedures we shall consider different statistical approaches (classical Bayes, empirical Bayes and generalized likelihood), sampling schemes (fixed sample size, sequential, and group sequential), genetic models (recombination fractions, map distances, misclassification parameters, incomplete penetrance), and sources of genetic information (phase-known backcross system and generic pedigree structure). The key feature of the ordering procedures we shall develop is to control the probability of committing decision errors. The second goal of this project is to develop a general statistical theory for estimating the genetic risk and to evaluate how the uncertainty on the gene order and genetic distances reflects on the precision of genetic risks estimates, used in genetic counseling. The statistical methods will be implemented in computer programs and evaluated with simulated and real data.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM045979-01A1
Application #
3305469
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1993-05-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
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Rebbeck, T R; Jordan, H A; Schnur, R E et al. (1997) Utility of linked markers in genetic counseling: estimation of carrier risks in X-linked ocular albinism. Am J Med Genet 70:58-66
Rogatko, A (1995) Risk prediction with linked markers: theory. Am J Med Genet 59:14-23
Rogatko, A; Rebbeck, T; Zacks, S (1995) Risk prediction with linked markers: pedigree analysis. Am J Med Genet 59:24-32