TY - JOUR
T1 - A strategy for using multiple linked markers for genetic counseling
AU - Chakravarti, A.
AU - Buetow, K. H.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1985
Y1 - 1985
N2 - A strategy for using multiple linked markers for genetic counseling is to test sequentially individual markers until a diagnosis can be made. We show that in order to minimize the number of tests performed per case while diagnosing all informative cases the order in which the markers are to be tested is critical. We describe an algorithm to obtain this order using the parameter 'I', the frequency of informative cases. The I value for a specific locus used depends on the marker frequency, association with the disease locus, and also on the informativeness of the marker loci already tested. Realizing that a direct assay for the β(S) gene already exists, and that most cases of β-thalassemia in Mediterraneans can be directly diagnosed using synthetic oligonucleotide probes, we illustrate the above technique by examining nine DNA polymorphisms in the human β-globin cluster for their ability to diagnose sickle-cell anemia in American blacks and β-thalassemia in Mediterraneans. This analysis shows that 95.39% of all sickle-cell pregnancies can be diagnosed by testing a subset of only six markers chosen by our algorithm. Furthermore, six markers can also diagnose 88.03% of β-thalassemia in Greeks and 83.56% of β-thalassemia in Italians. The test set is different from that suggested by the individual informative frequencies due to nonrandom associations between the restriction sites.
AB - A strategy for using multiple linked markers for genetic counseling is to test sequentially individual markers until a diagnosis can be made. We show that in order to minimize the number of tests performed per case while diagnosing all informative cases the order in which the markers are to be tested is critical. We describe an algorithm to obtain this order using the parameter 'I', the frequency of informative cases. The I value for a specific locus used depends on the marker frequency, association with the disease locus, and also on the informativeness of the marker loci already tested. Realizing that a direct assay for the β(S) gene already exists, and that most cases of β-thalassemia in Mediterraneans can be directly diagnosed using synthetic oligonucleotide probes, we illustrate the above technique by examining nine DNA polymorphisms in the human β-globin cluster for their ability to diagnose sickle-cell anemia in American blacks and β-thalassemia in Mediterraneans. This analysis shows that 95.39% of all sickle-cell pregnancies can be diagnosed by testing a subset of only six markers chosen by our algorithm. Furthermore, six markers can also diagnose 88.03% of β-thalassemia in Greeks and 83.56% of β-thalassemia in Italians. The test set is different from that suggested by the individual informative frequencies due to nonrandom associations between the restriction sites.
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M3 - Article
C2 - 2996337
AN - SCOPUS:0022409224
VL - 37
SP - 984
EP - 997
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -