• Diehl, Scott (PI)
  • Kendler, Kenneth Seedman (PI)
  • Straub, Richard Eric (PI)

Project Details


Family, twin and adoption studies have consistently shown that genetic
factors are of major etiologic importance in schizophrenia. Since early
in this century, it has been suggested that there are single genes of
"major effect" for schizophrenia. Recent advances in molecular biology
and in statistical approaches to linkage analysis now provide us, for the
first time, with the techniques to rigorously evaluate this claim. This is a proposal to conduct linkage analyses on a large number of
multiplex pedigrees for schizophrenia that are currently being
ascertained and sampled in Ireland (MH-41953). This study will utilize
the abundant, highly polymorphic DNA markers that have recently become
available to span virtually the entire human genome as well as potential
candidate genes. This proposal seeks to capitalize on the unique resource
of high density Irish schizophrenic pedigrees that include: i) a
relatively homogeneous ethnic composition of the population, which should
reduce the problems of genetic heterogeneity; ii) enhanced ability to
determine optimal diagnostic criteria, and estimates of gene frequency
and penetrance necessary for linkage analyses by utilizing data obtained
from a large sample epidemiologically based family study currently
nearing completion in the West of Ireland and iii) the close genetic
relationship between Ireland and both Iceland and England, the countries
in which pedigrees have been ascertained that demonstrate significant
linkage to markers on chromosome 5. Genetic markers throughout the genome will be typed for the high density
schizophrenic families, first concentrating in areas that previous
studies suggest might be of potential relevance to schizophrenia. Several
distinct statistical methodologies of segregation and linkage analysis
will be applied to the data in order to fully utilize their potential.
Any strong positive findings will be pursued by cloning additional
markers from that part of the genome where a major locus for
schizophrenia might lie, in order to map the locus more precisely.
Effective start/end date9/1/894/30/01


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $362,010.00


  • Medicine(all)

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