Statistical Genetic Analysis-
Dr. Lange’s primary
research interests are in the development and application of statistical
methods
to genetic
data. His methodological
work
has focused on developing techniques for haplotype-based association
analyses, linkage analysis, and genetic power analyses. He has been
involved in
past projects that have successfully localized susceptibility
genes for the Mendelian
traits ataxia-telangiectasia and the Nijmegen breakage syndrome. Unfortunately,
susceptibility for many traits is governed by complex interactions
between many genes and numerous environmental exposures. This complexity
creates
new challenges for geneticists. Fortunately, great strides have been
made recently in the fields of genetics and computer science that
have provided
researchers the ability to access and analyze a tremendous amount
of potentially useful data. The ultimate challenge for statistical geneticists
may be
how to best utilize all of this information. Clearly, strong collaborations
between clinicians, molecular geneticists, epidemiologists and statistical
geneticists, among others, will be vital for success in future gene
mapping. Dr. Lange hopes to develop methodology that will make good
use of all
the
available data to assist in these gene mapping efforts.
Prostate Cancer Susceptibility-
Since 1997, in collaboration with Kathleen Cooney at the University of
Michigan, Dr. Lange has also has been actively involved in the efforts
to identify prostate cancer susceptibility genes. To date, no definitive
prostate cancer susceptibility genes have been identified. Some putative
susceptibility genes have been recently suggested, but it remains to
be seen just how relevant these candidates are. The difficulty in identifying
prostate cancer susceptibility genes is typical of the difficulties
encountered when attempting to map genes for many other complex traits.
There are likely to be many prostate cancer susceptibility genes, each
with small but contributing effects. Recently, Dr. Cooney and Dr. Lange
joined a large international linkage consortium called the International
Consortium for Prostate Cancer Genetics (ICPCG). This group is combining
their resources in order to achieve sufficient power to detect genes
with modest effects. Together, the ICPCG has uncovered a number of interesting
linkage regions that have encouraged further investigation. Selected
Publications:
Lange EM, Robbins CM, Gillanders EM, Zheng SL, Xu J, Wang Y, White KA, Chang BL, Ho LA, Trent JM, Carpten JD, Isaacs WB, Cooney KA. (2007) Fine-mapping the putative chromosome 17q21-22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis. Hum Genet.121:49-55.
Lange EM, Ho LA, Beebe-Dimmer JL, Wang Y, Gillanders EM, Trent JM, Lange LA, Wood DP, Cooney KA. (2006) Genome-wide linkage scan for prostate cancer susceptibility genes in men with aggressive disease: significant evidence for linkage at chromosome 15q12. Hum Genet. 119:400-7.
Slager SL, Zarfas KE, Brown WM, Lange EM, McDonnell SK, Wojno KJ,
Cooney KA. (2006) Genome-wide linkage scan for prostate cancer aggressiveness
loci using families from the University of Michigan Prostate Cancer
Genetics Project. Prostate 66:173-9.
Lange
EM, Boehnke M (2004) The haplotype runs test: The parent-parent-affected-offspring
trio design. Genet Epidemiol 27:118-130.
Gillanders EM, Xu J, Chang B, Lange EM, Wiklund F, Bailey-Wilson
JE, Baffoe-Bonnie A, Jones MP, Gildea D, Riedesel E, Albertus J,
Isaacs SD, Wiley KE, Mohai CE, Matikainen MP, Tammela TLJ, Zheng
SL, Brown WM, Rokman A, Meyers DA, Schleutker J, Gronberg H, Cooney
KA, Isaacs WB, Trent JM (2004) Combined genome-wide scan for prostate
cancer susceptibility genes in four hereditary prostate cancer populations:
evidence for linkage at 17q22. J Natl Cancer Inst 96:1240-1247.
Ambrosius WT, Lange EM, Langefeld CD (2004) Power for genetic association
studies with random allele frequencies and genotype distributions. Am
J Hum Genet 74: 683-693.
Lange EM, Lange K (2004) Powerful allele-sharing statistics for
nonparametric linkage analysis. Hum Hered 57:49-58.
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