Post by Caipira on Dec 1, 2003 0:51:04 GMT -5
Genetic Structure
of Human Populations
Noah A. Rosenberg,1* Jonathan K. Pritchard,2 James L. Weber,3
Howard M. Cann,4 Kenneth K. Kidd,5 Lev A. Zhivotovsky,6
Marcus W. Feldman7
...Thus, for many applications in epidemiology,
as well as for assessing individual disease
risks, self-reported population ancestry
likely provides a suitable proxy for genetic
ancestry. Self-reported ancestry can be obtained
less intrusively than genetic ancestry,
and if self-reported ancestry subdivides a genetic
cluster into multiple groups, it may
provide useful information about unknown
environmental risk factors (23, 25). One exception
to these general comments may arise
in recently admixed populations, in which
genetic ancestry varies substantially among
individuals; this variation might correlate
with risk as a result of genetic or cultural
factors (24). In some contexts, however, use
of genetic clusters is more appropriate than
use of self-reported ancestry. In genetic casecontrol
association studies, false positives
can be obtained if disease risk is correlated
with genetic ancestry (24, 26). Basing analyses
on self-reported ancestry reduces the
proportion of false positives considerably
(25). However, association studies are usually
analyzed by significance testing, in which
slight differences in genetic ancestry between
cases and controls can produce statistically
significant false-positive associations in large
samples. Thus, errors incurred by using selfreported
rather than genetic ancestry might
cause serious problems in large studies that
will be required for identifying susceptibility
loci with small effects (26). Genetic clustering
is also more appropriate for some types of
population genetic studies, because unrecognized
genetic structure can produce false positives
in statistical tests for population growth
or natural selection (27).
The challenge of genetic studies of human
history is to use the small amount of genetic
differentiation among populations to infer the
history of human migrations. Because most
alleles are widespread, genetic differences
among human populations derive mainly
from gradations in allele frequencies rather
than from distinctive “diagnostic” genotypes.
Indeed, it was only in the accumulation of
small allele-frequency differences across
many loci that population structure was identified.
Patterns of modern human population
structure discussed here can be used to guide
construction of historical models of migration
and admixture that will be useful in inferential
studies of human genetic history.
of Human Populations
Noah A. Rosenberg,1* Jonathan K. Pritchard,2 James L. Weber,3
Howard M. Cann,4 Kenneth K. Kidd,5 Lev A. Zhivotovsky,6
Marcus W. Feldman7
...Thus, for many applications in epidemiology,
as well as for assessing individual disease
risks, self-reported population ancestry
likely provides a suitable proxy for genetic
ancestry. Self-reported ancestry can be obtained
less intrusively than genetic ancestry,
and if self-reported ancestry subdivides a genetic
cluster into multiple groups, it may
provide useful information about unknown
environmental risk factors (23, 25). One exception
to these general comments may arise
in recently admixed populations, in which
genetic ancestry varies substantially among
individuals; this variation might correlate
with risk as a result of genetic or cultural
factors (24). In some contexts, however, use
of genetic clusters is more appropriate than
use of self-reported ancestry. In genetic casecontrol
association studies, false positives
can be obtained if disease risk is correlated
with genetic ancestry (24, 26). Basing analyses
on self-reported ancestry reduces the
proportion of false positives considerably
(25). However, association studies are usually
analyzed by significance testing, in which
slight differences in genetic ancestry between
cases and controls can produce statistically
significant false-positive associations in large
samples. Thus, errors incurred by using selfreported
rather than genetic ancestry might
cause serious problems in large studies that
will be required for identifying susceptibility
loci with small effects (26). Genetic clustering
is also more appropriate for some types of
population genetic studies, because unrecognized
genetic structure can produce false positives
in statistical tests for population growth
or natural selection (27).
The challenge of genetic studies of human
history is to use the small amount of genetic
differentiation among populations to infer the
history of human migrations. Because most
alleles are widespread, genetic differences
among human populations derive mainly
from gradations in allele frequencies rather
than from distinctive “diagnostic” genotypes.
Indeed, it was only in the accumulation of
small allele-frequency differences across
many loci that population structure was identified.
Patterns of modern human population
structure discussed here can be used to guide
construction of historical models of migration
and admixture that will be useful in inferential
studies of human genetic history.