A high-density admixture map for disease gene discovery in african americans.
Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
Smith
Michael W
MW
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA.
Patterson
Nick
N
Lautenberger
James A
JA
Truelove
Ann L
AL
McDonald
Gavin J
GJ
Waliszewska
Alicja
A
Kessing
Bailey D
BD
Malasky
Michael J
MJ
Scafe
Charles
C
Le
Ernest
E
De Jager
Philip L
PL
Mignault
Andre A
AA
Yi
Zeng
Z
De The
Guy
G
Essex
Myron
M
Sankale
Jean-Louis
JL
Moore
Jason H
JH
Poku
Kwabena
K
Phair
John P
JP
Goedert
James J
JJ
Vlahov
David
D
Williams
Scott M
SM
Tishkoff
Sarah A
SA
Winkler
Cheryl A
CA
De La Vega
Francisco M
FM
Woodage
Trevor
T
Sninsky
John J
JJ
Hafler
David A
DA
Altshuler
David
D
Gilbert
Dennis A
DA
O'Brien
Stephen J
SJ
Reich
David
D
D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods*; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000208:ethnology* / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005828:Genetics, Population; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
D005819:Genetic Markers