A High-Density Admixture Map for Disease Gene Discovery in African Americans

• Published in: American journal of human genetics Vol. 74; no. 5; pp. 1001 - 1013
• Main Authors: Smith, Michael W., Patterson, Nick, Lautenberger, James A., Truelove, Ann L., McDonald, Gavin J., Waliszewska, Alicja, Kessing, Bailey D., Malasky, Michael J., Scafe, Charles, Le, Ernest, De Jager, Philip L., Mignault, Andre A., Yi, Zeng, de Thé, Guy, Essex, Myron, Sankalé, Jean-Louis, Moore, Jason H., Poku, Kwabena, Phair, John P., Goedert, James J., Vlahov, David, Williams, Scott M., Tishkoff, Sarah A., Winkler, Cheryl A., De La Vega, Francisco M., Woodage, Trevor, Sninsky, John J., Hafler, David A., Altshuler, David, Gilbert, Dennis A., O’Brien, Stephen J., Reich, David
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-05-2004; University of Chicago Press; American Society of Human Genetics
• Subjects: African Americans - genetics; Alleles; Biological and medical sciences; Chromosome Mapping - methods; Ethnic Groups - genetics; European Continental Ancestry Group - genetics; Gene Frequency - genetics; General aspects. Genetic counseling; Genetic Diseases, Inborn - ethnology; Genetic Diseases, Inborn - genetics; Genetic Markers - genetics; Genetics, Population; Genome, Human; Haplotypes - genetics; Humans; Linkage Disequilibrium - genetics; Medical genetics; Medical sciences; Microsatellite Repeats; Polymorphism, Single Nucleotide - genetics; Human; Cartography; Gene; Disease; Admixture; Genetics; Density; African American
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/420856

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 ∼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 ∼450,000 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 3,011 as a MALD map (1.2 cM average spacing). We estimate that this map is ∼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.