Price Alkes L, Patterson Nick, Yu Fuli, Cox David R, Waliszewska Alicja, McDonald Gavin J, Tandon Arti, Schirmer Christine, Neubauer Julie, Bedoya Gabriel, Duque Constanza, Villegas Alberto, Bortolini Maria Catira, Salzano Francisco M, Gallo Carla, Mazzotti Guido, Tello-Ruiz Marcela, Riba Laura, Aguilar-Salinas Carlos A, Canizales-Quinteros Samuel, Menjivar Marta, Klitz William, Henderson Brian, Haiman Christopher A, Winkler Cheryl, Tusie-Luna Teresa, Ruiz-Linares Andres, Reich David
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Am J Hum Genet. 2007 Jun;80(6):1024-36. doi: 10.1086/518313. Epub 2007 Apr 13.
Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.
混合映射是一种经济且强大的方法,用于在近期混合血统的人群中定位疾病基因,并且已在非裔美国人中证明是成功的。该方法对拉丁裔同样具有前景,他们通常继承了欧洲、美洲原住民和非洲血统的混合。然而,由于缺乏在美洲原住民和其他人群中验证过的祖先信息标记图谱,拉丁裔中的混合映射并不实用。为了解决这个问题,我们筛选了包含数百万个标记的多个数据库,以识别4186个标记,这些标记被认为对确定拉丁裔人群中染色体片段的祖先具有信息价值。我们在至少232个新的拉丁裔、欧洲、美洲原住民和非洲样本中对这些标记进行了实验验证,并选择了1649个标记的子集来形成一个混合图谱。我们策略的一个优点是,我们将图谱重点放在区分美洲原住民与其他血统的标记上,并将其限制在欧洲人和非洲人频率非常相似的标记上,这减少了所需标记的数量,并将错误疾病关联的可能性降至最低。我们评估了我们的图谱在定位来自北美洲和南美洲的四个拉丁裔人群中疾病基因方面的有效性。