Smith M W, Lautenberger J A, Shin H D, Chretien J P, Shrestha S, Gilbert D A, O'Brien S J
Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute, MD 21702, USA.
Am J Hum Genet. 2001 Nov;69(5):1080-94. doi: 10.1086/323922.
Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite delta, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide-polymorphism databases and the literature, to achieve a 3-10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans.
群体连锁不平衡是由突变、选择、遗传漂变以及不同遗传背景的种族群体混合产生的群体亚结构导致的。非裔美国人和西班牙裔群体在其亲本群体之间存在显著的基因流动历史,这在病例对照研究和传递/不平衡检验设计中对影响疾病基因发现的基因组扫描可能具有重要价值。利用混合连锁不平衡定位(MALD)进行疾病基因发现需要一张多态性标记图谱,该图谱要能区分奠基群体,同时还要体现疾病基因等位基因频率的差异。我们通过评估非裔美国人、西班牙裔、欧裔美国人和亚洲人中744个短串联重复序列(STR)的等位基因频率,选择那些在复合δ、对数似然比和/或用于MALD的I*(2)上有较大差异的STR标记,来描述适合MALD定位的标记。通过利用快速增长的单核苷酸多态性数据库和文献,可以在这张MALD图谱上添加更多标记,以实现3 - 10厘摩的扫描尺度。该图谱将有助于研究西班牙裔或非裔美国人的奠基群体之间发病率有很大差异的疾病,包括前列腺癌、乳腺癌、糖尿病、高血压和终末期肾病。