Colistro Valentina, Mut Patricia, Hidalgo Pedro C, Carracedo Angel, Quintela Inés, Rojas-Martínez Augusto, Sans Mónica
Universidad de la República, Facultad de Medicina, Departamento de Métodos Cuantitativos, Montevideo, Uruguay.
Universidad de la República, Facultad de Humanidades y Ciencias de la Educación, Departamento de Antropología Biológica, Montevideo, Uruguay.
Genet Mol Biol. 2020 Nov 13;43(4):e20200143. doi: 10.1590/1678-4685-GMB-2020-0143. eCollection 2020.
Genome-wide association studies focused on searching genes responsible for several diseases. Admixture mapping studies proposed a more efficient alternative capable of detecting polymorphisms contributing with a small effect on the disease risk. This method focuses on the higher values of linkage disequilibrium in admixed populations. To test this, we analyzed 10 genomic regions previously defined as related with colorectal cancer among nine populations and studied the variation pattern of haplotypic structures and heterozygosity values on seven categories of SNPs. Both analyses showed differences among chromosomal regions and studied populations. Admixed Latin-American samples generally show intermediate values. Heterozygosity of the SNPs grouped in categories varies more in each gene than in each population. African related populations have more blocks per chromosomal region, coherently with their antiquity. In sum, some similarities were found among Latin American populations, but each chromosomal region showed a particular behavior, despite the fact that the study refers to genes and regions related with one particular complex disease. This study strongly suggests the necessity of developing statistical methods to deal with di- or tri-hybrid populations, as well as to carefully analyze the different historic and demographic scenarios, and the different characteristics of particular chromosomal regions and evolutionary forces.
全基因组关联研究专注于寻找导致多种疾病的基因。混合映射研究提出了一种更有效的替代方法，能够检测对疾病风险有微小影响的多态性。该方法关注混合人群中连锁不平衡的较高值。为了验证这一点，我们分析了九个群体中先前定义为与结直肠癌相关的10个基因组区域，并研究了七类单核苷酸多态性（SNP）的单倍型结构和杂合度值的变异模式。两项分析均显示出染色体区域和所研究群体之间的差异。混合的拉丁裔样本通常显示出中间值。按类别分组的SNP的杂合度在每个基因中比在每个群体中变化更大。与非洲相关的群体每个染色体区域有更多的基因块，这与它们的古老程度一致。总之，在拉丁裔群体中发现了一些相似之处，但尽管该研究涉及与一种特定复杂疾病相关的基因和区域，每个染色体区域仍表现出特定的行为。这项研究强烈表明，有必要开发统计方法来处理二倍体或三倍体群体，以及仔细分析不同的历史和人口统计学情况，以及特定染色体区域的不同特征和进化力量。
