Detecting and Removing Ascertainment Bias in Microsatellites from the HGDP-CEPH Panel

G3: Genes, Genomes, Genetics

Anders Eriksson¹  Andrea Manica¹ 

[1] Evolutionary Ecology Group, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, United KingdomEvolutionary Ecology Group, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, United KingdomEvolutionary Ecology Group, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, United Kingdom

关键词: microsatellites;    ascertainment bias;    HGDP-CEPH;    rarefaction;   

DOI  :  10.1534/g3.111.001016

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Although ascertainment bias in single nucleotide polymorphisms is a well-known problem, it is generally accepted that microsatellites have mutation rates too high for bias to be a concern. Here, we analyze in detail the large set of microsatellites typed for the Human Genetic Diversity Panel (HGDP)-CEPH panel. We develop a novel framework based on rarefaction to compare heterozygosity across markers with different mutation rates. We find that, whereas di- and tri-nucleotides show similar patterns of within- and between-population heterozygosity, tetra-nucleotides are inconsistent with the other two motifs. In addition, di- and tri-nucleotides are consistent with 16 unbiased tetra-nucleotide markers, whereas the HPGP-CEPH tetra-nucleotides are significantly different. This discrepancy is due to the HGDP-CEPH tetra-nucleotides being too homogeneous across Eurasia, even after their slower mutation rate is taken into account by rarefying the other markers. The most likely explanation for this pattern is ascertainment bias. We strongly advocate the exclusion of tetra-nucleotides from future population genetics analysis of this dataset, and we argue that other microsatellite datasets should be investigated for the presence of bias using the approach outlined in this article.

【 授权许可】

Unknown