PMID- 25787242
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20181113
IS  - 2160-1836 (Electronic)
IS  - 2160-1836 (Linking)
VI  - 5
IP  - 5
DP  - 2015 Mar 17
TI  - Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 
      1000 Genomes Project Phase I Data.
PG  - 931-41
LID - 10.1534/g3.114.015784 [doi]
AB  - Next-generation sequencing (NGS) technologies have become the standard for data 
      generation in studies of population genomics, as the 1000 Genomes Project 
      (1000G). However, these techniques are known to be problematic when applied to 
      highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) 
      genes. Because accurate genotype calls and allele frequency estimations are 
      crucial to population genomics analyses, it is important to assess the 
      reliability of NGS data. Here, we evaluate the reliability of genotype calls and 
      allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported 
      by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take 
      advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G 
      samples and use this as a gold standard to benchmark the 1000G data. We document 
      that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele 
      frequencies are estimated with an error greater than +/-0.1 at approximately 25% of 
      the SNPs in HLA genes. We found a bias toward overestimation of reference allele 
      frequency for the 1000G data, indicating mapping bias is an important cause of 
      error in frequency estimation in this dataset. We provide a list of sites that 
      have poor allele frequency estimates and discuss the outcomes of including those 
      sites in different kinds of analyses. Because the HLA region is the most 
      polymorphic in the human genome, our results provide insights into the challenges 
      of using of NGS data at other genomic regions of high diversity.
CI  - Copyright (c) 2015 Brandt et al.
FAU - Brandt, Debora Y C
AU  - Brandt DY
AD  - Department of Genetics and Evolutionary Biology, University of Sao Paulo, 
      05508-090 Sao Paulo, SP, Brazil.
FAU - Aguiar, Vitor R C
AU  - Aguiar VR
AD  - Department of Genetics and Evolutionary Biology, University of Sao Paulo, 
      05508-090 Sao Paulo, SP, Brazil.
FAU - Bitarello, Barbara D
AU  - Bitarello BD
AUID- ORCID: 0000-0001-7676-9367
AD  - Department of Genetics and Evolutionary Biology, University of Sao Paulo, 
      05508-090 Sao Paulo, SP, Brazil.
FAU - Nunes, Kelly
AU  - Nunes K
AD  - Department of Genetics and Evolutionary Biology, University of Sao Paulo, 
      05508-090 Sao Paulo, SP, Brazil.
FAU - Goudet, Jerome
AU  - Goudet J
AD  - Department of Ecology and Evolution, Biophore, University of Lausanne, CH-1015 
      Lausanne, Switzerland.
FAU - Meyer, Diogo
AU  - Meyer D
AUID- ORCID: 0000-0002-7155-5674
AD  - Department of Genetics and Evolutionary Biology, University of Sao Paulo, 
      05508-090 Sao Paulo, SP, Brazil diogo@ib.usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150317
PL  - England
TA  - G3 (Bethesda)
JT  - G3 (Bethesda, Md.)
JID - 101566598
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Alleles
MH  - *Chromosome Mapping
MH  - *Gene Frequency
MH  - Genetics, Population
MH  - Genome, Human
MH  - *Genomics/methods
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
PMC - PMC4426377
OTO - NOTNLM
OT  - 1000 Genomes
OT  - HLA
OT  - NGS
OT  - mapping bias
EDAT- 2015/03/20 06:00
MHDA- 2016/02/03 06:00
PMCR- 2015/03/17
CRDT- 2015/03/20 06:00
PHST- 2015/03/20 06:00 [entrez]
PHST- 2015/03/20 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2015/03/17 00:00 [pmc-release]
AID - g3.114.015784 [pii]
AID - GGG_015784 [pii]
AID - 10.1534/g3.114.015784 [doi]
PST - epublish
SO  - G3 (Bethesda). 2015 Mar 17;5(5):931-41. doi: 10.1534/g3.114.015784.