FastMap: Fast eQTL mapping in homozygous populations

Abstract

Motivation: Gene expression Quantitative Trait Locus (eQTL) mapping measures the association between transcript expression and genotype in order to find genomic locations likely to regulate transcript expression. The availability of both gene expression and high-density genotype data has improved our ability to perform eQTL mapping in inbred mouse and other homozygous populations. However, existing eQTL mapping software does not scale well when the number of transcripts and markers are on the order of 105 and 105–106, respectively.Results: We propose a new method, FastMap, for fast and efficient eQTL mapping in homozygous inbred populations with binary allele calls. FastMap exploits the discrete nature and structure of the measured single nucleotide polymorphisms (SNPs). In particular, SNPs are organized into a Hamming distance-based tree that minimizes the number of arithmetic operations required to calculate the association of a SNP by making use of the association of its parent SNP in the tree. FastMap's tree can be used to perform both single marker mapping and haplotype association mapping over an m-SNP window. These performance enhancements also permit permutation-based significance testing.Availability: The FastMap program and source code are available at the website: http://cebc.unc.edu/fastmap86.htmlContact: iir@unc.edu; nobel@email.unc.eduSupplementary information: Supplementary data are available at Bioinformatics online.

Replication and narrowing of gene expression quantitative trait loci using inbred mice

“…eQTL mapping in the BXD panel was carried out using FastMap (Gatti et al 2009) configured to perform single-marker mapping and 1,000 permutations per transcript to produce per-transcript significance thresholds. A subset of 2,486 transcripts (out of 20,868 on the array) were selected by retaining all transcripts with known genomic locations (in Mouse Genome Build 36) and a maximum eQTL peak with a p-value ≤ 0.05.…”

“…Association mapping was carried out using FastMap (Gatti et al 2009) as detailed above. Population structure was identified using a PCA plot of the SNP data and two major strata were identified; C57BL/6J, C57BL/10J, C57BLKS/J, C57BR/cdJ & C57L/J were in one stratum and the remaining strains were in the other.…”

Sex-specific gene expression in the BXD mouse liver

“…eQTL mapping was performed by using single marker mapping in FastMap (21), which uses sample permutation to produce per-gene significance thresholds. Heritability was estimated with the strain intraclass correlation.…”

Computational Tools for Discovery and Interpretation of Expression Quantitative Trait Loci

“…Issues of experimental design, sample size and considerations of the statistical power are considered in detail by Kendziorski and Wang [16]. While the processing of data collected in both genotyping and gene-expression experiments, including normalization and quality control, may also be challenging with some of the newer technologies [20], the major impediments of eQTL analyses lie in the underlying statistical assumptions and ensuring proper error control [21], as well as the need for computational efficiency [22]. Batch-effect correction – of either population stratification or technical artifacts – is not automatically performed by the eQTL packages reviewed here.…”

“…FastMap [108] is a Java-based eQTL tool that has a graphical user interface [22]. FastMap visualizes findings for any given transcript using Manhattan plots with a zoom function, and provides one-click connection to the University of California Santa Cruz (CA, USA) Genome Browser.…”