title: Characterizing regions in the human genome unmappable by next-generation-sequencing at the read length of 1000 bases.
abstract: Repetitive and redundant regions of a genome are particularly problematic for mapping sequencing reads. In the present paper, we compile a list of the unmappable regions in the human genome based on the following definition: hypothetical reads with length 1 kb which cannot be uniquely mapped with zero-mismatch alignment for the described regions, considering both the forward and reverse strand. The respective collection of unmappable regions covers 0.77% of the sequence of human autosomes and 8.25% of the sex chromosomes in the reference genome GRCh37/hg19 (overall 1.23%). Not surprisingly, our unmappable regions overlap greatly with segmental duplication, transposable elements, and structural variants. About 99.8% of bases in our unmappable regions are part of either segmental duplication or transposable elements and 98.3% overlap structural variant annotations. Notably, some of these regions overlap units with important biological functions, including 4% of protein-coding genes. In contrast, these regions have zero intersection with the ultraconserved elements, very low overlap with microRNAs, tRNAs, pseudogenes, CpG islands, tandem repeats, microsatellites, sensitive non-coding regions, and the mapping blacklist regions from the ENCODE project.
authors.affiliation: The Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: wtli2012@gmail.com.
authors.forename: Wentian
authors.initials: W
authors.lastname: Li
authors.affiliation: The Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Freudenberg
mesh_terms: D058674:Chromosome Duplication; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D021901:DNA, Intergenic; D014644:Genetic Variation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000706:statistics & numerical data*
chemical_list: D004251:DNA Transposable Elements; D021901:DNA, Intergenic