Mapping the human reference genome's missing sequence by three-way admixture in Latino genomes

Am J Hum Genet. 2013 Sep 5;93(3):411-21. doi: 10.1016/j.ajhg.2013.07.002. Epub 2013 Aug 8.


A principal obstacle to completing maps and analyses of the human genome involves the genome's "inaccessible" regions: sequences (often euchromatic and containing genes) that are isolated from the rest of the euchromatic genome by heterochromatin and other repeat-rich sequence. We describe a way to localize these sequences by using ancestry linkage disequilibrium in populations that derive ancestry from at least three continents, as is the case for Latinos. We used this approach to map the genomic locations of almost 20 megabases of sequence unlocalized or missing from the current human genome reference (NCBI Genome GRCh37)-a substantial fraction of the human genome's remaining unmapped sequence. We show that the genomic locations of most sequences that originated from fosmids and larger clones can be admixture mapped in this way, by using publicly available whole-genome sequence data. Genome assembly efforts and future builds of the human genome reference will be strongly informed by this localization of genes and other euchromatic sequences that are embedded within highly repetitive pericentromeric regions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Mapping*
  • Chromosomes, Human / genetics
  • Gene Frequency / genetics
  • Gene Pool*
  • Genealogy and Heraldry
  • Genome, Human / genetics*
  • Genotype
  • Hispanic or Latino / genetics*
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Reference Standards
  • Reproducibility of Results
  • Software