RT Journal
A1 Suk, Eun-Kyung
A1 McEwen, Gayle K.
A1 Duitama, Jorge
A1 Nowick, Katja
A1 Schulz, Sabrina
A1 Palczewski, Stefanie
A1 Schreiber, Stefan
A1 Holloway, Dustin T.
A1 McLaughlin, Stephen
A1 Peckham, Heather
A1 Lee, Clarence
A1 Huebsch, Thomas
A1 Hoehe, Margret R.
T1 A comprehensively molecular haplotype-resolved genome of a European individual
JF Genome Research 
JO Genome Research 
YR 2011 
FD October 01 
VO 21 
IS 10 
SP 1672 
OP 1685 
DO 10.1101/gr.125047.111 
UL http://genome.cshlp.org/content/21/10/1672.abstract 
AB Independent determination of both haplotype sequences of an individual genome is essential to relate genetic variation to genome function, phenotype, and disease. To address the importance of phase, we have generated the most complete haplotype-resolved genome to date, “Max Planck One” (MP1), by fosmid pool-based next generation sequencing. Virtually all SNPs (>99%) and 80,000 indels were phased into haploid sequences of up to 6.3 Mb (N50 ∼1 Mb). The completeness of phasing allowed determination of the concrete molecular haplotype pairs for the vast majority of genes (81%) including potential regulatory sequences, of which >90% were found to be constituted by two different molecular forms. A subset of 159 genes with potentially severe mutations in either cis or trans configurations exemplified in particular the role of phase for gene function, disease, and clinical interpretation of personal genomes (e.g., BRCA1). Extended genomic regions harboring manifold combinations of physically and/or functionally related genes and regulatory elements were resolved into their underlying “haploid landscapes,” which may define the functional genome. Moreover, the majority of genes and functional sequences were found to contain individual or rare SNPs, which cannot be phased from population data alone, emphasizing the importance of molecular phasing for characterizing a genome in its molecular individuality. Our work provides the foundation to understand that the distinction of molecular haplotypes is essential to resolve the (inherently individual) biology of genes, genomes, and disease, establishing a reference point for “phase-sensitive” personal genomics. MP1's annotated haploid genomes are available as a public resource.