Recombination mapping using Boolean logic and high-density SNP genotyping for exome sequence filtering

Thomas C. Markello*, Ted Han, Hannah Carlson-Donohoe, Chidi Ahaghotu, Ursula Harper, Mary Pat Jones, Settara Chandrasekharappa, Yair Anikster, David R. Adams, William A. Gahl, Cornelius F. Boerkoel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Whole genome sequence data for small pedigrees has been shown to provide sufficient information to resolve detailed haplotypes in small pedigrees. Using such information, recombinations can be mapped onto chromosomes, compared with the segregation of a disease of interest and used to filter genome sequence variants. We now show that relatively inexpensive SNP array data from small pedigrees can be used in a similar manner to provide a means of identifying regions of interest in exome sequencing projects. We demonstrate that in those situations where one can assume complete penetrance and parental DNA is available, SNP recombination mapping using Boolean logic identifies chromosomal regions identical to those detected by multipoint linkage using microsatellites but with much less computation. We further show that this approach is successful because the probability of a double crossover between informative SNP loci is negligible. Our observations provide a rationale for using SNP arrays and recombination mapping as a rapid and cost-effective means of incorporating chromosome segregation information into exome sequencing projects intended for disease-gene identification.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number3
StatePublished - Mar 2012


FundersFunder number
Office of Rare Disease Research
National Institutes of Health
National Human Genome Research InstituteZIAHG000215
NIH Clinical Center
Office of the Director


    • Exome sequencing
    • Linkage
    • Mapping
    • Recombination
    • Single nucleotide variants


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