title: Recombination mapping using Boolean logic and high-density SNP genotyping for exome sequence filtering.
abstract: 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.
authors.affiliation: National Human Genome Research Institute, NIH, Bethesda, MD 20892-1611, USA. markellot@mail.nih.gov
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.forename: Ted
authors.initials: T
authors.lastname: Han
authors.forename: Hannah
authors.initials: H
authors.lastname: Carlson-Donohoe
authors.forename: Chidi
authors.initials: C
authors.lastname: Ahaghotu
authors.forename: Ursula
authors.initials: U
authors.lastname: Harper
authors.forename: MaryPat
authors.initials: M
authors.lastname: Jones
authors.forename: Settara
authors.initials: S
authors.lastname: Chandrasekharappa
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
authors.forename: David R
authors.initials: DR
authors.lastname: Adams
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000032:analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA