PMC:4564992 / 6987-9360
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4564992","sourcedb":"PMC","sourceid":"4564992","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4564992","text":"Most existing methods for investigating parent-of-origin effects operate on a SNP-by-SNP basis, and each SNP is analyzed individually. When an ambiguous configuration with respect to parental origin is encountered at a SNP (such as observations in which both parents and an offspring are heterozygous), then either some sort of “averaging” over the possible parental transmissions is performed or else these ambiguous observations are discarded. In theory, greater information regarding parental origin could be obtained by considering several nearby SNPs simultaneously, as was done in the long-range phasing approach employed in the Icelandic study.5 Extensions to the PAT that take into account haplotypes of multiple tightly linked SNPs22,23 have demonstrated that increased power can indeed be obtained through this strategy, but these extensions suffer from the same problem as the original PAT of being sensitive to the presence of maternal-genotype effects. Gjessing and Lie24 present an extension to the log-linear modeling approach17 that models the effects of haplotypes defined by alleles at several nearby SNPs. Their extension is implemented in the software package HAPLIN. As pointed out by Shi et al.,25 estimation of risks for all haplotypes, as done by HAPLIN, becomes rapidly intractable with more than a few SNPs, on account of the fact that the number of possible haplotypes (and thus parameters to estimate) grows exponentially with the number of SNPs. Shi et al.25 propose their own haplotype-based extension to the log-linear modeling approach that uses the HAPLORE program26 to perform the initial haplotype estimation (phasing) step. Shi et al. achieve higher computational efficiency than Gjessing and Lie by focusing on candidate haplotypes that are nominated a priori based on prior knowledge. Although computationally convenient, this thus represents a somewhat restricted application. Modification of haplotype effects according to parental origin has also been incorporated in the UNPHASED software.27 However, UNPHASED, like HAPLIN, is limited (for computational reasons) to haplotypes comprised of no more than about five or six SNPs, meaning that a genome-wide analysis would need to be performed through repeated phasing across small sliding windows of haplotypes, a procedure that is both operationally and computationally inconvenient.","tracks":[{"project":"2_test","denotations":[{"id":"26320892-20016592-2052513","span":{"begin":651,"end":652},"obj":"20016592"},{"id":"26320892-17047336-2052514","span":{"begin":743,"end":745},"obj":"17047336"},{"id":"26320892-19077428-2052514","span":{"begin":743,"end":745},"obj":"19077428"},{"id":"26320892-16674560-2052515","span":{"begin":982,"end":984},"obj":"16674560"},{"id":"26320892-9529360-2052516","span":{"begin":1041,"end":1043},"obj":"9529360"},{"id":"26320892-19344450-2052517","span":{"begin":1217,"end":1219},"obj":"19344450"},{"id":"26320892-19344450-2052518","span":{"begin":1485,"end":1487},"obj":"19344450"},{"id":"26320892-15231536-2052519","span":{"begin":1597,"end":1599},"obj":"15231536"},{"id":"26320892-18382088-2052520","span":{"begin":2031,"end":2033},"obj":"18382088"}],"attributes":[{"subj":"26320892-20016592-2052513","pred":"source","obj":"2_test"},{"subj":"26320892-17047336-2052514","pred":"source","obj":"2_test"},{"subj":"26320892-19077428-2052514","pred":"source","obj":"2_test"},{"subj":"26320892-16674560-2052515","pred":"source","obj":"2_test"},{"subj":"26320892-9529360-2052516","pred":"source","obj":"2_test"},{"subj":"26320892-19344450-2052517","pred":"source","obj":"2_test"},{"subj":"26320892-19344450-2052518","pred":"source","obj":"2_test"},{"subj":"26320892-15231536-2052519","pred":"source","obj":"2_test"},{"subj":"26320892-18382088-2052520","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93eca0","default":true}]}]}}