Abstract
Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T), OPRKA843G (with alleles A and G), and OPRKC846T (with alleles C and T), at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008). With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance.
Highlights
In diploid organisms, there are two copies at every autosomal gene, one inherited from the maternal parent and the other from the paternal parent
A traditional view assumes that the maternally and paternally derived alleles of each gene are expressed simultaneously at a similar level, there are many exceptions where alleles are expressed from only one of the two parental chromosomes [1,23]. This so-called genetic imprinting or parent-of-origin effect has been thought to play a pivotal role in regulating the phenotypic variation of a complex trait [24,25,26,27]
With the discovery of more imprinting genes involved in trait control through molecular and bioinformatics approaches, we will be in a position to elucidate the genetic architecture of quantitative variation for various organisms including humans
Summary
There are two copies at every autosomal gene, one inherited from the maternal parent and the other from the paternal parent. Both copies are expressed to affect a trait for a majority of these genes. There is a small subset of genes for which one copy from a particular parent is turned off These genes, whose expression depends on the parent of origin due to the epigenetic or imprinted mark of one copy in either the egg or the sperm, have been thought to play an important role in complex diseases and traits, imprinted expression can vary between tissues, developmental stages, and species [1]. Genomic imprinting evolves in mammals with the advent of live birth through a parental battle between the sexes to control the maternal expenditure of resources to the offspring [7]
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