Privacy-Preserving Genetic Relatedness Test

An increasing number of individuals are turning to Direct-To-Consumer (DTC) genetic testing to learn about their predisposition to diseases, traits, and/or ancestry. DTC companies like 23andme and Ancestry.com have started to offer popular and affordable ancestry and genealogy tests, with services allowing users to find unknown relatives and long-distant cousins. Naturally, access and possible dissemination of genetic data prompts serious privacy concerns, thus motivating the need to design efficient primitives supporting private genetic tests. In this paper, we present an effective protocol for privacy-preserving genetic relatedness test (PPGRT), enabling a cloud server to run relatedness tests on input an encrypted genetic database and a test facility's encrypted genetic sample. We reduce the test to a data matching problem and perform it, privately, using searchable encryption. Finally, a performance evaluation of hamming distance based PP-GRT attests to the practicality of our proposals.Comment: A preliminary version of this paper appears in the Proceedings of the 3rd International Workshop on Genome Privacy and Security (GenoPri'16

Modeling and Testing for Joint Association Using a Genetic Random Field Model

Substantial progress has been made in identifying single genetic variants predisposing to common complex diseases. Nonetheless, the genetic etiology of human diseases remains largely unknown. Human complex diseases are likely influenced by the joint effect of a large number of genetic variants instead of a single variant. The joint analysis of multiple genetic variants considering linkage disequilibrium (LD) and potential interactions can further enhance the discovery process, leading to the identification of new disease-susceptibility genetic variants. Motivated by the recent development in spatial statistics, we propose a new statistical model based on the random field theory, referred to as a genetic random field model (GenRF), for joint association analysis with the consideration of possible gene-gene interactions and LD. Using a pseudo-likelihood approach, a GenRF test for the joint association of multiple genetic variants is developed, which has the following advantages: 1. considering complex interactions for improved performance; 2. natural dimension reduction; 3. boosting power in the presence of LD; 4. computationally efficient. Simulation studies are conducted under various scenarios. Compared with a commonly adopted kernel machine approach, SKAT, GenRF shows overall comparable performance and better performance in the presence of complex interactions. The method is further illustrated by an application to the Dallas Heart Study.Comment: 17 pages, 4 tables, the paper has been published on Biometric

forqs: Forward-in-time Simulation of Recombination, Quantitative Traits, and Selection

forqs is a forward-in-time simulation of recombination, quantitative traits, and selection. It was designed to investigate haplotype patterns resulting from scenarios where substantial evolutionary change has taken place in a small number of generations due to recombination and/or selection on polygenic quantitative traits. forqs is implemented as a command- line C++ program. Source code and binary executables for Linux, OSX, and Windows are freely available under a permissive BSD license.Comment: preprint include Supplementary Information. https://bitbucket.org/dkessner/forq

Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans

Hybridization and extensive mitochondrial introgression among fire salamanders in peninsular Italy

Discordance between mitochondrial and nuclear patterns of population genetic structure is providing key insights into the eco-evolutionary dynamics between and within species, and their assessment is highly relevant to biodiversity monitoring practices based on DNA barcoding approaches. Here, we investigate the population genetic structure of the fire salamander Salamandra salamandra in peninsular Italy. Both mitochondrial and nuclear markers clearly identified two main population groups. However, nuclear and mitochondrial zones of geographic transition between groups were located 600 km from one another. Recent population declines in central Italy partially erased the genetic imprints of past hybridization dynamics. However, the overall pattern of genetic variation, together with morphological and fossil data, suggest that a rampant mitochondrial introgression triggered the observed mitonuclear discordance, following a post-glacial secondary contact between lineages. Our results clearly show the major role played by reticulate evolution in shaping the structure of Salamandra salamandra populations and, together with similar findings in other regions of the species’ range, contribute to identify the fire salamander as a particularly intriguing case to investigate the complexity of mechanisms triggering patterns of mitonuclear discordance in animals

Proof of the Feldman-Karlin Conjecture on the Maximum Number of Equilibria in an Evolutionary System

Feldman and Karlin conjectured that the number of isolated fixed points for deterministic models of viability selection and recombination among n possible haplotypes has an upper bound of 2^n - 1. Here a proof is provided. The upper bound of 3^{n-1} obtained by Lyubich et al. (2001) using Bezout's Theorem (1779) is reduced here to 2^n through a change of representation that reduces the third-order polynomials to second order. A further reduction to 2^n - 1 is obtained using the homogeneous representation of the system, which yields always one solution `at infinity'. While the original conjecture was made for systems of viability selection and recombination, the results here generalize to viability selection with any arbitrary system of bi-parental transmission, which includes recombination and mutation as special cases. An example is constructed of a mutation-selection system that has 2^n - 1 fixed points given any n, which shows that 2^n - 1 is the sharpest possible upper bound that can be found for the general space of selection and transmission coefficients.Comment: 9 pages, 1 figure; v.4: final minor revisions, corrections, additions; v.3: expands theorem to cover all cases, obviating v.2 distinction of reducible/irreducible; details added to: discussion of Lyubich (1992), example that attains upper bound, and homotopy continuation method

The genetic architecture underlying the evolution of a rare piscivorous life history form in brown trout after secondary contact and strong introgression

Identifying the genetic basis underlying phenotypic divergence and reproductive isolation is a longstanding problem in evolutionary biology. Genetic signals of adaptation and reproductive isolation are often confounded by a wide range of factors, such as variation in demographic history or genomic features. Brown trout ( ) in the Loch Maree catchment, Scotland, exhibit reproductively isolated divergent life history morphs, including a rare piscivorous (ferox) life history form displaying larger body size, greater longevity and delayed maturation compared to sympatric benthivorous brown trout. Using a dataset of 16,066 SNPs, we analyzed the evolutionary history and genetic architecture underlying this divergence. We found that ferox trout and benthivorous brown trout most likely evolved after recent secondary contact of two distinct glacial lineages, and identified 33 genomic outlier windows across the genome, of which several have most likely formed through selection. We further identified twelve candidate genes and biological pathways related to growth, development and immune response potentially underpinning the observed phenotypic differences. The identification of clear genomic signals divergent between life history phenotypes and potentially linked to reproductive isolation, through size assortative mating, as well as the identification of the underlying demographic history, highlights the power of genomic studies of young species pairs for understanding the factors shaping genetic differentiation

gap: Genetic Analysis Package

A preliminary attempt at collecting tools and utilities for genetic data as an R package called gap is described. Genomewide association is then described as a specific example, linking the work of Risch and Merikangas (1996), Long and Langley (1997) for family-based and population-based studies, and the counterpart for case-cohort design established by Cai and Zeng (2004). Analysis of staged design as outlined by Skol et al. (2006) and associate methods are discussed. The package is flexible, customizable, and should prove useful to researchers especially in its application to genomewide association studies.