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Crossover interference and sex-specific genetic maps shape identical by descent sharing in close relatives
- Source :
- PLoS Genetics, Vol 15, Iss 12, p e1007979 (2019), PLoS Genetics
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the standard deviation of pairwise IBD proportions by 10.4% on average in full siblings through second cousins. By contrast, sex-specific maps increase this standard deviation by 4.2% on average, and also impact the number of segments relatives share. Most notably, using sex-specific maps, the number of segments half-siblings share is bimodal; and when combined with interference modeling, the probability that sixth cousins have non-zero IBD sharing ranges from 9.0 to 13.1%, depending on the sexes of the individuals through which they are related. We present new analytical results for the distributions of IBD segments under these models and show they match results from simulations. Finally, we compared IBD sharing rates between simulated and real relatives and find that the combination of sex-specific maps and interference modeling most accurately captures IBD rates in real data. Ped-sim is open source and available from https://github.com/williamslab/ped-sim.<br />Author summary Simulations are ubiquitous throughout statistical genetics in order to generate data with known properties, enabling tests of inference methods and analyses of real world processes in settings where experimental data are challenging to collect. Simulating genetic data for relatives in a pedigree requires the synthesis of chromosomes parents transmit to their children. These chromosomes form as a mosaic of a given parent’s two chromosomes, with the location of switches between the two parental chromosomes known as crossovers. Detailed information about crossover generation based on real data from humans now exists, including the fact that men and women have overall different rates (women produce ∼1.6 times more crossovers) and that real crossovers are subject to interference—whereby crossovers are further apart from one another than expected under a model that selects their locations randomly. Our new method, Ped-sim, can simulate pedigree data using these less commonly modeled crossover features, and we used it to evaluate the impact of sex-specific rates and interference compared to real data. These comparisons show that both factors shape the amount of DNA two relatives share, and that their inclusion in models of crossover better fit data from real relatives.
- Subjects :
- Male
Cancer Research
Heredity
Crossover
Physical Mapping
QH426-470
Interference (genetic)
Identity by descent
Standard deviation
0302 clinical medicine
Statistics
Poisson Distribution
Cell Cycle and Cell Division
Genetics (clinical)
Genetic Interference
0303 health sciences
Sex Characteristics
Chromosome Biology
Simulation and Modeling
Contrast (statistics)
Chromosome Mapping
Pedigree
Genetic Mapping
Meiosis
Cell Processes
Physical Sciences
symbols
Female
Research Article
Probability density function
Biology
Research and Analysis Methods
03 medical and health sciences
symbols.namesake
Genetics
Humans
Crossover Interference
Computer Simulation
Poisson regression
Molecular Biology Techniques
Molecular Biology
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Models, Genetic
Genome, Human
Gene Mapping
Genetic Variation
Biology and Life Sciences
Cell Biology
Probability Theory
Probability Density
Genetics, Population
Haplotypes
Pairwise comparison
030217 neurology & neurosurgery
Mathematics
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 15
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....df2c87573ff0c97a0b9d35511bec13ed