Pedigree Reconstruction Using Identity by Descent

Kirkpatrick, Bonnie; Li, Shuai Cheng; Karp, Richard M.; Halperin, Eran

doi:10.1007/978-3-642-20036-6_15

Cited by 18 publications

(29 citation statements)

References 29 publications

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“…The choice of the Log scale for the dissimilarity scores deserves some explanation as well. In open populations, the dissimilarity metric defined here is related to the number of generations separating the pair (Kirkpatrick et al, 2011). Whereas the interpretation of this metric in our case is more complicated, we chose to retain it mainly because of the observation that the distribution of this metric is approximately normal within and between clans (see Supplementary Figure S1).…”

Section: Methodsmentioning

confidence: 99%

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

2013

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The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping.

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Section: Methodsmentioning

confidence: 99%

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

2013

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“…Pedigree reconstruction is a hard problem and even constructing sibling relationships is known to be NP-hard (Kirkpatrick et al, 2011). In this work, we focus on reconstruction methods using genotype data.…”

Section: Introduction Imentioning

confidence: 99%

“…One of the challenges in our approach is to compute the expected IBD length between a pair of extant individuals efficiently in the presence of inbreeding. The CIP and COP methods of Kirkpatrick et al (2011) are efficient for outbreed pedigrees but very inefficient for inbred pedigrees. This is because for the inbreeding case the alleles from an extant individual can be inherited in an exponential number of ways from his or her ancestors with respect to the number of nodes in the pedigree graph.…”

Section: Introduction Imentioning

confidence: 99%

“…Our algorithm follows the approach of Kirkpatrick et al (2011), starts from extant individuals, and reconstructs the pedigree generation by generation moving backward in time. For each generation, we predict the pairwise relationships between the individuals at the current generation and create parents for them according to their relationships.…”

Section: Introduction Imentioning

confidence: 99%

“…However, their model, in which every individual passes on a trace of their haplotypes to all of their descendants, is unrealistic. Kirkpatrick et al (2011) proposed an algorithm to reconstruct pedigrees based on pairwise identity-by-descent (IBD) information without reconstructing the ancestral haplotypes. A generation-by-generation approach is employed, and the pedigree is reconstructed backward in time, one generation at a time.…”

Section: Introduction Imentioning

confidence: 99%

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IPED: Inheritance Path-based Pedigree Reconstruction Algorithm Using Genotype Data

Wang

Han

et al. 2013

Journal of Computational Biology

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The problem of inference of family trees, or pedigree reconstruction, for a group of individuals is a fundamental problem in genetics. Various methods have been proposed to automate the process of pedigree reconstruction given the genotypes or haplotypes of a set of individuals. Current methods, unfortunately, are very time-consuming and inaccurate for complicated pedigrees, such as pedigrees with inbreeding. In this work, we propose an efficient algorithm that is able to reconstruct large pedigrees with reasonable accuracy. Our algorithm reconstructs the pedigrees generation by generation, backward in time from the extant generation. We predict the relationships between individuals in the same generation using an inheritance path-based approach implemented with an efficient dynamic programming algorithm. Experiments show that our algorithm runs in linear time with respect to the number of reconstructed generations, and therefore, it can reconstruct pedigrees that have a large number of generations. Indeed it is the first practical method for reconstruction of large pedigrees from genotype data.

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Non-identifiable Pedigrees and a Bayesian Solution

Kirkpatrick

2012

Bioinformatics Research and Applications

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Some methods aim to correct or test for relationships or to reconstruct the pedigree, or family tree. We show that these methods cannot resolve ties for correct relationships due to identifiability of the pedigree likelihood which is the probability of inheriting the data under the pedigree model. This means that no likelihood-based method can produce a correct pedigree inference with high probability. This lack of reliability is critical both for health and forensics applications.Pedigree inference methods use a structured machine learning approach where the objective is to find the pedigree graph that maximizes the likelihood. Known pedigrees are useful for both association and linkage analysis which aim to find the regions of the genome that are associated with the presence and absence of a particular disease. This means that errors in pedigree prediction have dramatic effects on downstream analysis.In this paper we present the first discussion of multiple typed individuals in non-isomorphic pedigrees, P and Q, where the likelihoods are non-identifiable, P r[G | P, θ] = P r[G | Q, θ], for all input data G and all recombination rate parameters θ. While there were previously known non-identifiable pairs, we give an example having data for multiple individuals.Additionally, deeper understanding of the general discrete structures driving these non-identifiability examples has been provided, as well as results to guide algorithms that wish to examine only identifiable pedigrees. This paper introduces a general criteria for establishing whether a pair of pedigrees is non-identifiable and two easy-to-compute criteria guaranteeing identifiability. Finally, we suggest a method for dealing with non-identifiable likelihoods: use Bayes rule to obtain the posterior from the likelihood and prior. We propose a prior guaranteeing that the posterior distinguishes all pairs of pedigrees.Shortened version published as: B. Kirkpatrick. Non-identifiable pedigrees and a Bayesian solution. Int. Symp. on Bioinformatics Res. and Appl. (ISBRA), 7292:139-152 2012.

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Pedigree Reconstruction Using Identity by Descent

Cited by 18 publications

References 29 publications

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

IPED: Inheritance Path-based Pedigree Reconstruction Algorithm Using Genotype Data

Non-identifiable Pedigrees and a Bayesian Solution

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