A SNP Streak Model for the Identification of Genetic Regions Identical-by-descent

Leibon, Gregory; Rockmore, Daniel N.; Pollak, Martin R.

doi:10.2202/1544-6115.1340

Cited by 27 publications

(32 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be mentioned, that several methods for simultaneous inference of IBD/IBS regions among multiple individuals have already been proposed, both by us ) and others (Leibon et al 2008; Thomas et al 2008;Thomas 2010) for cases in which some pedigree information or information about IBD sharing is available. However, here we consider the general case where no pedigree information nor other prior information about IBD sharing patterns is available.…”

mentioning

confidence: 99%

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

Moltke¹,

Albrechtsen²,

Hansen³

et al. 2011

Genome Res.

View full text Add to dashboard Cite

All individuals in a finite population are related if traced back long enough and will, therefore, share regions of their genomes identical by descent (IBD). Detection of such regions has several important applications-from answering questions about human evolution to locating regions in the human genome containing disease-causing variants. However, IBD regions can be difficult to detect, especially in the common case where no pedigree information is available. In particular, all existing non-pedigree based methods can only infer IBD sharing between two individuals. Here, we present a new Markov Chain Monte Carlo method for detection of IBD regions, which does not rely on any pedigree information. It is based on a probabilistic model applicable to unphased SNP data. It can take inbreeding, allele frequencies, genotyping errors, and genomic distances into account. And most importantly, it can simultaneously infer IBD sharing among multiple individuals. Through simulations, we show that the simultaneous modeling of multiple individuals makes the method more powerful and accurate than several other non-pedigree based methods. We illustrate the potential of the method by applying it to data from individuals with breast and/or ovarian cancer, and show that a known disease-causing mutation can be mapped to a 2.2-Mb region using SNP data from only five seemingly unrelated affected individuals. This would not be possible using classical linkage mapping or association mapping.[Supplemental material is available for this article. The MCMC software is freely available at http://people.binf.ku.dk/ida/ Software/MCMC_IBDfinder/.] Identity by descent (IBD) is a fundamental concept in genetics. Two or more individuals share a region of their genomes IBD if they have identical nucleotide sequences in this region due to common ancestry. The concept of IBD has existed for a long time. It was introduced in the 1940s (Malecot 1946(Malecot , 1948 and has since then received attention within a number of fields of genetic research, ranging from forensic genetics (Evett and Weir 1998) to molecular ecology (Thompson 1975;Queller and Goodnight 1989;Ritland 1996;Lynch and Ritland 1999). But, most importantly, during the last several decades it has played an essential role within the field of human disease mapping. Until the beginning of this century, the main focus within this field was the development of methods for analyzing data from families with known pedigrees (Elston and Stewart 1971;Ott 1974;Cannings et al. 1978;Lander and Green 1987;Kruglyak et al. 1996;Abecasis et al. 2002). However, the concept of IBD has recently received renewed attention in the context of genomic data without any external pedigree information (Purcell et al. 2007;Browning 2008;Thompson 2008;Albrechtsen et al. 2009Albrechtsen et al. , 2010Gusev et al. 2009;Browning and Browning 2010).There are a number of different definitions of IBD in different contexts. In most human single nucleotide polymorphism (SNP) data, each SNP is caused by a single mutation. Therefo...

show abstract

mentioning

confidence: 99%

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

Moltke¹,

Albrechtsen²,

Hansen³

et al. 2011

Genome Res.

View full text Add to dashboard Cite

show abstract

“…The same idea has also been published by Leibon et al (2008) who defined the same statistic, but evaluated significance by extending methods derived by Miyazawa et al (2007) for evaluating the distribution of regions shared homozygously in a set of individuals, to the case of heterozygous sharing. Both the gene drop approach of Thomas et al (2008) and the distributions derived by Leibon et al (2008) assume that the genetic loci are in linkage equilibrium. This is simplifying assumption that is clearly inappropriate for dense single nucleotide polymorphism, or SNP, maps, as the above authors point out.…”

Section: Discussionmentioning

confidence: 99%

In Silico Genome Mismatch Scanning to Map Breast Cancer Genes in Extended Pedigrees

Thomas¹

2009

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of Utah Salt Lake City, UT 84112 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThis project aims to map breast cancer genes using dense single nucleotide polymorphism arrays in large extended pedigrees. Data has been collected using a 1,000,000 SNP genotype assay for 25 women affected by breast cancer in three high risk Utah pedigrees. Preliminary analysis of control data has been performed and significant progress has been made on the problem of modeling linkage disequilibrium between genetic loci at the density and scale required by this project. Programs to perform the modeling and analysis have been written and tested. Two papers describing the methodological developments have been published and a third describing initial analyses of control data is in preparation. The project is proceeding as planned and we expect to carry out the remainder in good time. References 11 SUBJECT TERMSAppendices 12 IntroductionThe purpose of this project is to exploit high density single nucleotide polymorphism (SNP) assays to map genes for breast cancer in clusters of cases related through large extended pedigrees. The central idea is to search for long runs of markers where cases share a common allele. Unusually long runs indicate regions where the cases share a segment of chromosome identical by descent from a common ancestor. If sharing of such a segment is sufficiently rare by chance, the segment becomes a candidate as a region containing a gene for breast cancer. The probability that a random segment reaches or exceeds the length of the longest observed shared segment can be assessed by simulation. One of the major challenges in this project is to properly account for linkage disequilibrium, (LD), that is, the fact that in high density marker p...

show abstract

“…Methods to use group-wise IBD relationships or IBD tracts shared by multiple individuals to increase the power for short IBD tracts detection have been proposed. Hansen et al (2009), Leibon et al (2008) and Thomas et al (2007) have proposed methods to detect group-wise IBD tracts for cases in which some pedigree information or information about IBD sharing is available. Moltke et al (2011) proposed a more general Markov Chain Monte Carlo (MCMC) method where it does not assume any previous information about IBD sharing patterns.…”

Section: Introductionmentioning

confidence: 99%

IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships

2013

Bioinformatics

View full text Add to dashboard Cite

Motivation: Detecting IBD tracts is an important problem in genetics. Most of the existing methods focus on detecting pairwise IBD tracts, which have relatively low power to detect short IBD tracts. Methods to detect IBD tracts among multiple individuals simultaneously, or group-wise IBD tracts, have better performance for short IBD tracts detection. Group-wise IBD tracts can be applied to a wide range of applications, such as disease mapping, pedigree reconstruction and so forth. The existing group-wise IBD tract detection method is computationally inefficient and is only able to handle small datasets, such as 20, 30 individuals with hundreds of SNPs. It also requires a previous specification of the number of IBD groups, or partitions of the individuals where all the individuals in the same partition are IBD with each other, which may not be realistic in many cases. The method can only handle a small number of IBD groups, such as two or three, because of scalability issues. What is more, it does not take LD (linkage disequilibrium) into consideration.Results: In this work, we developed an efficient method IBD-Groupon, which detects group-wise IBD tracts based on pairwise IBD relationships, and it is able to address all the drawbacks aforementioned. To our knowledge, our method is the first practical group-wise IBD tracts detection method that is scalable to very large datasets, for example, hundreds of individuals with thousands of SNPs, and in the meanwhile, it is powerful to detect short IBD tracts. Our method does not need to specify the number of IBD groups, which will be detected automatically. And our method takes LD into consideration, as it is based on pairwise IBD tracts where LD can be easily incorporated.Contact: dhe@us.ibm.com

show abstract

A SNP Streak Model for the Identification of Genetic Regions Identical-by-descent

Cited by 27 publications

References 6 publications

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

In Silico Genome Mismatch Scanning to Map Breast Cancer Genes in Extended Pedigrees

IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships

Contact Info

Product

Resources

About