Recombination as a Point Process along Sequences

Wiuf, Carsten; Hein, Jotun

doi:10.1006/tpbi.1998.1403

Cited by 191 publications

(210 citation statements)

References 9 publications

Supporting

Mentioning

209

Contrasting

Unclassified

Order By: Relevance

“…it has a Markovian structure; Hudson 1983). In contrast, the alternative approach of simulating genealogies while moving along a sequence (Wiuf & Hein 1999) has a complex nonMarkovian structure in that the distribution of the next genealogy depends not just on the current genealogy, but also all previous ones. Both approaches, however, can make use of the separation of the genealogical and mutational processes under neutrality (Hudson 1990).…”

Section: Introductionmentioning

confidence: 99%

Approximating the coalescent with recombination

McVean

Cardin

2005

Phil. Trans. R. Soc. B

365

419

View full text Add to dashboard Cite

The coalescent with recombination describes the distribution of genealogical histories and resulting patterns of genetic variation in samples of DNA sequences from natural populations. However, using the model as the basis for inference is currently severely restricted by the computational challenge of estimating the likelihood. We discuss why the coalescent with recombination is so challenging to work with and explore whether simpler models, under which inference is more tractable, may prove useful for genealogy-based inference. We introduce a simplification of the coalescent process in which coalescence between lineages with no overlapping ancestral material is banned. The resulting process has a simple Markovian structure when generating genealogies sequentially along a sequence, yet has very similar properties to the full model, both in terms of describing patterns of genetic variation and as the basis for statistical inference.

show abstract

Section: Introductionmentioning

confidence: 99%

Approximating the coalescent with recombination

McVean

Cardin

2005

Phil. Trans. R. Soc. B

365

419

View full text Add to dashboard Cite

show abstract

“…The sequence of binary labels at any given locus x specifies a unique vertex of the hypercube, and how this vertex changes as one moves along the chromosome determines the block structure. Note that some of this mathematical framework is close in spirit to that used for studying the coalescent in the presence of recombination; there the central object is the so-called ancestral recombination graph, and the problem (Wiuf and Hein 1999;McVean and Cardin 2005) is to describe how this graph changes with position along a continuous chromosome. This is a very difficult problem and so the authors of those studies derived relatively few exact results.…”

mentioning

confidence: 99%

Distribution of Parental Genome Blocks in Recombinant Inbred Lines

Martin

Hospital

2011

Genetics

View full text Add to dashboard Cite

We consider recombinant inbred lines obtained by crossing two given homozygous parents and then applying multiple generations of self-crossings or full-sib matings. The chromosomal content of any such line forms a mosaic of blocks, each alternatively inherited identically by descent from one of the parents. Quantifying the statistical properties of such mosaic genomes has remained an open challenge for many years. Here, we solve this problem by taking a continuous chromosome picture and assuming crossovers to be noninterfering. Using a continuous-time random walk framework and Markov chain theory, we determine the statistical properties of these identical-by-descent blocks. We find that successive block lengths are only very slightly correlated. Furthermore, the blocks on the ends of chromosomes are larger on average than the others, a feature understandable from the nonexponential distribution of block lengths. WITH the advent of dense genomic maps, in particular based on single-nucleotide polymorphism (SNP) data, the study of haplotypes has become central for modern analyses in population genetics (Buckler and Gore 2007;Carlton 2007;Frazer et al. 2007;Mott 2007;Jakobsson et al. 2008;Bryc et al. 2010). Here, the term haplotype refers to the series of alleles that an individual carries on a chromosome pair at a collection of (possibly many) loci and contrasts with single-locus genotypes that were the objects of many past studies. Haplotypic information can be used for association studies (Gold et al. 2008), for diversity studies (Lindblad-Toh et al. 2005), or for recognizing signals of positive selection using various measures of haplotype homozygosity (Sabeti et al. 2002;Zhang et al. 2006;Lencz et al. 2007;Tang et al. 2007;Curtis et al. 2008). Many approaches capitalize on the apparent "block" structure of haplotypes (Stumpf 2002;Cardon and Abecasis 2003;Wall and Pritchard 2003;Altshuler et al. 2005;Zheng and McPeek 2007).Various causes can be called upon to explain the apparent structuration of genomes in haplotype blocks (Tishkoff and Verrelli 2003;Zondervan and Cardon 2004;Pe'er et al. 2006), among which are recombination hotspots (Goldstein 2001;Jeffreys et al. 2001) and population structure (Pritchard et al. 2000;Grote 2007;Slate and Pemberton 2007). However, the situation is often complicated (Shifman et al. 2003;Yalcin et al. 2004;Cuppen 2005;Kauppi et al. 2005;Greenawalt et al. 2006;Moore et al. 2008). In particular, the theoretical properties of many of the objects mentioned above, e.g., haplotype block lengths, remain largely unknown. Often, the distribution of blocks is declared "nonrandom" (Curtis et al. 2008) although the null hypothesis is not clearly specified.The task of determining statistical properties of chromosomal block structures has arisen in many different contexts. These can be classified into two types according to the kind of populations considered and lead to different mathematical techniques. In the first class, one asks how the genome of one or more parents in a populatio...

show abstract

“…However, recombination breaks up the chromosomes each generation and reduces LD, which increases haplotype diversity. Thus different regions on the genome may produce different trees due to recombination [17,18]. If two loci are close to each other and recombination rarely occurred between them, the two trees are likely to be the same.…”

Section: Recombination In Human Population and Its Implicationmentioning

confidence: 99%