The Evolutionary Dynamics of Complex Polymorphisms

Lewontin, Richard C; Kojima, Ken-ichi

doi:10.2307/2405995

Cited by 419 publications

(316 citation statements)

References 7 publications

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“…The classical LD coefficient measuring deviation from random association between alleles at different loci is delta (D). 31 D is the absolute measure of LD; it is defined by the difference between the observed haplotype frequency and the haplotype frequency that would be expected from the genotype frequency of the alleles in the haplotype, in the absence of LD. We calculated the D for the 5 locus haplotypes and also for all possible 2 locus haplotypes.…”

Section: Methodsmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

Bone Marrow Transplant

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The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing Xgrade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of Xgrade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

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Section: Methodsmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

Bone Marrow Transplant

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“…The result of Liberman and Feldman (2005) for the case where the major loci are in linkage disequilibrium at the equilibrium with M 1 fixed at the modifier locus utilizes knowledge of a class of equilibria which can be obtained in closed form, in terms of r, for the Lewontin and Kojima (1960) symmetric viability model. The Lewontin-Kojima model is a special case of the general two-locus symmetric viability model introduced by Bodmer and Felsenstein (1967), where the fitness matrix W takes the form If we denote by x 1 , x 2 , x 3 , x 4 the frequencies of the four gametes AB, Ab, aB, ab, respectively, then this two-locus, two-allele viability model with recombination rate r between the two loci has symmetric equilibria (x̂1, x̂2, x̂3, x̂4) with…”

Section: The Interaction Matrix δmentioning

confidence: 99%

“…They also showed that in the special case where W add is alsosymmetric, α 1 = α 3 and β 1 = β 3 , in which case for all ε W = W add + εΔ is a special case of the Lewontin and Kojima (1960) symmetric fitness matrix, if the initial state where M 1 is fixed is in linkage disequilibrium (D ≠ 0) with the major loci, then for positive r and R, M 2 increases in frequency if (ε 2 -ε 1 ) is small and ε 2 >ε 1 > 0.…”

Section: Introductionmentioning

confidence: 99%

On the evolution of epistasis II: A generalized Wright–Kimura framework

Liberman

Puniyani

Feldman

2007

Theoretical Population Biology

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The evolution of fitness interactions between genes at two major loci is studied where the alleles at a third locus modify the epistatic interaction between the two major loci. The epistasis is defined by a parameter ε and a matrix structure that specifies the nature of the interactions. When ε = 0 the two major loci have additive fitnesses, and when these are symmetric the interaction matrices studied here produce symmetric viabilities of the Wright (1952)-Kimura (1956) form. Two such interaction matrices are studied, for one of which epistasis as measured by |ε| always increases, and for the other it increases when the linkage between the major loci is tight enough and there is initial linkage disequilibrium. Increase of epistasis does not necessarily coincide with increase in equilibrium mean fitness.

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“…Suppose that the frequency of A1A1B1B1 is close to 1, so that the frequency of A1B1 is also close to 1 and the frequencies of the other gametes are small. If Cj, c, c and c are the frequencies of the gametes A1B1, A2B1, A1B2, A2B2 going to make up the following generation then the recurrence relations for gamete frequencies (Lewontin and Kojima, 1960) show that, in particular,…”

Section: Additive Fitnessesmentioning

confidence: 99%

A note on the fixation of a favoured gene

Ewens

1969

Heredity

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The Evolutionary Dynamics of Complex Polymorphisms

Cited by 419 publications

References 7 publications

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

On the evolution of epistasis II: A generalized Wright–Kimura framework

A note on the fixation of a favoured gene

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