Interlocus non‐random association of multiallelic polymorphisms spanning the coagulation factor VIII gene on human chromosome distalmost Xq28

Medina‐Acosta, Enrique

doi:10.1111/j.1365-2516.2009.02161.x

Cited by 3 publications

(12 citation statements)

References 46 publications

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“…It is evident in other biological systems [49, 82] that measuring global gametic disequilibrium alone is insufficient to define the evolutionary forces at equilibrium for either physically or non-physically linked loci. We showed that eleven of the 91 possible two-locus combinations that were in apparent global equilibrium exhibited at least one significant, sign-based non-random multiallelic interallelic association.…”

Section: Discussionmentioning

confidence: 99%

“…Given that there is no information about the rates of mutation for any of the microsatellite loci genotyped in the present study, we used the scoring method applied for human microsatellite loci [49]. Briefly, we measured the values for four estimates of the levels of mutability that correlate positively with mutation rate: allele span, the number of alleles per locus, expected heterozygosity (H E ) and locus diversity ( h locus ) [49, 50].…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, we measured the values for four estimates of the levels of mutability that correlate positively with mutation rate: allele span, the number of alleles per locus, expected heterozygosity (H E ) and locus diversity ( h locus ) [49, 50]. The values were multiplied, and the products were ranked by their ratio with the highest score.…”

Section: Methodsmentioning

confidence: 99%

“…Genotypes were tested for global gametic (linkage) disequilibrium using the Genetic Data Analysis (GDA) 1.0 software [59]. The intensity and significance of coupling and repulsion non-random multiallelic interallelic associations were determined using the Multiallelic Interallelic Disequilibrium Analysis Software v .1 (MIDAS) [60] according to the methodology described in [49]. The strength of sign-based overall disequilibrium for the two-locus combinations was determined using the formulas worked in Ref.…”

Section: Methodsmentioning

confidence: 99%

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Population genetic structure of Guiana dolphin (Sotalia guianensis) from the southwestern Atlantic coast of Brazil

et al. 2017

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Sotalia guianensis is a small dolphin that is vulnerable to anthropogenic impacts. Along the Brazilian Atlantic coast, this species is threatened with extinction. A prioritized action plan for conservation strategies relies on increased knowledge of the population. The scarcity of studies about genetic diversity and assessments of population structure for this animal have precluded effective action in the region. Here, we assessed, for the first time, the genetic differentiation at 14 microsatellite loci in 90 S. guianensis specimens stranded on the southeastern Atlantic coast of the State of Espírito Santo, Brazil. We estimated population parameters and structure, measured the significance of global gametic disequilibrium and the intensity of non-random multiallelic interallelic associations and constructed a provisional synteny map using Bos taurus, the closest terrestrial mammal with a reference genome available. All microsatellite loci were polymorphic, with at least three and a maximum of ten alleles each. Allele frequencies ranged from 0.01 to 0.97. Observed heterozygosity ranged from 0.061 to 0.701. The mean inbreeding coefficient was 0.103. Three loci were in Hardy-Weinberg disequilibrium even when missing genotypes were inferred. Although 77 of the 91 possible two-locus associations were in global gametic equilibrium, we unveiled 13 statistically significant, sign-based, non-random multiallelic interallelic associations in 10 two-locus combinations with either coupling (D' values ranging from 0.782 to 0.353) or repulsion (D' values -0.517 to -1.000) forces. Most of the interallelic associations did not involve the major alleles. Thus, for either physically or non-physically linked loci, measuring the intensity of non-random interallelic associations is important for defining the evolutionary forces at equilibrium. We uncovered a small degree of genetic differentiation (FST = 0.010; P-value = 0.463) with a hierarchical clustering into one segment containing members from the southern and northern coastal regions. The data thus support the scenario of little genetic structure in the population of S. guianensis in this geographic area.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Population genetic structure of Guiana dolphin (Sotalia guianensis) from the southwestern Atlantic coast of Brazil

et al. 2017

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“…This is the reason why it urges to characterize more markers that are highly informative. Surprisingly, there is scarcity of reports on direct estimates of recombination between extragenic and F8 ‐intronic STR markers, and addressing whether the tried‐and‐tested markers constitute stable gametic disequilibrium (GD) blocks [17].…”

Section: Introductionmentioning

confidence: 99%

Informativeness of a novel multiallelic marker-set comprising an F8 intron 21 and three tightly linked loci for haemophilia A carriership analysis

et al. 2010

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The extraordinary heterogeneous nature of the deleterious mutations in the F8 gene that lead to functional deficiency of clotting factor VIII in haemophilia A makes routine direct mutation profiling difficult. When direct mutation analysis cannot be performed or a causative/candidate mutation is not found, a second-line approach to track the defective F8 gene within at-risk families is linkage genetic analysis with, tried-and-tested, F8-intragenic and/or extragenic non-recombining multiallelic short tandem repeats (STR). Although several typing STR loci within and around F8 have been described, there is need for improving assessment, because the combined informativeness of available assays rarely reaches 100%. Here, we characterized a newly identified 0.28 cM-resolution marker-set, consisting of a dinucleotide STR located on F8 intron 21 (F8Int21; [AC](n)) and three extragenic tetranucleotide STR located on GAB3 intron 1 (GAB3Int1; [TAAA](n)) and TMLHE intron 1 (TMLHEInt1.1; [GAAA](n) and TMLHEInt1.3; [ATTC](n)). Heterozygosity rates determined in 100 unrelated females ranged from 0.25 (GAB3Int1) to 0.63 (F8Int21). The set rendered a combined informativeness of 0.91 for at least one marker and 0.60 for a minimum of two loci, with at least one F8-intragenic. Multiallelic interlocus non-random association analysis revealed that GAB3Int1 is not in significant gametic disequilibrium (GD) with F8Int21, F8Int9.2, TMLHEInt1.3 or TMLHEInt1.1. Gametic disequilibrium breakdown attests historical recombination between GAB3Int1 and the F8 gene. Through computational analysis of reference assembly sequence data, we note in the GD breakdown region and in the F8 gene a higher than average density of the 13-mer CCNCCNTNNCCNC consensus motif, commonly associated with recombination hotspots.

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Accurate tracking genetic markers in haemophilia linkage analysis: a matter beyond scientific priority

Machado¹,

Medina‐Acosta²

2012

Haemophilia

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Interlocus non‐random association of multiallelic polymorphisms spanning the coagulation factor VIII gene on human chromosome distalmost Xq28

Cited by 3 publications

References 46 publications

Population genetic structure of Guiana dolphin (Sotalia guianensis) from the southwestern Atlantic coast of Brazil

Population genetic structure of Guiana dolphin (Sotalia guianensis) from the southwestern Atlantic coast of Brazil

Informativeness of a novel multiallelic marker-set comprising an F8 intron 21 and three tightly linked loci for haemophilia A carriership analysis

Accurate tracking genetic markers in haemophilia linkage analysis: a matter beyond scientific priority

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