Linkage Disequilibrium Statistics and Block Visualization

Author(s):  
Jacob Marsh
2020 ◽  
Author(s):  
Lungwani Muungo

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene andadjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium,R54W showed a prominent association (p ? 0.0003), which was more striking when examined among 309 eldersubjects (>50 years; p ? 0.0001). Contribution for postmenopausal bone loss was suggested.Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis(HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have beenproposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene(GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essentialmodifier of pituitary peptide hormones, including GnRH.Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locuswith adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) wasanalyzed by haplotype estimation and calculation of D? and r2. Multiple regression analysis was applied forevaluating the combined effects of the variations.Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of theQPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD,among which R54W (nt ? 160C?T) presented the most prominent association (p ? 0.0003). Striking associationwas observed for these SNPs among the 309 subjects ?50 years of age (R54W, p ? 0.0001; ?1095T?C, p ?0.0002; ?1844C?T, p ? 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might actin combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are theimportant factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The datashould provide new insight into the etiology of the disease and may suggest a new target to be considered duringtreatment.J Bone Miner


2018 ◽  
Vol 39 (1) ◽  
Author(s):  
Mohamed Allam ◽  
Bernardo Ordás ◽  
Abderahmane Djemel ◽  
William F. Tracy ◽  
Pedro Revilla

1997 ◽  
Vol 88 (5) ◽  
pp. 445-448 ◽  
Author(s):  
Giorgio Dell'Acqua ◽  
Licia Iacoviello ◽  
Andria D'Orazio ◽  
Rosa Di Bitondo ◽  
Augusto Di Castelnuovo ◽  
...  

BMC Genetics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Luiz F. Brito ◽  
Mohsen Jafarikia ◽  
Daniela A. Grossi ◽  
James W. Kijas ◽  
Laercio R. Porto-Neto ◽  
...  

Genetics ◽  
1999 ◽  
Vol 151 (3) ◽  
pp. 1053-1063 ◽  
Author(s):  
Ilik J Saccheri ◽  
Ian J Wilson ◽  
Richard A Nichols ◽  
Michael W Bruford ◽  
Paul M Brakefield

Abstract Polymorphic enzyme and minisatellite loci were used to estimate the degree of inbreeding in experimentally bottlenecked populations of the butterfly, Bicyclus anynana (Satyridae), three generations after founding events of 2, 6, 20, or 300 individuals, each bottleneck size being replicated at least four times. Heterozygosity fell more than expected, though not significantly so, but this traditional measure of the degree of inbreeding did not make full use of the information from genetic markers. It proved more informative to estimate directly the probability distribution of a measure of inbreeding, σ2, the variance in the number of descendants left per gene. In all bottlenecked lines, σ2 was significantly larger than in control lines (300 founders). We demonstrate that this excess inbreeding was brought about both by an increase in the variance of reproductive success of individuals, but also by another process. We argue that in bottlenecked lines linkage disequilibrium generated by the small number of haplotypes passing through the bottleneck resulted in hitchhiking of particular marker alleles with those haplotypes favored by selection. In control lines, linkage disequilibrium was minimal. Our result, indicating more inbreeding than expected from demographic parameters, contrasts with the findings of previous (Drosophila) experiments in which the decline in observed heterozygosity was slower than expected and attributed to associative overdominance. The different outcomes may both be explained as a consequence of linkage disequilibrium under different regimes of inbreeding. The likelihood-based method to estimate inbreeding should be of wide applicability. It was, for example, able to resolve small differences in σ2 among replicate lines within bottleneck-size treatments, which could be related to the observed variation in reproductive viability.


Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1269-1278 ◽  
Author(s):  
Bernhard Haubold ◽  
Jürgen Kroymann ◽  
Andreas Ratzka ◽  
Thomas Mitchell-Olds ◽  
Thomas Wiehe

Abstract Arabidopsis thaliana is a highly selfing plant that nevertheless appears to undergo substantial recombination. To reconcile its selfing habit with the observations of recombination, we have sampled the genetic diversity of A. thaliana at 14 loci of ~500 bp each, spread across 170 kb of genomic sequence centered on a QTL for resistance to herbivory. A total of 170 of the 6321 nucleotides surveyed were polymorphic, with 169 being biallelic. The mean silent genetic diversity (πs) varied between 0.001 and 0.03. Pairwise linkage disequilibria between the polymorphisms were negatively correlated with distance, although this effect vanished when only pairs of polymorphisms with four haplotypes were included in the analysis. The absence of a consistent negative correlation between distance and linkage disequilibrium indicated that gene conversion might have played an important role in distributing genetic diversity throughout the region. We tested this by coalescent simulations and estimate that up to 90% of recombination is due to gene conversion.


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