Exploring Diallelic Genetic Markers: The<b>HardyWeinberg</b>Package

Graffelman, Jan

doi:10.18637/jss.v064.i03

Cited by 203 publications

(164 citation statements)

References 33 publications

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“…For the X-linked set, specific HWE two-sided exact tests were applied using the R package HardyWeinberg [47]. Resulting p -values were ranked and corrected for multiple testing using the Benjamini-Hochberg (BH) procedure [48].…”

Section: Methodsmentioning

confidence: 99%

Novel efficient genome-wide SNP panels for the conservation of the highly endangered Iberian lynx

et al. 2017

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BackgroundThe Iberian lynx (Lynx pardinus) has been acknowledged as the most endangered felid species in the world. An intense contraction and fragmentation during the twentieth century left less than 100 individuals split in two isolated and genetically eroded populations by 2002. Genetic monitoring and management so far have been based on 36 STRs, but their limited variability and the more complex situation of current populations demand more efficient molecular markers. The recent characterization of the Iberian lynx genome identified more than 1.6 million SNPs, of which 1536 were selected and genotyped in an extended Iberian lynx sample.MethodsWe validated 1492 SNPs and analysed their heterozygosity, Hardy-Weinberg equilibrium, and linkage disequilibrium. We then selected a panel of 343 minimally linked autosomal SNPs from which we extracted subsets optimized for four different typical tasks in conservation applications: individual identification, parentage assignment, relatedness estimation, and admixture classification, and compared their power to currently used STR panels.ResultsWe ascribed 21 SNPs to chromosome X based on their segregation patterns, and identified one additional marker that showed significant differentiation between sexes. For all applications considered, panels of autosomal SNPs showed higher power than the currently used STR set with only a very modest increase in the number of markers.ConclusionsThese novel panels of highly informative genome-wide SNPs provide more powerful, efficient, and flexible tools for the genetic management and non-invasive monitoring of Iberian lynx populations. This example highlights an important outcome of whole-genome studies in genetically threatened species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3946-5) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Novel efficient genome-wide SNP panels for the conservation of the highly endangered Iberian lynx

et al. 2017

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“…Hardy-Weinberg Equilibrium (HWE) was tested using the Chi Square Goodness of fit test with one degree of freedom for each SNP ( rs9930506 and rs9939609 ) for both cases and controls. The analysis was performed using the CRAN “The Hardy Weinberg Package” for R software environment for statistical computing and graphics, following procedures reported by Graffelman [45]. Haplotype-based association test including frequencies and D′ [46] was performed using the 3BY3 program included in the Statistical Genetics Utility Programs (UtilWin) by Jurg Ott.…”

Section: Methodsmentioning

confidence: 99%

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Salgado-Montilla

Rodríguez-Cabán

Sánchez-García

et al. 2017

Can Res

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Background Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men. Methods and findings The study population consisted of 513 Puerto Rican men age ranging from 40–79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40–79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs). Results and discussion BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31–0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68–1.62). Importantly, among the cases that were overweight, those with mutated rs9939609 had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84–2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects. Conclusion Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.

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“…Hardy-Weinberg equilibrium exact tests were calculated using the R package HardyWeinberg [16]. For each population, three modes of gene action were tested: additive, dominant (both C and derived T allele), and over-dominant.…”

Section: Methodsmentioning

confidence: 99%

Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A

et al. 2016

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BackgroundThe gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied.MethodsUsing a range of Polynesian populations (Tongan, Māori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (F ST, integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima’s D and Fay and Wu’s H) were conducted on the PPARGC1A locus.ResultsNo statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F ST) was smallest between Asian and Pacific populations (New Zealand Māori ≤ 0.35, Samoan ≤ 0.20). When compared to European (New Zealand Māori ≤ 0.40, Samoan ≤ 0.25) or African populations (New Zealand Māori ≤ 0.80, Samoan ≤ 0.66) this differentiation was larger. We did not find any strong evidence for departure from neutral evolution at this locus when applying any of the other statistical tests for selection. However, using the same analytical methods, we found evidence for selection in specific populations at previously identified loci, indicating that lack of selection was the most likely explanation for the lack of evidence of selection in PPARGC1A.ConclusionWe conclude that there is no compelling evidence for selection at this locus, and that this gene should not be considered a candidate thrifty gene locus in Pacific populations. High levels of population differentiation at this locus and the reported absence of the derived 482Ser allele in some Melanesian populations, can alternatively be explained by multiple out-of-Africa migrations by ancestral progenitors, and subsequent genetic drift during colonisation of Polynesia. Intermediate 482Ser allele frequencies in extant Western Polynesian populations could therefore be due to recent admixture with Melanesian progenitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0341-z) contains supplementary material, which is available to authorized users.

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Exploring Diallelic Genetic Markers: TheHardyWeinbergPackage

Cited by 203 publications

References 33 publications

Novel efficient genome-wide SNP panels for the conservation of the highly endangered Iberian lynx

Novel efficient genome-wide SNP panels for the conservation of the highly endangered Iberian lynx

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A

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