The Structure of Haplotype Blocks in the Human Genome

Gabriel, Stacey; Schaffner, Stephen F.; Nguyen, Huy; Moore, Jamie; Roy, Jessica; Blumenstiel, Brendan; Higgins, John M.; DeFelice, Matthew; Lochner, Amy L.; Faggart, Maura; Liu-Cordero, Shau Neen; Rotimi, Charles N.; Adeyemo, Adebowale; Cooper, Richard S.; Ward, Ryk; Lander, Eric S.; Daly, Mark J.; Altshuler, David

doi:10.1126/science.1069424

Cited by 5,138 publications

(4,590 citation statements)

References 28 publications

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“…Subsequent Haploview analysis of these D' values and their confidence bounds revealed that they lie outside the default D' confidence interval (upper bound 0.98; lower bound 0.70) defined by Gabriel et al . as constituting a tightly bound block of high allelic association [25]. These data are indicative that the alleles of SNPs residing on the same chromosomes can segregate independently of one another, thereby retaining their informativity as unique identifiers.…”

Section: Discussionmentioning

confidence: 99%

“…Using Haploview [27], EM algorithm was then applied to SNP genotype data to determine the level of linkage disequilibrium (D') observed between markers on the same chromosome. Subsequent comparison of observed D' confidence bounds to a default D' confidence interval, defined as being indicative of significant allelic association by Gabriel et al [25], was undertaken using Haploview [27]. This permitted determination of whether pairs of SNP alleles analysed displayed significant levels of linkage disequilibrium/allelic association, or were able to segregate independently.…”

Section: Methodsmentioning

confidence: 99%

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Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

et al. 2010

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Background Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP) markers would offer considerable advantages over current short tandem repeat (STR) based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM) algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland. Results 6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from each of the breeds were obtained and were observed to be superior to those conferred by the industry standard STR assay. Conclusions The 43 SNPs characterised herein may constitute a starting point for the development of a SNP based DNA identification test for European cattle.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

et al. 2010

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“…Genetic data were extracted from the International HapMap project (http://hapmap.ncbi.nlm.nih.gov/, Phase I. June 2005, CEPH population and AFD_EUR_18‐MAY‐2004 panel). Gabriel method implemented in the HaploView software package was used to identify htSNPs with minimum pairwise correlation r 2 = 0.8 (Gabriel et al 2002a). The list and minor allele frequencies of the selected SNPs can be seen in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Juhász

Csépány

Magyar

et al. 2016

Genes Brain and Behavior

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One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross‐sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID‐Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression‐ and anxiety‐related phenotypes. In addition, a Bayesian systems‐based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

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“…Porcine transcripts and annotation were downloaded from the porcine Ensembl data base (build9) and aligned with the human RefSeq mRNA sequences using BLAT [34]. The human-porcine comparative map was calculated based on the orthologous human-porcine transcripts and for the syntenic regions annotations were downloaded from the NCBI database (build37).…”

Section: Methodsmentioning

confidence: 99%

A genome-wide association study on androstenone levels in pigs reveals a cluster of candidate genes on chromosome 6

Duijvesteijn¹,

Knol²,

Merks³

et al. 2010

BMC Genet

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BackgroundIn many countries, male piglets are castrated shortly after birth because a proportion of un-castrated male pigs produce meat with an unpleasant flavour and odour. Main compounds of boar taint are androstenone and skatole. The aim of this high-density genome-wide association study was to identify single nucleotide polymorphisms (SNPs) associated with androstenone levels in a commercial sire line of pigs. The identification of major genetic effects causing boar taint would accelerate the reduction of boar taint through breeding to finally eliminate the need for castration.ResultsThe Illumina Porcine 60K+SNP Beadchip was genotyped on 987 pigs divergent for androstenone concentration from a commercial Duroc-based sire line. The association analysis with 47,897 SNPs revealed that androstenone levels in fat tissue were significantly affected by 37 SNPs on pig chromosomes SSC1 and SSC6. Among them, the 5 most significant SNPs explained together 13.7% of the genetic variance in androstenone. On SSC6, a larger region of 10 Mb was shown to be associated with androstenone covering several candidate genes potentially involved in the synthesis and metabolism of androgens. Besides known candidate genes, such as cytochrome P450 A19 (CYP2A19), sulfotransferases SULT2A1, and SULT2B1, also new members of the cytochrome P450 CYP2 gene subfamilies and of the hydroxysteroid-dehydrogenases (HSD17B14) were found. In addition, the gene encoding the ß-chain of the luteinizing hormone (LHB) which induces steroid synthesis in the Leydig cells of the testis at onset of puberty maps to this area on SSC6. Interestingly, the gene encoding the α-chain of LH is also located in one of the highly significant areas on SSC1.ConclusionsThis study reveals several areas of the genome at high resolution responsible for variation of androstenone levels in intact boars. Major genetic factors on SSC1 and SSC6 showing moderate to large effects on androstenone concentration were identified in this commercial breeding line of pigs. Known and new candidate genes cluster especially on SSC6. For one of the most significant SNP variants, the difference in the proportion of animals surpassing the threshold of consumer acceptance between the two homozygous genotypes was as much as 15.6%.

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The Structure of Haplotype Blocks in the Human Genome

Cited by 5,138 publications

References 28 publications

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

A genome-wide association study on androstenone levels in pigs reveals a cluster of candidate genes on chromosome 6

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