Genetic risk variants in African Americans with multiple sclerosis.
Neurology. 2013 Jun 14;
Authors: Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P, Maiers M, Spellman S, Cereb N, Yang S, Pando MJ, Piccio L, Cross AH, De Jager PL, Cree BA, Hauser SL, Oksenberg JR
OBJECTIVES: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). METHODS: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. RESULTS: The following major histocompatibility complex risk alleles were replicated: HLA-DRB1*15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54-2.63], p = 2.50e-07), HLA-DRB1*03:01 (OR = 1.58 [1.29-1.94], p = 1.11e-05), as well as HLA-DRB1*04:05 (OR = 2.35 [1.26-4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1*15:03 (OR = 1.26 [1.05-1.51], p = 0.012). The protective association of HLA-A*02:01 was confirmed (OR = 0.72 [0.55-0.93], p = 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p < 0.01, outside the major histocompatibility complex region, 8 MS SNPs were also found to be associated with MS in African Americans. CONCLUSION: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.
PMID: 23771490 [PubMed - as supplied by publisher]
Allele frequencies for 40 autosomal SNP loci typed for US population samples using electrospray ionization mass spectrometry.
Croat Med J. 2013 Jun 15;54(3):225-31
Authors: Kiesler KM, Vallone PM
Aim. To type a set of 194 US African American, Caucasian, and Hispanic samples (self-declared ancestry) for 40 autosomal single nucleotide polymorphism (SNP) markers intended for human identification purposes. Methods. Genotyping was performed on an automated commercial electrospray ionization time-of-flight mass spectrometer, the PLEX-ID. The 40 SNP markers were amplified in eight unique 5plex PCRs, desalted, and resolved based on amplicon mass. For each of the three US sample groups statistical analyses were performed on the resulting genotypes. Results. The assay was found to be robust and capable of genotyping the 40 SNP markers consuming approximately 4 nanograms of template per sample. The combined random match probabilities for the 40 SNP assay ranged from 10-16 to 10-21. Conclusion. The multiplex PLEX-ID SNP-40 assay is the first fully automated genotyping method capable of typing a panel of 40 forensically relevant autosomal SNP markers on a mass spectrometry platform. The data produced provided the first allele frequencies estimates for these 40 SNPs in a National Institute of Standards and Technology US population sample set. No population bias was detected although one locus deviated from its expected level of heterozygosity.
PMID: 23771752 [PubMed - in process]
C332C Genotype of Glyoxalase 1 and its Association with Late Diabetic Complications.
Exp Clin Endocrinol Diabetes. 2013 Jun 17;
Authors: Groener JB, Reismann P, Fleming T, Kalscheuer H, Lehnhoff D, Hamann A, Roser P, Bierhaus A, Nawroth PP, Rudofsky G
Glyoxalase 1 catalyses the detoxification of methylglyoxal, a major precursor of advanced glycation end products associated with aging, neurodegenerative diseases, and microvascular complications of diabetes. Here, we examine a possible association of a single nucleotide polymorphism of glyoxalase 1 gene (Glo1 A332C, rs4746 or rs2736654) with the prevalence of microvascular diabetic complications in patients with type 1 and type 2 diabetes.Genotyping was performed in 209 patients with type 1 and 524 patients with type 2 diabetes using polymerase chain reaction and subsequent cleavage by restriction endonuclease Bsa I.Frequencies of the glyoxalase 1 genotypes were different with respect to diabetes type with a significantly higher prevalence of A332A-genotype in type 1 diabetes (35.9% vs. 27.3%; p=0.03). In type 1 diabetes, there was no correlation of any genotype with diabetic retinopathy, nephropathy or neuropathy. In contrast, type 2 diabetic patients homozygous for the C332C allele showed a significantly increased prevalence of diabetic neuropathy (p=0.03; OR=1.49 [95%-CI: 1.04; 2.11]), while no association with diabetic nephropathy or retinopathy was found. However, the significance of this association was lost after correction for multiple testing.Our data suggest a possible association of C332C-genotype of the glyoxalase 1 gene with diabetic neuropathy in type 2 diabetes, supporting the hypothesis that methylglyoxal might be an important mediator of diabetic neuropathy in type 2 diabetes.
PMID: 23775136 [PubMed - as supplied by publisher]
Accuracy of genomic prediction using an evenly spaced, low-density single nucleotide polymorphism panel in broiler chickens.
Poult Sci. 2013 Jul;92(7):1712-23
Authors: Wang C, Habier D, Peiris BL, Wolc A, Kranis A, Watson KA, Avendano S, Garrick DJ, Fernando RL, Lamont SJ, Dekkers JC
One approach for cost-effective implementation of genomic selection is to genotype training individuals with a high-density (HD) panel and selection candidates with an evenly spaced, low-density (ELD) panel. The purpose of this study was to evaluate the extent to which the ELD approach reduces the accuracy of genomic estimated breeding values (GEBV) in a broiler line, in which 1,091 breeders from 3 generations were used for training and 160 progeny of the third generation for validation. All birds were genotyped with an Illumina Infinium platform HD panel that included 20,541 segregating markers. Two subsets of HD markers, with 377 (ELD-1) or 766 (ELD-2) markers, were selected as ELD panels. The ELD-1 panel was genotyped using KBiosciences KASPar SNP genotyping chemistry, whereas the ELD-2 panel was simulated by adding markers from the HD panel to the ELD-1 panel. The training data set was used for 2 traits: BW at 35 d on both sexes and hen house production (HHP) between wk 28 and 54. Methods Bayes-A, -B, -C and genomic best linear unbiased prediction were used to estimate HD-marker effects. Two scenarios were used: (1) the 160 progeny were ELD-genotyped, and (2) the 160 progeny and their dams (117 birds) were ELD-genotyped. The missing HD genotypes in ELD-genotyped birds were imputed by a Gibbs sampler, capitalizing on linkage within families. In scenario (1), the correlation of GEBV for BW (HHP) of the 160 progeny based on observed HD versus imputed genotypes was greater than 0.94 (0.98) with the ELD-1 panel and greater than 0.97 (0.99) with the ELD-2 panel. In scenario (2), the correlation of GEBV for BW (HHP) was greater than 0.92 (0.96) with the ELD-1 panel and greater than 0.95 (0.98) with the ELD-2 panel. Hence, in a pedigreed population, genomic selection can be implemented by genotyping selection candidates with about 400 ELD markers with less than 6% loss in accuracy. This leads to substantial savings in genotyping costs, with little sacrifice in accuracy.
PMID: 23776257 [PubMed - in process]
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