Independent associations of TOMM40 and APOE variants with body mass index

The TOMM40‐APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40‐APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE variants coding the ε2/ε3/ε4 polymorphism on body mass index (BMI) in age‐aggregated and age‐stratified cohort‐specific and cohort‐pooled analysis of 27,863 Caucasians aged 20–100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (β = ?1.29, p = 3.97 × 10^?9; β = ?1.38, p = 2.78 × 10^?10; and β = 0.58, p = 3.04 × 10^?2, respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI‐lowering associations for minor alleles (β = ?0.63, p = 3.99 × 10^?2 and β = ?0.94, p = 2.17 × 10^?3, respectively). Polygenic mega‐analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (β = ?1.68, p = 3.00 × 10^?9), and the strongest BMI‐lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (β = ?4.11, p = 2.78 × 10^?3). Conditional analysis with four polymorphisms identified independent BMI‐lowering (rs2075650, rs157580, and rs429358) and BMI‐increasing (rs7412) associations of heterozygous genotypes with BMI. Age‐stratified conditional analysis revealed well‐powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and older individuals, β = 0.58, 95% confidence interval (CI) = ?1.18, 2.35, p = 5.18 × 10^?1 for 3,068 individuals aged ≤30 years and β = ?4.28, CI = ?5.65, ?2.92, p = 7.71 × 10^?10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ε4‐coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals.     

Association between Type 2 Diabetes and CDKN2A/B: a meta-analysis study

Cyclin-dependent kinase inhibitor-2A/B (CDKN2A/B) has been reported as a candidate gene of type 2 diabetes (T2D) based on its chromosomal position and its important role in β-cell function and regeneration. However, studies to date have reported inconsistent findings regarding the association between T2D and CDKN2A/B. To clarify this inconsistence, we conducted a meta-analysis based on alleles and genotypes prevalence of rs10811661 and rs564398 in CDKN2A/B. The PubMed, EMBASE, and Medline databases were systematically reviewed for studies published between January, 2006, and November, 2010. A total of 35 reports were collected, among of them only 16 studies (including 24,407 cases and 33,937 controls) match the inclusion criteria and were selected for the statistical test. In the meta-analysis of published data, our results suggest that the rs10811661 T allele (OR 1.28, 95% CI 1.21–1.36, P < 1 × 10⁻⁵) and TT genotype (OR 1.32, 95% CI 1.22–1.43, P < 1 × 10⁻⁵) of CDKN2A/B were associated with type 2 diabetes respectively, but rs564398 was not (for allele only: OR 0.96, 95% CI 0.88–1.05, P = 0.35). The association between rs10811661 T allele and T2D was observed both in Asia (P < 1 × 10⁻⁴) and Europe ethnicity groups (P = 0.002). This meta-analysis yielded evidence that rs10811661 of CDKN2A/B confers risk for T2D. Larger studies with mixed ethnicity subjects are required to validate our findings.     

Temporal variation in coat colour (genotypes) supports major changes in the Nordic cattle population after Iron Age

Variation in coat colour genotypes of archaeological cattle samples from Finland was studied by sequencing 69 base pairs of the extension locus (melanocortin 1‐receptor, MC1R) targeting both a transition and a deletion defining the three main alleles, such as dominant black (E^D), wild type (E⁺) and recessive red (e). The 69‐bp MC1R sequence was successfully analysed from 23 ancient (1000–1800 AD) samples. All three main alleles and genotype combinations were detected with allele frequencies of 0.26, 0.17 and 0.57 for E^D, E⁺ and e respectively. Recessive red and dominant black alleles were detected in both sexes. According to the best of our knowledge, this is the first ancient DNA study defining all three main MC1R alleles. Observed MC1R alleles are in agreement with calculated phenotype frequencies from historical sources. The division of ancient Finnish cattle population into modern Finnish breeds with settled colours was dated to the 20th century. From the existing genotyped populations in Europe (43 breeds, n = 2360), the closest match to ancient MC1R genotype frequencies was with the Norwegian native multicoloured breeds. In combined published genotype data of ancient (n = 147) and genotypes and phenotypes of modern Nordic cattle (n = 738), MC1R allele frequencies showed temporal changes similar to neutral mitochondrial DNA and Y‐chromosomal haplotypes analysed earlier. All three markers indicate major change in genotypes in Nordic cattle from the Late Iron Age to the Medieval period followed by slower change through the historical periods until the present.     

Genetic investigation of equine recurrent uveitis in Appaloosa horses

Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10⁻⁵, P = 5.91 × 10⁻⁶, P = 4.91 × 10⁻⁵, P = 6.46 × 10⁻⁵). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10⁻⁵). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.     

MHC region and risk of systemic lupus erythematosus in African American women

The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case–control study (380 cases, 765 age-matched controls) nested within the prospective Black Women’s Health Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control for population stratification due to population admixture. The most strongly associated SNP with SLE was the rs9271366 (odds ratio, OR = 1.70, p = 5.6 × 10⁻⁵) near the HLA-DRB1 gene. Conditional haplotype analysis revealed three other SNPs, rs204890 (OR = 1.86, p = 1.2 × 10⁻⁴), rs2071349 (OR = 1.53, p = 1.0 × 10⁻³), and rs2844580 (OR = 1.43, p = 1.3 × 10⁻³), to be associated with SLE independent of the rs9271366 SNP. In univariate analysis, the OR for the C4A deletion was 1.38, p = 0.075, but after simultaneous adjustment for the other four SNPs the odds ratio was 1.01, p = 0.98. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk alleles (OR = 1.67 per high-risk allele, p < 0.0001). Our strongest signal, the rs9271366 SNP, was also associated with higher risk of SLE in a previous Chinese genome-wide association study (GWAS). In addition, two SNPs found in a GWAS of European ancestry women were confirmed in our study, indicating that African Americans share some genetic risk factors for SLE with European and Chinese subjects. In summary, we found four independent signals in the MHC region associated with risk of SLE in African American women.     

Use of Real-Time PCR Technique in Studying Rumen Cellulolytic Bacteria Population as Affected by Level of Roughage in Swamp Buffalo

A real-time polymerase chain reaction approach was used in this study to determine the population of major ruminal bacterial species (Fibrobacter succinogenes, Ruminococcus albus, and Ruminococcus flavefaciens) in digesta and rumen fluid of swamp buffalo (Bubalus bubalis). Four rumen-fistulated, male swamp buffalo were randomly assigned according to a 4 × 4 Latin square design to evaluate the effect of the urea-treated rice straw (roughage source)-to-concentrate ratio on cellulolytic bacterial distribution. Animals were fed roughage-to-concentrate (R:C) ratios of 100:0, 75:25, 50:50, and 25:75, respectively. At the end of each period, rumen fluid and digesta were collected at 0 h and 4 h post-morning-feeding. It was found that feeding urea-treated rice straw solely increased these three cellulolytic bacteria numbers up to 2.65 × 10⁹ and 3.54 × 10⁹ copies per milliliter for F. succinogenes, 5.10 × 10⁷ and 7.40 × 10⁷ copies per millilter for R. Flavefaciens, and 4.00 × 10⁶ and 6.00 × 10⁶ copies per milliliter for R. albus in rumen fluid and digesta, respectively. The distribution of the three cellulolytic bacteria species in digesta were highest at 3.21 × 10⁹, 4.55 × 10⁷, and 4.56 × 10⁶ copies per milliliter for F. succinogenes, R. flavefaciens, and R. albus, respectively. Moreover, at 4 h post-morning-feeding, the populations of the three cellulolytic bacteria were higher than found at 0 h post-morning-feeding. It is most notable that F. succinogenes were the highest in population in the rumen of swamp buffalo and cellulolytic bacteria mostly adhered to feed digesta in the rumen.     

CDKN2B-AS1 gene rs4977574 A/G polymorphism and coronary heart disease: A meta-analysis of 40,979 subjects

It has been implied that there is a possible relationship between cyclin-dependent protein kinase inhibitors antisense RNA 1 (CDKN2B-AS1) gene rs4977574 A/G polymorphism and coronary heart disease (CHD) susceptibility. However, as the research results are discrepant, no distinct consensus on this issue has been reached so far. In order to further elaborate the latent association of the CDKN2B-AS1 gene rs4977574 A/G polymorphism and CHD, this present meta-analysis was conducted. There were 40,979 subjects of 17 individual studies in the present meta-analysis. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to determine the association strength. Considering the significant heterogeneity among the individual studies, the random-effect models were used. In the current meta-analysis, a significant association between CDKN2B-AS1 gene rs4977574 A/G polymorphism and CHD was found under allelic (OR: 1.18, 95% CI: 1.08–1.29, p = 4.83×10⁻⁴), recessive (OR: 1.36, 95% CI: 1.11–1.67, p = 0.003), dominant (OR: 0.71, 95% CI: 0.58–0.86, p = 6.26×10⁻⁴), heterozygous (OR:1.210, 95% CI: 1.076–1.360, p = 0.001), homozygous (OR: 1.394, 95% CI: 1.163–1.671, p = 3.31×10⁻⁴) and additive (OR: 1.180, 95% CI: 1.075–1.295, p = 4.83×10⁻⁴) genetic models. A more significant association between them was found in the Asian population than that in the whole population under these genetic models (p < 0.05). However, no significant association between them was found in the Caucasian population (p > 0.05). CDKN2B-AS1 gene rs4977574 A/G polymorphism was associated with CHD susceptibility, especially in the Asian population. G allele of CDKN2B-AS1 gene rs4977574 A/G polymorphism is the risk allele for CHD.     

PDCD1 gene polymorphisms as regulators of T‐lymphocyte activity in cutaneous melanoma risk and prognosis

This study aimed to evaluate whether PD1.1 (c.‐606G>A), PD1 (c.627 + 252C>T), PD1.5 (c.804C>T), and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects, and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89‐fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 versus 1.28 arbitrary units, p = .03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4⁺ lymphocytes (16.6 versus 12.5%, p = .01; 17.0 versus 13.1%, p = .006). At 60 months of follow‐up, short recurrence‐free survival was seen in patients with PD1.1 AA genotype (33.3 versus 71.8%, p = .03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provide preliminary evidence that abnormalities in regulation of T lymphocyte alter CM risk, clinical aspects, and prognosis.     

Manufacturing and validation of Good Manufacturing Practice–compliant regulatory dendritic cells for infusion into organ transplant recipients

Background aimsRegulatory (or “tolerogenic”) dendritic cells (DCregs) are a highly promising, innovative cell therapy for the induction or restoration of antigen-specific tolerance in immune-mediated inflammatory disorders. These conditions include organ allograft rejection, graft-versus-host disease following bone marrow transplantation and various autoimmune disorders. DCregs generated for adoptive transfer have potential to reduce patients’ dependence on non-specific immunosuppressive drugs that can induce serious side effects and enhance the risk of infection and certain types of cancer. Here, our aim was to provide a detailed account of our experience manufacturing and validating comparatively large numbers of Good Manufacturing Practice–grade DCregs for systemic (intravenous) infusion into 28 organ (liver) transplant recipients and to discuss factors that influence the satisfaction of release criteria and attainment of target cell numbers.ResultsDCregs were generated in granulocyte-macrophage colony stimulating factor and interleukin (IL)-4 from elutriated monocyte fractions isolated from non-mobilized leukapheresis products of consenting healthy adult prospective liver transplant donors. Vitamin D3 was added on day 0 and 4 and IL-10 on day 4 during the 7-day culture period. Release and post-release criteria included cell viability, purity, phenotype, sterility and functional assessment. The overall conversion rate of monocytes to DCregs was 28 ± 8.2%, with 94 ± 5.1% product viability. The mean cell surface T-cell co-inhibitory to co-stimulatory molecule (programmed death ligand-1:CD86) mean fluorescence intensity ratio was 3.9 ± 2.2, and the mean ratio of anti-inflammatory:pro-inflammatory cytokine product (IL-10:IL-12p70) secreted upon CD40 ligation was 60 ± 63 (median = 40). The mean total number of DCregs generated from a single leukapheresis product (n = 25 donors) and from two leukapheresis products (n = 3 donors) was 489 ± 223 × 10⁶ (n = 28). The mean total number of DCregs infused was 5.9 ± 2.8 × 10⁶ per kg body weight. DCreg numbers within a target cell range of 2.5–10 × 10⁶/kg were achieved for 25 of 27 (92.6%) of products generated.ConclusionsHigh-purity DCregs meeting a range of quality criteria were readily generated from circulating blood monocytes under Good Manufacturing Practice conditions to meet target cell numbers for infusion into prospective organ transplant recipients.     

Replication study of novel risk variants in six genes with type 2 diabetes and related quantitative traits in the Han Chinese lean individuals

To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of the risk C allele, P = 8.10 × 10⁻⁷). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840 (P < 1.0 × 10⁻⁴) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at CDKAL1 (P < 1×10⁻⁴) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10⁻⁴). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels is consistent with the potential function of CDKAL1 gene in pancreatic islets.     

Phenotype changes inherited by crossing pyrethroid susceptible and resistant genotypes from the cattle tick <Emphasis Type="Italic">Riphicephalus</Emphasis> (<Emphasis Type="Italic">Boophilus</Emphasis>) <Emphasis Type="Italic">microplus</Emphasis>

Dialelic crosses and backcrosses of pyrethroid resistant (RR) and susceptible (SS) Rhipicephalus (Boophilus) microplus tick strains were carried out and the substitution (Phe-Ile) within the sodium channel gene was monitored in order to analyze the effects of the genotype on the pyrethroid resistance phenotype as measured by the larval packet test (LPT). Parental strains: susceptible (SS) and resistant (RR); dialelic crosses: RS (♂RR × ♀SS), and SR (♂SS × ♀RR); and backcrosses: RS × SS, RS × RR, SR × SS and SR × RR were infested on 280 kg calves. Resistance type (monogenic or polygenic) and effective dominance were determined based on the discriminant concentration (DC) for cipermethrine (0.5%), deltamethrine (0.09%) and flumethrine (0.01%). Allele specific PCR (AS-PCR) was used for genotyping, looking at a sodium channel mutation (Phe-Ile substitution). The mortality rates and allele frequency of susceptible and pyrethroid resistant reference strains were 0% mortality and 90% RR alleles for resistant strain, and 100% mortality and 0% RR alleles as measured by the larval packet test (LPT) and allele specific PCR (AS-PCR) respectively. Backcrossed strain SR × RR showed an effective dominance (D_ML) of 0.605 for cypermethrin, 0.639 for deltamethrin and 0.498 for flumethrin, while survival of backcrosses RS × SS, RS × RR and SR × SS showed a significant tendency to recesivity. Backcrossed strain SR × RR (69.4%) also showed a higher RR genotype frequency with regards to RS × SS (25.5%), RS × RR (36.7%) and SR × SS (32.0%), however, susceptible allele was inherited in general as an incomplete dominant trait. Monogenic inheritance hypothesis was tested and the results showed monogenic inheritance for cypermethrin and flumethrin (P < 0.05) but not for deltamethrin (P > 0.05). However, significant correlation was found between RR genotype and the survival rate for all three pyrethroids used (P < 0.05), suggesting that a single substitution on the sodium channel gene can be responsible for resistance to pyrethroids as a class, due to the high frequency for RR genotypes. Combination with different mutations or metabolic resistance mechanisms cannot be excluded.     

Chemiluminescence method for the determination of piroxicam by the enhancement of the tris‐(4,7‐diphenyl‐1,10‐phenanthrolinedisulphonic acid) ruthenium(II) (RuBPS)–cerium(IV) system and its application

A simple, rapid chemiluminescence (CL) method was described for the determination of piroxicam, a commonly used analgesic agent drug. A strong CL signal was detected when cerium(IV) sulphate was injected into tris‐(4,7‐diphenyl‐1,10‐phenanthrolinedisulphonic acid) ruthenium(II) (RuBPS)–piroxicam solution. The CL signal was proportional to the concentration of piroxicam in the range 2.8 × 10^–8–1.2 × 10^–5 mol/L. The detection limit was 2 × 10^–8 mol/L and the relative standard deviation (RSD) was 3.7% (c = 7.0 × 10^–7 mol/L piroxicam; n = 11). The proposed method was applied to the determination of piroxicam in pharmaceutical preparations in capsules, spiked serum and urine samples with satisfactory results. Copyright © 2008 John Wiley & Sons, Ltd.     

Genomewide association study for susceptibility genes contributing to familial Parkinson disease

Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10⁻⁶; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10⁻⁵; OR = 1.35) and MAPT (recessive model: p = 2.0 × 10⁻⁵; OR = 0.56). Both of these genes have been implicated previously in PD susceptibility; however, neither was identified in previous GWAS studies of PD. Meta-analysis was performed using data from a previous case–control GWAS, and yielded improved p values for several regions, including GAK/DGKQ (additive model: p = 2.5 × 10⁻⁷) and the MAPT region (recessive model: p = 9.8 × 10⁻⁶; additive model: p = 4.8 × 10⁻⁵). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. N. Pankratz and J. B. Wilk are joint first authors.     

Phylogeny,ecology and deep time: 2D outline analysis of anuran skulls from the Early Cretaceous to the Recent

Anurans have a long fossil record, spanning from the Early Jurassic to the Recent. However, specimens are often severely flattened, limiting their inclusion in quantitative analyses of morphological evolution. We perform a two‐dimensional morphometric analysis of anuran skull outlines, incorporating 42 Early Cretaceous to Miocene species, as well as 93 extant species in 32 families. Outlines were traced in tpsDig2 and analysed with elliptical Fourier analysis. Fourier coefficients were used in MANOVAs, phylogenetic MANOVAs (as significant phylogenetic signal was found) and disparity analyses across multiple ecological and life history groupings. The Neotropical realm showed higher disparity than the Australian, Palaearctic and Oriental realms (p = 0.007, 0.013, 0.038, respectively) suggesting concordance of disparity and diversity. Developmental strategy had a weak effect on skull shape (R² = 0.02, p = 0.039) and disparity was similar in metamorphosing and direct developing frogs. Ecological niche was a significant discriminator of skull shape (F = 1.43, p = 0.004) but not after phylogenetic correction. Evolutionary allometry had a small but significant influence on the cranial outlines of the combined extant and fossil dataset (R² = 0.05, p = 0.004). Finally, morphospace occupation appears to have changed over time (F = 1.59, p = 5 × 10^?10). However, as with ecological signal, this shift appears to be largely driven by phylogeny and was not significant after phylogenetic correction (R² = 0.26, p = 0.22). This study thus suggests that frog skull evolution is shaped more by phylogenetic constraints than by ecology.     

Common loci underlie field resistance to soybean sudden death syndrome in Forrest,Pyramid, Essex,and Douglas

Soybean [Glycine max (L.) Merr.] sudden death syndrome (SDS) caused by Fusarium solani f. sp. glycines results in severe yield losses. Resistant cultivars offer the most-effective protection against yield losses but resistant cultivars such as ’Forrest’ and ’Pyramid’ vary in the nature of their response to SDS. Loci underlying SDS resistance in ’Essex’ × Forrest are well defined. Our objectives were to identify and characterize loci and alleles that underlie field resistance to SDS in Pyramid×’Douglas’. SDS disease incidence and disease severity were determined in replicated field trials in six environments over 4 years. One hundred and twelve polymorphic DNA markers were compared with SDS disease response among 90 recombinant inbred lines from the cross Pyramid×Douglas. Two quantitative trait loci (QTLs) for resistance to SDS derived their beneficial alleles from Pyramid, identified on linkage group G by BARC-Satt163 (261-bp allele, P=0.0005, R²=16.0%) and linkage group N by BARC-Satt080 (230-bp allele, P=0.0009, R²=15.6%). Beneficial alleles of both QTLs were previously identified in Forrest. A QTL for re- sistance to SDS on linkage group C2 identified by BARC-Satt307 (292-bp allele, P=0.0008, R²=13.6%) derived the beneficial allele from Douglas. A beneficial allele of this QTL was previously identified in Essex. Recombinant inbred lines that carry the beneficial alleles for all three QTLs for resistance to SDS were significantly (P≤0.05) more resistant than other recombinant inbred lines . Among these recombinant inbred lines resistance to SDS was environmentally stable. Therefore, gene pyramiding will be an effective method for developing cultivars with stable resistance to SDS. Received: 20 October 1999 / Accepted: 22 May 2001     

Obesity‐susceptibility loci and the tails of the pediatric BMI distribution

Objective: To determine whether previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution. Design and Methods: Children were recruited through the Children's Hospital of Philadelphia (n = 7,225). Associations between the following loci and BMI were assessed using quantile regression: FTO (rs3751812), MC4R (rs12970134), TMEM18 (rs2867125), BDNF (rs6265), TNNI3K (rs1514175), NRXN3 (rs10146997), SEC16B (rs10913469), and GNPDA2 (rs13130484). BMI z‐score (age and gender adjusted) was modeled as the dependent variable, and genotype risk score (sum of risk alleles carried at the 8 loci) was modeled as the independent variable. Results: Each additional increase in genotype risk score was associated with an increase in BMI z‐score at the 5th, 15th, 25th, 50th, 75th, 85th, and 95th BMI z‐score percentiles by 0.04 (±0.02, P = 0.08), 0.07 (±0.01, P = 9.58 × 10^?7), 0.07 (±0.01, P = 1.10 × 10^?8), 0.09 (±0.01, P = 3.13 × 10^?22), 0.11 (±0.01, P = 1.35 × 10^?25), 0.11 (±0.01, P = 1.98 × 10^?20), and 0.06 (±0.01, P = 2.44 × 10^?6), respectively. Each additional increase in genotype risk score was associated with an increase in mean BMI z‐score by 0.08 (±0.01, P = 4.27 × 10^?20). Conclusion: Obesity risk alleles were more strongly associated with increases in BMI z‐score at the upper tail compared to the lower tail of the distribution.     

Polymorphism of bovine Y-STR UMN0929 and its correlation with carcass traits in five Chinese beef cattle populations

The correlations between Y chromosome polymorphisms and the carcass traits were studied in five Chinese beef cattle populations by PCR, single strand conformation polymorphism and Y-STR sequence analysis. Nine alleles and their frequencies were identified on Y-STR UMN0929 region in Qinchuan (n = 116), Luxi (n = 112), Jinnan (n = 104) pure breeds, Simmental × Qinchuan crossbred (n = 80) and Angus × Qinchuan crossbred (n = 96). The most popular A-176 and B-178 alleles were presented in all 5 cattle populations in the range of 12% (Jinnan) to 66% (Simmental × Qinchuan). The allele I-194 presented Luxi and Angus × Qinchuan. In Qinchun cattle, G-190 and E-186 alleles had bigger effect on BPI (4.23 ± 0.32 and 4.22 ± 0.48 kg/cm, P < 0.01) and CW (325.40 ± 49.42 and 316.73 ± 45.29 kg, P < 0.01), respectively. In Luxi cattle, I-194 allele affected higher BPI (4.08 ± 0.35 kg/cm, P < 0.01) and CW (302.07 ± 17.55 kg, P < 0.01), respectively. In Jinnan cattle breed, H-192 had higher BPI (4.32 ± 0.50 kg/cm, P < 0.05) and CW (327.87 ± 59.37 kg, P < 0.05), respectively. In Simmental × Qinchuan cross breed, C-180 allele affected largely on BPI (5.16 ± 0.25 kg/cm, P < 0.05) and CW (393.16 ± 25.92 kg, P < 0.05). In Angus × Qinchuan cross breed, I-194 had higher BPI (4.43 ± 0.33 kg, P < 0.05) and CW (346.63 ± 29.77 kg, P < 0.05). Correlations between alleles and other carcass traits (net meat weight, top grade weight, slaughter rate, net meat rate, loin-eye muscle area, carcass length, meet tenderness and shear force) were also analyzed using mixed-effect model. Cattle Y-STR UMN0929 loci alleles and its correlation with carcass traits in beef cattle populations could be implemented into the cattle breeding program for choosing beef cattle with better carcass traits.     

HLA association with nasopharyngeal carcinoma in southern Tunisia

In order to study the association of HLA-A, -B and/or DRB1, DQB1 and the nasopharyngeal carcinoma (NPC), 141 patients affected with NPC were typed for the HLA class I by serology method of microlymphocytotoxicity. Among these patients 101 were genotyped for HLA class II system by the PCR-SSP technique. HLA typing results were compared to those of 116 controls. We found that the HLA-A31 and -A33 antigens were significantly more expressed in patients than in the controls (P = 0.016 and 0.010, respectively) and the HLA-A19 antigen, was significantly more frequent in patients when compared to the controls (P = 0.007). The HLA-DRB1*03 and DRB1*13 alleles were significantly more frequent in patients as compared to the controls. The DRB1*01 allele was expressed with a frequency of 20.69% in the controls whereas it was only detected in 3.96% of the NPC patients. Furthermore, the DQB1*05 allele was expressed at a frequency which was significantly less important in affected patient (P = 0.03), whereas, the DQB1*02 allele was more frequent in patients (P = 0.643 × 10⁻⁴). Thus our study revealed a significant increase of HLA-A31, A33, A19, B16, B53 and DRB1*03, DRB1*13 and DQB1*02 alleles in our patients. These markers could play a predisposing role in the development of NPC. In contrast, a decrease of HLA-B14, -B35 and DRB1*01 and DQB1*05 alleles was found suggesting a likely protective effect.     

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID‐north population with 694 AF cases and 710 controls, adjusted P_‐adj = 6.25 × 10^?3 with an odds ratio was 0.77, GeneID‐central population with 1106 cases and 1501 controls, P_‐adj = 9.88 × 10^?5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non‐hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.