bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor Ck-dependent signaling regulates hTERT gene transcription
Authors: Sikand Kavleen , Kaul Deepak , Varma Neelam 
Published: January 2006

Abstract

Background
Available evidence suggests that the regulation of telomerase activity primarily depends on the transcriptional control of the human telomerase reverse transcriptase (hTERT) gene. Although several activators and repressors of hTERT gene transcription have been identified, the exact mechanism by which hTERT transcription is repressed in normal cells and activated in cancer cells remains largely unknown. In an attempt to identify possible novel mechanisms involved in the regulation of hTERT transcription, the present study examined the role of Receptor Ck, a cell surface receptor specific for cholesterol, in the transcription of hTERT gene in normal human peripheral blood mononuclear cells.

Results
Activated Receptor Ck was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling was also found to down-regulate the mRNA expression of the gene coding for the ligand inducible transcription factor, peroxisome proliferator-activated receptor γ (PPARγ). The ligand activation of PPARγ resulted in the down-regulation of c-myc and hTERT mRNA expression. By using specific activator and inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck dependent down-regulation of hTERT gene transcription involved inhibition of PKC. In addition, 25-hydroxycholesterol was found to contribute to the transcriptional regulation of hTERT gene.

Conclusion
Taken together, the findings of this study present evidence for a molecular link between cholesterol-activated Receptor Ck and hTERT transcription, and provide new insights into the regulation of hTERT expression in normal human peripheral blood mononuclear cells.
RCAS-RNAi: A loss-of-function method for the developing chick retina
Authors: Harpavat Sanjiv , Cepko Constance L 
Published: January 2006

Abstract

Background
The embryonic chick provides an excellent model system for studies of development. However, it has lacked an efficient loss-of-function method for studies of gene function.

Results
We show that avian retroviruses can deliver hairpins mediating RNA interference to the developing chick eye. These viruses 'knock down' specific genes in infected areas of the retina. The knock down persists as the retina matures and can be detected using in situ hybridization. Furthermore, the amount of retinal tissue affected can be controlled by manipulating the degree of infection.

Conclusion
This technique provides a rapid and efficient loss-of-function option for studies in the developing chick retina.
Diversity begets diversity: host expansions and the diversification of plant-feeding insects
Authors: Janz Niklas , Nylin Sören , Wahlberg Niklas 
Published: January 2006

AbstractBackgroundPlant-feeding insects make up a large part of earth's total biodiversity. While it has been shown that herbivory has repeatedly led to increased diversification rates in insects, there has been no compelling explanation for how plant-feeding has promoted speciation rates. There is a growing awareness that ecological factors can lead to rapid diversification and, as one of the most prominent features of most insect-plant interactions, specialization onto a diverse resource has often been assumed to be the main process behind this diversification. However, specialization is mainly a pruning process, and is not able to actually generate diversity by itself. Here we investigate the role of host colonizations in generating insect diversity, by testing if insect speciation rate is correlated with resource diversity.ResultsBy applying a variant of independent contrast analysis, specially tailored for use on questions of species richness (MacroCAIC), we show that species richness is strongly correlated with diversity of host use in the butterfly family Nymphalidae. Furthermore, by comparing the results from reciprocal sister group selection, where sister groups were selected either on the basis of diversity of host use or species richness, we find that it is likely that diversity of host use is driving species richness, rather than vice versa.ConclusionWe conclude that resource diversity is correlated with species richness in the Nymphalidae and suggest a scenario based on recurring oscillations between host expansions – the incorporation of new plants into the repertoire – and specialization, as an important driving force behind the diversification of plant-feeding insects.
Comparison of single-nucleotide polymorphisms and microsatellites in detecting quantitative trait loci for alcoholism: The Collaborative Study on the Genetics of Alcoholism
Authors: Kim Helen , Hutter Carolyn M , Monks Stephanie A , Edwards Karen L 
Published: January 2006

Abstract

Background
The feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known. The purpose of this study was to compare variance components linkage results using different density marker maps in data from the Collaborative Study on the Genetics of Alcoholism (COGA). Marker maps having an average spacing of 10 cM (microsatellite), 0.78 cM (SNP1), and 0.31 cM (SNP2) were used to identify quantitative trait loci (QTLs) affecting maximum number of alcoholic drinks consumed in a 24-hour period (lnmaxalc).

Results
Heritability of lnmaxalc was estimated to be 15%. Multipoint variance components linkage analysis revealed similar linkage patterns among the three marker panels, with the SNP maps consistently yielding higher LOD scores. Robust LOD scores > 1.0 were observed on chromosomes 1 and 13 for all three marker maps. Additional LODs > 1.0 were observed on chromosome 4 with both SNP maps and on chromosomes 18 and 21 with the SNP2 map. Peak LOD scores for lnmaxalc were observed on chromosome 1, although none reached genome-wide statistical significance. Quantile-quantile plots revealed that the multipoint distribution of SNP results appeared to fit the asymptotic null distribution better than the twopoint results.

Conclusion
In conclusion, variance-components linkage analysis using high-density SNP maps provided higher LOD scores compared with the standard microsatellite map, similar to studies using nonparametric linkage methods. Widespread application of SNP maps will depend on further improvements in the computational methods implemented in current software packages.
On normality, ethnicity, and missing values in quantitative trait locus mapping
Authors: Labbe Aurélie , Wormald Hanna 
Published: January 2006

Abstract

Background
This paper deals with the detection of significant linkage for quantitative traits using a variance components approach. Microsatellite markers were obtained for the Genetic Analysis Workshop 14 Collaborative Study on the Genetics of Alcoholism data. Ethnic heterogeneity, highly skewed quantitative measures, and a high rate of missing values are all present in this dataset and well known to impact upon linkage analysis. This makes it a good candidate for investigation.

Results
As expected, we observed a number of changes in LOD scores, especially for chromosomes 1, 7, and 18, along with the three factors studied. A dramatic example of such changes can be found in chromosome 7. Highly significant linkage to one of the quantitative traits became insignificant when a proper normalizing transformation of the trait was used and when analysis was carried out on an ethnically homogeneous subset of the original pedigrees.

Conclusion
In agreement with existing literature, transforming a trait to ensure normality using a Box-Cox transformation is highly recommended in order to avoid false-positive linkages. Furthermore, pedigrees should be sorted by ethnic groups and analyses should be carried out separately. Finally, one should be aware that the inclusion of covariates with a high rate of missing values reduces considerably the number of subjects included in the model. In such a case, the loss in power may be large. Imputation methods are then recommended.
Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study
Authors: Li Yi-Ju , Martin Eden R , Zhang Ling , Allen Andrew S 
Published: January 2006

Abstract
Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.
Locally weighted transmission/disequilibrium test for genetic association analysis
Authors: Hsu Li , Yu Xuesong , Houwing-Duistermaat Jeanine J , Uh Hae-Won , El Galta Rachid , Lebrec Jeremie JP , Tang Hua 
Published: January 2006

Abstract
The transmission/disequilibrium test statistic has been used for assessing genetic association in affected-parent trios. In the presence of multiple tightly linked marker loci where local dependency may exist, haplotypes are reconstructed statistically to estimate the joint effects of these markers. In this manuscript, we propose an alternative to the haplotype approach by taking a weighted average of multiple loci, where the weight is proportional to the product of (1-2X recombination fraction) and the linkage disequilibrium between markers. As an illustration, we applied the method to the simulated Aipotu data.
Fine-mapping using the weighted average method for a case-control study
Authors: Song Kijoung , Orloff Mohammed S , Lu Qing , Elston Robert C 
Published: January 2006

Abstract
We present a new method for fine-mapping a disease susceptibility locus using a case-control design. The new method, termed the weighted average (WA) statistic, averages the Cochran-Armitage (CA) trend test statistic and the difference between the Hardy-Weinberg disequilibrium test statistic for cases and controls (the HWD trend). The main characteristics of the WA statistic are that it improves on the weaknesses, and maintains the strengths, of both the CA trend test and the HWD trend test. Data from three different populations in the Genetic Analysis Workshop 14 (GAW14) simulated dataset (Aipotu, Karangar, and Danacaa) were first subjected to model-free linkage analysis to find regions exhibiting linkage. Then, for fine-scale mapping, 140 SNPs within the significant linkage regions were analyzed with the WA test statistic on replicates of the three populations, both separately and combined. The regions that were significant in the multipoint linkage analysis were also significant in this fine-scale mapping. The most significant regions that were obtained using the WA statistic were regions in chromosome 3 (B03T3056–B03T3058, p-value < 1 × 10-10 ) and chromosome 9 (B09T8332–B09T8334, p-value 1 × 10-6 ). Based on the results of the simulated GAW14 data, the WA test statistic showed good performance and could narrow down the region containing the susceptibility locus. However, the strength of the signal depends on both the strength of the linkage disequilibrium and the heterozygosity of the linked marker.
A comparison of five methods for selecting tagging single-nucleotide polymorphisms
Authors: Burkett Kelly M , Ghadessi Mercedeh , McNeney Brad , Graham Jinko , Daley Denise 
Published: January 2006

Abstract
Our goal was to compare methods for tagging single-nucleotide polymorphisms (tagSNPs) with respect to the power to detect disease association under differing haplotype-disease association models. We were also interested in the effect that SNP selection samples, consisting of either cases, controls, or a mixture, would have on power. We investigated five previously described algorithms for choosing tagSNPS: two that picked SNPs based on haplotype structure (Chapman-haplotypic and Stram), two that picked SNPs based on pair-wise allelic association (Chapman-allelic and Cousin), and one control method that chose equally spaced SNPs (Zhai). In two disease-associated regions from the Genetic Analysis Workshop 14 simulated data, we tested the association between tagSNP genotype and disease over the tagSNP sets chosen by each method for each sampling scheme. This was repeated for 100 replicates to estimate power. The two allelic methods chose essentially all SNPs in the region and had nearly optimal power. The two haplotypic methods chose about half as many SNPs. The haplotypic methods had poor performance compared to the allelic methods in both regions. We expected an improvement in power when the selection sample contained cases; however, there was only moderate variation in power between the sampling approaches for each method. Finally, when compared to the haplotypic methods, the reference method performed as well or worse in the region with ancestral disease haplotype structure.
Haplotypic structure of the X chromosome in the COGA population sample and the quality of its reconstruction by extant software packages
Authors: Marroni Fabio , Toni Chiara , Pennato Benedetto , Tsai Ya-Yu , Duggal Pryia , Bailey-Wilson Joan E , Presciuttini Silvano 
Published: January 2006

Abstract

Background
The haplotypes of the X chromosome are accessible to direct count in males, whereas the diplotypes of the females may be inferred knowing the haplotype of their sons or fathers. Here, we investigated: 1) the possible large-scale haplotypic structure of the X chromosome in a Caucasian population sample, given the single-nucleotide polymorphism (SNP) maps and genotypes provided by Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the performances of widely used programs in reconstructing haplotypes from population genotypic data, given their known distribution in a sample of unrelated individuals.

Results
All possible unrelated mother-son pairs of Caucasian ancestry (N = 104) were selected from the 143 families of the Collaborative Study on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers were inferred from the X chromosomes of their sons. The marker set included 313 SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of markers was computed by the parameter D', whereas for measuring multilocus disequilibrium, we developed here an index called D*, and applied it to all possible sliding windows of 5 markers each. Results showed a complex pattern of haplotypic structure, with regions of low linkage disequilibrium separated by regions of high values of D*. The following programs were evaluated for their accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2) PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances were evaluated by Pearson correlation (r) coefficient between the true and the inferred distribution of haplotype frequencies.

Conclusion
The SNP haplotypic structure of the X chromosome is complex, with regions of high haplotype conservation interspersed among regions of higher haplotype diversity. All the tested programs were accurate (r = 1) in reconstructing the distribution of haplotype frequencies in case of high D* values. However, only the program PHASE realized a high correlation coefficient (r > 0.7) in conditions of low linkage disequilibrium.
Identification of polymorphisms explaining a linkage signal: application to the GAW14 simulated data
Authors: Chen Ming-Huei , Van Eerdewegh Paul , Dupuis Josée 
Published: January 2006

Abstract
We applied three approaches for the identification of polymorphisms explaining the linkage evidence to the Genetic Analysis Workshop 14 simulated data: 1) the genotype-IBD sharing test (GIST); 2) an approach suggested by Horikawa and colleagues; and 3) the homozygote sharing test (HST). These tests were compared with a family-based association test. Two linked regions with highest nonparametric linkage scores were selected to apply these methods. In the first region, Horikawa's method identified the most SNPs within the region containing the disease susceptibility locus, while HST performed best in the second region. However, Horikawa's method also had the most type I errors. These methods show potential as additional tools to complement family-based association tests for the identification of disease susceptibility variants.
Whole-genome association studies of alcoholism with loci linked to schizophrenia susceptibility
Authors: Namkung Junghyun , Kim Youngchul , Park Taesung 
Published: January 2006

Abstract

Background
Alcoholism is a complex disease. There have been many reports on significant comorbidity between alcoholism and schizophrenia. For the genetic study of complex diseases, association analysis has been recommended because of its higher power than that of the linkage analysis for detecting genes with modest effects on disease.

Results
To identify alcoholism susceptibility loci, we performed genome-wide single-nucleotide polymorphisms (SNP) association tests, which yielded 489 significant SNPs at the 1% significance level. The association tests showed that tsc0593964 (P-value 0.000013) on chromosome 7 was most significantly associated with alcoholism. From 489 SNPs, 74 genes were identified. Among these genes, GABRA1 is a member of the same gene family with GABRA2 that was recently reported as alcoholism susceptibility gene.

Conclusion
By comparing 74 genes to the published results of various linkage studies of schizophrenia, we identified 13 alcoholism associated genes that were located in the regions reported to be linked to schizophrenia. These 13 identified genes can be important candidate genes to study the genetic mechanism of co-occurrence of both diseases.
Selection of single-nucleotide polymorphisms in disease association data
Authors: Joo Jungnam , Tian Xin , Zheng Gang , Lin Jing-Ping , Geller Nancy L 
Published: January 2006

AbstractWe studied several methods for selecting single-nucleotide polymorphisms (SNPs) in a disease association study. Two major categories for analytical strategy are the univariate and the set selection approaches. The univariate approach evaluates each SNP marker one at a time, while the set selection approach tests disease association of a set of SNP markers simultaneously. We examined various test statistics that can be utilized in testing disease association and also reviewed several multiple testing procedures that can properly control the family-wise error rates when the univariate approach is applied to multiple markers. The set association methods were then briefly reviewed. Finally, we applied these methods to the data from Collaborative Study on the Genetics of Alcoholism (COGA).
Microsatellite linkage analysis, single-nucleotide polymorphisms, and haplotype associations with ECB21 in the COGA data
Authors: Kraja Aldi T , Borecki Ingrid B , Province Michael A 
Published: January 2006

AbstractThis study, part of the Genetic Analysis Workshop 14 (GAW14), explored real Collaborative Study on the Genetics of Alcoholism data for linkage and association mapping between genetic polymorphisms (microsatellite and single-nucleotide polymorphisms (SNPs)) and beta (16.5–20 Hz) oscillations of the brain rhythms (ecb21). The ecb21 phenotype underwent the statistical adjustments for the age of participants, and for attaining a normal distribution. A total of 1,000 subjects' available phenotypes were included in linkage analysis with microsatellite markers. Linkage analysis was performed only for chromosome 4 where a quantitative trait locus with 5.01 LOD score had been previously reported. Previous findings related this location with theγ-aminobutyric acid type A (GABAA) receptor. At the same location, our analysis showed a LOD score of 2.2. This decrease in the LOD score is the result of a drastic reduction (one-third) of the available GAW14 phenotypic data. We performed SNP and haplotype association analyses with the same phenotypic data under the linkage peak region on chromosome 4. Seven Affymetrix and two Illumina SNPs showed significant associations with ecb21 phenotype. A haplotype, a combination of SNPs TSC0044171 and TSC0551006 (the latter almost under the region of GABAAgenes), showed a significant association with ecb21 (p= 0.015) and a relatively high frequency in the sample studied. Our results affirmed that the GABA region has potential of harboring genes that contribute quantitatively to the beta oscillation of the brain rhythms. The inclusion of the remaining 614 subjects, which in the GAW14 had missing data for the ecb21, can improve the strength of the associations as they have already shown that they contribute quite important information in the linkage analysis.
Mapping of panda plumage color locus on the microsatellite linkage map of the Japanese quail
Authors: Miwa Mitsuru , Inoue-Murayama Miho , Kobayashi Naoki , Kayang Boniface Baboreka , Mizutani Makoto , Takahashi Hideaki , Ito Shin'ichi 
Published: January 2006

Abstract

Background
Panda (s) is an autosomal recessive mutation, which displays overall white plumage color with spots of wild-type plumage in the Japanese quail (Coturnix japonica). In a previous study, the s locus was included in the same linkage group as serum albumin (Alb) and vitamin-D binding protein (GC) which are mapped on chicken (Gallus gallus) chromosome 4 (GGA4). In this study, we mapped the s locus on the microsatellite linkage map of the Japanese quail by linkage analysis.

Results
Segregation data on the s locus were obtained from three-generation families (n = 106). Two microsatellite markers derived from the Japanese quail chromosome 4 (CJA04) and three microsatellite markers derived from GGA4 were genotyped in the three-generation families. We mapped the s locus between GUJ0026 and ABR0544 on CJA04. By comparative mapping with chicken, this locus was mapped between 10.0 Mb and 14.5 Mb region on GGA4. In this region, the endothelin receptor B subtype 2 gene (EDNRB2), an avian-specific paralog of the mammalian endothelin receptor B gene (EDNRB), is located. Because EDNRB is responsible for aganglionic megacolon and spot coat color in mouse, rat and equine, EDNRB2 is suggested to be a candidate gene for the s locus.

Conclusion
The s locus and the five microsatellite markers were mapped on CJA04 of the Japanese quail. EDNRB2 was suggested to be a candidate gene for the s locus.