CiteULike: Author Kardia

Gene-expression profiles predict survival of patients with lung adenocarcinoma

David Beer — 2008-07-14T13:53:46-00:00

Nat Med, Vol. 8, No. 8. (2002), pp. 816-824.

Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas.

DR Schwartz — 2008-06-13T13:09:30-00:00

Cancer research, Vol. 62, No. 16. (15 August 2002), pp. 4722-4729.

Biologically and clinically meaningful tumor classification schemes have long been sought. Some malignant epithelial neoplasms, such as those in the thyroid and endometrium, exhibit more than one pattern of differentiation, each associated with distinctive clinical features and treatments. In other tissues, all carcinomas, regardless of morphological type, are treated as though they represent a single disease. To better understand the biological and clinical features seen in the four major histological types of ovarian carcinoma (OvCa), we analyzed gene expression in 113 ovarian epithelial tumors using oligonucleotide microarrays. Global views of the variation in gene expression were obtained using PCA. These analyses show that mucinous and clear cell OvCas can be readily distinguished from serous OvCas based on their gene expression profiles, regardless of tumor stage and grade. In contrast, endometrioid adenocarcinomas show significant overlap with other histological types. Although high-stage/grade tumors are generally separable from low-stage/grade tumors, clear cell OvCa has a molecular signature that distinguishes it from other poor-prognosis OvCas. Indeed, 73 genes, expressed 2- to 29-fold higher in clear cell OvCas compared with each of the other OvCa types, were identified. Collectively, the data indicate that gene expression patterns in ovarian adenocarcinomas reflect both morphological features and biological behavior. Moreover, these studies provide a foundation for the development of new type-specific diagnostic strategies and treatments for ovarian cancer.

Imputing missing genotypic data of single-nucleotide polymorphisms using neural networks

Yan Sun — 2008-01-17T18:08:21-00:00

European Journal of Human Genetics, Vol. aop, No. current.

KGraph: a system for visualizing and evaluating complex genetic associations.

Reagan J Kelly — 2006-11-01T10:54:47-00:00

Bioinformatics (10 October 2006)

SUMMARY: The KGraph is a data visualization system that has been developed to display the complex relationships between the univariate and bivariate associations among an outcome of interest, a set of covariates, and a set of genetic factors such as single nucleotide polymorphisms (SNPs). It allows for easy viewing and interpretation of genetic associations, correlations among covariates and SNPs, and information about the replication and cross-validation of the associations. The KGraph allows the user to more easily investigate multicollinearity and confounding through visualization of the multidimensional correlation structure underlying genetic associations. It emphasizes gene-environment and gene-gene interaction, both important components of any genetic system that are often overlooked in association frameworks. AVAILABILITY: http://www.epidkardia.sph.umich.edu/software/kgrapher. SUPPLEMENTARY INFORMATION: A description of system requirements and a full user manual are available at http://www.epidkardia.sph.umich.edu/software/kgrapher.

Multiple genes for essential-hypertension susceptibility on chromosome 1q.

YP Chang — 2007-01-27T15:30:42-00:00

Am J Hum Genet, Vol. 80, No. 2. (February 2007), pp. 253-264.

Essential hypertension, defined as elevated levels of blood pressure (BP) without any obvious cause, is a major risk factor for coronary heart disease, stroke, and renal disease. BP levels and susceptibility to development of essential hypertension are partially determined by genetic factors that are poorly understood. Similar to other efforts to understand complex, non-Mendelian phenotypes, genetic dissection of hypertension-related traits employs genomewide linkage analyses of families and association studies of patient cohorts, to uncover rare and common disease alleles, respectively. Family-based mapping studies of elevated BP cover the large intermediate ground for identification of genes with common variants of significant effect. Our genomewide linkage and candidate-gene-based association studies demonstrate that a replicated linkage peak for BP regulation on human chromosome 1q, homologous to mouse and rat quantitative trait loci for BP, contains at least three genes associated with BP levels in multiple samples: ATP1B1, RGS5, and SELE. Individual variants in these three genes account for 2-5-mm Hg differences in mean systolic BP levels, and the cumulative effect reaches 8-10 mm Hg. Because the associated alleles in these genes are relatively common (frequency >5%), these three genes are important contributors to elevated BP in the population at large.

Influence of genomic loci on measures of chronic kidney disease in hypertensive sibships.

ST Turner — 2007-08-24T02:52:12-00:00

J Am Soc Nephrol, Vol. 17, No. 7. (July 2006), pp. 2048-2055.

Genomewide linkage analyses were conducted of serum creatinine, estimated GFR (eGFR), and urine albumin-creatinine ratio (UACR) in search of genetic susceptibility loci for chronic kidney disease in 1351 black (median age 63 yr, 70% women, 79% hypertensive) and 1022 white individuals (median age 61 yr, 56% women, 75% hypertensive) from sibships in which two or more members had essential hypertension diagnosed before age 60 yr. After adjustment for gender, age, diabetes, and use of angiotensin inhibitors, the logarithm-transformed measure of serum creatinine was heritable in both ethnic groups (0.45 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]), as was eGFR (0.52 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]). Log UACR was heritable in black individuals (0.30, P < 0.001) but not in white individuals (0.12; P = 0.059). In black individuals, the univariate maximum multipoint logarithm of odds scores (MLS) were observed on chromosome 7 for log serum creatinine (MLS = 3.65, at 43 cM from pter; P = 0.00002) and eGFR (MLS = 2.52, at 45 cM from pter; P = 0.00033) and for log UACR (MLS = 2.91, at 112 cM from pter; P = 0.00012). In white individuals, only one MLS for log serum creatinine and one for eGFR achieved the logarithm of odds score criterion for "suggestive" evidence of linkage (2 < or = MLS < 3), both on chromosome 3 (at 211 and 209 cM, respectively); however, none did so for log UACR. In black individuals, bivariate linkage analyses of log serum creatinine and pulse pressure (i.e., systolic-diastolic BP) provided "suggestive" evidence of a region on chromosome 5 with pleiotropic effects on both traits (MLS = 3.62, at 85 cM from pter; P = 0.00023). These findings support the utility of genetic linkage analyses for identification of novel risk factors that influence measures of chronic kidney disease, particularly among black individuals.

Aromatase gene (CYP 19) polymorphisms and endogenous androgen concentrations in a multiracial/multiethnic, multisite study of women at midlife.

MR Sowers — 2007-06-14T17:08:00-00:00

Am J Med, Vol. 119, No. 9 Suppl 1. (September 2006)

A limited number of studies have focused on androgens in women's health, particularly at the genetic level. We evaluated testosterone and estradiol (E2) levels among women in relation to 5 single nucleotide polymorphisms (SNPs) of the aromatase (CYP 19) gene, the cytochrome P450 enzyme that converts androgens to estrogens. We related 5 aromatase SNPs (CYP 19 rs2414096, CYP 19 rs936306, CYP 19 rs2446405, CYP 19 rs1008805, and CYP 19 rs749292) to serum androgen and E2 markers in 1,538 participants of the Study of Women's Health Across the Nation (SWAN), including 412 African American, 807 Caucasian, 151 Chinese, and 168 Japanese women. Aromatase allele and genotype frequencies differed significantly among racial/ethnic groups. Compared with other genotypes of the CYP 19 rs936306 polymorphism, the TT genotype was associated with a significant difference in the testosterone to E2 (T:E2) ratio--lower testosterone and higher E2 levels--especially in African American women. Japanese women with the AA genotype of the CYP 19 rs749292 polymorphism had lower testosterone and E2 levels but higher levels of sex hormone-binding globulin (SHBG) compared with Japanese women with the AG and GG genotypes. Among Caucasian women, there was markedly lower SHBG levels among those with the AA genotype of the CYP 19 rs2414096 polymorphism compared with other genotypes, after adjusting for age and body mass index. Three of 5 aromatase gene SNPs were associated with variation in serum androgen concentrations among women, both within and between racial/ethnic groups. Aromatase genetic markers may be important in understanding the emerging associations reported between endogenous androgens and women's health status.

ChromoScan: a scan statistic application for identifying chromosomal regions in genomic studies.

YV Sun — 2007-04-19T18:05:13-00:00

Bioinformatics, Vol. 22, No. 23. (1 December 2006), pp. 2945-2947.

ChromoScan is an implementation of a genome-based scan statistic that detects genomic regions, which are statistically significant for targeted measurements, such as genetic associations with disease, gene expression profiles, DNA copy number variations, as well as other genome-based measurements. A Java graphic user interface (GUI) is provided to allow users to select appropriate data transformations and thresholds for defining the significant events. AVAILABILITY: ChromoScan is freely available from http://www.epidkardia.sph.umich.edu/software/chromoscan/

Exploring the Public Understanding of Basic Genetic Concepts

Angela Lanie — 2006-10-18T14:15:41-00:00

Journal of Genetic Counseling, Vol. V13, No. 4. (2004), pp. 305-320.

A model-based scan statistic for identifying extreme chromosomal regions of gene expression in human tumors.

AM Levin — 2006-08-11T12:23:26-00:00

Bioinformatics, Vol. 21, No. 12. (15 June 2005), pp. 2867-2874.

MOTIVATION: The analysis of gene expression data in its chromosomal context has been a recent development in cancer research. However, currently available methods fail to account for variation in the distance between genes, gene density and genomic features (e.g. GC content) in identifying increased or decreased chromosomal regions of gene expression. RESULTS: We have developed a model-based scan statistic that accounts for these aspects of the complex landscape of the human genome in the identification of extreme chromosomal regions of gene expression. This method may be applied to gene expression data regardless of the microarray platform used to generate it. To demonstrate the accuracy and utility of this method, we applied it to a breast cancer gene expression dataset and tested its ability to predict regions containing medium-to-high level DNA amplification (DNA ratio values >2). A classifier was developed from the scan statistic results that had a 10-fold cross-validated classification rate of 93% and a positive predictive value of 88%. This result strongly suggests that the model-based scan statistic and the expression characteristics of an increased chromosomal region of gene expression can be used to accurately predict chromosomal regions containing amplified genes. AVAILABILITY: Functions in the R-language are available from the author upon request. CONTACT: fcouples@umich.edu.