Biomedical subjects

Sharon Kardia

Publications and source records attributed to Sharon Kardia.

5 recordsLinked to original sources

PubMed2005

Blood Pressure Sunday: introducing genomics to the community through family history.

BACKGROUND: Family history of a chronic disease, such as high blood pressure, is an important predictor of future disease. The integration of genomics information into public health activities offers the opportunity to help raise awareness among populations at high risk for high blood pressure. CONTEXT: The prevalence of high blood pressure in blacks at any age is about twice that of whites. Detroit is second among major U.S. cities in the percentage of residents who are black (81.6%). According to data from the Behavioral Risk Factor Surveillance System 1998-2002, the perceived health status of Detroit respondents was one of the worst in Michigan; 17.4% of Detroit respondents reported no health care coverage; 69.6% reported being obese or overweight; and 33.1% reported no physical activity. METHODS: The Michigan Department of Community Health and the University of Michigan's Center for Genomics and Public Health collaborated on a pilot program to develop a worksheet emphasizing the importance of personal family history of high blood pressure. The handout was distributed to individuals at primarily black, Detroit-area churches during an annual screening event for high blood pressure and stroke. CONSEQUENCES: Approximately 500 handouts were distributed; a collaborative effort was achieved; genomics information was integrated into an existing program; the ability to reach churches in a predominantly black community was demonstrated; consumers reported interest in the subject matter; and an appropriate literacy level for the handout was attained. INTERPRETATION: The strengths of this pilot program and suggested modifications may serve to guide others in genomics and/or chronic disease programs in future endeavors.

Black or African American↗

PubMed2004

Ethnicity and human genetic linkage maps.

Human genetic linkage maps are based on rates of recombination across the genome. These rates in humans vary by the sex of the parent from whom alleles are inherited, by chromosomal position, and by genomic features, such as GC content and repeat density. We have examined--for the first time, to our knowledge--racial/ethnic differences in genetic maps of humans. We constructed genetic maps based on 353 microsatellite markers in four racial/ethnic groups: whites, African Americans, Mexican Americans, and East Asians (Chinese and Japanese). These maps were generated using 9,291 subjects from 2,900 nuclear families who participated in the National Heart, Lung, and Blood Institute-funded Family Blood Pressure Program, the largest sample used for map construction to date. Although the maps for the different groups are generally similar, we did find regional and genomewide differences across ethnic groups, including a longer genomewide map for African Americans than for other populations. Some of this variation was explained by genotyping artifacts--namely, null alleles (i.e., alleles with null phenotypes) at a number of loci--and by ethnic differences in null-allele frequencies. In particular, null alleles appear to be the likely explanation for the excess map length in African Americans. We also found that nonrandom missing data biases map results. However, we found regions on chromosome 8p and telomeric segments with significant ethnic differences and a suggestive interval on chromosome 12q that were not due to genotype artifacts. The difference on chromosome 8p is likely due to a polymorphic inversion in the region. The results of our investigation have implications for inferences of possible genetic influences on human recombination as well as for future linkage studies, especially those involving populations of nonwhite ethnicity.

Black or African American↗

PubMed2002

Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism.

Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted epsilon2, epsilon3, and epsilon4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for different traits and varied among the six gender-population strata. The role that noncoding variable sites play in the explanation of pleiotropic effects on different measures of lipid metabolism reveals that both regulatory and structural functional variation in the APOE gene influences measures of lipid metabolism. This study demonstrates that resequencing of the complete gene in a sample of >/=20 individuals and an evaluation of all combinations of the identified variable sites, separately for each population and interacting environmental context, may be necessary to fully characterize the impact that a gene has on variation in related traits of a metabolic system.

Alleles↗

PubMedDate not supplied

Proteomic analysis of cytokeratin isoforms uncovers association with survival in lung adenocarcinoma.

Cytokeratins (CK) are intermediate filaments whose expression is often altered in epithelial cancer. Systematic identification of lung adenocarcinoma proteins using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry has uncovered numerous CK isoforms. In this study, 93 lung adenocarcinomas (64 stage I and 29 stage III) and 10 uninvolved lung samples were quantitatively examined for protein expression. Fourteen of 21 isoforms of CK 7, 8, 18, and 19 occurred at significantly higher levels (P < .05) in tumors compared to uninvolved adjacent tissue. Specific isoforms of the four types of CK identified correlated with either clinical outcome or individual clinical-pathological parameters. All five of the CK7 isoforms associated with patient survival represented cleavage products. Two of five CK7 isoforms (nos. 2165 and 2091), one of eight CK8 isoforms (no. 439), and one of three CK19 isoforms (no. 1955) were associated with survival and significantly correlated to their mRNA levels, suggesting that transcription underlies overexpression of these CK isoforms. Our data indicate substantial heterogeneity among CK in lung adenocarcinomas resulting from posttranslational modifications, some of which correlated with patient survival and other clinical parameters. Therefore, specific isoforms of individual CK may have utility as diagnostic or predictive markers in lung adenocarcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Integrative biology and the developing limb bud.

The identification or selective construction of mutations within genes has allowed researchers to explore the downstream effects of gene disruption. Although these approaches have been successful, a limitation in our assessment of the consequences of conditional changes, and thereby our understanding of roles or function of genes, limits the degree to which we examine the effects of our manipulations. It is also clear that linear associations are incorrect models for describing development, and newer methods now give us an opportunity to practice an integrative biology. In our attempts to explore the consequences of Hoxa13 disruption in mice and humans, it has become clear that a better understanding of the consequences of gene alteration may be achievable by taking a broader approach with a long-term view. Fundamental questions regarding Hox gene function in vertebrates, including those related to the number of target genes; the degree of overlap of target gene regulation among paralogs; the magnitude of modulation exerted; and the identity of genes that are activated versus repressed need to be explored if a more thorough mechanistic understanding is to be achieved. To begin to address these questions, we undertook a comprehensive analysis of the expression of genes within developing limb buds of mice, and here we present some of our preliminary results. Our efforts will further (1) the exploration of the broader genetic relationships of expressed genes, (2) the determination of parallels or variations in target usage for a given gene in different tissues and between different organisms, (3) the evaluation of limb patterning mechanisms in other animal model systems, and (4) the exploration of gene expression hierarchies regulated by HOX proteins in developmental systems.

Animals↗