Current Genomics - Volume 6, Issue 2, 2005

The recent completion of the draft of the chicken genome sequence, the first for an agriculturally important animal species, confirms the utility of this extensively-studied and most understood avian species, as well as the utility of other little-studied birds in vertebrate biology and human medicine. The emerging information from the chicken genome is expected to increase our understanding of phenomena important in human biology and that of other avian and livestock species. Insight into the genomes of the chicken and other birds may help us validate and also discover genetic mechanisms that underlie many important human diseases and conditions. An understanding of the budgerigar genome, for example, may provide information about the molecular mechanisms that influence the budgie's apparent resistance to oxidative stress. Similarly, our understanding of the turkey genome may help us define the relationship between oxidative stress and dilated cardiomyopathy in humans and other species. In this review, we will discuss the progress in avian genomics and provide a road map about where this progress will lead in the broad area of comparative genomics and our understanding of medically and biologically important phenomena.

To date, many genetic changes have been described and reported in the cancer process. Since the first mutations were described, several attempts to establish genotype-phenotype correlations for these genetic alterations have been reported. Moreover, in vitro data have suggested effects of mutant proteins in proliferation. Genotype-phenotype correlations are not only important for predicting the clinical course of the disease and to allow tailor-made surveillance of individuals at risk, but also have implications for the elucidation of the molecular genetic mechanisms underlying genesis of cancer and the development of gene-based therapies. Here, we discuss genotype-phenotype correlation of cancer in mouse and man, and the functional aspects that may account for these observations important to both understand and treat the human disease process.

There are three methods for making chronic myelogenous leukemia (CML) mouse models: xenotransplantation of primary Ph-positive CML cells into immunodeficient mice, BCR/ABL-expressing transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. These animal models have provided us with important new insights into the molecular pathophysiology of CML and answered directly many questions regarding this disease. To date, The model mice using the BCR/ABL retroviral bone marrow transduction and transplantation method has provided the most valuable knowledge compared with the other two methods. After a long history of failure, however, recent studies have reported successful establishment of making the CMLphenotype in transgenic mice. The transgenic CML mouse model now appears to be more accurate, informative and advantageous model for studying CML. This article reviews the history of BCR/ABL-expressing CML mouse models and the recent findings in the transgenic mice with the CML-phenotype.

The ability to interrogate gene expression levels of an organism's entire transcriptome has provided researchers with a powerful tool. This power has been brought to bear on biological questions in the areas of development, aging, cell biology, disease models, stress and toxicology. Many novel insights into biological processes have been obtained from these studies and have led to connections to other systems level approaches including RNA interference and bioinformatics. In this article, we review microarray studies that have used the nematode Caenorhabditis elegans. Specific considerations of C. elegans as a model organism in this context are derived and inferences based on combining microarray data sets with other model organisms are presented and discussed. Sources for obtaining microarray data as well as the microarrays themselves are listed. Finally, we take a look into the future of this remarkable and still evolving field of expression profiling in C. elegans.

Multilocus HLA haplotypes could be investigated by family analysis, and there are salient differences in the distributions of HLA alleles among different populations. In the present study, HLA -A, B and DRB1 alleles and haplotypes were investigated based on 166 families in Shanghai Han population by molecular biological HLA typing methods and the distribution characteristic of HLA alleles and haplotypes were analyzed. The results of our investigation showed that allele frequencies of more than 10% for HLA alleles were A*0201 / 07, A*1101, A*2402, B*4001, B*4601, DRB1*090102, DRB1*1202 and DRB1*15. In the analysis of HLA haplotypes, we identified 185 kinds of A-B haplotypes , 241 kinds of B-DRB1 haplotypes and 164 kinds of A-DRB1 haplotypes. Fifteen kinds of A-B haplotypes and 15 kinds of B-DRB1 haplotypes and 7 kinds of A-DRB1 haplotypes occurred at frequencies of more than 0.5% (linkage disequilibrium value Δ > 0, c2> 6.63). Three hundred eighty-three kinds of A-B-DRB1 haplotypes were found and 20 kinds of A-B-DRB1 haplotypes occurred at frequencies of more than 0.5% (Δ > 0). The common A-B-DRB1 haplotypes were A*3001-B*1302-DRB1*0701 (4.2%), A*0201 / 07-B*4601-DRB1*090102 (3.0%), A*3303-B*5801-DRB1*0301 (2.7%), A*3303-B*5801-DRB1*1301 / 02 (1.8%), A*1101-B*1502-DRB1*1202 (1.5%) and A*1101-B*3901-DRB1*0803 (1.1%). Comparison of the distribution of A-B-DRB haplotype among different populations revealed that Shanghai Han population has its own genetic characteristics, but are closed to East Asian populations and show more abundant polymorphism in the distribution of HLA alleles compare to East Asian populations. The result obtained in this study will be useful to provide information and instruction on Shanghai Han population for genetics, anthropology, association in diseases and forensic paternity testing. Equally encouraging is the potential benefit in helping patients search out healthy, matching hematopoietic stem cells.

It is well recognized that most medications exhibit wide interindividual variability in their efficacy and toxicity. These differences may be due to genetic factors affecting the metabolism and action of these drugs, as well as to environmental factors. Genetic polymorphisms (SNPs and haplotypes) that may play a role in the differences in response to lipid lowering therapy have recently been identified, including genetic variants of apoproteins (apo AI, apo E, apo B), several enzymes (lipoprotein lipase, lecithin cholesterol acyl transferase, hepatic lipase), membrane transporters (ABCA1, ABCG5/8), and receptors (LDL cholesterol receptor). Clinical studies analysing relations between these genetic variants and the response to hypolipemiant drugs are exposed in this review.