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Human Medical Genomics

The completion of the Human Genome Sequencing Project was promised to start a revolution in human medicine. Researchers at the Foundation recognize that this revolution will come, but only if answers to "Why?" questions are placed upon the molecular structures that the human genome project generated.

These answers will come through a historical analysis of genomes. Similarities and differences between genomes from different vertebrates identify where and how molecular structure has changed to support new function, or to conserve ancient function in a changing environment.

Evolutionary analyses help address some of the most important questions when developing diagnostics and therapeutics. What proteins should be targeted? What animal models should be used to develop a human medicine? What are the likely side effects of a drug? How will different patients react differently to a treatment?

Sulfotransferases

The human body uses many enzymes to excrete foreign compounds, both toxins and pharmaceuticals. Scientists working at the Foundation have used an evolutionary analysis of one class of these, sulfotransferases, to better understand the differences between humans and our nearest primate relatives.

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Phylogenomic approaches to common problems encountered in the analysis of low copy repeats: The sulfotransferase IA gene family example
Bradley, ME; Benner, SA
BMC Evol. Biol. 5 22 (2005)
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Leptin and obesity

Obesity and its consequent diseases, including diabetes, hypertension, and cardiovascular disease, is today an epidemic. The Foundation is working to understand some of the molecules that influence obesity, and how animal models should be be designed to help develop treatments to manage the disease.

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Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein
Gaucher, EA; Miyamoto, MM; Benner, SA
Genetics 163 (4) 1549-1553 (2003)
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Natural history of prostate cancer

Fossils suggest that the prostate arose in mammals ca. 120 million years ago. A set of genes arose in our ancestors at approximately the same time. Scientists at the Foundation are working to exploit this connection to improve the management of prostate cancer.

Cystic fibrosis

Cystic fibrosis is the tragic consequence of mutation in the human germ line, and similar mutations create a variety of human disease. The Foundation has used an evolutionary analysis of these mutations to better understand deleterious polymorphisms in the human population.

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Application of DETECTER, an Evolutionary Genomic Tool to Analyze Genetic Variation, to the Cystic Fibrosis Gene Family
Gaucher, EA; DeKee, DW; Benner, SA
BMC Genomics 7 44 (2006)
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