Our Science – Raymond Website

Marilyn Raymond, Ph.D.

Laboratory of Genomic Diversity Genetics Section Staff Scientist Bldg. 560, Room 11-38 NCI-Frederick Frederick, MD 21702 Phone:   301-846-7486 Fax:   Fax Number not listed E-Mail:   raymond@ncifcrf.gov

Biography

Dr. Raymond's research focuses on the development and application of genomic resources in the domestic cat to contribute to our understanding of human hereditary disease analogues, neoplasia and genetic factors associated with host response to infectious disease. The development of comprehensive genetic linkage and radiation hybrid maps has been a major focus over the past several years. In the last two years, Dr. Raymond's group has utilized the cat maps and other genomic resources to map and characterize mutations in unique genes for spinal muscular ( LIX1 ) and retinal atrophy segregating in cat pedigrees. They have additionally mapped and characterized several genes associated with coat color in the cat, including variants at the tyrosinase locus ( siamese, burmese ), the tyrosinase related protein locus ( TYRP1 ) responsible for brown and cinnamon coat color, and the causative mutation for dilute phenotype.

Additionally, Dr. Raymond has been involved with application of genetic markers in the cat for forensic analysis, which was responsible for the first introduction of an animal DNA fingerprint into trial and the development of a simple tandem repeat (STR) forensic genotyping system for genetic individualization of cat specimens funded by the National Institute of Justice.

Dr. Raymond's academic background is in Bacteriology and Molecular Genetics. She received a B.S. in Bacteriology from Syracuse University , followed by an M.S. and Ph.D. in Molecular Biology from Syracuse University , examining gene regulation and molecular evolution of the duplicated alcohol dehydrogenase locus in Drosophila hydeii . She completed post-doctoral training at the Laboratory of Genomic Diversity, NCI, with focus on the molecular genetics of the domestic cat and exotic cat species.

Research

Autosomal recessive retinitis pigmentosa (arRP)

Is a genetically and clinically heterogeneous and progressive degenerative disorder of the retina, leading usually to severe visual handicap in adulthood. Linkage mapping in a colony of Abyssinian cats with progressive retinal atrophy (rdAc), has identified an important large animal model for a frequent cause of human retinal blinding disease. The cat model will be important in both functional studies and as a gene therapy model. We plan development of a gene therapy vector which will be examined in the rdAc pedigree.

Spinal Muscular Atrophy

The molecular basis has been established for only a few of the spinal muscular atrophies (SMAs). We have mapped and characterized a novel gene for spinal muscular atrophy in the cat. A full genome scan linkage resulted in identification of a ~140 kb deletion that abrogates expression of LIX1 on cat A1q (Fyfe et al. 2006). Though the function of LIX1 is unknown, the predicted secondary protein structure is compatible with a role in RNA metabolism. The feline SMA gene implicates a previously undetected mechanism of motor neuron maintenance and mandates its consideration as a novel candidate gene for human SMA when mutations in the known disease genes are not found.

Mapping and Characterization of Genes Causative of Hair Color and Length Phenotypic Variation in the Cat

The coat color loci influence the development, maturation and migration of melanocytes as well as the synthesis of melanin and the formation, transport and transfer of melanosomes. Genes involved in the determination of melanosomes often have pleiotropic effects, which impact other important biochemical pathways. We have mapped and characterized four alleles associated with coat color variation in the cat (brown, cinnamon, Siamese, Burmese), which are products of two key enzymes of the melanogenic pathway, tyrosinase (TYR) and tyrosinase related protein 1 (TYRP1) (Schmidt-Kuntzel et al. 2005). Additionally, the mutation in melanophilin (MLPH) characterized for coat color dilution, dilute (Ishida et al. 2006), and four independent mutations in the fibroblast growth factor 5 gene (FGF-5), a major determinant in cell cycle control and a recognized oncogene, have been characterized as causative of the long hair phenotype in the cat (Keeler et al. submitted).

Development of a Forensic Genotyping System in the Cat

In 1997, utilizing ten short tandem repeat (STR) markers, we contributed to the establishment of a legal precedent for employing genetic individualization of animal tissue in homicide cases (Menotti-Raymond et al. 1997a; Menotti-Raymond et al. 1997b). With support from the National Institute of Justice, we have continued this research by developing an STR forensic typing system and genetic database of cat breeds for genetic individualization of cat specimens. A multiplex of 11 tetranucleotide repeat loci has been developed (Menotti-Raymond et al. 2005) and genotyped in a panel of 1040 cats representing 38 recognized breeds in the United States. The STR panel demonstrates good power for genetic individualization of domestic cat samples, moderate to high within cat breeds, with a probability of match (Pm) of 2.4E-06 - 1.3E-14, and high in outbred cats, (representing approximately 97% of household cats), with a Pm of 7.8E-13.

This page was last updated on 7/15/2008.