A goal of our research is to to characterize genetic organization in the domestic cat and to develop genomic resources facilitating and establishing Felis catus as a useful animal model contributing to our understanding of human hereditary disease analogues, neoplasia, genetic factors associated with host response to infectious disease and mammalian genome evolution. In order to map and characterize genes associated with inherited pathologies in the domestic cat which mirror inherited human conditions, we have recently completed a second generation linkage map of integrated microsatellite(Type II) and Type I (coding genes) in the domestic cat. The genetic map was generated using a 134-member, multi-generation backcross pedigree between the domestic cat and the Asian leopard cat ( Prionailurus bengalensis ). We selected this latter species because of the substantive evolutionary genetic distance between the species and our ability to make fertile F1 females. Approximately 8 million years of evolutionary distance increased the number of polymorphic sites in homologous Type I coding genes in hybrid females which ultimately could be tracked in pedigree analyses in the generation of a Type I linkage map. Over 25 F1 females, generated primarily by artificial insemination, have produced 84 back-cross individuals. Type I markers were integrated with markers in a previously generated Type II linkage map genotyped in the interspecies pedigree. Type I markers incorporated in the map were selected from polymerase chain reaction (PCR) based primer sets generated for typing in a radiation-hybrid panel of the cat and incorporated in a radiation-hybrid map of the cat (see """"""""Developing the Feline Radiation Hybrid Map"""""""", Project Number Z01 BC 10265-04 LGD). These primers were designed in 3' untranslated regions of either feline-specific expressed sequence tags (248), feline genes deposited in GenBANK(77)and Conserved Anchor Tagged Sequences(CATS)(68)primers designed in conserved exonic regions as comparative mapping anchor tagged sequences for mammalian species. Type I PCR products were screened using 3 single strand conformational polymorphism gel conditions and approximately 25% of PCR products exhibited a polymorphism between the domestic cat and leopard cat. One hundred eight of these Type I loci generated interpretable genotype patterns in the interspecies pedigree and were incorporated with the Type II markers as a collaborative effort with Alejandro Schaffer at NHGRI/DRB. The integrated map consists of 334 markers including 81 Type I loci and 253 TypeII loci(246 autosomal and 7 X-linked microsatellites) identifying 49 linkage groups, all of which have been mapped to a specific cat chromosome using our rodent x cat somatic cell hybrid panel. Assignment has been made to all of the feline 18 autosomes and the X chromosome. The average intragroup inter-marker distance equals 11 centimorgans (cM) and we estimate the genetic length of the sex-averaged map at 3300 cM. Two hundred forty seven markers (71 Type I,176 Type II) act as cross reference between the genetic linkage and radiation-hybrid maps of the cat. The integrated Type I linkage map confirms a remarkable conservation of genome conservation with human, previously observed in physical and radiation-hybrid maps of the cat as well as reciprocal chromosome paints of human and cat. The map provides a valuable resource for mapping phenotypic variation in the species and relating it to gene maps of other mammals, including human. Additionally, the high heterozygosity of the marker set in the Asian leopard cat and other species of exotic felids suggests that the markers will prove valuable in potential mapping exercises examining exotic felid populations which have evolved adaptive strategies relative to infectious disease or genetic factors associated with host response to infection.
