Defining and Mapping Mammalian Coat Pattern Genes: Multiple Genomic Regions Implicated in Domestic Cat Stripes and Spots

doi:10.1534/genetics.109.109629

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Originally published as Genetics Published Articles Ahead of Print on October 26, 2009.

Defining and Mapping Mammalian Coat Pattern Genes: Multiple Genomic Regions Implicated in Domestic Cat Stripes and Spots

Eduardo Eizirik^^,^,^,1, Victor A. David^, Valerie Buckley-Beason^*^,2, Melody E. Roelke, Alejandro A. Schäffer^**, Steven S. Hannah, Kristina Narfström, Stephen J. O'Brien^* and Marilyn Menotti-Raymond^*

^* Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil, Instituto Pró-Carnívoros, Atibaia, Sao Paulo 12945-010, Brazil, Laboratory of Genomic Diversity, SAIC-Frederick, National Cancer Institute, Frederick, Maryland 21702, ^** PetCare Company, National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20894, Nestlé Purina, Saint Louis, Missouri 63164 and Department of Ophthalmology, Mason Eye Institute, University of Missouri, Columbia, Missouri 65211

^¹ Corresponding author: Faculdade de Biociências, PUCRS, Av. Ipiranga 6681, Prédio 12, Porto Alegre, RS 90619-900, Brazil.
E-mail: eduardo.eizirik{at}pucrs.br

Mammalian coat patterns (e.g., spots, stripes) are hypothesizedto play important roles in camouflage and other relevant processes,yet the genetic and developmental bases for these phenotypesare completely unknown. The domestic cat, with its diversityof coat patterns, is an excellent model organism to investigatethese phenomena. We have established three independent pedigreesto map the four recognized pattern variants classically consideredto be specified by a single locus, Tabby; in order of dominance,these are the unpatterned agouti form called "Abyssinian" or"ticked" (T^a), followed by Spotted (T^s), Mackerel (T^M), andBlotched (t^b). We demonstrate that at least three differentloci control the coat markings of the domestic cat. One locus,responsible for the Abyssinian form (herein termed the Tickedlocus), maps to an $~$ 3.8-Mb region on cat chromosome B1. A secondlocus controls the Tabby alleles T^M and t^b, and maps to an $~$ 5-Mbgenomic region on cat chromosome A1. One or more additionalloci act as modifiers and create a spotted coat by alteringmackerel stripes. On the basis of our results and associatedobservations, we hypothesize that mammalian patterned coatsare formed by two distinct processes: a spatially oriented developmentalmechanism that lays down a species-specific pattern of skincell differentiation and a pigmentation-oriented mechanism thatuses information from the preestablished pattern to regulatethe synthesis of melanin profiles.

Defining and Mapping Mammalian Coat Pattern Genes: Multiple Genomic Regions Implicated in Domestic Cat Stripes and Spots

Eduardo Eizirik*,,,1, Victor A. David*, Valerie Buckley-Beason*,2, Melody E. Roelke, Alejandro A. Schäffer**, Steven S. Hannah, Kristina Narfström, Stephen J. O'Brien* and Marilyn Menotti-Raymond*

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Eduardo Eizirik^^,^,^,1, Victor A. David^, Valerie Buckley-Beason^*^,2, Melody E. Roelke, Alejandro A. Schäffer^**, Steven S. Hannah, Kristina Narfström, Stephen J. O'Brien^* and Marilyn Menotti-Raymond^*