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WO 2012/158772 Al 22 November 2012 (22.11.2012) P O P C T

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WO 2012/158772 Al 22 November 2012 (22.11.2012) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/158772 Al 22 November 2012 (22.11.2012) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12N 15/06 (2006.01) C12Q 1/68 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US2012/038101 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (22) International Filing Date: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, 16 May 2012 (16.05.2012) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/487,987 19 May 201 1 (19.05.201 1) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): THE RE¬ GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, GENTS OF THE UNIVERSITY OF CALIFORNIA UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/US]; 1111 Franklin Street, 12th Floor, Oakland, Cali TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, fornia 94607-5200 (US). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (72) Inventors; and TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (75) Inventors/Applicants (for US only): LYONS, Leslie A. ML, MR, NE, SN, TD, TG). [US/US]; 1355 Tyler Drive, Woodland, California 95616 (US). KURUSHIMA, Jennifer D. [US/US]; 4735 Cowell Declarations under Rule 4.17 : Boulevard, Apt. 74, Davis, California 95618 (US). — as to applicant's entitlement to apply for and be granted a FROENICKE, Lutz [DE/US]; 520 Alvarado Avenue, patent (Rule 4.1 7(H)) Apt. 204, Davis, California 9561 6 (US). LIPINSKI, Monika J. [US/US]; 2301 Summer Creek Drive, Apt. #7, Published: Santa Rosa, California 95404 (US). GANDOLFI, Bar¬ — with international search report (Art. 21(3)) bara [IT/US]; 2985 Layton Drive, Davis, California 9561 8 (US). (74) Agents: WAHLSTEN, Jennifer L. et al; Weaver Austin Villeneuve & Sampson LLP, P.O. Box 70250, Oakland, California 94612-0250 (US). GENETIC IDENTIFICATION OF DOMESTIC CAT BREEDS AND POPULATIONS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S. C. § 119(e) of U.S. Provisional Application No. 61/487,987, filed on May 19, 201 1, which is hereby incorporated herein in its entirety for all purposes. STATEMENT OF GOVERNMENTAL SUPPORT [0002] This invention was made with government support under Grant No. R24 RROO16094 awarded by the National Institutes of Health, National Center for Research Resources (NCRR). The government has certain rights in the invention. FIELD OF THE INVENTION [0003] The invention relates to determining the contribution of one or more feline populations to the genome of a feline using a predetermined set of genetic markers, including single nucleotide polymorphisms (SNPs), short tandem repeats (STRs) and DNA- based phenotypic markers. BACKGROUND OF THE INVENTION [0004] The domestication of the cat has been a slow and prolonged process, especially when compared to most species associated with human agricultural development. Indeed, the cat is often considered to be only semi-domesticated. Archaeological remains of cats in close proximity to and even buried alongside humans suggest that cats were first domesticated in Cyprus during the Neolithic age 5,000-10,000 BP (Vigne et al, (2004) Science 304, 259-259.) but popular culture suggests cats were domesticated in Egypt (Malek, (1993) The cat in ancient Egypt British Museum Pr. for the Trustees of the British Museum, London; Nowell, (1996) Status Survey and Conservation Action Plan: Wild Cats IUCN, Gland, Switzerland.). Genetic studies using STR and mtDNA analysis of feral and wildcats from throughout Africa and Eurasia identified the Near Eastern Arabian/Northern African wildcat subspecies (Felis silvestris libyca) as the species most closely related to the domestic cat (Driscoll et al., (2007) Science 317, 519-523). Other early human civilizations developed near the Yellow River region of China and the Indus Valley of present day Pakistan. However, sufficient sampling or documentation of wildcats in these regions is inadequate. Only the Fertile Crescent lies within the range of F. s. lybica, which has better documentation and sampling. In addition to the wildcat studies, an independent STR study of both feral and pedigreed cats found the highest genetic diversity of the sampled cats in the region of the eastern Mediterranean Sea, supporting a Fertile Crescent origin of cat domestication (Lipinski et al, (2008) Genomics 91, 12-21.). However, neither study sampled the cats of the Fertile Crescent and Egypt sufficiently to closely examine cat populations in this historically important region, which is necessary for pinpointing the site of cat domestication. [0005] Genetic markers that arise through a variety of mutational mechanisms help to resolve population stratifications and trace historical migrations (Zeder et al., (2006) Trends in Genetics 22:139-155). STRs and have long been the preferred tool for genetic analyses of recently diverged populations, such as cat breeds, due to their high mutation rate and relative cost effectiveness in comparison to sequencing techniques (Brown et al, (1979) Proc. Natl. Acad. Sci. USA 76: 1967-1971). Analysis of different areas of the mtDNA, particularly gene sequences provide evidence of the matrilineal history of the domesticated cat and of the closest common ancestor, the African wildcat from the Near East (Driscoll et al., 2007, supra). In addition, the mtDNA control region (CR), with its fast rate of mutation, provides evidence of recent admixture of most of the worldwide cat populations (Grahn et al, Forensic Sci Int Genet. (201 1) 1:33-42). The advent of high-throughput SNP typing platforms allows the genotyping of many markers with slower mutation rates, rates which can help define a population's more ancient origins and provide finer-scale evidence for the first domesticated cat populations. Thus, genetic analysis of the same cat populations, using an assortment of DNA markers with a variety of mutation patterns, will better define cat population stratification but not obfuscate the more ancient lineages, further clarifying the domestication progression from ancient to modern cats. [0006] Data presented herein shows that the domestic cat origins lie within the Northern region of the Fertile Crescent, where the earliest agriculture and civilizations began. Random bred domestic cat populations from around the world, specifically the region of the Fertile Crescent and Egypt, were genetically investigated to improve the resolution of cat population structures within this important site of cat domestication. Two types of genetic markers, STRs and SNPs, were genotyped in the same cat populations, including several larger populations from the Fertile Crescent region. [0007] The genetic markers further find application in determining the breed pedigree or population origins of a subject feline. Over the past 125 years, mankind has imposed artificial selection to further the previously unchecked process of cat domestication resulting in pedigreed cats. Since the first USA cat show in 1895, which presented five breeds, the development of pedigreed cats has increased in popularity (Gebhardt (1991) The Complete Cat Book. Howell Book House, New York.). Forty-one breeds are currently recognized for competition by the Cat Fanciers' Association (CFA, on the internet at cfa.org/) and 57 are accepted by The International Cat Association (TICA, on the internet at tica.org/). A majority of the breeds recognized by these two large registries is also recognized around the world. A common, sometimes obsessive hobby of cat breeders is feline genealogy, or tracing the true genetic ancestry of the breed and even of one's own random bred pet cat. Many commercial service laboratories are marketing genetic tests for dogs, promising the elucidation of "the breed ancestry of your best friend". Random bred house cats, however, have a different story to their genetic origins. Whereas the average feline mutt found in the streets of most developed countries is more likely a cross-bred individual from multiple purebred breeds, the average random bred cat is not a descendant of their pedigreed counterparts. For cats, the opposite scenario is more likely - pedigreed feline stocks are the descendants of common street cats from distinct parts of the world that have been selected for a distinctive trait (Table 8) (CFA (1993) The Cat Fanciers' Association Cat Encyclopedia, Simon & Schuster, New York). Random bred cats are the original populations from which the breeds developed, not a population of pedigreed cats gone feral. In addition, also converse to most dog registries, to improve population health and reduce the effects of inbreeding depression, cat breeding associations often seek to diversify their breed populations with random bred cats from their ancestral origin. For this reason, most cat registries use the term "pedigreed" and not "purebred". [0008] Two studies have evaluated the genetic distinction of cat breeds. Lipinski et al. ((2008) Genomics, 91:12-21) defined the connections between the random bred cat populations and their descendant pedigreed lines using a DNA marker panel containing two tetranucleotide and 36 dinucleotide STR markers.
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