On the origin of the longhair mutation in cats · non-domestic cats (n=68) was used. The domestic...
Transcript of On the origin of the longhair mutation in cats · non-domestic cats (n=68) was used. The domestic...
On the origin of the longhair mutation in cats Ali$AlHaid1,$B.$Gandolfi2,$L.$A.$Lyons2,$and$H.$Alhaddad1$1) Department of Biological Science, Kuwait University, Kuwait
2) College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO
Fig.2. Sample sizes of cat breeds and feral cat populations genotyped for FGF5 (C-475) mutation.
Introduction • The fibroblast growth factor 5 (FGF5) is a gene expressed in mammals.
Mutations within FGF5 are responsible for longhair phenotype in cats [1-2] and other mammals.
• In the domestic cat, six non-synonymous mutations are associated with longhair trait [1-2]. Four substitution and two InDel mutations are distributed through the three exons of FGF5 transcript (Fig.1).
Objectives 1. Examine the frequency of the longhair (C-475) allele across cat
breeds.
2. Investigate the frequency of the longhair (C-475) allele in world-wide feral populations.
3. Infer the likely origin of the (C-475) mutation by testing Turkey and Iran as two focal origins.
Conclusion The FGF5 (c.475 A>C) mutation is the most prevalent longhair mutation in longhair breeds and likely to have originated in the Mediterranean/
Middle-east region and most likely in Turkey.
Dataset and Analyses • A comprehensive dataset (n=2571) representing domestic (n=2503) and
non-domestic cats (n=68) was used. The domestic cat samples belong to 38 breeds (n=1832) and feral cats (n=671) sampled from 21 geographical locations, including Turkey and Iran (Fig.2).
Birman 312
Scottish Fold 164
Perisan 163Burmese 121
Bengal 98
Siamese 80
La Perm 66
Siberian 61
Ragdoll 60
Maine Coon 57
Abyssinian 56
Oriental 56
Munchkin 40
Sphynx 40
British Shorthair 40
Toyger 34
Peterbald 31Lykoi 27
Turkish Van 26Cornish Rex 26American Curl 25
Japanese Bobtail 22Selkirk Rex 22
Korat 22Tennesse REX 21
Egypt 115 Iran 104Israel 45
Turkey 42Kenya 36
South Korea 34Singapore 33
Cyprus 30India 30
Brazil 29
Italy 27Sri Lanka 23
Germany 22China 20Vietnam 19Lamu 18Dubai 10
European wild cat 59
Asian Leopard Cats 9
*Devon Rex 21Norweigian Forest Cat 20
Manx 20Egyptian Mau 18
American Shorthair 14Russian Blue 12
Turkish Angora 11Bombay 11
Chartreaux 11American Wirehair 9
Somali 6Ocicat 5
Havana Brown 4
**Hawaii 10Missouri-US 9
Pate 9Cornell-US 6
*
**
Fig.1. Illustration of cat FGF5 mature transcript and the positions of all non-synonymous mutations.
5' UTR 3' UTR
182 T>A
194 C>A
356 Ins T
406 C>T
474 Del T
475 A>C
1 bp 813 bpCat FGF5 Full Transcript
• Most longhair breeds possess the (475) mutation in high frequencies with the exception of Ragdoll, Norwegian Forest Cats, and Maine Coon cats, which have (356), (406), and (474), respectively [1].
• The missense (c.475 A>C) mutation substitutes threonine with proline in FGF5 protein (p.T159P).
• The inheritance of longhair allele (C-475) is autosomal recessive and longhair phenotype is shown when the allele is homozygous or heterozygous with any of the other five FGF5 mutations.
• Genotypes of FGF5-475 alleles were obtained from the 63K Feline Array Consortium and the feral population dataset from L.A. Lyons laboratory.
• Allele and genotype frequencies were calculated using R package “genetics”.
• Geographical locations of feral populations were used to calculate the distance from Turkey and Iran. The correlation between longhair (C-475) allele frequency and distance from an origin (Turkey, Iran) was tested using standard R.
Findings • In agreement with previous studies [1], the majority of longhair breeds
exhibit the longhair phenotype through the (C-475) mutation with the exception of three breeds (Fig.3).
• The high (C-475) allele frequency and high genotype frequency of (C/C) and (C/A) suggests that C-475 mutation is associated with “longhairness” in most longhair breeds either in a homozygous state or in a compound heterozygous state with other FGF5 mutations (Fig.3).
• Breeds that are not defined by longhair and allow BOTH short and longhair varieties show high frequency of the (C-475) allele in homozygous and heterozygous genotypes, which suggests that longhair within such breeds is determined by the FGF5-475 mutation (Fig.3).
Fig.3. Frequencies of the Short/Long hair alleles and genotypes across cat breeds.
Frequency1.0 0.8 0.6 0.4 0.2 0.0
Shorthair Allele (475-A)
Frequency Frequency0.0 0.2 0.4 0.6 0.8 1.0
Longhair Allele (475-C)
Frequency
BirmanTurkish Angora
Turkish VanPerisanSiberianSomali
Maine CoonRagdoll
Norweigian Forest Cat La Perm
American CurlTennesse REXMunchkin
Selkirk RexJapanese Bobtail
Scottish FoldManxSphynxPeterbaldLykoiBombay
American ShorthairBritish Shorthair
Devon RexChartreauxOriental
American WirehairBengal
Cornish RexAbyssinianKorat
SiameseBurmese
Egyptian MauHavana Brown
ToygerOcicat
Russian BlueAsian Leopard CatEuropean Wild Cat
Frequency0.0 0.2 0.4 0.6 0.8 1.0
Longhair (C/C)
Frequency Frequency0.0 0.2 0.4 0.6 0.8 1.0
Longhair Carrier (C/A)
Frequency Frequency0.0 0.2 0.4 0.6 0.8 1.0
Shorthair (A/A)
Frequency
• Excluding the locations in North and South America where cats were introduced anthropologically, 17 feral cat populations in the Mediterranean/Middle-east regions exhibit a relatively higher frequency of the Longhair (C-475) allele (Fig.4-Top).
• Assuming that the C-475 mutation arose (1) once in the past, and (2) in a specific location and (3) that its frequency in the origin is high and decreases further away, two likely origins were tested (Turkey and Iran).
• The correlation between C-475 frequency and distance from the origin was found to be more significant for Turkey (p < 2x10-5) compared to Iran (p = 0.0015) (Fig.4-Right).
BrazilBrazilBrazilBrazilBrazilBrazilBrazilBrazilBrazil
ChinaChinaChinaChinaChinaChinaChinaChinaChinaCornellCornellCornellCornellCornellCornellCornellCornellCornell CyprusCyprusCyprusCyprusCyprusCyprusCyprusCyprusCyprus
UAEUAEUAEUAEUAEUAEUAEUAEUAEEgyptEgyptEgyptEgyptEgyptEgyptEgyptEgyptEgypt
GermanyGermanyGermanyGermanyGermanyGermanyGermanyGermanyGermany
HawaiiHawaiiHawaiiHawaiiHawaiiHawaiiHawaiiHawaiiHawaii IndiaIndiaIndiaIndiaIndiaIndiaIndiaIndiaIndia
IranIranIranIranIranIranIranIranIran
ISRISRISRISRISRISRISRISRISR
ItalyItalyItalyItalyItalyItalyItalyItalyItaly
KenyaKenyaKenyaKenyaKenyaKenyaKenyaKenyaKenyaLamuLamuLamuLamuLamuLamuLamuLamuLamu
MissourriMissourriMissourriMissourriMissourriMissourriMissourriMissourriMissourri
PatePatePatePatePatePatePatePatePate
SingaporeSingaporeSingaporeSingaporeSingaporeSingaporeSingaporeSingaporeSingapore
South KoreaSouth KoreaSouth KoreaSouth KoreaSouth KoreaSouth KoreaSouth KoreaSouth KoreaSouth Korea
Sri LankaSri LankaSri LankaSri LankaSri LankaSri LankaSri LankaSri LankaSri Lanka
TurkeyTurkeyTurkeyTurkeyTurkeyTurkeyTurkeyTurkeyTurkey
VietnamVietnamVietnamVietnamVietnamVietnamVietnamVietnamVietnam
Short-hair AlleleLonghair AlleleShort-hair GenotypeShort/Long hair GenotypeLonghair Genotype
Distance from origin (Km)
Long
hair
Alle
le (C
) Fre
quen
cy
0 2000 4000 6000 8000 10000
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Turkey OriginIran OriginFig.4. Longhair (C-475) allele in relation to
the geographic location of feral cat populations. (Top): Short/Longhair allele and genotype frequencies in 21 geographic locations. (Right): Relationship between longhair (C-475) allele frequency and distance (Km) from a possible mutation origin (Turkey, Iran). Dots represent feral populations and lines represent the best fitting line of the correlation.
References 1. Kehler et al., J. Hered 98, 555-566 (2007). 2. Drogemuller et al., Anim Genet 38, 218-221 (2007).