This was my presentation at the Plant and Animal Genome Conference 2019 in San Diego. My talk was a presentation of the thesis project of my student Mona Abdi. The focus of the presentation and project was the genomic signatures of selection in the domestic cat breeds.
2. Study Objectives
• Identify signatures of selection for individual cat
breeds using multiple methods.
• Compare the candidate regions under selection
between breeds.
• Provide an overall view of the genomic
landscape of the domestic cat.
4. Domestication and breed formation
Personal Synthesis
A. Ecological domestication
B. Selection from standing variation in RB
C. Selection from standing variation in breed
D. Breeds from de novo mutation
E. Hybridizing two (more) breeds
F. Interspecies hybridization
10. Samples
2162 cat samples
41 cat breeds
Wild cats
Pedigree cats
Markers
~63K SNPs
Autosomal SNPs
X-Chr SNPs
UN-Chr SNPs
Applications and efficiencies of the
first cat 63K DNA array
BarbaraGandolfi1
, HasanAlhaddad2
, MonaAbdi2
, Leslie H. Bach3,4
, Erica K.Creighton1
,
BrianW. Davis 5
,Jared E. Decker 6
, Nicholas H. Dodman7
,JenniferC.Grahn3,8
, RobertA.
Grahn3,8
, Bianca Haase9
,Jens Haggstrom10
, MichaelJ. Hamilton3,11
,Christopher R. Helps12
,
Jennifer D. Kurushima3,13
, Hannes Lohi14
, Maria Longeri15
, Richard Malik16
, Kathryn M. Meurs17
,
MichaelJ. Montague 18
,JamesC. Mullikin 19
,WilliamJ. Murphy5
,Sara M. Nilson6
,
NielsC. Pedersen20
,Carlyn B. Peterson3
,Clare Rusbridge21
, RashidSaif22
,G. DianeShelton23
,
WesleyC.Warren24
, MuhammadWasim25
& LeslieA. Lyons1
The development of high throughput SNP genotyping technologies has improved the genetic dissection
of simple and complex traits in many species including cats.The properties of feline 62,897 SNPs
Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most
extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species.
Accuracy and efficiency of the array’s genotypes and its utility in performing population-based analyses
were evaluated.Average marker distance across the array was 37,741 Kb, and across the dataset, only
1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors.
Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all
markers across domestic cats was 0.21. Population structure analysis confirmed aWestern to Eastern
structural continuum of cat breeds.Genome-wide linkage disequilibrium ranged from 50–1,500 Kb for
domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris).Array use in trait association
mapping was investigated under different modes of inheritance, selection and population sizes.The
efficient array design and cat genotype dataset continues to advance the understanding of cat breeds
and will support monogenic health studies across feline breeds and populations.
1
Department ofVeterinary Medicine andSurgery,College ofVeterinary Medicine,University of Missouri -Columbia,
Columbia, MO, USA. 2
Department of Biological Sciences, Kuwait University, Safat, Kuwait. 3
Department of
Population Health and Reproduction,School ofVeterinary Medicine,University ofCalifornia – Davis, Davis,CA,USA.
4
University ofSan Francisco,San Francisco,CA,USA. 5
Department ofVeterinary Integrative Biosciences,TexasA&M
University,CollegeStation,TX,USA. 6
Division ofAnimalSciences,University of Missouri -Columbia,Columbia, MO,
USA. 7
Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. 8
Veterinary Genetics
Laboratory, School of Veterinary Medicine, University of California - Davis, Davis, CA, USA. 9
Sydney School of
VeterinaryScience,University ofSydney,Sydney,Australia. 10
Department ofClinicalSciences,SwedishUniversity of
AgriculturalSciences,Uppsala,Sweden. 11
Department of Biochemistry,University ofCalifornia – Riverside, Riverside,
CA, USA. 12
LangfordVets, University of Bristol, Bristol, United Kingdom. 13
FoothillCollege, LosAltos Hills,CA, USA.
14
Department of Veterinary Biosciences, Research Programs Unit, Molecular Neurology, University of Helsinki,
andThe Folkhälsan Institute of Genetics, Helsinki, Finland. 15
Department ofVeterinary Medicine, Università degli
Studi di Milano, Milan, Italy. 16
Centre forVeterinary Education, University of Sydney, New South Wales, Australia.
17
Department ofClinicalSciences,College ofVeterinary Medicine, NorthCarolinaStateUniversity, Raleigh, NC,USA.
18
Department of Neuroscience, Parelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
19
NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD,USA. 20
Center forCompanionAnimal Health,School ofVeterinary Medicine,University ofCalifornia -
Davis, Davis,CA,USA. 21
School ofVeterinary Medicine, Faculty of Health and MedicalSciences,University ofSurrey,
Guildford,Surrey,United Kingdom. 22
Institute of Biotechnology,Gulab Devi EducationalComplex, Lahore, Pakistan.
23
Department of Pathology, University of California, San Diego, La Jolla, CA, USA. 24
McDonnell Genome Institute,
Washington University School of Medicine, St Louis, MO, USA. 25
Institute of Biochemistry and Biotechnology,
University ofVeterinary and Animal Sciences, Lahore, Pakistan. Barbara Gandolfi and Hasan Alhaddad contributed
Received: 17 October 2017
Accepted: 16 April 2018
Published: xx xx xxxx
OPEN
Correction: Author Correction
Original Dataset
12. Sample size
Mean (di) per 500Kb
Frequency
-40 -20 0 20 40 60 80
02006001000
Bengal1
Bengal2
-40 -20 0 20 40 60 80
-40-20020406080
Mean (di) Bengal (1)
Mean(di)Bengal(2)
-40 -20 0 20 40 60 80
-40-20020406080
Mean (di) Bengal
Mean(di)non-Bengal
Mean (Fst) per 500Kb
Frequency
0.0 0.1 0.2 0.3 0.4 0.5
02006001000
Bengal1
Bengal2
0.0 0.1 0.2 0.3 0.4 0.5
0.00.10.20.30.40.5
Mean (Fst) Bengal (1)
Mean(Fst)Bengal(2)
0.0 0.1 0.2 0.3 0.4 0.5
0.00.10.20.30.40.5
Mean (Fst) Bengal
Mean(Fst)non-Bengal
13. -0.04 -0.02 0.00 0.02 0.04 0.06 0.08
-0.15-0.10-0.050.000.05
PC1 (28.9%)
PC2(9.5%)
a.
-0.045 -0.035 -0.025 -0.015
-0.04-0.03-0.02-0.010.000.01
BSH
MCOON
MANX
NFC
PER
SFOLD
SREX
WIR
CHR
LYK
b.
-0.02 -0.01 0.00 0.01 0.02
-0.04-0.020.000.020.04
ABY
BEN
DREX
EGY
JBOB
PERM
OCI
RAG
RBLUE
SPH
Van
ACURL
CREX
SOM
c.
0.03 0.04 0.05 0.06 0.07 0.08
-0.15-0.10-0.050.000.05
BIR
BUR
MANEE
KOR
ORI
PBALD
SIA
d.
Group 1
Western Breeds
Group 2
Middle Breeds
Group 3
Eastern Breeds
14. -0.04 -0.02 0.00 0.02 0.04 0.06 0.08
-0.15-0.10-0.050.000.05
PC1
PC2
Birman
a.
-0.04 -0.02 0.00 0.02 0.04 0.06 0.08-0.15-0.10-0.050.000.05
PC1
PC3
Bengal
b.
-0.04 -0.02 0.00 0.02 0.04 0.06 0.08
-0.10-0.050.000.05
PC1
PC4
c.
-0.04 -0.02 0.00 0.02 0.04 0.06 0.08
-0.15-0.10-0.050.000.05
PC2
PC3
Bengal
d.
-0.04 -0.02 0.00 0.02 0.04 0.06 0.08
-0.06-0.04-0.020.000.020.04
PC2
PC4
Bengal
Birman
e.
-0.15 -0.10 -0.05 0.00 0.05
-0.06-0.04-0.020.000.020.04
PC3
PC4
Bengal
f.
Group 1
Western Breeds
Group 2
Middle Breeds
Group 3
Eastern Breeds
16. • Frequency (Fst, di).
• Haplotype (iHS- integrated haplotype homozygosity
score).
• Window: a window of 500Kb size with at least 5 SNPs.
• Threshold: significance (0.01) of the empirical
distribution of the three statistics.
• Candidate Regions :Consecutive significant windows
(two or more).
19. To the Root of the Curl: A Signature of a Recent Selective
Sweep Identifies a Mutation That Defines the Cornish
Rex Cat Breed
Barbara Gandolfi1
*, Hasan Alhaddad1
, Verena K. Affolter2
, Jeffrey Brockman3
, Jens Haggstrom4
,
Shannon E. K. Joslin1
, Amanda L. Koehne2
, James C. Mullikin5
, Catherine A. Outerbridge6
,
Wesley C. Warren7
, Leslie A. Lyons1
1 Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, California, United States of America,
2 Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California - Davis, Davis, California, United States of America, 3 Hill’s
Pet Nutrition Center, Topeka, Kansas, United States of America, 4 Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University
of Agricultural Sciences, Uppsala, Sweden, 5 Comparative Genomics Unit, Genome Technology Branch, National Human Genome Research Institute, National Institutes of
Health, Bethesda, Maryland, United States of America, 6 Department of Veterinary Medicine & Epidemiology, School of Veterinary Medicine, University of California - Davis,
Davis, California, United States of America, 7 The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America
Abstract
The cat (Felis silvestris catus) shows significant variation in pelage, morphological, and behavioral phenotypes amongst its
over 40 domesticated breeds. The majority of the breed specific phenotypic presentations originated through artificial
selection, especially on desired novel phenotypic characteristics that arose only a few hundred years ago. Variations in coat
texture and color of hair often delineate breeds amongst domestic animals. Although the genetic basis of several feline coat
colors and hair lengths are characterized, less is known about the genes influencing variation in coat growth and texture,
especially rexoid – curly coated types. Cornish Rex is a cat breed defined by a fixed recessive curly coat trait. Genome-wide
analyses for selection (di, Tajima’s D and nucleotide diversity) were performed in the Cornish Rex breed and in 11
phenotypically diverse breeds and two random bred populations. Approximately 63K SNPs were used in the analysis that
aimed to localize the locus controlling the rexoid hair texture. A region with a strong signature of recent selective sweep
was identified in the Cornish Rex breed on chromosome A1, as well as a consensus block of homozygosity that spans
approximately 3 Mb. Inspection of the region for candidate genes led to the identification of the lysophosphatidic acid
receptor 6 (LPAR6). A 4 bp deletion in exon 5, c.250_253_delTTTG, which induces a premature stop codon in the receptor,
was identified via Sanger sequencing. The mutation is fixed in Cornish Rex, absent in all straight haired cats analyzed, and is
also segregating in the German Rex breed. LPAR6 encodes a G protein-coupled receptor essential for maintaining the
structural integrity of the hair shaft; and has mutations resulting in a wooly hair phenotype in humans.
Citation: Gandolfi B, Alhaddad H, Affolter VK, Brockman J, Haggstrom J, et al. (2013) To the Root of the Curl: A Signature of a Recent Selective Sweep Identifies a
Mutation That Defines the Cornish Rex Cat Breed. PLoS ONE 8(6): e67105. doi:10.1371/journal.pone.0067105
Editor: Arnar Palsson, University of Iceland, Iceland
Received March 26, 2013; Accepted May 14, 2013; Published June 27, 2013
Copyright: ß 2013 Gandolfi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This project was supported by the National Center for Research Resources and the Office of Research Infrastructure Programs of the National Institute
of Health through Grant Number R24 RR016094, the Winn Feline Foundation (W10-14, W11-041), the Center for Companion Animal Health at University of
California Davis (2010-09-F) (http://www.vetmed.ucdavis.edu/ccah/index.cfm), and the George and Phyllis Miller Feline Health Fund of the San Francisco
Foundation (2008-36-F). Support for the development of the Illumina Infinium Feline 63K iSelect DNA array was provided by the Morris Animal Foundation (http://
www.morrisanimalfoundation.org) via a donation from Hill’s Pet Food, Inc. The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing Interests: JB works for a private company (Hill’s Pet Food, Inc) that partially sponsored the development of the 63k feline SNP array. The funder had
no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
* E-mail: bgandolfi@ucdavis.edu
Introduction
Phenotypic traits under strong artificial selection within cat
breeds vary from body types, muzzle shape, tail length to
aesthetically pleasant traits, such as hair color, length and texture.
Hair represents one of the defining characteristic of mammals.
Hair provides body temperature regulation, protection from
environmental elements, and adaptive advantages of camouflage,
as well as often having aesthetic value to humans. The hair follicle
has a highly complex structure with eight distinct cell layers, in
which hundreds of gene products play a key role in the hair cycle
maintenance [1,2]. In the past decade, numerous genes expressed
in the hair follicle have been identified and mutations in some of
these genes have been shown to underlie hereditary hair diseases
in humans and other mammals [3]. Hereditary hair diseases in
mammals show diverse hair phenotypes, such as sparse or short
hairs (hypotrichosis), excessive or elongated hairs (hypertrichosis),
and hair shaft anomalies, creating rexoid/woolly hairs [3–12].
Causative genes for the diseases encode various proteins with
different functions, such as structural proteins, transcription
factors, and signaling molecules. Mutations within structural
proteins, such as epithelial and hair keratins, are often associated
with hair disease. To date, mutations in several hair keratin genes
underlined two hereditary hair disorders: monilethrix, character-
PLOS ONE | www.plosone.org 1 June 2013 | Volume 8 | Issue 6 | e67105
0.00.10.20.30.40.5
Fst
-20020406080
di
01234
Chromosome
iHS
A1
A2
A3
B1
B2
B3
B4
C1
C2
D1
D2
D3
D4
E1
E2
E3
F1
F2
Cornish Rex breed
Positive Control
Chr.A1 (LPAR6)
35. Leslie A. Lyons, PhD
Department of Veterinary Medicine and Surgery
Acknowledgment
Mona Abdi, M.Sc.
Department of Biological Sciences
36. Disclaimer
Figures, photos, and graphs in my presentations are
collected using google searches. I do not claim to have
personally produced all the material (except for some).
I do cite only articles or books used. I thank all owners
of the visual aid that I use and apologize for not citing
each individual item. If anybody finds the inclusion of
their material into my presentations a violation of their
copy rights, please contact me via email.
hhalhaddad@gmail.com