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Signatures of selection analysis using whole-genome
sequence data reveals novel candidate genes for pony
and light horse types
Siavash Salek Ardestani, Mehdi Aminafshar, Mohammad Bagher Zandi Baghche Maryam,
Mohammad Hossein Banabazi, Mehdi Sargolzaei, and Younes Miar

Abstract: Natural selection and domestication have shaped modern horse populations, resulting in a vast range
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of phenotypically diverse breeds. Horse breeds are classified into three types (pony, light, and draft) generally
based on their body type. Understanding the genetic basis of horse type variation and selective pressures related
to the evolutionary trend can be particularly important for current selection strategies. Whole-genome sequences
were generated for 14 pony and 32 light horses to investigate the genetic signatures of selection of the horse type
in pony and light horses. In the overlapping extremes of the fixation index and nucleotide diversity results, we
found novel genomic signatures of selective sweeps near key genes previously implicated in body measurements
including C4ORF33, CRB1, CPN1, FAM13A, and FGF12 that may influence variation in pony and light horse types. This
study contributes to a better understanding of the genetic background of differences between pony and light
horse types.
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Key words: fixation index, horse type, nucleotide diversity, signatures of selection, whole-genome sequence.
Résumé : La sélection naturelle et la domestication ont façonné les populations modernes de chevaux, ce qui a
produit une vaste gamme de races distinctes sur le plan phénotypique. Les races de chevaux sont classifiées en trois
types (poney, cheval de selle et cheval de trait) selon leur morphologie. Une compréhension de l’assise génétique
de la variation pour la morphologie et des pressions sélectives liées à la tendance évolutive peut s’avérer impor-
tante pour les stratégies de sélection actuelles. Des séquences génomiques ont été générées pour 14 poneys et
32 chevaux de selle pour étudier les signatures génétiques de la sélection du type chevalin chez les poneys et les
chevaux de selle. Au sein des extrêmes chevauchant pour l’indice de fixation et la diversité nucléotidique, les
auteurs ont trouvé des signatures génomiques inédites de balayages sélectifs à proximité de gènes clés déjà
rapportés comme étant impliqués dans le déterminisme de caractères morphologiques incluant C4ORF33, CRB1,
CPN1, FAM13A et FGF12, lesquels influencent possiblement la variation pour la morphologie corporelle chez les
poneys et les chevaux de selle. Cette étude fournit un éclairage qui contribuera à une meilleure compréhension de
l’assise génétique des différences phénotypiques entre les poneys et les chevaux de selle.
Mots-clés : indice de fixation, type de cheval, diversité nucléotidique, signatures de sélection, séquençage gé-
nomique complet.

Introduction history including agriculture, transportation, and sport

Horse domestication started in Western Asia approxi- (Bowling and Ruvinsky 2000; Jun et al. 2014). Domestica-
mately 5000–6000 years ago (Bowling and Ruvinsky tion, intensive selection, and various environmental con-
2000). Horses have played pivotal roles in the human ditions, as well as horse industry modernization, have

Received 2 January 2020. Accepted 6 May 2020.

S. Salek Ardestani and M. Aminafshar. Department of Animal Science, Science and Research Branch, Islamic Azad University,
Tehran 1477893855, Iran.
M.B. Zandi Baghche Maryam. Department of Animal Science, University of Zanjan, Zanjan 4537138791, Iran.
M.H. Banabazi. Department of Biotechnology, Animal Science Research Institute of Iran, Agricultural Research, Education &
Extension Organization, Karaj 3146618361, Iran.
M. Sargolzaei. Department of Pathobiology, University of Guelph, Guelph, ON NIG 2W1, Canada; Select Sires Inc., Plain City,
OH 43064, USA.
Y. Miar. Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS B2N 5E3, Canada
Corresponding author: Younes Miar (email: miar@dal.ca).
Copyright remains with the author(s) or their institution(s). This work is licensed under a Creative Commons Attribution 4.0 International
License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source
are credited.

Genome 63: 387–396 (2020) dx.doi.org/10.1139/gen-2020-0001 Published at www.nrcresearchpress.com/gen on 14 May 2020.

388 Genome Vol. 63, 2020

shaped the more than 400 horse breeds with different Although most studies suggested employing single nu-
physiology, behavior, and body measurements (Brooks cleotide polymorphism (SNP) array data as a useful and
et al. 2010; Metzger et al. 2014; Frischknecht et al. 2016). economical tool for identification of selective signatures,
Based on their type, horse breeds are categorized into the detection power is limited compared to whole-
pony, light, and draft (Dall’Olio et al. 2010; Gurgul et al. genome sequence data, due to their low-density cover-
2019). Performance and marketability improvement of age. In our former study (Salek Ardestani et al. 2020),
horses are significantly related to their types and body selective signals were identified by utilizing different se-
measurements in different fields (Meira et al. 2014). Po- lection signatures methods in sport (German and Dutch
nies have small skeletal structure and have been used for warmblood) and non-sport horse groups (Arab, Akhal-
child horseback riding (Dall’Olio et al. 2010), and during Teke, Thoroughbred, Standardbred, draft, and pony
the industrial revolution they were used for coal mining breeds). However, the main objective of our current
in the UK (Colby 1921). Their height is typically shorter study was to identify the genetic signatures of selection
than 14.2 hands (1.44 m), with a distinctive characteristic for horse type using whole-genome sequence data of
of short legs in relation to the body depth (Draper et al. pony and light horses and different population combina-
2014). In contrast, light horses have long thin muscles tions. This study may help us to better understand the
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with longer wither heights and have been used in differ- role of selection during evolutionary process and recent
ent fields such as sports (show jumping, dressage, and breeding efforts in light and pony horse types. Moreover,
eventing), endurance, harness racing, and racing. Draft it may be helpful to optimize horse SNP array panels that
horses are heavy and extremely muscular with tall stat- are extensively used for breeding purposes, e.g., horse
ure; they have been commonly used for meat produc- genomic evaluation.
tion, working in farms, and pulling carriages (Dall’Olio
et al. 2010; Draper et al. 2014). In general, horse type Materials and methods
classification is based on some phenotypic traits, such as Animals
body shape and specifically body stature (Dall’Olio et al. Whole-genome sequence data of 46 horses with Illu-
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2010; Petersen et al. 2013; Gurgul et al. 2019). mina HiSeq (2000, 2500, and 3000) and NextSeq 500 plat-
Typically, deciphering the genetic foundation of body forms, including 32 light (11 breeds) and 14 pony horses (6
measurements is important for performance improve- breeds) (Table S11), were downloaded from the European
ment of horses (Kader et al. 2015). Today, signatures of Nucleotide Archive (https://www.ebi.ac.uk). The light
selection studies that identify the genomic regions that group included Akhal-Teke (n = 3), Arabian (n = 2), Baden-
have been subjected to selective pressures have become Wurttemberg (n = 1), Dutch warmblood (n = 1), Hanover-
feasible in most animal species (Wang et al. 2016; Salek ian (n = 6), Holstein (n = 2), Oldenburg (n = 3),
Ardestani et al. 2020). Signatures of selection and Standardbred (n = 6), Thoroughbred (n = 5), Trakehner
genome-wide association studies have played key roles (n = 1), and Westphalian (n = 2). The pony group included
in identifying the genomic regions underlying body mea- American Miniature (n = 2), Dülmen (n = 1), Connemara
surements in several animal species such as horse (Kader (n = 4), Jeju pony (n = 2), Shetland pony (n = 4), and Welsh
et al. 2015; Grilz-Seger et al. 2019), cattle (W. Zhang et al. pony (n = 1) (Table S21).
2016), and swine (Rubin et al. 2012) using sequencing and
genotyping technologies. Several signatures of selection Alignment and variant calling
studies have been able to detect candidate genes associ- After converting the Sequence Read Archives to Fastq
ated with horse type (Gurgul et al. 2019) and body mea- paired-end format using fastq-dump command of SRA
surements, especially wither height (Petersen et al. 2013; Toolkit (version 2.9, https://github.com/ncbi/sra-tools),
Kader et al. 2015; Frischknecht et al. 2016; Al Abri et al. the quality control was performed by FastQC (version 0.11.6,
2018). A signatures of selection study in Shetland ponies http://www.bioinformatics.babraham.ac.uk/projects/fastqc)
detected IGF1R and ADAMTS17 genes as selective signals for each sample. Adaptors and low quality reads were
related to wither height (Frischknecht et al. 2016). Simi- filtered using Trimmomatic 0.36 (Bolger et al. 2014). The
larly, a study of Debao ponies pointed to candidate genes clean reads were aligned to the reference genome of
such as TBX3 and HMGA2 underlying body size (Kader equine (EquCab2.0) using Burrows-Wheeler Aligner
et al. 2015). Furthermore, ANKRD1 gene was found to be 0.7.17-r1188 (Li and Durbin 2009) and converted to binary
associated with wither height using selective sweep anal- with SAMtools 1.7 (Li et al. 2009). Picard 2.17.11 (https://
ysis in American Miniature horses (Al Abri et al. 2018). broadinstitute.github.io/picard) was used to remove the
Gurgul et al. (2019) identified LCORL, NCAPG, TBX3, and potential PCR duplications as well as avoiding systematic
LASP1 genes as selective signals in draft and pony horses. biases. The base quality score recalibration was per-

1Supplementary data are available with the article through the journal Web site at http://nrcresearchpress.com/doi/suppl/10.1139/gen-

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Salek Ardestani et al. 389

formed according to the recommended workflow in Ge- where f̄ and ␴f2 are the mean and variance of allele fre-
nome Analysis Toolkit 3.8 (McKenna et al. 2010).
Variant calling was performed by applying “Haplo-

quencies, respectively; wi is the ratio of ni to M wi ⫽

in which, ni and M are the number of individuals in ith
typeCaller”, “stand emit conf 10”, and “stand call conf
population and the total number of individuals in both
30” options to detect insertion/deletions (Indels) and
populations, respectively.
SNPs in the genomic variant call format file. We sepa-
The ␪␲ values were calculated through
rated SNPs and Indels through “selectVariant” option in
Genome Analysis Toolkit and discarded the sex chromo-
somes. High-quality SNPs were identified using the fol- ␪␲ ⫽
N⫺1 兺p p ␲
i j ij

lowing stringent filtration criteria: (1) Phred-scaled

quality score (QUAL) < 40.0, (2) Quality by depth
(QD) < 2.0, (3) Mapping quality (MQ) < 25.0, (4) Phred- where N is the total number of individuals in a popula-
scaled p-value using Fisher’s exact test to detect strand tion, ␲ij is the number of different nucleotides per site
bias (FS) > 60.0, (5) Mapping quality rank sum test between ith and jth sequences, and pi and pj are allele
frequencies in ith and jth sequences, respectively. To nor-
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(MQRankSum) < −12.50, (6) Read position rank sum test

(ReadPosRankSum) < −8.0. All filtered SNPs were anno- malize the FST values, Z-transformation was performed
tated using Variant Effect Predictor (https://www.ensembl. using “scale” command in R program. Also, the ␪␲ values
org/info/docs/tools/vep/). Additionally, SNPs were filtered were transformed using log2 function (Yang et al. 2016).
Top 1% windows that overlapped between Z(FST) and

冉 冊
using PLINK 2.0 (Purcell et al. 2007) according to the fol-
lowing criteria: minor allele frequency (maf) 0.01, Hardy– log2 values were defined as strong selective sig-
Weinberg p-value (hwe) 0.001, individuals with more ␪␲共light兲
nals in pony and light groups (Yang et al. 2016; Li et al.
than 10% missing genotypes (mind) 0.1, and missing rate
2017). These windows were mapped to genes using
per SNP (geno) 0.1. Visualization of SNP densities per
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“biomaRt” package (https://bioconductor.org/packages/

each 100 kb window was performed by utilizing circos
biomaRt). To reveal the functional enrichment of
0.69.6 (Krzywinski et al. 2009).
genomic regions underlying selection pressures, gene
Phylogenetic analysis ontology analysis was executed according to biological
The phylogenetic analysis can describe the genetic re- processes using gprofiler (https://biit.cs.ut.ee/gprofiler)
lationship between different breeds based on genetic di- and Benjamini–Hochberg FDR correction.
versity, and thus, it can be applied as a useful tool for
managing the genetic diversity (Davies et al. 2008). To Results and discussion
decipher the genetic relationship among all individuals, Genomic variants
the phylogenetic tree was constructed for the whole SNP The whole-genome sequences of pony and light horses
data using neighbour-joining method in VCF-kit 0.1.6 (1786 Gb) were aligned to 94.59%–99.84% of the equine
(Cook and Andersen 2017). FigTree 1.4.3 (http://tree.bio. genome reference assembly at 14.7× average depth. After
ed.ac.uk/software/figtree) was also used to visualize removing the marked PCR duplicates,and performing
the phylogenetic network. Additionally, the neighbour- base quality score recalibration as well as variant calling,
joining tree was converted to the genetic distance matrix we detected 16 075 591 SNPs (Table S31). The annotation
by employing a python script. of SNPs distribution for all samples is shown in Table S41.
We calculated SNP densities per each 100 kb window in
Selective signals and gene ontology
which the highest density of SNPs was located on horse
As cross-population and allele-frequency based meth-
chromosome (ECA) 20: 32.7–32.8 Mb with 3343 SNPs
ods of signatures of selection, fixation index (FST) (Weir
(Fig. S11). This genomic region contains MHC class II DQ-
and Cockerham 1984) and pairwise nucleotide diversity
alpha chain and MHC class II DR-beta chain genes (Fig. S11).
(␪␲) (Nei and Li 1979) were used to detect selective signals
The group of MHC genes, known as high polymorphic
in pony and light horse breeds. The FST and ␪␲ values
and recombinative genomic regions (Gaudieri et al. 2000), is
were calculated for pony and light horses using the slid-
associated with disease resistance (Van Oosterhout 2009).
ing window approach (100 kb with a step size of 50 kb)
The highest nucleotide diversities for light and pony
in VCFtools 0.1.15 (Danecek et al. 2011). The formula of
groups in 100 kb windows were located on ECA 2: 107.85–
Weir and Cockerham (1984) was used to calculate the
107.95 Mb and ECA 12: 13.05–13.15 Mb, respectively
FST values:
(Fig. S11). ECA 12: 13.05–13.15 Mb includes olfactory receptor

关兺 兴
2 5D18-like and 4P4-like genes. ECA 12 is enriched by copy
␴f2 2 wi(f̄i ⫺ f̄)
i⫽1 number of variants (CNV) due to the existence of major
FST ⫽ ⫽
f̄(1 ⫺ f̄) f̄(1 ⫺ f̄) clusters of olfactory receptor genes (Ghosh et al. 2014).

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390 Genome Vol. 63, 2020

Fig. 1. Neighbour-joining tree for light and pony breeds. ous studies (C. Zhang et al. 2018; Asadollahpour Nanaei
The light breeds are Akhal-Teke (AKT), Dutch warmblood et al. 2019).
(KW), Baden-Wurttemberg (BW), Hanoverian (HAN),
Holstein (HOL), Oldenburg (OLD), Trakehner (TRA), Genome-wide signatures of selection analysis
Westphalian (WF), Arabian (AR), Standardbred (ST), and Previous studies have indicated that signatures of se-
Thoroughbred (TH). The Pony breeds are Welsh pony (WP), lection analyses are particularly helpful for detecting
Shetland pony (SHP), American Miniature (AMP), Dülmen genes related to body measurements and specifically
(DUP), Connemara (CONP), and Jeju pony (JEP). wither height in horse (Kader et al. 2015; Frischknecht
et al. 2016; Al Abri et al. 2018). A lot of qualitative evi-
dence has proved that there are several effective genetic
factors in body morphology variation, such as wither
height which is controlled by lots of minor effect genes
in naturally evolving species, whereas in domesticated
animals it is controlled by a few major effect genes
(Kader et al. 2015). Therefore, regarding the conservative
role of genes in body morphology regulation, signatures
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of selection analyses can potentially provide an opportu-

nity to detect genomic regions associated with horse
type. To identify genomic regions under putative selec-
tion, several statistical methods based on allele fre-
quency variation have been developed such as FST (Weir
and Cockerham 1984) and ␪␲ (Nei and Li 1979).
In this study, we calculated the mean of FST(pony-light)
for each window of 100 kb with a step size of 50 kb. After
FST Z-transformation, the Z(FST) values followed a normal
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distribution that is presented in Fig. 2. A total number of

446 windows including 377 genes were detected in the
top 1% of Z(FST) values, ranged from 3.20 to 10.44
(Table S61). The highest Z(FST) value was located at 51.25–
51.35 Mb of ECA 7. This region consists of the putative
Phylogenetic analysis gustatory receptor clone (LOC100061702) gene and a novel
In this study, the phylogenetic neighbour-joining tree identified gene in horse (ENSECAG00000002851) with hu-
divided pony and light groups into two separate clusters man ortholog of L1TD1. In human, L1TD1 gene is related to
(Fig. 1). In the light cluster, similar to the study by bone mineral density (Chesi et al. 2017) and lip morphol-
Petersen et al. (2013), there were three main branches ogy (Cha et al. 2018). Furthermore, we could identify
including Arabian–Akhal-Teke, Standardbred, and 13 genes in the top 1% of Z(FST) values that had been
German warmblood–Thoroughbred. All German previously reported as candidate genes for body mea-
warmblood breeds including Dutch warmblood, Baden- surements (Fig. 3) in human (N=Diaye et al. 2011;
Wurttemberg, Hanoverian, Holstein, Oldenburg, Cousminer et al. 2013; Wood et al. 2014; Bae et al. 2016)
Trakehner, and Westphalian were classified in one and other species such as horse (Makvandi-Nejad et al.
branch, indicating the genetic similarity and probable 2012; Metzger et al. 2013; Staiger et al. 2016), cattle
sharing of founder lines. Our phylogenetic results (W. Zhang et al. 2016; Han et al. 2017), and swine (Rubin
showed two Westphalians (WF1, WF2) in separate sub- et al. 2012). These candidate genes are LCORL, NCAPG,
branches; a Hanoverian (HAN6) was located near WF2, DCAF16, FAM189A1, C4ORF33, BMP2, CRB1, IGFBP3, OPCML,
which might be due to hybridization among German FGF12, DDX55, FAM13A, and CPN1.
warmblood breeds. In the pony cluster, two main Identifying processes governing diversity of genome
branches were illustrated, one of which belongs to Con- has played an effective role in evolutionary genetics
nemara, and the other consists of Dülmen, Welsh pony, (Ellegren and Galtier 2016) and is a spotlight for selective
Jeju pony, Shetland pony, and American Miniature. Sim- sweep studies (Moon et al. 2015; Yang et al. 2016; Li et al.
ilar to the study by Petersen et al. (2013), there was a close 2017; Z. Zhang et al. 2018). Approaches based on nucleo-
genetic distance between Shetland pony and American tide diversity such as pairwise nucleotide diversity have
Miniature breeds (Table S51). It should be noted that in been used to detect selective signals for animal species
the phylogenetic analysis the interpretation of the re- such as sheep (Yang et al. 2016), goat (Li et al. 2017), duck
sults related to the breeds with one individual, such (Z. Zhang et al. 2018b), and horse (Moon et al. 2015). In this
as Baden-Wurttemberg, Dutch warmblood, Trakehner,
Dülmen, and Welsh pony can still be reliable due to the study, the transformed ␪␲ values log2 冉 冉 ␪␲共pony兲
␪␲共light兲冊冊 were
large number of SNPs used in this study similar to previ- calculated for each window of 100 kb with a step size of

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Salek Ardestani et al. 391

Fig. 2. The distribution of (A) Z-transformed fixation index or Z(FST) and (B) logarithm of transformed nucleotide diversity or
log2 冉
␪␲共light兲 冊
values in 100 kb windows with sliding windows of 50 kb.
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Fig. 3. The distribution of Z-transformed fixation index (Z(FST)) values in horse autosomes. Data points above the blue
horizontal line are the top 1% of Z(FST) values. The NCAPG, LCORL, and DCAF16 genes were not overrepresented in the top 1% of
log2 冉
␪␲共light兲 冊

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392 Genome Vol. 63, 2020

冉 冉
Fig. 4. The distribution of transformed nucleotide diversity log2 冊冊
values in horse autosomes. Data points above the

blue horizontal line are the top 1% of log2

values. The HMGA2 gene was not overrepresented in the top 1% of Z(FST)
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50 kb (Fig. 4). These values followed a normal distribu- with three other loci located near HMGA2, ZFAT, and
tion (Fig. 2). A total number of 446 windows including LASP1 genes explaining approximately 83% of wither
366 genes were identified in the top 1% of transformed ␪␲ height variation. On the other hand, Signer-Hasler et al.
values, ranged from 0.91 to 2.64 (Table S61). To identify (2012) indicated a quantitative trait loci (QTL) on ECA 3
more reliable selective signals, we determined the over- near LCORL gene and another QTL on ECA 9, together
lapped windows between the top 1% of Z(FST) and trans- explaining 18.2% of de-regressed estimated breeding val-
formed ␪␲ values by the cut-off ratio (Fig. 5). ues for horse wither height (Signer-Hasler et al. 2012). A
We detected 139 overlapped genes as selective signals majority of former studies (Makvandi-Nejad et al. 2012;
in the pony and light groups (Table S61), 10 of which Kader et al. 2015; Metzger et al. 2018) illuminated the
including BMP2, CPN1, IGFBP3, OPCML, DDX55, FGF12, effective role of LCORL gene in controlling horse wither
FAM13A, FAM189A1, C4ORF33, and CRB1 genes have been height variation. Sevane et al. (2017) also revealed a
detected to be related to body measurements (Table 1) in strong association between one SNP on LCORL gene and
human (N=Diaye et al. 2011; Cousminer et al. 2013; Wood several other body measurements such as hock circum-
et al. 2014; Bae et al. 2016) and animals (Fang et al. 2010; ference, knee perimeter, hind cannon circumference,
Fan et al. 2011; Olivieri et al. 2016; Xia et al. 2017). The and fore cannon circumference. In contrast to the
LCORL, DCAF16, and NCAPG genes were not overrepre- HMGA2, LCORL, and NCAPG genes, the CPN1 and DDX55
sented by transformed ␪␲ approach, conversely, HMGA2 genes were identified in the top 1% of both Z(FST) and
gene was only screened in the top 1% of transformed ␪␲ transformed ␪␲ values. These genes have significant as-
values; however, these genes were detected as functional sociations with human height (Allen et al. 2010) and
candidate genes for body measurements in previous pubertal height growth (Cousminer et al. 2013). Addition-
genome-wide association studies (Makvandi-Nejad et al. ally, DDX55 gene was also detected as a selective signal in
2012; Kader et al. 2015; W. Zhang et al. 2016; Sevane et al. German warmbloods (Nolte et al. 2019).
Genes associated with skeletal confirmation and growth
Genes associated with wither height BMP2, FGF12, and IGFBP3 are known as candidate genes
The genetic background of horse wither height varia- for growth and skeletal development. The insulin-like
tion has been studied by Makvandi-Nejad et al. (2012), growth factor (IGF) axis is known as a conserved evolu-
who reported one locus near LCORL and NCAPG genes tionarily system (Teumer et al. 2016) and some genes in

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Salek Ardestani et al. 393

Fig. 5. (A) Overrepresented windows of the top 1% of transformed ␪␲ and Z(FST) values. Data points located in the right side of
the vertical line (the top 1% of transformed ␪␲ values, where transformed ␪␲ value is 0.91) and above the horizontal line (the
top 1% of Z(FST) values, where Z(FST) value is 3.20) were detected as selective signals. (B) The venn diagram for the number of
overlapped genes between the top 1% of transformed ␪␲ and Z(FST) values.
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Table 1. Overrepresented horse type candidate genes between Z(FST) and transformed ␪␲ values.
Candidate Transformed
gene Chromosome Window (Mbp) Z(FST) ␪␲ values Associated phenotype Study
DDX55 8 23.47–23.49 6.83 1.32 Pubertal height growth in human Cousminer et al. 2013
CRB1 30 24.99–25.19 4.36 1.27 Body mass index in broiler chickens Akiyama et al. 2017
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BMP2 22 16.42–16.70 4.21 1.05 Growth and skeletal development in human Huang et al. 2002
FGF12 19 29.30–29.53 4.01 1.18 Skeletal growth in human Zhang et al. 2016a
C4ORF33 2 100.09–100.18 4.04 1.31 Body mass index in human Locke et al. 2015
CPN1 1 29.69–29.71 3.67 0.97 Height in human Allen et al. 2010
OPCML 7 40.70–40.90 4.20 1.52 Body mass index in human Huckins et al. 2018
IGFBP3 4 16.29–16.30 4.71 1.94 Skeletal development in human Chan et al. 2015
FAM189A1 1 107.65–107.75 5.35 1.00 Body mass index in human Frischknecht et al. 2016
FAM13A 3 48.99–49.26 3.36 0.95 Bone weight and fiber muscles size in cattle Xia et al. 2017

this family group are associated with cellular growth Shetland ponies (Frischknecht et al. 2016). Also, in a
regulators (Cheng et al. 2007), such as IGFBP3 that is re- genome-wide association study, Xia et al. (2017) demon-
lated to skeletal development (Chan et al. 2015). The strated the relation of FAM13A with bone weight, size,
BMP2 gene plays a key role in shaping bones, growth, and and number of muscle fibers in skeletal muscles of Sim-
skeletal development (Huang et al. 2002). This gene was mental cattle.
found to be associated with body trunk in goat (Fang Our selection signatures analysis between pony and
et al. 2010), and body depth, length, and width in swine light horses allowed the detection of 10 genes including
(Fan et al. 2011). Both BMP2 and IGFBP3 genes were previ- BMP2, CPN1, IGFBP3, OPCML, DDX55, FGF12, FAM13A,
ously confirmed as selective signals in German warm- FAM189A1, C4ORF33, and CRB1 as direct selective signals.
bloods (Nolte et al. 2019). The fibroblast growth factor These genes were found to be associated with body mea-
family consists of 22 members and genes, such as FGF12 surements in some species, and thus they might poten-
that plays a pivotal role in growth and formation of tially be related to pony and light horse type variation. To
bones (F. Zhang et al. 2016). FAM189A1, CRB1, OPCML, and the best of our knowledge, except for DDX55, BMP2,
C4ORF33 are known as candidate genes for body mass IGFBP3, OPCML, and FAM189A1 genes, the other five iden-
index in human (Frischknecht et al. 2015; Locke et al. tified selective signals have not been previously detected
2015; Akiyama et al. 2017; Huckins et al. 2018). Moreover, for horse type variation.
the OPCML gene was found to be associated with body
weight and growth rate in broiler chickens (Gu et al. Gene ontology of selective signal
2011). This gene was confirmed by Gurgul et al. (2019) as a To further detect biological function of selective signal
selective signal between draft and light horse breeds that candidate genes, we classified the significant biological
might have potentially contributed to developing differ- processes of 139 genes underlying selection pressures in
ent types of horse. Frischknecht et al. (2016) detected pony and light horses. These significant biological pro-
FAM189A1 as a selective signal for body mass index in cesses (Table S71) include insulin-like growth factor re-

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394 Genome Vol. 63, 2020

ceptor signaling pathway (GO:0048009, p-value = 0.01), decision to publish, or preparation of the manuscript.
regulation of insulin-like growth factor receptor signal- The specific roles of this author are articulated in the
ing pathway (GO:0043567, p-value = 0.04), positive regu- author contributions section.
lation of presynaptic cytosolic calcium concentration
Competing interests
(GO:0099533, p-value = 0.04), and induction of synaptic
Author M.S. is employed at Select Sires Inc. This orga-
vesicle exocytosis by positive regulation of presynaptic
nization did not play any role in the study design, data
cytosolic calcium ion concentration (GO:0099703,
collection and analysis, decision to publish, or prepara-
p-value = 0.04). A former study revealed the effective role
tion of the manuscript and only provided financial sup-
of insulin-like growth factor receptor signaling pathway
port in the form of M.S.‘s salary. This does not alter our
in head circumference and development of the nervous
adherence to Genome journal policies on sharing data and
system (Yang et al. 2019). The selective pressures for this
materials. Other authors have declared that no compet-
biological pathway can be reasonable considering the
ing interests exist.
differences in head dimensions between light and pony
horses. The cytosolic calcium concentration can be effec- References
tive in skeletal muscle kinetics (Cho et al. 2017). It can be Akiyama, M., Okada, Y., Kanai, M., Takahashi, A.,
Genome Downloaded from cdnsciencepub.com by on 12/30/20

associated with positive regulation of presynaptic cyto- Momozawa, Y., Ikeda, M., et al. 2017. Genome-wide associa-
solic calcium concentration and induction of synaptic tion study identifies 112 new loci for body mass index in the
Japanese population. Nat. Genet. 49(10): 1458–1467. doi:10.
vesicle exocytosis by positive regulation of presynaptic 1038/ng.3951. PMID:28892062.
cytosolic calcium ion concentration pathways. These two Al Abri, M.A., Posbergh, C., Palermo, K., Sutter, N.B., Eberth, J.,
biological pathways could be under selective pressures Hoffman, G.E., and Brooks, S.A. 2018. Genome-wide scans
particularly in light breeds considering their athletic us- reveal a quantitative trait locus for withers height in horses
ages such as racing, endurance, and sports. near the ANKRD1 gene. J. Equine Vet. Sci. 60: 67–73.e61. doi:
Conclusions Allen, H.L., Estrada, K., Lettre, G., Berndt, S.I., Weedon, M.N.,
Rivadeneira, F., et al. 2010. Hundreds of variants clustered in
For personal use only.

In conclusion, the comprehensive comparison of genomic loci and biological pathways affect human height.
whole-genome sequences of pony and light horses iden- Nature, 467(7317): 832–838. doi:10.1038/nature09410. PMID:
tified genomic regions and biological processes underly- 20881960.
ing selective pressures for light and pony horse types. In Asadollahpour Nanaei, H., Ayatollahi Mehrgardi, A., and
Esmailizadeh, A. 2019. Comparative population genomics
pony and light groups, 139 genes were detected as signa- unveils candidate genes for athletic performance in Ha-
tures of selection that are enriched for four significant noverians. Genome, 62(4): 279–285. doi:10.1139/gen-2018-
biological pathways. We detected five under-selective- 0151. PMID:30779599.
pressure novel genes including CPN1, FGF12, FAM13A, Bae, S., Choi, S., Kim, S.M., and Park, T. 2016. Prediction of
C4ORF33, and CRB1 that might possibly be related to body quantitative traits using common genetic variants: applica-
tion to body mass index. Genomics Inform. 14(4): 149–159.
measurement differences between light and pony types,
doi:10.5808/GI.2016.14.4.149. PMID:28154505.
such as wither height, skeletal confirmation, and Bolger, A.M., Lohse, M., and Usadel, B. 2014. Trimmomatic: a
growth. Moreover, these results can provide a better ge- flexible trimmer for Illumina sequence data. Bioinformatics,
netic perspective of phenotypic differences among pony 30(15): 2114–2120. doi:10.1093/bioinformatics/btu170. PMID:
and light groups. Obviously, there might have been some 24695404.
Bowling, A.T., and Ruvinsky, A. (Editors). 2000. The genetics of
limitation due to the small number of horses in this
the horse. CABI. 26 pp.
study, and therefore, further investigation and valida- Brooks, S., Makvandi-Nejad, S., Chu, E., Allen, J., Streeter, C.,
tion using genome-wide association and signatures of Gu, E., et al. 2010. Morphological variation in the horse: de-
selection studies are required with larger populations fining complex traits of body size and shape. Anim. Genet.
and multiple horse breeds. 41(s2): 159–165. doi:10.1111/j.1365-2052.2010.02127.x. PMID:
Author contributions Cha, S., Lim, J.E., Park, A.Y., Do, J.-H., Lee, S.W., Shin, C., et al.
S.S.A., M.A., Y.M., and M.B.Z.M. conceived and de- 2018. Identification of five novel genetic loci related to facial
morphology by genome-wide association studies. BMC
signed this experiment. S.S.A. wrote the first draft of the Genomics, 19(1): 481. doi:10.1186/s12864-018-4865-9. PMID:
manuscript and analyzed data under Y.M.’s supervision. 29921221.
S.S.A., M.A., Y.M., M.S., M.H.B., and M.B.Z.M. discussed Chan, Y., Salem, R.M., Hsu, Y.-H.H., McMahon, G., Pers, T.H.,
the results and contributed to the final manuscript. S.S.A Vedantam, S., et al. 2015. Genome-wide analysis of body pro-
and Y.M. wrote the final manuscript. All authors re- portion classifies height-associated variants by mechanism
of action and implicates genes important for skeletal devel-
viewed and approved the final manuscript. opment. Am. J. Hum. Genet. 96(5): 695–708. doi:10.1016/j.ajhg.
2015.02.018. PMID:25865494.
Funding statement
Cheng, I., DeLellis Henderson, K., Haiman, C.A., Kolonel, L.N.,
Select Sires Inc. provided support in the form of sala- Henderson, B.E., Freedman, M.L., and Le Marchand, L.C. 2007.
ries for author M.S., but they did not have any additional Genetic determinants of circulating insulin-like growth fac-
role in the study design, data collection and analysis, tor (IGF)-I, IGF binding protein (BP)-1, and IGFBP-3 levels in a

Published by NRC Research Press

Salek Ardestani et al. 395

multiethnic population. J. Clin. Endocrinol. Metab. 92(9): Genet. 10(10): e1004712. doi:10.1371/journal.pgen.1004712.
3660–3666. doi:10.1210/jc.2007-0790. PMID:17566087. PMID:25340504.
Chesi, A., Mitchell, J.A., Kalkwarf, H.J., Bradfield, J.P., Grilz-Seger, G., Druml, T., Neuditschko, M., Mesarič, M.,
Lappe, J.M., Cousminer, D.L., et al. 2017. A genomewide asso- Cotman, M., and Brem, G. 2019. Analysis of ROH patterns in
ciation study identifies two sex-specific loci, at SPTB and the Noriker horse breed reveals signatures of selection for
IZUMO3, influencing pediatric bone mineral density at mul- coat color and body size. Anim. Genet. 50(4): 334–346. doi:10.
tiple skeletal sites. J. Bone Miner. Res. 32(6): 1274–1281. doi: 1111/age.12797. PMID:31199540.
10.1002/jbmr.3097. PMID:28181694. Gu, X., Feng, C., Ma, L., Song, C., Wang, Y., Da, Y., et al. 2011.
Cho, C.-H., Woo, J.S., Perez, C.F., and Lee, E.H. 2017. A focus on Genome-wide association study of body weight in chicken F2
extracellular Ca2+ entry into skeletal muscle. Exp. Mol. Med. resource population. PLoS ONE, 6(7): e21872. doi:10.1371/
49(9): e378. doi:10.1038/emm.2017.208. PMID:28912570. journal.pone.0021872. PMID:21779344.
Colby, F.M. 1921. New International Yearbook: A Compendium Gurgul, A., Jasielczuk, I., Semik-Gurgul, E., Pawlina-Tyszko, K.,
of the World’s Progress for the Year 1920. Dodd, Mead & Co., Stefaniuk-Szmukier, M., Szmatoła, T., et al. 2019. A genome-
New York. 171 pp. wide scan for diversifying selection signatures in selected
Cook, D.E., and Andersen, E.C. 2017. VCF-kit: assorted utilities horse breeds. PLoS ONE, 14(1): e0210751. doi:10.1371/journal.
for the variant call format. Bioinformatics, 33(10): 1581–1582. pone.0210751. PMID:30699152.
doi:10.1093/bioinformatics/btx011. PMID:28093408. Han, Y., Chen, Y., Liu, Y., and Liu, X. 2017. Sequence variants of
Cousminer, D.L., Berry, D.J., Timpson, N.J., Ang, W., Thiering, E., the LCORL gene and its association with growth and carcass
Genome Downloaded from cdnsciencepub.com by on 12/30/20

Byrne, E.M., et al. 2013. Genome-wide association and longi- traits in Qinchuan cattle in China. J. Genet. 96(1): 9–17. doi:
tudinal analyses reveal genetic loci linking pubertal height 10.1007/s12041-016-0732-0. PMID:28360384.
growth, pubertal timing and childhood adiposity. Hum. Mol. Huang, W., Rudkin, G.H., Carlsen, B., Ishida, K., Ghasri, P.,
Genet. 22(13): 2735–2747. doi:10.1093/hmg/ddt104. PMID: Anvar, B., et al. 2002. Overexpression of BMP-2 modulates
23449627. morphology, growth, and gene expression in osteoblastic
Dall’Olio, S., Fontanesi, L., Nanni Costa, L., Tassinari, M., cells. Exp. Cell Res. 274(2): 226–234. doi:10.1006/excr.2002.
Minieri, L., and Falaschini, A. 2010. Analysis of horse myosta- 5483. PMID:11900483.
tin gene and identification of single nucleotide polymor- Huckins, L., Hatzikotoulas, K., Southam, L., Thornton, L.,
phisms in breeds of different morphological types. J. BioMed. Steinberg, J., Aguilera-McKay, F., et al. 2018. Investigation of
Biotechnol. 2010: 542945. doi:10.1155/2010/542945. PMID: common, low-frequency and rare genome-wide variation in
20706663. anorexia nervosa. Mol. Psychiatry, 23(5): 1169–1180. doi:10.
For personal use only.

Danecek, P., Auton, A., Abecasis, G., Albers, C.A., Banks, E., 1038/mp.2017.88. PMID:29155802.
DePristo, M.A., et al. 2011. The variant call format and Jun, J., Cho, Y.S., Hu, H., Kim, H.-M., Jho, S., Gadhvi, P., et al.
VCFtools. Bioinformatics, 27(15): 2156–2158. doi:10.1093/ 2014. Whole genome sequence and analysis of the Marwari
bioinformatics/btr330. PMID:21653522. horse breed and its genetic origin. BMC Genomics, 15(Suppl. 9):
Davies, T.J., Fritz, S.A., Grenyer, R., Orme, C.D.L., Bielby, J., S4. doi:10.1186/1471-2164-15-S9-S4. PMID:25521865.
Bininda-Emonds, O.R., et al. 2008. Phylogenetic trees and the Kader, A., Li, Y., Dong, K., Irwin, D.M., Zhao, Q., He, X., et al.
future of mammalian biodiversity. Proc. Natl. Acad. Sci. 2015. Population variation reveals independent selection to-
U.S.A. 105(Suppl. 1): 11556–11563. doi:10.1073/pnas.0801917105. ward small body size in Chinese Debao pony. Genome Biol.
PMID:18695230. Evol. 8(1): 42–50. doi:10.1093/gbe/evv245. PMID:26637467.
Draper, J., Sly, D., and Muir, S. 2014. The ultimate book of the Krzywinski, M.I., Schein, J.E., Birol, I., Connors, J., Gascoyne, R.,
horse and rider. Lorenz Books. Horsman, D., et al. 2009. Circos: an information aesthetic for
Ellegren, H., and Galtier, N. 2016. Determinants of genetic di- comparative genomics. Genome Res. 19(9): 1639–1645. doi:10.
versity. Nat. Rev. Genet. 17(7): 422–433. doi:10.1038/nrg.2016. 1101/gr.092759.109. PMID:19541911.
58. PMID:27265362. Li, H., and Durbin, R. 2009. Fast and accurate short read align-
Fan, B., Onteru, S.K., Du, Z.-Q., Garrick, D.J., Stalder, K.J., and ment with Burrows–Wheeler transform. Bioinformatics,
Rothschild, M.F. 2011. Genome-wide association study identi- 25(14): 1754–1760. doi:10.1093/bioinformatics/btp324. PMID:
fies loci for body composition and structural soundness traits 19451168.
in pigs. PLoS ONE, 6(2): e14726. doi:10.1371/journal.pone. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J.,
0014726. PMID:21383979. Homer, N., et al. 2009. The sequence alignment/map format
Fang, X., Xu, H., Zhang, C., Zhang, J., Lan, X., Gu, C., and Hong, C. and SAMtools. Bioinformatics, 25(16): 2078–2079. doi:10.1093/
2010. Polymorphisms in BMP-2 gene and their associations bioinformatics/btp352. PMID:19505943.
with growth traits in goats. Genes Genomics, 32(1): 29–35. Li, X., Su, R., Wan, W., Zhang, W., Jiang, H., Qiao, X., et al. 2017.
doi:10.1007/s13258-010-0762-6. Identification of selection signals by large-scale whole-
Frischknecht, M., Jagannathan, V., Plattet, P., Neuditschko, M., genome resequencing of cashmere goats. Sci. Rep. 7(1): 15142.
Signer-Hasler, H., Bachmann, I., et al. 2015. A non- doi:10.1038/s41598-017-15516-0. PMID:29123196.
synonymous HMGA2 variant decreases height in Shetland Locke, A.E., Kahali, B., Berndt, S.I., Justice, A.E., Pers, T.H.,
ponies and other small horses. PLoS ONE, 10(10): e0140749. Day, F.R., et al. 2015. Genetic studies of body mass index yield
doi:10.1371/journal.pone.0140749. PMID:26474182. new insights for obesity biology. Nature, 518(7538): 197–206.
Frischknecht, M., Flury, C., Leeb, T., Rieder, S., and doi:10.1038/nature14177. PMID:25673413.
Neuditschko, M. 2016. Selection signatures in Shetland Makvandi-Nejad, S., Hoffman, G.E., Allen, J.J., Chu, E., Gu, E.,
ponies. Anim. Genet. 47(3): 370–372. doi:10.1111/age.12416. Chandler, A.M., et al. 2012. Four loci explain 83% of size vari-
PMID:26857482. ation in the horse. PLoS ONE, 7(7): e39929. doi:10.1371/journal.
Gaudieri, S., Dawkins, R.L., Habara, K., Kulski, J.K., and pone.0039929. PMID:22808074.
Gojobori, T. 2000. SNP profile within the human major his- McKenna, A., Hanna, M., Banks, E., Sivachenko, A.,
tocompatibility complex reveals an extreme and interrupted Cibulskis, K., Kernytsky, A., et al. 2010. The Genome Analysis
level of nucleotide diversity. Genome Res. 10(10): 1579–1586. Toolkit: a MapReduce framework for analyzing next-
doi:10.1101/gr.127200. PMID:11042155. generation DNA sequencing data. Genome Res. 20(9): 1297–
Ghosh, S., Qu, Z., Das, P.J., Fang, E., Juras, R., Cothran, E.G., et al. 1303. doi:10.1101/gr.107524.110. PMID:20644199.
2014. Copy number variation in the horse genome. PLoS Meira, C.T., Farah, M.M., Fortes, M.R., Moore, S.S., Pereira, G.L.,

Published by NRC Research Press

396 Genome Vol. 63, 2020

Silva, J.A.I.V., et al. 2014. A genome-wide association study for Leeb, T., and Rieder, S. 2012. A genome-wide association
morphometric traits in quarter horse. J. Equine Vet. Sci. study reveals loci influencing height and other conformation
34(8): 1028–1031. doi:10.1016/j.jevs.2014.05.011. traits in horses. PLoS ONE, 7(5): e37282. doi:10.1371/journal.
Metzger, J., Schrimpf, R., Philipp, U., and Distl, O. 2013. Expres- pone.0037282. PMID:22615965.
sion levels of LCORL are associated with body size in horses. Staiger, E.A., Al Abri, M., Pflug, K.M., Kalla, S., Ainsworth, D.,
PLoS ONE, 8(2): e56497. doi:10.1371/journal.pone.0056497. Miller, D., et al. 2016. Skeletal variation in Tennessee Walk-
PMID:23418579. ing Horses maps to the LCORL/NCAPG gene region. Physiol.
Metzger, J., Tonda, R., Beltran, S., Águeda, L., Gut, M., and Genomics, 48(5): 325–335. doi:10.1152/physiolgenomics.
Distl, O. 2014. Next generation sequencing gives an insight 00100.2015. PMID:26931356.
into the characteristics of highly selected breeds versus non- Teumer, A., Qi, Q., Nethander, M., Aschard, H., Bandinelli, S.,
breed horses in the course of domestication. BMC Genomics, Beekman, M., et al. 2016. Genomewide meta-analysis identi-
15(1): 562. doi:10.1186/1471-2164-15-562. PMID:24996778. fies loci associated with IGF-I and IGFBP-3 levels with impact
Metzger, J., Rau, J., Naccache, F., Conn, L.B., Lindgren, G., and on age-related traits. Aging Cell, 15(5): 811–824. doi:10.1111/
Distl, O. 2018. Genome data uncover four synergistic key reg- acel.12490. PMID:27329260.
ulators for extremely small body size in horses. BMC Genom- Van Oosterhout, C. 2009. A new theory of MHC evolution: be-
ics, 19(1): 492. doi:10.1186/s12864-018-4877-5. PMID:29940849. yond selection on the immune genes. Proc. R. Soc. B Biol.
Moon, S., Lee, J.W., Shin, D., Shin, K.-Y., Kim, J., Choi, I.-Y., et al. Sci. 276(1657): 657–665. doi:10.1098/rspb.2008.1299. PMID:
2015. A genome-wide scan for selective sweeps in racing 18986972.
Wang, X., Liu, J., Zhou, G., Guo, J., Yan, H., Niu, Y., et al. 2016.
Genome Downloaded from cdnsciencepub.com by on 12/30/20

horses. Asian-Australas J. Anim. Sci. 28(11): 1525–1531. doi:10.

5713/ajas.14.0696. PMID:26333666. Whole-genome sequencing of eight goat populations for the
Nei, M., and Li, W.-H. 1979. Mathematical model for studying detection of selection signatures underlying production and
genetic variation in terms of restriction endonucleases. Proc. adaptive traits. Sci. Rep. 6: 38932. doi:10.1038/srep38932.
Natl. Acad. Sci. U.S.A. 76(10): 5269–5273. doi:10.1073/pnas.76.
Weir, B.S., and Cockerham, C.C. 1984. Estimating F-statistics for
10.5269. PMID:291943.
the analysis of population structure. Evolution, 38(6): 1358–
Nolte, W., Thaller, G., and Kuehn, C. 2019. Selection signatures
1370. doi:10.1111/j.1558-5646.1984.tb05657.x. PMID:28563791.
in four German warmblood horse breeds: tracing breeding
Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H.,
history in the modern sport horse. PLoS ONE, 14(4): e0215913.
Gustafsson, S., et al. 2014. Defining the role of common vari-
doi:10.1371/journal.pone.0215913. PMID:31022261.
ation in the genomic and biological architecture of adult
N=Diaye, A., Chen, G.K., Palmer, C.D., Ge, B., Tayo, B.,
human height. Nat. Genet. 46(11): 1173–1186. doi:10.1038/ng.
For personal use only.

Mathias, R.A., et al. 2011. Identification, replication, and fine- 3097. PMID:25282103.
mapping of loci associated with adult height in individuals of Xia, J., Fan, H., Chang, T., Xu, L., Zhang, W., Song, Y., et al. 2017.
African ancestry. PLoS Genet. 7(10): e1002298. doi:10.1371/ Searching for new loci and candidate genes for economically
journal.pgen.1002298. PMID:21998595. important traits through gene-based association analysis of
Olivieri, B.F., Mercadante, M.E.Z., Cyrillo, J.N., Branco, R.H., Simmental cattle. Sci. Rep. 7: 42048. doi:10.1038/srep42048.
Bonilha, S.F.M., de Albuquerque, L.G., et al. 2016. Genomic PMID:28169328.
regions associated with feed efficiency indicator traits in an Yang, J., Li, W.-R., Lv, F.-H., He, S.-G., Tian, S.-L., Peng, W.-F., et al.
experimental Nellore cattle population. PLoS ONE, 11(10): 2016. Whole-genome sequencing of native sheep provides
e0164390. doi:10.1371/journal.pone.0164390. PMID:27760167. insights into rapid adaptations to extreme environments.
Petersen, J.L., Mickelson, J.R., Rendahl, A.K., Valberg, S.J., Mol. Biol. Evol. 33(10): 2576–2592. doi:10.1093/molbev/
Andersson, L.S., Axelsson, J., et al. 2013. Genome-wide analy- msw129. PMID:27401233.
sis reveals selection for important traits in domestic horse Yang, X.-L., Zhang, S.Y., Zhang, H., Wei, X.-T., Feng, G.J., Pie, Y.F.,
breeds. PLoS Genet. 9(1): e1003211. doi:10.1371/journal.pgen. and Zhang, L. 2019. Three novel loci for infant head circum-
1003211. PMID:23349635. ference identified by a joint association analysis. Front.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Genet. 10: 947. doi:10.3389/fgene.2019.00947. PMID:31681408.
Bender, D., et al. 2007. PLINK: a tool set for whole-genome Zhang, C., Ni, P., Ahmad, H.I., Gemingguli, M., Baizilaitibei, A.,
association and population-based linkage analyses. Am. J. Gulibaheti, D., et al. 2018. Detecting the population structure
Hum. Genet. 81(3): 559–575. doi:10.1086/519795. PMID: and scanning for signatures of selection in horses (Equus
17701901. caballus) from whole-genome sequencing data. Evol. Bioinform.
Rubin, C.-J., Megens, H.-J., Barrio, A.M., Maqbool, K., Sayyab, S., Online, 14: 1176934318775106. doi:10.1177/1176934318775106.
Schwochow, D., et al. 2012. Strong signatures of selection in PMID:29899660.
the domestic pig genome. Proc. Natl. Acad. Sci. U.S.A. 109(48): Zhang, F., Dai, L., Lin, W., Wang, W., Liu, X., Zhang, J., et al. 2016.
19529–19536. doi:10.1073/pnas.1217149109. PMID:23151514. Exome sequencing identified FGF12 as a novel candidate
Salek Ardestani, S., Aminafshar, M., Zandi Baghche Maryam, M.B., gene for Kashin-Beck disease. Funct. Integr. Genomics, 16(1):
Banabazi, M.H., Sargolzaei, M., and Miar, Y. 2020. Whole-genome 13–17. doi:10.1007/s10142-015-0462-z. PMID:26290467.
signatures of selection in sport horses revealed selection Zhang, W., Li, J., Guo, Y., Zhang, L., Xu, L., Gao, X., et al. 2016.
footprints related to musculoskeletal system development Multi-strategy genome-wide association studies identify the
processes. Animals, 10(1): E53. doi:10.3390/ani10010053. DCAF16-NCAPG region as a susceptibility locus for average
PMID:31888018. daily gain in cattle. Sci. Rep. 6: 38073. doi:10.1038/srep38073.
Sevane, N., Dunner, S., Boado, A., and Cañon, J. 2017. Polymor- PMID:27892541.
phisms in ten candidate genes are associated with conforma- Zhang, Z., Jia, Y., Almeida, P., Mank, J.E., van Tuinen, M.,
tional and locomotive traits in Spanish purebred horses. Wang, Q., et al. 2018. Whole-genome resequencing reveals
J. Appl. Genet. 58(3): 355–361. doi:10.1007/s13353-016-0385-y. signatures of selection and timing of duck domestication.
PMID:27917442. GigaScience, 7(4): giy027. doi:10.1093/gigascience/giy027.
Signer-Hasler, H., Flury, C., Haase, B., Burger, D., Simianer, H., PMID:29635409.

Published by NRC Research Press